Dr Michel Pfeffer

Geneviève Stoll

Mélanie Boucher

Christophe Deraedt

Yann Cornaton

Binh Dang

Ho

Dang

Corinne Bailly

Je Remercie

Audrey Auffrant

for all the help you have given me during my three years. Thanks to Christophe DERAEDT for Mes études au LCSOM (

the experimental support and kinds of suggestions ; thanks to Yann CORNATON for the excellent computational studies ; thanks to Lydia KARMAZIN, Corinne BAILLY, Nathalie GRUBER for the help of X-ray characterization ; thanks to Maurice COPPE and Bruno VINCENT for the help of NMR ; thanks to Laurent Ruhlmann for his help with cyclic voltammetry ; thanks to Sylvie CHOUA and Nolwenn LE BRETON for our EPR experiments; thanks to all the members of the Elemental Analysis and Mass Spectroscopy services for their contribution and assistance. I would also like to thank Pr. Blanca MARTIN-VACA (Université Paul Sabatier), Dr. Audrey AUFFRANT (École Polytechnique) and Pr. Vincent RITLENG (Université de Strasbourg) for accepting to take part to this thesis jury and to evaluate this work.

My thanks would go to my beloved family for their loving considerations and great confidence in me all through these years. I also owe my sincere gratitude to my friends who have made my life in Strasbourg so enriching. Co(III) cobaltacycles with [Ph3C][BArF24] in DCM ............................................... Table 3. 3. Treatment with D2O/H2O that promotes the formation of [1c][BArF24] under an atmosphere of Air or Argon ................................................................................................................................................... ............................................................................................................... mechanism. ........................................................................................................................................... Figure 2. 4. Evolution of the ionic and covalent character of the Op-Co interaction in the course of the CMD process expressed as a percentage of the associated interatomic QTAIM-IQA energy of interaction Eint. ....................................................................................................................................... Ir-NHAc-ag-col complexes. .............................................. Figure 2. 9. NCI integrals for ag and Ir-NHAc-ag-col compounds. ...................................................... Figure 2. 10. Hag-Cag-Cb-Hb dihedral for ag and ag-col compounds. ................................................... ................................................................................................ TZP level. ............................................................... Figure 2. 14. Local Energy Decomposition (LED) analysis for the Ir and Co systems along the reaction coordinates of the CMD mechanism with plots of the inter fragment interaction energies Ei-j, where i XII and j are the considered molecular fragment numbers: a) fragmentation scheme and numbering for the LED analysis, b) interaction energy between fragment 2 (H + ) and the sum of fragments 3 and 4, c) interaction energy between fragments 2 and 5 (Cp* ligand), d) interaction energy between fragments 1 and 2. .................................................................................................................................................... Figure 2. 15. Effect of the solvent (THF vs DCM) on the yield in 1a upon cyclocobaltation of 2-phpyH by [Cp*CoI2]2 in the presence of various amounts of LiNHAc per Co atom (1, 3, 5, and 10 equiv) ...... probability.. ............................................................................................................................................ Figure 2. 17. ORTEP diagram of the structure of [1c][I3] and [1c'][I3], ellipsoids displayed at 50% probability. ............................................................................................................................................. reactions carried out under identical conditions in a sealed vessel in CH2Cl2 at 50°C with 2-phpyH and 2-(d5.ph)pyD. ......................................................................................................................................... Figure 2. 21. Excerpts of the 1 H coupled 13 C NMR spectrum of the raw product displaying isotope shifts of resonances for the characteristic signals used for the estimation of the KIE from their integration. . ........................................................................................................................................... probability. ............................................................................................................................................. probability. ............................................................................................................................................. probability. ............................................................................................................................................. probability. ...........................................................................................................................................

XI

List of figures

Figure 3. 2. ORTEP-type drawings of the structures of [1c]

[BArF24] at 50% probability with partial atom numbering. .......................................................................................................................................... Figure 3.3. ORTEP-type drawings of the structures of 7a (a) and 8a (b) at 50% probability with partial atom numbering. ................................................................................................................................. Figure 3. 4. ORTEP-type drawings of the structures of (a) [7c] + and (b) [8c] + at 50% probability with partial atom numbering. ....................................................................................................................

XIII Figure 3. 5. ORTEP-type drawings of the structures of [5a']

[BArF24] at 50% probability with partial atom numbering. The [BArF24] anion were omitted for clarity. ........................................................... Figure 3. 6. ORTEP-type drawings of the structures of (a) [7d][BArF24], and (b) [8d][BArF24] at 50% probability with partial atom numbering.. ............................................................................................ Figure 3. 7. ORTEP-type drawing of the structure of (a) 10a and (b) [10c][BArF24] at 50% probability with partial atom numbering.. .............................................................................................................. Figure 3. 8. Instrumentation of the typical isothermal titration calorimetry. ........................................ Figure 3. 9. Thermographic trace of the isotherm calorimetric titration of a solution of 1a (0.94 mM) by sequential addition of 2 μL of a solution of [Ph3C][BArF24] (19.6 mM) in DCE at 25°C in an argon-filled glovebox.. ............................................................................................................................................ Figure 3. 10. Cyclic voltammograms of {[Cp*Co]2(μ-I)3} [BArF24], TEAI, 1a and [1c][BArF24] (0.4 mmol L -1 ) on Pt electrode in a DCE solution in the presence of [N(nBu)4][PF6] (0.1 mol L -1 ). v = 100 mV s 2(μ-I3 + }[I3 -] (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s 2(μ-I3 + }[I3 -] and of TEAI (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s [BArF24] (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s -1 . .................................................... ). v = 100 mV s . Cyclic voltammograms of 8a (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s . Cyclic voltammograms of 1a and 10a (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s . Cyclic voltammograms of 10a (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s of reaction between 40 mM solutions of 1a and [Ph3C][BArF24] in DCM . The spectrum was recorded at a frequency of 9.345 GHz. ............................................................................................................................................................ Figure 3. 21. NCI plots [START_REF] Johnson | Revealing Noncovalent Interactions[END_REF]336 from ADFview2019 for optimized geometries of a) singlet ground state 1a, b) its singlet ground state Ir analogue Ir-1a, c) doublet ground state [1a'] + , d) doublet ground state [Ir-1a'] + (SCM-ADF2019 339 ZORA 340 -PBE 201 -D4(EEQ) 341 / all electron TZP / COSMO 342 (CH2Cl2) level).

. ........................................................................................................................................................... [START_REF] Johnson | Revealing Noncovalent Interactions[END_REF]336 from ADFview2019 for optimized geometries of a) doublet ground state [Cp*Co(SCF3)(phpy)] + and b) doublet ground state [9a'] + (SCM-ADF2019 339 ZORA 340 -PBE 201 -D4(EEQ) 341 / all electron TZP / COSMO 342 (CH2Cl2) level). ................................................................. ............................................................................................................................................... The hydrogen-atoms on the carbon and BArF24 ─ were omitted for clarity. ............................................... Figure 4. 4. Variable-temperature 1 H NMR spectra of the reaction of 1b with ethyl diazoacetate (600 MHz, THF-d8). ................................................................................................................................................... [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H NMR spectra for the reaction of 1a with [Ph3C][BArF24] with or without TEMPO. .............................................................................................................................................................. AgPF6 (bottom). The red stripe highlights the resonance of H5. ......................................................................................................................................... [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H NMR spectra of the reaction of 1a with acetic acid (top: 5 h; bottom: 24 h; blue point: starting materiel; red point: final product). In this reaction, the color slowly changed from red-brown to green. .................................................................................................................................................................. Figure 5. 5. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H NMR spectrum of the reaction of 1a with acetic acid after 24 h. .................................... Figure 5. 6. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H NMR spectra of the reaction of 1a with [Ph3C][BArF24] under argon (top) or air (bottom).. ............................................................................................................................................................ Figure 5. 7. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H NMR spectrum of the reaction mixture (bottom) resulting from the reaction of 5a (top) with [Ph3C][BArF24]. .......................................................................................................................................... Figure 5. 8. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H NMR spectrum of the reaction mixture (bottom) resulting from the reaction of 9a (top) or 1a (bottom) with [Ph3C][BArF24]. ................................................................................................................ Figure 5. 9. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H NMR spectrum of the reaction mixture produced by the reaction of 1b with [Ph3C][BArF24] after 17 h and 48 h. ................................................................................................................ Figure 5. 10. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H NMR spectrum of the reaction mixture resulting from the reaction of metallacycles with [Ph3C][BArF24]. .......................................................................................................................................... Figure 5. 11. Standard stoichiometric reaction of 1b with HSiEt3 monitored by 1 H NMR. (top: at 247 K;bottom: 298K). ................................................................................................................................................... 1 H NMR spectrum (500 MHz,CDCl3) of 1a ............................................................................ Figure A. 2. 13 C NMR spectrum (126 MHz,CDCl3) of 1a ........................................................................... Figure A. 3. 1 H NMR spectrum (500 MHz,CDCl3) of 3a ............................................................................ Figure A. 4. 13 C NMR spectrum (126 MHz,CDCl3) of 3a .......................................................................... Figure A. 5. 1 H NMR spectrum (500 MHz,CDCl3) of 4a ............................................................................ Figure A. 6. 13 C NMR spectrum (126 MHz,CDCl3) of 1a .......................................................................... Figure A. 7. 1 H NMR spectrum (500 MHz,CDCl3) of 5a ............................................................................ Figure A. 8. 13 C NMR spectrum (126 MHz,CDCl3) of 5a .......................................................................... Figure A. 9. 1 H NMR spectrum (500 MHz,CDCl3) of 6a ............................................................................ Figure A. 10. 13 C NMR spectrum (126 MHz,CDCl3) of 6a ........................................................................ Figure A. 11. 1 H NMR spectrum (500 MHz,CDCl3) of 7a .......................................................................... Figure A. 12. 13 C NMR spectrum (126 MHz,CDCl3) of 7a ........................................................................ Figure A. 13. 1 H NMR spectrum (500 MHz,CDCl3) of 8a .......................................................................... Figure A. 14. 13 C NMR spectrum (126 MHz,CDCl3) of 8a ........................................................................ Figure A. 15. 1 H NMR spectrum (400 MHz,CDCl3) of 9a .......................................................................... Figure A. 16. 1 H NMR spectrum (500 MHz,CDCl3) of 10a ........................................................................ Figure A. 17. 13 C NMR spectrum (126 MHz,CDCl3) of 10a ...................................................................... Figure A. 18. 1 H NMR spectrum (500 MHz,CD2Cl2) of 1b ........................................................................ Figure A. 19. 13 C NMR spectrum (126 MHz,CD2Cl2) of 1b ...................................................................... Figure A. 20. 1 H NMR spectrum (500 MHz,CD2Cl2) of 1b ' ....................................................................... Figure A. 21. 13 C NMR spectrum (126 MHz,CD2Cl2) of 1b ' ..................................................................... Figure A. 22. 1 H NMR spectrum (500 MHz,CDCl3) of 3b ......................................................................... Figure A. 23. 13 C NMR spectrum (126 MHz,CDCl3) of 3b ........................................................................ Figure A. 24. 1 H NMR spectrum (500 MHz,CDCl3) of 4b ......................................................................... Figure A. 25. 13 C NMR spectrum (126 MHz,CDCl3) of 4b ........................................................................ Figure A. 26. 1 H NMR spectrum (500 MHz,CDCl3) of 5b ......................................................................... Figure A. 27. 13 C NMR spectrum (126 MHz,CDCl3) of 5b ........................................................................ Figure A. 28. 1 H NMR spectrum (500 MHz,CDCl3) of 2b .......................................................................... Figure A. 29. 13 C NMR spectrum (126 MHz,CDCl3) of 2b ........................................................................ Figure A. 30. 1 H NMR spectrum (500 MHz,CDCl3) of 1f .......................................................................... Figure A. 31. 13 C NMR spectrum (126 MHz,CDCl3) of 1f ......................................................................... Figure A. 32. 1 H NMR spectrum (500 MHz,CDCl3) of [1c][BArF24] ......................................................... Figure A. 33. 13 C NMR spectrum (126 MHz,CDCl3) of [1c][BArF24] ........................................................ Figure A. 34. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 1 H COSY spectrum of [1c][BArF24] ................................................................................. . [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HSQC spectrum of [1c][BArF24] ................................................................................ Figure A. 37. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HMBC spectrum of [1c][BArF24] ................................................................................ Figure A. 38. 1 H NMR spectrum (500 MHz,CDCl3) of [7c][BArF24] ......................................................... Figure A. 39. 13 C NMR spectrum (126 MHz,CDCl3) of [7c][BArF24] ........................................................ Figure A. 40. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 1 H COSY spectrum of [7c][BArF24] .................................................................................. Figure A. 41. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H-1 H NOESY spectrum of [7c][BArF24] ............................................................................... Figure A. 42. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HSQC spectrum of [7c][BArF24] ................................................................................ Figure A. 43. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HMBC spectrum of [7c][BArF24] ................................................................................ Figure A. 44. 1 H NMR spectrum (500 MHz,CDCl3) of [8c][BArF24] ......................................................... Figure A. 45. 13 C NMR spectrum (126 MHz,CDCl3) of [8c][BArF24] ........................................................ Figure A. 46. . . [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HSQC spectrum of [8c][BArF24] ................................................................................ Figure A. 49. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HMBC spectrum of [8c][BArF24] ................................................................................ Figure A. 50. 1 H NMR spectrum (500 MHz,CD2Cl2) of [7d][BArF24] ........................................................ Figure A. 51. 13 C NMR spectrum (126 MHz,CD2Cl2) of [7d][BArF24] ...................................................... Figure A. 52. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H-1 H COSY spectrum of [7d][BArF24] .................................................................................. Figure A. 53. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H-1 H NOESY spectrum of [7d][BArF24] ............................................................................... Figure A. 54. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HMBC spectrum of [7d][BArF24] ................................................................................ Figure A. 55. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HMBC spectrum of [7d][BArF24] ................................................................................ Figure A. 56. 1 H NMR spectrum (500 MHz,CD2Cl2) of [8d][BArF24] ........................................................ Figure A. 57. 13 C NMR spectrum (126 MHz,CD2Cl2) of [8d][BArF24] ...................................................... Figure A. 58. . . [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HMBC spectrum of [8d][BArF24] ................................................................................ Figure A. 61. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HMBC spectrum of [8d][BArF24] ................................................................................ Figure A. 62. 1 H NMR spectrum (300 MHz,CD2Cl2) of [10c][BArF24] ...................................................... Figure A. 63. 13 C NMR spectrum (126 MHz,CD2Cl2) [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HSQC spectrum of [10c][BArF24] .............................................................................. Figure A. 67. [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H- 13 C HMBC spectrum of [10c][BArF24] .............................................................................. ............................................................................................. 19 as expected. ............................................................................................................ 278 19. .................................................................................................................................. 279 Figure A. 75. Mass spectrum (ESI) overview of the crude compound in negative mode. BArF24 -was observed at m/z 863.07, I -was observed at m/z 126. 90 ............................................................................. 280 95. ........................................................................................................................................................ 281 Figure A. 78. Zoomed mass spectrum of the crude compound. The Cp* Co(phpy) fragment was observed at m/z 348. 12. .................................................................................................................................. 281 Figure A. 79. Zoomed mass spectrum of the crude reaction mixture. ..................................................... 282 (positive mode). [1c] + at m/z 290.19 was observed. A dimer of protonated 2-phenylpyridine resulting from an homocoupling is observed at m/z 309. 14. ...................................................................................... 283 Figure A. 82. IQA analysis of anag, TS-ag, ag and TS-CH in CoOAc, CoNHAc, IrOAc and IrNHAc systems (and ag-col in IrNHAc). Histograms of atom-pair interaction energies within the reactive site (black coloured, total Eint in kcal/mol) are decomposed into their covalent component (blue colored bars) and ionic component (red colored bars). ............................................................................................. 292 Figure A. 83. LED analysis for Co-OAc (red lines), Co-NHAc (green lines), Ir-OAc (blue lines) and Ir-NHAc (brown lines) systems along the reaction coordinates of the CMD mechanism with plots of interfragment interaction energies Ei-j, where i and j are the considered molecular fragment numbers : a) interaction energy between fragments 2 (H + ) and 1 (metal), b) interaction energy between fragments 3 (auxiliary basis) and 1 (metal), c) interaction energy between fragments 4 (2-phpy -) and 1 (metal), d) interation energy between fragments 5 (Cp* ligand) and 1 (metal), e) interaction energy between fragments 3 (auxiliary basis) and 2 (H + ), f) interaction energy between fragments 4 (2-phpy -) and 2 (H + ), g) interaction energy between fragments 5 (Cp* ligand) and 2 (H + ), h) interaction energy between fragments 4 (2-phpy -) and 3 (auxiliary basis), i) interaction energy between fragments 5 (Cp* ligand) and 3 (auxiliary basis), j) interaction energy between fragments 5 (Cp* ligand) and 4 (2-phpy -). ........ 295 ........................................... 298 .................................................................... Table A. 2. Crystal data and structure refinement for 4a. .................................................................... Table A. 3. Crystal data and structure refinement for 5a. .................................................................... Table A. 4. Crystal data and structure refinement for 7a. .................................................................... Table A. 5. Crystal data and structure refinement for 8a. .................................................................... Table A. 6. Crystal data and structure refinement for 10a. .................................................................. Table A. 7. Crystal data and structure refinement for 1b. .................................................................... Table A. 8. Crystal data and structure refinement for 3b. .................................................................... Table A. 9. Crystal data and structure refinement for 4b. .................................................................... Table A. 10. Crystal data and structure refinement for 5b. .................................................................. Table A. 11. Crystal data and structure refinement for 1b '. ................................................................. Table A. 12. Crystal data and structure refinement for 1f. ................................................................... Table A. 13. Crystal data and structure refinement for 2b. .................................................................. ......................................................... Table A. 16. Crystal data and structure refinement for 2c. .................................................................. Table A. 17 .............................................. Table A. 24. Crystal data and structure refinement for [5a'][BArF24]. ............................................... Table A. 25 .......................................................... ......................................................... COSMO(CH2Cl2) level ...........................................................................................................................

XIV Figure 3. 22. NCI plots

Chapter 5. Figure 5. 1. Comparison of

Figure 5. 2. 1 H NMR spectra of 1a with [Ph3C][PF6] (top) or

XV XVI

List of annexes

XVII

XIX

Résultats et discussions

Dans

Conclusion générale

Les and C-X (heteroatom) bonds, and also providing a new approach to the synthesis of natural products and various organic molecules, which became a powerful tool in organic synthesis [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF][2][START_REF] Balcells | C-H Bond Activation in Transition Metal Species from a Computational Perspective[END_REF][START_REF] Chavan | Cp*Co(III)-Catalyzed C-H Functionalization Cascade of N-Methoxyamides with Alkynedione for the Synthesis of Indolizidines[END_REF] . In the general case, the traditional cross-coupling reaction is one of the most useful synthetic methods for the formation of C-C bonds. However, this reaction needs extra procedures to prepare organohalides or triflate compounds, as well as organoboron compounds or metal-compounds [START_REF] Rat | C-H Bond Activation Mediated by Inorganic and Organometallic Compounds of Main Group Metals[END_REF][START_REF] Lyons | Palladium-Catalyzed Ligand-Directed C-H Functionalization Reactions[END_REF] . In contrast, the C-H activation approach does not require pre-functionalization of the starting materials (halogenation or borylation), simplifying the synthesis process and reducing undesired by-products, which is more economical and environmentally friendly in terms of atoms and steps (Scheme 1.1).

Scheme 1. 1. Comparison between traditional cross-coupling approach and C-H activation approach.

Although the activation and functionalization of C-H bond have attracted widespread attention and have become the basis of modern chemistry, it is still limited by two significant challenges [START_REF] Rat | C-H Bond Activation Mediated by Inorganic and Organometallic Compounds of Main Group Metals[END_REF][START_REF] Xu | Recent Advances in Transition-Metal-Catalyzed Silylations of Arenes with Hydrosilanes: C-X Bond Cleavage or C-H Bond Activation Synchronized with Si-H Bond Activation[END_REF][8][START_REF] De Azambuja | The Challenge of C-H Activation in Organic Synthesis[END_REF][START_REF] Li | Challenge and progress: palladium-catalyzed sp(3) C-H activation[END_REF][START_REF] Schwarz | Electronic Effects on Room-Temperature, Gas-Phase C-H Bond Activations by Cluster Oxides and Metal Carbides: The Methane Challenge[END_REF] :

1) Reactivity of C-H bond.

It is well known that the C-H bond is usually considered to be an inert chemical bond due to its high bond energy and low polarity. Therefore, the cleavage of the C-H bond and the formation of new carbon-containing chemical bonds under mild conditions is a significant challenge, and a large kinetic barrier needs to be overcome, so that high reaction temperature is required for most reactions associated with C-H activation, which would undoubtedly impose a detrimental effect. Subsequently, various transition metals were found to promote the cleavage of C-H bonds, and have been successfully

applied for C-H activation and functionalization, such as Pd, Rh, Fe, Co, Ni, Cu [START_REF] Yang | Recent advances in transition metal (Pd, Ni)-catalyzed C(sp(3)) H bond activation with bidentate directing groups[END_REF][13][START_REF] Landaeta | Insights on the C-H Bond activation by Transition Metal Complexes from Groups 8-10 Bearing (P-N) Chelates[END_REF] .

The main reason is that the M-C bond formed via transition metals-catalyzed C-H bond activation is more reactive than C-H bond and can be further converted under mild conditions. In addition, transition metals-catalyzed C-H activation has redefined the organic synthesis and this approach was widely used in the synthesis of natural products, pharmaceutical molecules, and other organic compounds [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF][START_REF] Xu | Recent Advances in Transition-Metal-Catalyzed Silylations of Arenes with Hydrosilanes: C-X Bond Cleavage or C-H Bond Activation Synchronized with Si-H Bond Activation[END_REF][START_REF] Yang | Recent Advances in Transition-Metal-Catalyzed/Mediated Transformations of Vinylidenecyclopropanes[END_REF][START_REF] Yin | Transition-Metal-Catalyzed Carbonylative Synthesis and Functionalization of Heterocycles[END_REF][START_REF] Tang | Palladium-Catalyzed Allylic C-H Functionalization: The Development of New Catalytic Systems[END_REF][START_REF] Yan | Transition-metal-catalyzed additions of C-H bonds to C-X (X = N, O) multiple bonds via C-H bond activation[END_REF] . In contrast, the directing group-based approach is more broadly applicable and has considerable potential [START_REF] Yang | Recent advances in transition metal (Pd, Ni)-catalyzed C(sp(3)) H bond activation with bidentate directing groups[END_REF][START_REF] Wu | Directing group assists in transition metal-catalyzed site-selective C-H bond activation/transformations[END_REF] . This approach typically proceeds by the formation of a Although great progress has been made by this approach in the last few decades, there are some limitations in the process of construction of the directing groups in the substrate and also the removal at the end, and can also reduce the efficiency and compatibility of the reaction. More recently, these limitations can be overcome by introducing covalent or noncovalent interactions between the substrate and transitionmetal center. For the covalent interaction, the desired C-H bond is activated by introducing a designed transient directing group that binds to the substrate as well as the metal center, and then this directing group can be easily removed without changing the substrate (Scheme 1.3b). On the other hand, noncovalent interactions are introduced to direct the selective activation of C-H bond, such as hydrogen, halogen, and also ion-π, agostic, anagostic, mainly involves weak inter-or intra-molecular attractions (Scheme 1.3c) [START_REF] Hamdaoui | CHAPTER 27 Noncovalent Interactions in Key Metal-centred Catalytic Intermediates: Structure-Electronic Relationship[END_REF][START_REF] Johnson | Revealing Noncovalent Interactions[END_REF] . For the present, the strategy of utilizing noncovalent interactions is potentially powerful and relatively unexplored.

2) Selectivity of C-H bond

Despite

Development of cobalt in C-H activation

In the preliminary stage of C-H activation, the 4d and 5d transition metals dominate this field, such as rhodium, ruthenium, iridium, palladium and platinum, benefiting from the variable valence and strong coordination. Regrettably, these transition metals are not only costly but also toxic. Hence, more environmentally and economically alternatives are increasingly attracting attention. Accordingly, the less toxic, inexpensive, and earth-abundant 3d transition metals have gained enormous interest and became a hot topic recently [START_REF] Gandeepan | 3d Transition Metals for C-H Activation[END_REF] .

Among these 3d transition metals, cobalt complexes have emerged as efficient and versatile catalysts for C-H activation, which is evidenced by the increasing number of papers on cobalt-catalyzed C-H activation that are recently disclosed (Figure 1.1 blue). In addition, the Grignard reagents also lead to low functional group compatibility [START_REF] Gao | Low-valent cobalt catalysis: new opportunities for C-H functionalization[END_REF][START_REF] Oliveira | Insights into the Mechanism of Low-Valent Cobalt-Catalyzed C-H Activation[END_REF][START_REF] Baccalini | Recent advances in cobalt-catalysed C-H functionalizations[END_REF][START_REF] Wang | C-H functionalization by high-valent Cp*Co(III) catalysis[END_REF][START_REF] Cong | Low-valent cobalt-catalyzed C-H allylation[END_REF] . Therefore, it is essential to develop new cobalt catalysts for C-H activation under mild conditions without the use of Grignard reagents.

High-valent cobalt-catalyzed C-H activation

The low-valent cobalt-catalyzed C-H activation and functionalization have been widely utilized in organic synthesis, in contrast, the high-valent cobalt-catalysts for CH activation has been gradually attracting attention more recently [START_REF] Wang | C-H functionalization by high-valent Cp*Co(III) catalysis[END_REF] . Therefore, in this section, the discussion will mainly focus on the development of high-valent cobalt in C-H activation, especially the Cp*Co(III)-complexes. Thereafter, the Cp*Co(III)-catalysts have attracted an increasing amount of attention in synthetic organic chemistry, and a range of C-H functionalization has been further extended, mainly involving reactions such as terminal coupling reactions as well as the formation of heterocycle.

Terminal coupling using Cp*Co(III) catalysts

Terminal coupling via transition metal-catalyzed C-H bond activation has developed into a diverse field of research. The applicable catalysts are multifaceted and the products obtained are diverse, ranging from basic chemicals to complex molecules. As a consequence, a significant number of examples of this type of coupling reaction catalyzed by Cp*Co(III)-catalysts will be discussed in this section. And these examples will be classified according to the type of bond that is formed in the coupling reaction, which can divide into C-C bond formation and C-X bond formation. Ackermann reported the C-H alkynylation of indoles by using 1-bromoalkynes and cyclopropanes as coupling partner (Scheme 1.9 d and f) [START_REF] Sauermann | Cobalt(III)-Catalyzed C-H Alkynylation with Bromoalkynes under Mild Conditions[END_REF][START_REF] Zell | Mild C-H/C-C Activation by Z-Selective Cobalt Catalysis[END_REF] . Subsequently, the use of alkynes as coupling partners was further developed by Chen and Yu in 2016 (Scheme 1.9 e and k) [START_REF] Wang | Cobalt(III)-catalyzed alkenylation of arenes and 6-arylpurines with terminal alkynes: efficient access to functional dyes[END_REF] , in the case of use phenylacetylene, the C-H alkenylation could also be achieved efficiently. [START_REF] Gensch | Cobalt(III)-Catalyzed Directed C-H Allylation[END_REF] . But the yield was significantly lower when compared to the previously mentioned C-H alkenylation of indoles (Scheme 1.9b) [START_REF] Gensch | Cobalt(III)-Catalyzed Directed C-H Allylation[END_REF] . In addition, Yoshino and

Matsunaga have also described a method for the allylation of benzamide substrates, by replacing the allyl carbonate with allyl alcohol (Scheme 1.10e) [START_REF] Bunno | Cp*Co(III)-Catalyzed Dehydrative C-H Allylation of 6-Arylpurines and Aromatic Amides Using Allyl Alcohols in Fluorinated Alcohols[END_REF] .

In 2016, Li and co-workers have explored the potential of cobalt(III)-catalyzed αfluoroalkenylation (Scheme 1.10f) [START_REF] Kong | Cobalt(III)-Catalyzed Regio-and Stereoselective alpha-Fluoroalkenylation of Arenes with gem-Difluorostyrenes[END_REF] . Notably, an unusual product observed when using ethyl benzimidates as arene substrate, which was also demonstrating the potential of Moreover, oxazolone can act as an efficient amidating agent (Scheme 1.11b) 57 .

Additionally, another example disclosing the alkylation of 8-methylquinoline with diazo compounds has been reported by Shi and co-workers (Scheme 1.11c) [START_REF] Yan | Cobalt(III)-Catalyzed Alkylation of Primary C(sp 3 )-H Bonds with Diazo Compounds[END_REF] . (Scheme 1.11d) [START_REF] Li | Cobalt(III)/Rhodium(III)-Catalyzed Regio-and Stereoselective Allylation of 8-Methylquinoline via sp 3 C-H Activation[END_REF] . In this reaction, either cobalt(III) or rhodium(III) catalysts can achieve this conversion with good efficiency as well as high regio-and stereoselectivity, but seem to be more reactive and selective under Rh(III)-catalyzed conditions. In 2020, an efficient and economical cobalt-catalyzed C(sp 3 )-H method was first proposed by Fan and co-workers for the addition of 8-methylquinolines with azabenzonorbornadienes (Scheme 1.11e) [START_REF] Tan | Cobalt-catalyzed ring-opening addition of azabenzonorbornadienes via C(sp3)-H bond activation of 8-methylquinoline[END_REF] , which exhibited a wide range of substrate scope as well as good functional group tolerance.

C-X bond formation

In Scheme 1. 12. Selected Cp*Co(III)-catalyzed C-X bond formations.

1) C-H amidation

Due to the specificity of the amide functional group in organic synthesis, the formation of C-N bond with an economical approach via C-H amidation has attracted much attention [START_REF] Wan | Recent advances in copper-catalyzed C-H bond amidation[END_REF] . In this reaction, azides, 1,4,2-dioxazol-5-ones and acetoxy carbamates are generally used as the reaction source of amide.

In 2014, the formation of C-N bond by using the Cp*Co(III) complex as a catalyst was first time demonstrated by Matsunaga and Kanai (Scheme 1.12a) phosphoryl azides could be also as coupling partners for amidation of indoles base substrate (Scheme 1.12b) [START_REF] Sun | A Cp*CoI2-dimer as a precursor for cationic Co(III)catalysis: application to C-H phosphoramidation of indoles[END_REF] .

P(OAr) 2 N 3 O O N O O R N N N R' NH O R c) Jiao, 2015 f) Ackermann, 2016 X N R N H O R N R N H O R N N N R' N H O N N R R d) Jiao, 2015 O N R N H O R R N H O R O N R X N R' N H O O R N N R' N H O O R N N R g) Chang, 2014 R O O NHCO 2 R N O O X X = I or Br N R' X k) Glorius, 2014 N N R' X N N R l) Pawar, 2016 O N R R I m) Glorius, 2015 R SH N N N R' S R n) Glorius, 2016 X N R SCF 3 o) Wang, 2017 N N R' SCF 3 N N R p) Yoshino
Afterward, 1,4,2-dioxazol-5-ones can also act as amidating agents, the group of Jiao and Ackermann further developed amidation protocols (Scheme 1.12 c-f) [START_REF] Liang | Cationic Cobalt(III)-Catalyzed Aryl and Alkenyl C-H Amidation: A Mild Protocol for the Modification of Purine Derivatives[END_REF][START_REF] Mei | Oxazolinyl-Assisted C-H Amidation by Cobalt(III) Catalysis[END_REF] . A wide range of substrates was found to be able to convert via this optimized amidation procedure, such as indoles-base substrate (Scheme 1.12c and f) [START_REF] Liang | Cationic Cobalt(III)-Catalyzed Aryl and Alkenyl C-H Amidation: A Mild Protocol for the Modification of Purine Derivatives[END_REF][START_REF] Mei | Oxazolinyl-Assisted C-H Amidation by Cobalt(III) Catalysis[END_REF] , 6-arylpurines, 2-phenylpyridines (Scheme 1.12d) [START_REF] Liang | Cationic Cobalt(III)-Catalyzed Aryl and Alkenyl C-H Amidation: A Mild Protocol for the Modification of Purine Derivatives[END_REF][START_REF] Mei | Oxazolinyl-Assisted C-H Amidation by Cobalt(III) Catalysis[END_REF] , phenyloxazolines as well as phenyloxazines (Scheme 1.12e) [START_REF] Liang | Cationic Cobalt(III)-Catalyzed Aryl and Alkenyl C-H Amidation: A Mild Protocol for the Modification of Purine Derivatives[END_REF][START_REF] Mei | Oxazolinyl-Assisted C-H Amidation by Cobalt(III) Catalysis[END_REF] Later, Chang and co-workers proposed the amidation of 2-aryl N-containing heterocyclic substrates via Cp*Co(III)-complex, using acetoxy carbamates as a reactive source of amide (Scheme 1.12g) [START_REF] Patel | Cobalt(III)-Catalyzed C-H Amidation of Arenes using Acetoxycarbamates as Convenient Amino Sources under Mild Conditions[END_REF] . In contrast, the formation of C-N bond cannot be achieved with sulfonyl azides (N3-Ts) with the optimized conditions. Scheme 1. 13. A general mechanism of C-H amidation with 1,4,2-dioxazol-5-ones.

2) C-H halogenation

Halogenation is one of the most fundamental transformations in organic chemistry and has a wide range of applications in agrochemicals, pharmaceuticals and material sciences [START_REF] Tu | Visible-light-induced halogenation of aliphatic C H bonds[END_REF] . Although many methods have been developed for introducing halogen atoms into organic molecules, direct C-H halogenation has remained the most effective tool for the synthesis of halogenated molecules.

In 2014, a new example of C-H bromination and iodination of 2-aryl pyridines was described by Glorius and co-workers (Scheme 1.12h) [START_REF] Yu | Co(III)-catalyzed C-H activation/formal SN-type reactions: selective and efficient cyanation, halogenation, and allylation[END_REF] . In those reactions, Nbromophthalimide (NBP) and N-iodosuccinimide (NIS) were used as brominating and iodinating agents respectively. The brominated products were found to be in low yields.

Other substrates were subsequently investigated and provided modest conversions.

Later, the halogenation protocols has been further developed and applied by Pawar and co-worker (Scheme 1.12i) [START_REF] Pawar | Cobalt(III)-catalyzed C-H halogenation of 6-arylpurines: facile entry into arylated, sulfenylated and alkoxylated 6-arylpurines[END_REF] . In addition, Glorius and co-workers expanded the range of substrate scope for their iodination protocol to include benzamide substrates (Scheme 1.12j) [START_REF] Yu | Co(III)-catalyzed C-H activation/formal SN-type reactions: selective and efficient cyanation, halogenation, and allylation[END_REF] . An unusual example for the C-H iodination of N-alkenylbenzamides was presented, and the potential applicability was further demonstrated.

3) C-H thiolation and trifluoromethylthiolation

The thioether groups are common in biologically active compounds and intermediates in organic material synthesis and the direct C-H thiolation provides an attractive strategy. Despite recent progress in this direction, there were few investigations on Cp*Co(III)-catalyzed C-H thiolation.

Most recently, Glorius and co-workers reported a thiolation protocol via crossdehydrogenative coupling of thiols with indoles (Scheme 1.12k) [START_REF] Gensch | Cobalt-Catalyzed C-H Thiolation through Dehydrogenative Cross-Coupling[END_REF] , which is a novel mode of the formation of C-X bonds by Cp*Co(III) catalyst. Under optimized reaction conditions, a variety of indoles with protecting groups can be directly thiolated.

Given the wide range of biological activities of SCF3-substituted (hetero)aromatic compounds, many efforts have been expanded to explore an efficient synthetic method for these compounds. Recently, the first trifluoromethylthiolation via [Cp*Co(CO)I2] was proposed by Wang and co-workers (Scheme 1.12l) [START_REF] Liu | Pentamethylcyclopentadienyl)cobalt(III)-Catalyzed Direct Trifluoromethylthiolation of Arenes via C-H Activation[END_REF] . However, this reaction was limited by the range of substrates, only in the case of 2-arylpyridine and 2-arylpyrimidine substrates. In a recent report, the substrate scope has further expended by Yoshino/Matsunaga and co-workers, and also included 6-arylpurines, with the use of N-trifluoromethylthiodibenzenesulfonimide as a trifluoromethyl source (Scheme 1.12m) [START_REF] Yoshida | Cp*Co(III)-catalyzed directed C-H trifluoromethylthiolation of 2-phenylpyridines and 6-arylpurines[END_REF] .

Heterocycle formation using Cp*Co(III) catalysis

In the past decade, transition metals-catalyzed C-H bond activation to form C-C and C-X bonds has emerged as a promising for the formation of heterocycles, which is more atom-and step-economy than the traditional methods. Despite the significant efforts made in the past few years, these approaches are still in their infancy.

Heterocycles formation by alkynes

One of the effective and powerful methods to form heterocycle is the annulation reaction using alkynes as a coupling partner.

In 2016, the first examples of using alkynes as coupling partner to form indolesubstrates via Cp*Co(III)-catalyzed C-H functionalization was provided by Ackermann and co-workers (Scheme 1.14a) [START_REF] Wang | Selective Synthesis of Indoles by Cobalt(III)-Catalyzed C-H/N-O Functionalization with Nitrones[END_REF] . And the Cp*Co(CO)I2 is widely applicable to the annulation of nitrones with alkynes via C-H/N-O functionalization and has good functional group tolerance and unique regioselectivity. Interestingly, indoles could also be synthesized efficiently with the help of [Cp*Co(MeCN)3](SbF6)2, thereby avoided using additional silver salt. Following on from this work, Zhang and co-workers described a novel method for the formation of quinoline-N-oxides via the annulation of aryl nitrones with alkynes (Scheme 1.14i) [START_REF] Liu | Synthesis of QuinolineN-Oxides by Cobalt-Catalyzed Annulation of Arylnitrones and Alkynes[END_REF] .

N-nitrosoanilines, arylhydrazines and Boc-protected hydrazines can be equally used as substrates for the preparation of indoles via Cp*Co(III)-catalyzed C-H functionalization, which was further developed by Jiao, Zhu, Glorius and their coworkers (Scheme 1.14b-d) [START_REF] Liang | Cationic Cobalt(III) Catalyzed Indole Synthesis: The Regioselective Intermolecular Cyclization of N-Nitrosoanilines and Alkynes[END_REF][START_REF] Zhou | Co(III)-Catalyzed, Internal and Terminal Alkyne-Compatible Synthesis of Indoles[END_REF][START_REF] Lerchen | Cobalt(III)-Catalyzed Redox-Neutral Synthesis of Unprotected Indoles Featuring an N-N Bond Cleavage[END_REF] . In 2016, both the groups of Glorius and Shi reported a protocol for the formation of indoles by using of N-arylureas as substrates (Scheme 1.14e, f) [START_REF] Lu | Control over Organometallic Intermediate Enables Cp*Co(III) Catalyzed Switchable Cyclization to Quinolines and Indoles[END_REF][START_REF] Zhang | Indole Synthesis via Cobalt(III)-Catalyzed Oxidative Coupling of N-Arylureas and Internal Alkynes[END_REF] . Additionally, Glorius and co-workers found that the dehydrative cyclization was greatly accelerated when Lewis acid was introduced, thus allowing for the selective formation of quinolines (Scheme 1.14g) ] was used to catalyze the dehydrative annulation of oximes with different alkynes without the involvement of any external oxidants. In this protocol, the presence of -OH groups are important in the catalytic cycle as the substitution of -OH groups by -OMe and -OAc groups leads to a dramatic decrease in product yield. However, further studies demonstrated that the high yield of isoquinolines could also be obtained by replacing the -OH group from oximes with -OAc group, which was reported by the group of Ackermann and Kanai/Matsunaga (Scheme 1.14k, l) [START_REF] Wang | Cobalt(III)-Catalyzed C-H/N-O Functionalizations: Isohypsic Access to Isoquinolines[END_REF][START_REF] Sun | Cp*CoIIICatalyzed Site-Selective C-H Activation of Unsymmetrical O-Acyl Oximes: Synthesis of Multisubstituted Isoquinolines from Terminal and Internal Alkynes[END_REF] . Li and co-workers found that when the N-sulfinyl group is used instead of -OAc group, it can also be used to synthesize isoquinolines (Scheme 18m) [START_REF] Wang | Cobalt-catalyzed redox-neutral synthesis of isoquinolines: C-H activation assisted by an oxidizing N-S bond[END_REF] . To synthesize quaternary ammonium salts, there are many methods by using Cp*Co(III) catalysts with different kinds of substrates were reported by Cheng's 87 and

[Co III ] N R 1 O R 2 R 3 alkyne insertion [Co III ] N R 1 O R 2 R 3 [Co III ] N R 2 R 3 R 1 O O O R 1 R 3 R 2 [Co I ] [Co III ] Ag 2 O + HOAc Ag + H 2 O + OAc - cyclometallation reductive elimination isomerization [Co III ] N [Co III ] R 1 O R 3 R 2 nucleophilic addition promoted by LA dehydration process cyclometallation N R 1 R 3 R 2 + H 2 H N R 1 O HOAc + OAc -
Wang's groups 88 in 2016. In these work, 2-arylpyridines (Scheme 1.14 p, q), arylketimines (Scheme 1.14 r, s), azobenzenes (Scheme 1.14t) and 2-vinylpyridines (Scheme 1.14u) were successfully annulated with alkyne to affords the corresponding quaternary heteroaromatic ammonium salts, but the use of unsymmetrical alkynes leads to low regioselectivity. Furthermore, a comparable approach was followed by Li and co-workers, using indole-based substrates containing pyridyl directing group, which yielded a wide range of annulated ammonium salts (Scheme 1.14v) [START_REF] Yang | Cp*CoIII-Catalyzed Synthesis of Pyrido[2′,1′:2,3]pyrimido[1,6-a]indol-5-iums via Tandem C-H Activation and Subsequent Annulation from 1-(Pyridin-2-yl)-1H-indoles and Internal Alkynes[END_REF] . Later, Zhang and co-workers developed an approach Cp*Co(III)-catalyzed annulation of enamides and benzoic to facilitate the preparation of multi-substituted pyrroles and indenones (Scheme 1.14w,x) [START_REF] Yu | Cobalt(iii)-catalyzed synthesis of pyrroles from enamides and alkynes[END_REF][START_REF] Yu | Cobalt(iii)-catalyzed annulation of esters and alkynes: a facile route to indenones[END_REF] . After, the annulation of N-methoxybenzamides with alkynes was developed by Jegamohan and co-workers (Scheme 1.14y) [START_REF] Sivakumar | Cobalt-Catalyzed Cyclization of N-Methoxy Benzamides with Alkynes using an Internal Oxidant through C-H/N-O Bond Activation[END_REF] . More recently, a simple method to synthesize isocoumarins was described Sundararaju and co-workers, using [Cp*Co(CO)I2] to catalyzed the annulation of carboxylic acids with alkynes (Scheme 1.14z) [START_REF] Mandal | Cp*Co(III)-Catalyzed Annulation of Carboxylic Acids with Alkynes[END_REF] .

In In 2017, a highly efficient method to synthesize NH-isoquinolones via a "one-pot reaction" was described by both the groups of Li and Zhu (Scheme 1.16 d, e) [START_REF] Wang | Cobalt(III)-and Rhodium(III)-Catalyzed C-H Amidation and Synthesis of 4-Quinolones: C-H Activation Assisted by Weakly Coordinating and Functionalizable Enaminone[END_REF][START_REF] Shi | Co(III)-Catalyzed Enaminone-Directed C-H Amidation for Quinolone Synthesis[END_REF] . The reaction is generally divided into two steps: the C-H amidation of enaminones with dioxazolones was catalyzed by Cp*Co(CO)I2 to form the amidated intermediates firstly, and the electrophilicity of the enaminone group then further utilized in subsequent hydrolysis-cyclization reactions to obtain quinolones in telescoping reactions.

Two different and highly efficient methods for the preparation of isoquinolin-3-ones were presented by Glorius and coworkers (Scheme 1.16 f, g) [START_REF] Zhao | Cobalt(III)-Catalyzed Directed C H Coupling with Diazo Compounds: Straightforward Access towards Extended π-Systems[END_REF][START_REF] Kim | Cooperative Lewis Acid/Cp*Co III Catalyzed C-H Bond Activation for the Synthesis of Isoquinolin-3-ones[END_REF] . Both of them use diazo esters as coupling partners. Noteworthy, in Scheme 1.16 f, the Co species have a dual role, not only as catalysts but also as Lewis acids.

A novel approach for the formation of 1-aminoisoquinoline by cobalt(III)-catalyzed C-H/N-H bond functionalization was proposed by Ackermann and co-workers (Scheme 1.16h) 100 . With this approach, the diazo compounds act as coupling partners with various easily accessible aryl amidines to synthesize the target quinolines efficiently.

In addition to the alkynes, dioxazolones and diazo compounds mentioned above, some other compounds can also be used as coupling partners for the synthesis of heterocyclics, such as CO, aldehydes, anthranils, and vinylene carbonate (Scheme 1.17). In 2015, an approach to synthesis coumarins via direct cyclocarbonylation of 2vinylphenols with CO was proposed by Wang and co-workers (Scheme 1.17a) 101 .

Interestingly, this cyclocarbonylation can occur easily and reactively under a fairly mild reaction condition, and only required balloon pressure of CO. The range of substrates is generally good, with good functional groups tolerance.

The synthesis of indolizines via Cp*Co(III)-catalyzed cycloaddition of 2-arylpyridines with aldehydes was developed by Zeng and co-workers (Scheme 1.17b) 102 , providing a simple approach to synthesize the indolizines indolizine derivatives with structural diversity (including benzoindolizines), and with a wide tolerance of functional group.

However, it is limited in scope for aldehydes, such as acetaldehyde and benzaldehyde which were not allowed to be used for this reaction.

1H-indazoles are commonly regarded as an important skeleton, because of their pharmacological activities, such as antimicrobial, antiviral, anti-inflammatory and anticancer activities. Therefore, there was a great need to develop cheap and efficient methods to synthesize 1H-indazole in a green and step-economical manner. In 2016,

Li and co-workers have developed a synergistic Cp*Co(III)/Cu(OAc) catalytic system for the formation of substituted 1H-indazoles using readily available aryl imidate and anthranils (Scheme 1.17c) 103 , where the anthranils also perform as an organic oxidant.

Meanwhile, the formation of N-N bond may involve a nitrogen radical intermediate species via the SET step by the copper, which was suggested by mechanistic studies.

Recently, the domino C-H/N-H allylation of aryl imidate to deliver the desired vinylsubstituted heterocycles was first proposed by Ackermann and co-workers (Scheme

1.3.1.

Mechanisms of cyclometallation reactions

The mechanism of cyclometallation is mainly determined by the electronic configuration of the metal center, as well as the nature of the C-H bond. Until now, the widely accepted mechanisms of cyclometallation are divided into three main pathways:

(1) electrophilic bond activation 106, 107 , (2) oxidative addition 108 , and (3) σ-bond metathesis 107 . However, for most cyclometallation processes, the exact mechanism is not yet completely understood, the theoretical and experimental studies just provide a most likely pathway.

1) electrophilic bond activation

In this mechanism pathway, cyclometallation is usually assisted by the coordinated leaving groups or free base in the reaction, which is more common in electron-poor late transition metals, such as palladium(II) and platinum(II) 106 . At any stage of this mechanism, the generation of metal hydride complex is not observed, so there is no change in the oxidation number of the metal center. 1.20, top). In this mechanism, the σ-complex (also known as a Wheland intermediate) is first formed, while the carbon bound to the metal becomes tetravalent so that the cyclic conjugation of the aromatic system is thus broken, and then the proton of the tetravalent carbon is eliminated and the aromaticity is regained to form the metallacycle with M-C bond.

2) oxidative addition

This oxidative addition is occurring most commonly in cyclometallations when using iridium(I) and rhodium(I), and also seems to be prevalent in most Calkyl-H bond activations when using late-transition metals 108 . This is mainly because the activation of C-H bonds requires an electron-rich metal center. Within this mechanism, the metalhydride bond will be formed, and the oxidation state of the metal center will be increased by 2, which is rapidly restored to its original valence by the subsequent reductive elimination stage. In addition, the reactivity of these five-membered iridacycles and rhodacycles with the various of unsaturated molecules has been further investigated by Jones and coworkers (Scheme 1.25) 115 . The reactions with carbon monoxide, they both formed 6membered metallacycles 9a and 9b, while ethylene producing two different products, which depends on the metal center. The reactions of ethylene with iridacycle afforded the coordinated product 10a, while that with rhodacycle yielded the inserted and rearranged product 10b, which suggested that reactibity might be affected by both steric and electronic factors. Scheme 1. 30. The approach for synthesis of polycyclic isoquinoline salt.

A novel catalytic method for the N-chelator-directed ortho-C-H bond amidation via

Cp*Rh(III)-complexes was first developed by Su and co-workers, by using sulfonamides as the amidating reagents under mild reaction conditions (Scheme 1.31) 125 . In this work, the pre-synthesized cyclometalated Cp*Rh(III) complex 18 could not only react with sulfonamide to produce the amidated product in 50% yield, but also acted as a catalyst to catalyze the C-H amidation and provided the desired product in 74% yield, which suggest that cyclometalated complex 18 could be a highly reactive intermediate in the C-H amidation reaction. was synthesised and used as a precatalyst for the hydrosilylation of amides (Scheme 1.32) 128 . The activity of this reaction could be improved by ligand modification when 1phenylisoquinoline ligand was used instead of 2-phenylpyridine, so that the related amines can be obtained in less time under the same conditions, using iridacycle 20 as catalyst.

N H N Ph Ph N M Cl Cp* N M Cl Cp* R R (1) [Cp*MCl 2 ] 2 , NaOAc, PhCHO, CH 2 Cl 2 , 5 h (2) DMAD, CH 3 CN/CH 2 Cl 2 , 6 h (3) CuCl 2 , CH 2 Cl 2 , overnight (1) (2)
Scheme 1. 32. The synthesis of iridacycles and catalyzed hydrosilylation of amides. The reactivity of a set of prototypical (η 6 -arene)tricarbonylchromium complexes with (

) H 2 O H 3 C NHPh H PhNH 2 22a MeOH, 2 h room temp. R 1 R 2 R 1 R 2 R 1 R 2 26a, R 1 = H, R 2 = H, 95 % 26b, R 1 = H, R 2 = Me, 95 % 26c, R 1 = OMe, R 2 = H, 100 % 26d, R 1 = NMe 2, R 2 = H, 100 % 26e, R 1 = CF 3, R 2 = H, 2
R = H, >99% R = p-CH 3, >99% R = p-Cl, >99% R = p-CF 3, >99% R = p-Ph, >99% R = p-NH 2, 0% R 1 =R 2 = Ph, >99% R 1 =Ph, R 2 =CH 3, >99% R 1 =p-Ph-OCH 3, R 2 =CH 3, >99% Hydrosilylation

Introduction

As introduced in the Chapter 1, a wide range of applications of Cp*Co(III)-catalysts for C-H bond functionalization have been reported by Kanai and Matsunaga 145-161 and by Ackerman et al. [162][163][164][165][166][167][168][169][170][171][172][173] and followed by a number of other reports 174,175 . In many reported cases this powerful class of cobalt catalysts 176 presents reactivity profiles that differ from their rhodium and iridium analogues. It has been argued that this difference is likely due to the lower electronegativity and increased Lewis acidity of cobalt compared to rhodium and iridium. 177 However, there has been seldom 171 attempts to construct a rational around the key problem of how to activate C-H bonds using 3d metals 178, 179 that would connect all the dimensions of chemical bonding, including the role of noncovalent interactions, which play a crucial role in transition metal catalytic systems in reducing the kinetic barriers of reactions by stabilizing transition states.

Moreover, prior to or in this transition state, the orchestrated action of various NCIs can also affect the selectivity of catalytic transformation.

In a recent report by our group 179 , we attempted to rationalize the differences existing between the well-established Pd(II)-acetate and the less documented Ni(II)-acetate cyclometallation by focusing mainly on the role of noncovalent interactions in CMD mechanism also assimilated to the AMLA mechanism [180][181][182] , which is now widely applied for the Pd(II) systems catalyzed C-H bond functionalization 178,183,184 .

In this study, the formation of an agostic intermediate (Figure 2.1), which is the key kinetic determining step in this mechanism, was analyzed systematically, by using state-of-the-art ab initio as well as DFT-based QTAIM analysis. It was also points out the crucial role played by electrostatic interactions, which control the whole process to some extent and are very sensitive to the charge carried by the metal center, and the electrostatic repulsion induced activation barriers for the formation of the pivotal Ni-ag is about twofold higher than in the case of Pd 179 . When acetamidate was used instead of acetate as an auxiliary base, the repulsive electrostatic interaction between the C-H bond and the metal was found to be abated 179 , thus significantly reducing the barrier to the formation of the key agostic intermediate.

Results and discussion

Theoretical aspects

DFT-D reaction energy profile

Most theoretical studies on the Cp*Co(III)-catalyzed C-H activation have not thoroughly investigate the mechanism of cyclometallation, simplifying this step and focusing on the influence of different substitutions on the reactive species [187][188][189][190][191][192][193] . Moreover, there are few DFT study of the cyclometallation via NCI-inclusive approach, so the cyclometallation via CMD mechanism will be investigated here in combination with noncovalent interactions and DFT study.

The CMD (or AMLA) mechanism is a simplified scenario that implies the formation of on the grounds of thermochemistry alone the cyclometallation with AcO -as auxiliary base is to be less efficient than that with AcNH -, which was verified experimentally later.

Noncovalent Interactions (NCIs)

Noncovalent interaction plot (NCIplot) 216,217 , a Quantum Theory of Atoms in Molecule As a chemical event, the CAr-HAr bond cleavage can be considered as an evolution of the precarious balance between the agostic interaction of the CAr-HAr bond in question with the metal center and the buildup of H-bonds mainly with Op and to a lesser extent with Od or Nd (Figure 2.3). Within the term "agostic interaction" that we use here we include the attractive and repulsive components that are constitutive of the CAr-HAr…metal interaction.

Interacting Quantum Atoms (IQA)

IQA-data show clearly that in all ag intermediates the CAr-metal interaction is attractive with a dominating covalent character. The HAr-metal interactions are more contrasted.

In To rationalize the effect of the base on the reaction energy profiles the difference of interaction energy Eint for the Op-metal bond in the acetamidate and acetate systems,

i.e ΔEint(Op-M) NHAc-OAc = Eint(Op-M) NHAc -Eint(Op-M) OAc , was calculated and is plotted in

NCI Indexes

In order to analyze both the attractive and the repulsive contributions to the C-H bond cleavage we have resorted with the collaboration Dr. Julia Contreras-Garcia (Sorbonne Université) of to the NCI index 216,217 in ag and the Ir-NHAc-ag-col geometries. NCI provides intuitive surfaces that identify local non covalent interactions in a system.

Strong and directional interactions are revealed as blue pellets, delocalized weak interactions appear as long green surfaces, and repulsive regions are revealed in red.

DLPNO-CCSD(T) Computations and Local Energy Decomposition Analysis

Recent reports have depicted DLPNO-CCSD(T) as a computationally time-effective ab initio method suited to the study of agostic interactions in organometallic compounds. [225][226][227][228] The DLPNO-CCSD(T) method combines the high accuracy of the coupled-cluster theory with a computational cost similar to DFT 212,228,229 arising from the localization of Hartree-Fock orbitals and the dichotomy between "strong" and "weak" pairs with respect to the inter-orbital distance. The DLPNO-CCSD(T) method, when associated with the Local Energy Decomposition 214 (LED) analysis, provides a sound access to the role of NCI (including dispersion) by assigning localized orbitals to userdefined fragments, thus allowing the differentiation between intra-and inter-fragment contributions to the interaction energies. The localized orbitals being assigned based on Mulliken charges analysis, an orbital expanding on more than one fragment will always be assigned to the fragment with the most electronegative involved atom. By construction, no counterpoise correction for the BSSE is needed for the calculation of interaction energies within the LED framework. In the Ni/Pd dyad case reported recently, 179 this method proved useful in outlining the weight of electrostatics particularly in the critical process of formation of the agostic transient ag. For the LED analysis, the studied systems have been subdivided into five chemically meaningful fragments, as shown in Figure 2.14a. Fragment 1 has been defined as the metal center, fragment 2 as HAr + , fragment 3 as the auxiliary base, fragment 4 as the [2-phpy] -ligand and fragment 5 as the Cp* ligand. As in the Ni/Pd dyad case, the interaction energy between all these fragments is mainly electrostatic in nature, except for the interactions involving fragment 2 that are purely electrostatic. Indeed, the hydrogen constituting fragment 2 being covalently bonded to either CAr of fragment 4

or the Op of fragment 5 throughout the reaction path, no orbital has been assigned to this fragment, thus being considered as a proton.

Here, we mainly focus on the interaction energies between the transferred H + and the four other fragments.

The interaction between the transferred H + , i.e fragment 2 ( The interaction between fragment 2 and the metal center, i.e fragment 1, is shown in Overall, agostic intermediates can be described in the LED analysis as an optimum in interaction between the "transferred H +" and other fragments. In accord with the QTAIM-IQA analysis, the LED analysis shows that stabilizing interactions with the ligands of the polarized C-H bond dominate over the destabilizing contribution of the HAr-metal interaction.

Experimental aspects

Synthesis and characterization of cobaltacycles

As mentioned earlier in Chapter 1, the synthesis of Cp*Ir-metalacycles 107 (Scheme 2. Therefore, the initial study of the optimal conditions for cyclocobaltation of 2-phpyH was carried out based on the optimal conditions for synthesis of Ir analogues, and Then, various lithium and sodium acetamidates were probed instead of auxiliary base.

The use of the neutral acetamide (Table 2.1, entry 3) surprisingly led to 3 % yield in 1a

after an overnight reaction, whereas the use of its conjugate base produced by deprotonation of the NH2 group, i.e. LiNHAc, yielded 1a in 68 % yield (Table 2.1, entry 4). By extending the reaction time to 2 days, 1a was isolated in 83% yield (Table 2.1, entry 5). Worthy to note, the latter yield was readily reproduced when the amounts of reactants and solvent were scaled up 10 times.

Three other amidate salts were also probed to evaluate the impact of steric on the performance of the cyclometallation, that is sodium N-ethylacetamidate, sodium Nisopropylacetamidate and sodium N-phenylacetamidate: all resulted in lower yields in 1a (Table 2.1, entries 6-8) suggesting that substitution at the N atom was strongly detrimental either on steric or electronic grounds.

Lowering the reaction temperature from 50 °C to room temperature (~20 °C), while keeping reactants' proportions identical resulted into a slight drop of the yield in 1a

when LiNHCOCH3 was the base: 60 % yield were achieved when the reaction was conducted at room temperature over 17 h (Table 2.1, entry 9). A longer reaction time of 48 h was not significantly beneficial (65% yield in 1a, Table 2.1, entry 10).

From the above comparative experiments, we found that acetamide could also promote cyclocobaltation with the yield of 3% (Table 2.1, entry 3), leading us to investigate the influence of the effect of higher amounts of 2-phpyH on the yield in 1a, because there must be a Brønstedt base in the medium to ensure the irreversibility of the CMD mechanism. When we increased the excess of 2-phpyH from 2-to 4-and 8fold in the presence of acetamide, the yield of 1a increased significantly that reached the threshold value of 18% (Table 2. 1, entries 11 and 12). Moreover, the addition of the poorly soluble Na2CO3 (2 equiv) pushed the yield in 1a further to 30% (Table 2.1, entry 13). These observations of great importance for further applications, suggesting that amidate salts are not absolutely required to achieve the cyclocobaltation as long To further demonstrate that acetamidate can effectively facilitate the cyclometallation reaction, the cycloiridation in the presence of LiNHAc was also attempted, under the identical conditions as cyclocobaltation (50 °C, DCM, 17 h, 3 equiv per Ir). Incredibly, the overall yield of iridacycle (the yield of 20%) was significantly lower than the yield of the standard reaction performed in the presence of NaOAc (the yield of 93%). However, after comparison of the 1 H NMR spectra, another iridacycle was found to be generated during the cycloiridation, which is the acetamidate derivative 2b in a 29% yield (Scheme 2.4). The overall yield in iridacycles have actually reached 49%. If the amount of LiNHAc was reduced to 1 equiv during this cycloiridation, the formation of complex 2b was no longer observed and only the desired complex 2a was produced in 92% yield. Therefore, we venture to speculate that the possible reason for this situation is the reaction of 2a with unreacted excess LiNHAc during the cyclometallation to form compound 2b, which leads to a low yield of the targeted product. 88.64 (7).

In addition, a large excess of base could promote the formation of a dinuclear Ir(III) amidate identified as complex 2c, resulting a significant decrease in the yield of 2a.

The structure of 2c was solved by X-ray diffraction analysis (Figure 2.19). This compound contains, apart from the Cp* ligand, one hydroxo and two acetamidate ligands all μ-bridging the two Ir(III) centers.

Kinetic Isotope Effect

In order to gain insight into the mechanism of this cyclocobaltation, one of the most effective ways to address this problem is the kinetic isotope effects (KIE). In particular, KIEs can give useful information regarding which bond was formed or cleavage in the rate-determining step of the reaction. Traditionally, KIEs are either obtained through parallel reactions or intermolecular competitions of isotopically substituted substrates.

Here, the KIE of the cyclocobaltation of 2-phpyH (Scheme 2.6) was determined by those two independent experimental methods.

Scheme 2. 6. The KIE of the cyclocobaltation of 2-phpyH.

1) Parallel experiments

The

2) Intermolecular competition experiment

The second method consisted of the room temperature cyclocobaltation of a 1:1 molar mixture of 2-phpyH and 2-(d5.ph)pyD with [Cp*CoI2]2 and lithium acetamidate followed by a 1 H-coupled 13 C NMR spectroscopy analysis and integration of the 13 C signals typical of 1a and d4-1a that are readily discriminated by isotope shifts. 234,235 The KIE was determined by comparing the integrations of 13 C signals of the Co-bound aromatic carbon of 1a and d4-1a as well as those of the vicinal H/D-bound ortho carbon.

The second method based on the analysis of a 1 H -coupled 13 The simplified Bigeleisen equation 243 offers ready access to KIEs of every single step in the CMD mechanism, it is deemed "semi-classical" as it neglects tunneling effects that may be relevant in the proton transfer step. 244,245 In cases where the rate determining step coincides with the bond breaking step computed values of KIE are known to be systematically underestimated. 240 Nevertheless, this approach has proven efficient in determining KIE for different proton-transfer reactions. Worthy to note, compounds 3-5b were also probed as potential hydrosilylation catalysts 133,134,247 but showed no activity in benchmark catalytic test runs of the dehydro-O-silylation of benzyl alcohol (see the chapter 4). 134 Therefore, we attempted to investigated the application of the acetamidate assisted C-H functionalization, and the role of base in the C-H functionalization.

Catalytic application of the acetamidate assisted C-H bond activation to the condensation of diphenylacetylene with aromatic substrates

The condensation of alkyne with metallacycles Given the accessibility of [Cp*CoI2]2 and its great temperature and air stability, several attempts to achieve the condensation of diphenylacetylene with 2-phpyH (Scheme 2.9)

were undertaken in this study so as to figure out whether an auxiliary base could be beneficial.

Scheme 2. 9. The condensation of diphenylacetylene with 2-phpyH Table 2.2 summarizes the methodology used therein, which was mostly inspired by that used by Perez-Temprano et al. [START_REF] Yang | Recent advances in transition metal (Pd, Ni)-catalyzed C(sp(3)) H bond activation with bidentate directing groups[END_REF][START_REF] Yin | Transition-Metal-Catalyzed Carbonylative Synthesis and Functionalization of Heterocycles[END_REF][START_REF] Wang | Cobalt(III)-catalyzed alkenylation of arenes and 6-arylpurines with terminal alkynes: efficient access to functional dyes[END_REF] The role of the silver salt is particularly important, for it contributes to halide abstraction and to the necessary oxidation of transient Cp*Co(I) species produced in the reductive coupling step: reducing its amount to molar 10 % and replacing it by NaBF4 for the purpose of ionic balance, expectedly cuts the yield in condensation product down to ~10 % (Table 2.2, entry 5). Worthy to note, its replacement by a copper(II) acetate in the presence of LiNHAc does not produce any annulation product (Table 2.2, entry 3).

Further condensation reactions (Table 2.3) were undertaken with other aromatic substrates using the conditions that afforded the best yields with 2-phpyH ( have indeed recently privileged the so-called base assisted intramolecular electrophilic-type substitution (BIES) mechanism rather than the CMD one even though the formulation of their mechanism is again very similar to that of the CMD where the formation of an agostic intermediate remains crucial.

However, this contribution might be minor if one considers that in the absence of AgBF4 the conversion in the conditions required for the CMD mechanism to operate corresponds to the maximum achievable value in the absence of any oxidizing agent with 10 mol% catalyst (Table 2 We evaluated the KIE of the cyclocobaltation of a modeled EA mechanism that most likely occurs in reactions wherein excess Ag(I) salt is used: this hypothesis entails the formation of a 14-electron dicationic π-complex, i.e EA-π from the fictitious [Cp*Co] 2+

species and 2-phpyH. In this mechanism a second exogenous molecule of 2-phpyH intervenes as a base to form reactive complex EA-pre-TS and abstract the HAr proton via EA-TS to afford a dicationic molecular complex between the cobaltacycle and the considering the Born-Oppenheimer approximation on the pentadeuterophenyl fragment that undergoes metalation in EA-pre-TS and EA-TS and on the non-bonded N-deuterio,2-phenylpyridinium and the tetra deuterated phenylene of the metallacycle in molecular complex EA-MC. In such a scenario the proton abstraction step is the kinetic determining step and requires a rather low Gibbs enthalpy of activation (+3 kcal/mol) as compared to that required to the acetamidate-promoted CMD mechanism (ca. +7 kcal/mol, Figure 2.2), which demonstrates clearly that the EA mechanism is indeed a serious challenger to the CMD mechanism discussed previously.

Scheme 2. 10. Kinetic isotope effects as determined by the Bigeleisen method from the Born-Oppenheimer treatment of the vibrational frequencies of protio and deuterio stationary points in Figure 2.26.

Conclusion

This chapter shows that cobaltacycles are not elusive and can be readily prepared in one dealing with cyclonickelation 179 wherein experimental validation was not sought, the benefit of using an acetamidate salt as base inferred from theory has now been confirmed experimentally. This study shows that the use of an acetamidate base/ligand reduces the residual chelation interaction with metal and consequently enhances the polarization of the C-H bond that is already engaged in a partly covalent partly noncovalent agostic interaction with the positively charged metal center. This is a promising basis for the further development of enantioselective C-H bond functionalization

Introduction

Cyclopentadienyl ligands have always played an important role in organometallic chemistry, mainly because they can stabilize metals with a variety of binding modes (Scheme 3.1). The η 5 -pentamethylcyclopentadienyl 260 , one widely used cyclopentadienyl ligand, generally shows more stability, solubility and crystallized easier when compared to its cyclopentadienyl analogues, so, it has received a lot of attention. In addition, Cp* has traditionally being considered an innocent ligand 260,261 in an abundant literature [262][263][264][265][266][267][268][269][270] , which means that it only provides electronic support for a metal and it is not involved in chemical reactions 271 .

Scheme 3. 1. Distinct bonding modes for the cyclopentadienyl ligand. structurally viable 278 candidate catalysts. 178,183,279,280 In the majority of reports dealing

Results and discussion

Synthetic outlook

In chapter 2, the compound [1c][I3] 281 was crystallized from a solution that originally contained 1a. The presence of I3 -as counter anion suggested that the initial solution of 1a might have been contaminated by either I2 or some I3 -salts introduced or formed in the course of the synthesis of [Cp*CoI2]2, 281 i.e the precursor of 1a. Suspecting an oxidoreductive process responsible for the formation of the condensation product [1c] + , 1a was hence reacted with two equiv. of I2 in DCM for 16 h at 20°C (Scheme 3.5). The Given the intricate mixture produced by the reaction of 1a with I2, as an alternative to the latter, we decided to probe the oxidizing property of the one-electron oxidant

[Ph3C][BArF24]
. 291 The tritylium [Ph3C] + , which undergoes a swift decomposition 292 in the gas phase, is in solution a well-known stable multi-facetted Lewis acidic cation 293- 297 that may act as a hydride 298 and/or a halide 299 abstraction agent but also as a oneelectron oxidant 300-306 (Ph3C / Ph3C + couple 307 ) in the ground as well as in the excited state 308,309 that may be involved also in the hydride abstraction process as reported by Mandon,Astruc et al. 310 Quite interestingly, to the best of our knowledge there has been no mention of any major drawbacks related to the oxidative properties of the tritylium as "activator", i.e as a halido ligand "remover", in transition metal-mediated homogeneous catalysis. For instance hydrosilylation catalysis otherwise ineffective with Cp*-bound chloridoiridacycles 133, 134 can be triggered if a [Ph3C][BArF24] salt is added to the reaction mixture seemingly acting as a chloride scavenger. [128][129][130][131] Subsequently, the reaction between 1a and [Ph3C][BArF24] carried out at 25°C in DCM for 16 h produced [1c][BArF24] with an NMR yield of 72% (Table 3.1, entry 1). In fact,

1 H NMR spectroscopy monitoring showed that the reaction reached 100% conversion after only 30 min. It is also noteworthy that same experiment carried out with the chloridoiridacycle analog left the substrate unchanged. In addition, this reaction was also performed in DCE and d5-PhCl to obtain the target product in 40% and 51% yields, respectively (Table 3.1, entries 5 and 6). The same reaction carried out using 2 equiv.

of AgPF6 as oxidant instead of [Ph3C][BArF24] was completed with 100% conversion of 1a into a mixture of [1c][PF6] in 70% NMR yield (Table 3.1, entry 2) and other aromatic products. Despite the fact that Ag + was also efficient in this reaction, the significant content in side organic products and the overall higher heterogeneity of the reaction mixture led us to privilege [Ph3C][BArF24] as a standard oxidant for further physical investigations.

Noteworthy, in order to check the radical mechanism, 1 or 4 equiv. of (2,2,6,6tetramethylpiperidin-1-yl)oxy (TEMPO) was added into the reaction mixture, which resulted in a significant inhibition (Table 3.1, entries 3 and 4) of the reaction perceptible from an NMR yield decrease to 35% after 17 h, suggesting that open shell species and radicals essential to the formation of [1c] + are partly trapped by the rather bulky nitroxyl radical. 3.2). The data listed in Table 3.2 were all acquired under standard conditions of reaction time of 17h at room temperature. Only the substrates bearing -Br and -CF3 substituents, i.e 7a and 8a (Table 3.2, entries 3 and 6), afforded cyclic pyridiniums [7c] + and [8c] + , the 1 H NMR signature of which could be recognized readily in the spectrum of the raw mixture from the specific pattern of methyl groups showing in the δ 0.9-2.5 ppm range. But, the reaction with compounds 4a and 6a yielded untraceable mixtures of soluble and insoluble residues with no distinguishable main product (Table 3.2, entries 1 and 2). The structures of 108.87( 14), C14-C13-C12 101.51 (15), C14-C15-C16 110.12( 17), C15-C16-N1

107.94( 14), C15-C14-C13 111.47 (17).

Cobaltacycle 5a 281 also conducted the cyclocondensation reaction, it is noteworthy that there was no observed generation of the target product in the presence of 3.2, entries 5 and 8), which were readily isolated as they showed much lower solubility in CDCl3 than their respective precursors. C11-C12 1.518( 5), C12-C13 1.563( 5), C13-O1 1.409( 6), C13-C14 1.506( 6), C14-C15

1.336( 6), C15-C16 1.519( 5), C16-N1 1.548( 5), C12-C16 1.553( 5 113.41 (12), C11-C12-C13 112.72 (11), C16-C12-C13 102.23 (11), O1-C13-C14

106.60 (12), O1-C13-C12 109.67 (12), C15-C14-C13 112.09( 13), C14-C15-C16 110.32 (13), C15-C16-N1 108.51 (12), C15-C16-C12 101.94 (12), N1-C16-C12 110.26 (11).

To gain more insights into whether the adventitious moisture of air affects the cyclocondensation reaction of the cobaltacycles bearing -Br and -CF3 substituents, the comparative experiments were also performed (Table 3.2, entries 4 and 7).

However, the results were unexpected, whereby the yields of the cyclocondensation were significantly higher in ambient air than under argon protection, in addition, the 99.79 (18), C16-C1-N1 109.58 (19), C12-C1-C13 115.43 (19), N1-C1-C13 111.97 (19), C16-C1-C13 103.60 (19), C14-C13-C1 105.63 (19), C15-C14-C13 102.8( 2), C16-C15-C14 113.5( 2), C15-C16-C1 111.5(2).

Isothermal titration calorimetry (ITC) experiments

Isothermal titration calorimetry (ITC) is one of the physical techniques that directly measures the heat discharged or consumed all along a bimolecular reaction. It is also the only method capable of determining the enthalpy, entropy, and the Gibbs free energy of a reaction in a single titration experiment. The microcalorimeter has two cells, as shown in Figure 3.8: one contains solvent and acts as a reference cell, the other contains the sample, into which a binding partner is titrated using an injection syringe.

Heat sensing devices detect temperature differences between the cells when binding occurs in the sample cell and give feedback to the heaters, which compensate for this difference and return the cells to equal temperature. the residual heat peaks at n>1.5:1 as ΔH= -13.7 ± 0.5 kcal/mol (from three independent titrations), which is the total exothermicity of all the chemical processes that take place under those conditions up to the heat inflexion point before athermicity, that is namely:

the oxidation of 1a and the cyclocondensation reaction, dechelation by protonation, possible radical captures and recombination in which it is expected that the solvent or any H-atom donor species might be a player.

A control reaction carried out under identical conditions was checked by 1 H NMR spectroscopy and showed that a yield of 40% in [1c] + could be achieved (Table 3.

Attempts to track down the H atom source

To trace the origin of the H atom incorporated in The latter result suggests that the most probable source of H atom is either the BArF24 It is worth noting that the treatment of 1a with 1 equiv. of CF3SO3H in CH2Cl2 (Scheme Also, the effect on the reaction of 1a with [Ph3C][BArF24] in the present of 5 equiv of H2O or D2O that was probed under an atmosphere of either argon or air (Table 3. General conditions: 1a (0.1 mmol, 1 eq), [Ph3C][BArF24] (0.1 mmol, 1 eq), DCM (5 mL), H2O or D2O (0.5 mmol, 5 eq), 25°C, 16 h. 1 H NMR yield in the presence of 1,3,5trimethoxybenzene as an internal standard.

The body of evidence gathered here points at 1a or some degraded from of it as a probable source of the H atom that incorporates into [1c] + . A contribution of the solvent cannot be completely excluded neither at this stage as a major kinetic barrier to deuterium incorporation (not addressed here) may well lead to the consumption of the residual protio-dichloromethane in the experiments ran in deuterated solvent.

Electrochemical experiments

The electrolyte consisted of a solution of 0.1 mol L -1 of anhydrous tetrabutylammonium 3.4). 2 I -→ I2 + 2 e - (Eq 1, step E1)

I2 + I -→ I3 - (Eq. 2, step C1, fast addition) I3 -→ 3/2I2 + e - (Eq. 3, step E2) 3/2I2 + 3/2 1,2-C2H4Cl2 → 3/2 [1,2-C2H4Cl2I] + [I] - (Eq. 4, step C2)
The second chemical process (C2) arising from the slow interaction of the generated I2

with DCE due to the small dielectric constant where substantial ion association begins to take place. DCE as a donor solvent promotes the ionization of covalent compounds to form intimate ion -pairs. Ionization is stimulated in a donor solvent by solvation of cations where iodine I2 is ionized in a donor solvent according to the reaction (Eq. 4) 321 .

For 1a, two irreversible oxidation peaks were detected at 0. Finally, compounds 7a, 8a and the new "CpCo" complex 10a give a redox behavior similar to that of 1a (Table 3 .4 and Figures 3.13-3.19) showing that the potential of but the collapse of the cobaltacycle was not observed in this report. Indeed, in an effort to clarify the mechanism of the catalysis reported by Glorius et al., 333 showed that the treatment of a trifluoromethylthiolato complex of a 2-phenyl,pyridine Cp*-bound cobaltacycle with excess Ag(I) salts may lead to the oxidation of the Co(III) center into a Co(IV) complex purportedly responsible for the formation of the expected orthosubstituted product of C-S coupling (Scheme 3.14) in various yields (from ca. 99% to 0%) depending on the amount and nature of oxidant. We speculate that in the context of complex catalytic mixtures containing reagents and co-catalysts endowed with oxidoreductive mediation roles where similar metallacycles are claimed to be key intermediates, 159,178,276 the occurrence of such an unwanted cyclocondensation pathway depends on the nature of the ligand X coordinated to the metal center.

Electron paramagnetic resonance (EPR) experiments

Scheme 3. 14. Two possible scenarios result from the oxidation of the Co(III)-X complexes.

DFT evaluation of the mechanism of formation of [1c] +

NCI plots and IBSI suggest a predisposition to cyclocondensation

A preliminary comparative study between the reactive cobalt complex 1a and the iodoiridium analogue Ir-1a was carried out to address the propensity of 1a to undergo the condensation of Cp* with phpy under oxidative conditions while its Ir analogue supposedly remains unchanged. The computed difference in the Gibbs free energy of oxidation for the Co(III) and Ir(III) complexes is negligible and cannot explain the difference of behavior (ΔΔG=0.1 kcal/mol). Our attention turned to the possible existence of attractive noncovalent interactions that could predispose 1a to its collapse by cyclocondensation. interactions in reactant complexes that may prefigure new bonds appearing once the transition state is passed. 335 NCI plots [START_REF] Johnson | Revealing Noncovalent Interactions[END_REF]336 were therefore scrutinized for peculiar features related to the uncommon cyclocondensation reported here.

The NCI plots [START_REF] Johnson | Revealing Noncovalent Interactions[END_REF]336 depicted in Figure 3. The circular attractive domain isosurface located underneath the Cp*ligand in all the cases depicted in Figure 3.21 is quite usually observed in η 5 -cyclopentadienyl and η 6arene-metal complexes. 337,338 One uncommon feature however is when this ring-like isosurface is no more circular like in Ir-1a but displays attractive outgrowths like in 1a

that are symptomatic of a peculiar attractive relationship between one carbon atom at the cyclopentadienyl moiety and an atom of a group of atoms at a different vicinal ligand. To get a more quantitative insight on the difference in interaction strength between the Co and and Ir complexes 1a and Ir-1a, at the +III and +IV formal oxidation states and for [Cp*Co(SCF3)(phpy)] and 9a at the +III and +IV formal oxidation state, the integrated independent Gradient Model (IGM)-based δg inter descriptor 283, 284 (also called Δg inter interaction score) was computed to quantify the interaction between phpy and each of the two other ligands. The IGM-δg inter descriptor compares density gradients of fragments with and without interference. Integrating this descriptor gives rise to the Δg inter interaction score that measures the interaction between two userdefined fragments. The recently developed Intrinsic Bond Strength Index 285 (IBSI) was also computed for the key atom pairs involved in the reaction. IBSI is an efficient quantitative index to intra-molecularly probe the "strength" of a given chemical bond or interaction. It is also based on the so-called Independent Gradient Model, 285 which was designed to reveal and quantify molecular interactions from the electron density topology, and was validated by tests on 677 bonds in 235 molecular systems. Both Δg inter score and IBSI have previously successfully been applied in mechanistic studies. 343 Like many QTAIM 221 -based analytical methods it is exempt of issues related to basis set superposition error. In the cases addressed here (cf. Table 3.5), Δg inter evidences a stronger interaction between the Cp* and phpy ligands in the Co case than in the Ir one, being in the +III or +IV formal oxidation state. Oxidation increases the interaction between Cp* and phpy in the Co case, while the increase is almost null in the Ir one.

Conversely, the interaction between phpy and I decrease with the oxidation on both cases and while it is stronger in the Co case than in the Ir one at the +III formal oxidation state, it is the opposite iat the +IV formal oxidation state.

IBSI evidences a stronger interaction between C3 of the Cp* moiety and C2' of the phpy ligand, as well as between C4 of the Cp* and N of the phpy, in 1a than in its Ir analogue, while the interaction between the four aforementioned atoms and the metal center is stronger in the Ir analogue. The same observation stands when the complex is oxidized. Moreover, oxidation increases, in the Co case, the strength of the interaction between the Cp* and the phpy, while decreasing the strength of the interaction

Early capture of H• and spin state in pathway 1

The formation of a hydrido cobalt(V) species by capture of H• was considered to account for the exclusive endo positioning of H5. The oxidation of singlet state 1a into doublet state [1a'] + followed by the capture of H• to yield a putative cationic hydrido cobalt(V) species corresponds formally to the capture of H + by 1a, which has already been ruled out experimentally, for it leads exclusively to the demetallation of the phpy ligand.

Moreover, all attempted optimizations of the hydrido Co(V) species in the singlet state, which is the intermediate arising from the capture of H• by [1a'] + (or of H + by 1a) 3.24), where the hydrogen is

evolved into "agostic" 196, 281 C-H•••Co complexes (Figure

Cyclocondensation in pathway 1

Considering the attack of the Cp* on the phpy from the (η 4 -Cp*H)Co complex in the triplet state, three possible paths can be followed, as for 1a, that is namely : i) attack of C3 of Cp* on the nitrogen of the phpy ligand first, then of C4 of the Cp* on the carbanionic C2' of phpy, ii) attack of C4 of Cp* on C2' of phpy, then of C3 of Cp* on N of phpy, iii) concerted attack of C3 and C4 of Cp* on N and C2' of phpy respectively.

Out of these possible paths, the attack of C4 of Cp* by C2' (phpy) displays the lowest activation barrier (ΔG= + 7 kcal/mol, while ΔG=+ 48 kcal/mol for the concerted attack and ΔG= + 42 kcal/mol for the attack on N). Considering these three paths from the agostic (η 4 -Cp*H) complex in the singlet state, each of these display an activation barrier higher than + 30 kcal/mol, causing all of these possible transition states to be higher in energy than the one for the attack on C2' (phpy) in the triplet state.

Following this path, the formation of the intermediate where the C-C bond has been formed, i.e [IntCH] + , is exergonic (ΔG= -14 kcal/mol). This intermediate is more stable in the triplet state than in the singlet by a ΔΔG of +15 kcal/mol. In the triplet state the formation of the final complex [pre-1c] + , i.e when the final condensation product [1c] + is still bound to the "CoI" moiety, from [IntCH] + is then endergonic (ΔG= + 6 kcal/mol).

Computations suggest this reaction as barrierless, the shift of the Co from a κN position to a η 2 position on the aryl fragment combined with the search for planarity of the phpy moiety leading to a proximity between C3 of the former Cp* and the N, which favors the formation of the C-N bond. Intermediate [pre-1c] + is more likely to stay in the triplet state, as its singlet equivalent lies 7 kcal/mol above.

Early C-C coupling in pathway 2 and 3:

Also considered was the attack of the Cp* by the phpy ligand in [1a'] + before the capture of the hydrogen atom occurs later in the process. Again, three possible paths can be considered. The prior attack of C4 at Cp* by C2' at the phpy ligand shows the lowest activation barrier (ΔG= + 19 kcal/mol, while ΔG= + 48 kcal/mol for the concerted attack and ΔG= + 42 for the prior attack on N). In these conditions, the formation of the The question of the fate of the "CoI" moiety when [1c] + is released has been addressed

heuristically. Calculation reveals that the release of "naked" CoI as such from tripletstate [pre-1c] + is highly unfavorable whatever the spin multiplicity of CoI may eventually be (ΔG= + 81 kcal/mol for the singlet, ΔG= + 48.

Conclusion

In this chapter, we described the method for the synthesis of cyclocondensation complex obtained in Chapter 2. Halogeno-Cp*Co(III) metallacycles derived from 2phenylpyridine (phpy-H) react in solution with one-electron oxidants to irreversibly structurally collapse by a cyclocondensation of the organic ligands with the capture of a H atom from the medium to afford new cationic alkaloids. Low temperature EPR

Chapter 4. Attempted catalytic reactions with

Cp*Co(III)-metallacycles

Introduction

As we mentioned in the chapter 1, the Cp*metallacycles are not only intermediates in the C-H functionalization, but also can act as efficient catalysts for organic transformations. In this chapter, we will discuss about our different attempts to apply these cobaltacycles in various catalytic reactions.

Hydrosilylation, the addition of Si-H bond across unsaturated bonds, which is a very powerful reaction for the generation of organosilicon compounds, has been widely used in the polymer chemistry, material science and inorganic synthesis 345 . In the recent years, our group has developed a series of iridium-base metallacycles and successfully applied to the hydrosilylation of alcohols, ketones, esters, nitrile, amides and imines showing very high activity 133,134,247 . These metallacycles derived from 2-

Results and discussion

Considering the hydrosilylation results obtained with the cationic iridacycles, the main idea was to reproduce the same chemistry but in the presence of homologous cobaltacycles. So, we started by checking the catalytic efficiency of complex 1b under the similar reaction conditions used for the Cp*Ir(III)-metallacycles catalyzed hydrosilylation of ketones and nitriles (room temperature in DCM using HSiEt3 silane

R HSiR' 3 3 equiv. R = n-C 3 H 7 , n-C 4 H 9 , n-C 6 H 13 HSiR' 3 = HSiEt 3 , HSi(OMe) 3 , HSiPhCl 2 Co 2 (CO) 8 (0.1 mol%) 25 ºC, neat R SiR' 3 R 3 SiCo(CO) 4 -CO R 3 SiCo(CO) 3 R 3 SiCo(CO) 3 R 3 Si Co(CO) 3 R 3 Si HCo(CO) 3 R 3 Si Co(CO) 3 SiR 3 H HSiR 3 R 3 Si Co 2 (CO) 8 + HSiR' 3 HCo(CO) n HCo(CO) n R Co(CO) n R R'' R Co(CO) n R' Co(CO) n SiR' 3 H R R' 3 SiCo(CO) 4 R SiR' 3
HSiR' 3 Reaction conditions: Ketone (1 mmol), catalyst (0.1 mol%), silane (1.2 mmol), DCM (0.5 mL), 1,3,5-trimethoxybenzene as internal reference.

Nevertheless, in order to further evaluate the activity of the Cp*Co(III)-metallacycles and also to gain insight into the catalytic reactions, we investigated the stoichiometric reaction of 1b with silane. The cationic cobaltacycle 1b was mixed with HSiEt3 (1 equiv.) in J. Young valve NMR tube in DCM-d2 at 298 K or 247 K, and the reaction was monitored by 1 H NMR spectroscopy. Unfortunately, no reaction occurred as no Si-H activation, or Co-H complex were observed in the 1 H NMR spectrum. Noteworthy, the Si-H activation is instantaneous with the iridacyles. ( Si-H bond and the formation of Co-H bond. So, we attempted to add a hydride source to promote this reaction, such as NaHBEt3 350,351 and Red-Al. Subsequently, the hydrosilylations of benzophenone were carried out with different set of cobaltcomplexes, replacing the DCM with toluene. As shown in the table 4.2, when complex 1b is used (5% mol) for the catalysis of benzophenone and HSiEt3 in toluene at 40°C during 5 hours, no any conversion was detected in toluene (Table 4.2, entry 1) and only 5.5% of silylated product A was observed when the reaction was performed in CH2Cl2 (Table 4.2, entry 2), showing the different reactivity of Ir and Co. When the neutral 1a was used as catalyst alone also no conversion of the starting benzophenone was detected by 1 H NMR after 5 hours of reaction (Table 4.2, entry 3). The addition of NaBHEt3 (10% mol) to 1a allows an interesting reactivity, transforming quite completely the benzophenone (Table 4.2, entry 4). Red-Al as source of hydride did not bring such result. Unfortunately, we observed the decomposition of the complex as discussed in detail in chapter 3.

Other attempted reactions with cobaltacycles

In addition to the hydrosilylation, we also attempted other catalytic reactions to further investigate the reactivity of the Cp*Co(III)-metallacycles, the hydroboration reaction, and the cycloaddition reaction of alkyne or ethyl diazoacetate were considered.

Hydroboration

In recent years, the hydroboration of alkenes catalyzed by cobalt-complexes have also recceived a significant attention, which provide a convenient route to aklylboronic acid derivative that can acts as versatile intermediates for a wide range of application in various bond-forming reactions [351][352][353][354] . While the cobalt-catalysts used in the vast majority of protocols were well-defined cobalt(II) complexes, a significant need remains for the development of new cobalt catalysts for hydroboration reactions, such as Cp*Co(III)-complexes.

Before starting the catalytic reaction, we also investigated the stoichiometric reaction of cobaltcycles with boranes, such as pinacolborane (HBPin), catecholborane (HBCat).

Complexes 1b or 5b were reacted with boranes (10 equiv) in NMR tube in DCM-d2 at room temperature, then this reaction was monitored by 1 H NMR spectroscopy.

Unfortunately, we did not observe the formation of the expected product similar to the [Ir-H-Si] complex, which is consistent with the reaction of 1b and HSiEt3.

It is worth noting that we obtained a crystal structure in the reaction of 1b and HBPin, which is shown in Figure 4.2. This structure is similar to that of 1b, where the NCMe coordinated to cobalt center was replaced by the -SMe2 ligand. Then the question arises, where does the -SMe2 group comes from? The only explanation is that the -SMe2 group could be arising from the pinacolborane, which can be synthesized from BH3•SMe2 355 , so tiny amount of SMe2 impurities were present in the commercial pinacolborane. However, this is only our hypothesis and has not been further investigated. We also attempted to activate HBR2 several times, with different temperature, changing the solvent and so on, but nothing happened positively. 82.99 (10).

Cycloaddition reaction of alkynes or diazo compounds

As introduced in the chapter 1, the alkenes and diazo compounds are usually employed as coupling partners in the vast majority of Cp*Co(III)-catalyzed annulation reaction 2,[START_REF] Liu | Synthesis of QuinolineN-Oxides by Cobalt-Catalyzed Annulation of Arylnitrones and Alkynes[END_REF] . The idea was to evaluate the reactivity of these neutral and cationic Cp*Co(III)-metallacycles in this kind of annulation reaction. Therefore, a series of stoichiometric reactions between cobaltacyles and alkene (or diazo compound) were performed.

Scheme 4. 4. Reaction of cobaltacyle with diphenylacetylene and ethyl diazoacetate.

The reaction of the 1b with diphenylacetylene and ethyl diazoacetate were monitored by [START_REF] Basu | Transition metal catalyzed C-H activation for the synthesis of medicinally relevant molecules: A Review[END_REF] H NMR spectroscopy at room temperature in CD2Cl2 and THF-d8, respectively. In the reaction with diphenylacetylene, we observed the conversion of 1b to the sevenmembered cationic cobaltacycle, which is consistent with the results reported by Perez-Temprano and co-workers 282 . Meanwhile, the six-membered cationic cobaltacycle was observed in the reaction with ethyl diazoacetate, which was evidenced by X-ray structure (Figure 4.3), however, the metal carbene complex was not observed. To further capture the metal carbene complex, the variable-temperature After, the cycloaddition reactions of ethyl diazoacetate were tried with different temperature and solvent, but we only observed that the homocoupling of ethyl diazoacetate.

Conclusion

As discussed in this section, we have attempted a variety of catalytic reactions with Cp*Co(III)-metallacycles, such as hydrosilylation, hydroboration, and the cycloaddition reaction of alkynes or diazo compounds. For the hydrosilylation, although Cp*Co(III)metallacycles do not exhibit catalytic properties under the same conditions used for analogs Ir complexes, we found in subsequently studies that it can also effective to catalyzed the hydrosilylation of ketones in the presence of NaBHEt3. Despite the results, the study was still in the initial stage. The unexpected crystal structure obtained by hydroboration, providing a new idea to develop new Cp*Co(III)-metallacycles.

Undoubtedly, the Cp*Co(III)-metallacycle as a promising catalyst that still has many applications to be developed.

Structural X-ray diffraction analyses

The crystals were placed in oil, and a single crystal was selected, mounted on a glass . 359 The refinement and all further calculations were carried out using SHELXL-2014 360 or SHELXL-2018. 360 The H-atoms were included in calculated positions and treated as riding atoms using SHELXL default parameters.

The non-H atoms were refined anisotropically, using weighted full-matrix least-squares on F 2 . A semi-empirical absorption correction was applied using SADABS in APEX3 358 .

For complexes 1f, 2b, 2c, 3b, 4b, 5b, 1a, 7a, 8a, The non-H atoms were refined anisotropically, using weighted full-matrix least-squares on F 2 . A semi-empirical absorption correction was applied using SADABS in APEX3 362 .

[1c][BArF24], [7c][BArF24], [8c][BArF24], [ 7d

Cyclic voltammetry

Cyclic analyses (IQA) were carried out using the embedded QTAIM functionalities of the ADF package. For technical reasons regular all electron TZP Slater type basis sets for all elements except for Ir, for which a basis set with a frozen core up to 3d was used for IQA. Drawings of molecular structures were produced with ADFview2019 and with CSD-Mercury. 369

DLPNO-CCSD(T) computations

For each of the four studied system, DLPNO-CCSD(T) [209][210][211][212][213][214][215] calculations with the TightPNO threshold on the PBE-D3(BJ) optimized geometries for anag, TS-ag, ag, TS-CH and MCH were performed using the ORCA 209 program system version 4.1.1.

The balanced Karlsruhe 2nd generation default triple-ζ valence plus polarization (def2-TZVP 370 ) basis set was used in these calculations, as well as automatically generated auxiliary basis set. The LED 214 analysis has been performed to quantify the different intra-and inter-fragment contributions to the energy.

NCI plots

The NCI index is based on the analysis of the reduced density gradient 216,217 : which depends on the electron density and its gradient.

Synthesis

Preparation of LiNHAc

Acetamide (945 mg, 15.9 mmol) was dissolved in ~20 mL of THF in a sealed Schlenk vessel under an Ar atmosphere and the resulting solution was cooled to -80°C. The resulting solution was vigorously stirred and added with a solution of n-BuLi in hexanes

(1.6 M, 1 eq, 10 mL) and the resulting suspension left to react overnight while the vessel was slowly warmed to room temperature. of acetonitrile at room temperature in a sealed Schlenk vessel. After reaction, washed and filtrated with H2O, the resulting residue was purified by recrystallization with CH2Cl2/n-pentane and/or washing with n-pentane, to afford the pure compound the analytical data which matched published data 138 (60 mg, 79 %). 1 H NMR (400 MHz, CDCl3) δ 9.24 (dt, J = 5.6, 1.2 Hz, 1H), 8.28 (dd, J = 7.7, 1.1 Hz, 1H), 7.70 -7.63 (m, 2H), 7.53 (dd, J = 7.6, 1.5 Hz, 1H), 7.32 (td, J = 7.4, 1.5 Hz, 1H), 7.15 -7.07 (m, 2H), 1.29 (s, 15H).

5.2.8.

General procedure for the oxidative cyclocondensation of 1c, 7c, 8c.

Under argon atmosphere, a mixture of Iodocobaltacycles (1 equiv) and [Ph3C][BArF24]

(1 equiv) was stirred overnight in ∼10-15 mL of CH2Cl2 at room temperature in a sealed Schlenk vessel. The reaction mixture was filtrated through Celite followed by removal of the solvent. The resulting residue was purified by column chromatography and then recrystallized with CH2Cl2/n-pentane and/or washed with n-pentane to obtain the white powder. 13 C NMR (126 MHz,CDCl3) δ 181.4,167.2,155.0,145.7,142.5,136.6,129.4,123.3,122.7,121.2,118.5,93.5,10.4 7, 167.9, 156.2, 144.5, 140.7, 136.4, 135.3, 127.9, 127.1, 122.1, 120.2, 94.0, 23.9, 10.3 ). 13 C NMR (126 MHz, CDCl3) δ 182. 2, 166.8, 160.4, 153.7, 150.4, 135.5, 124.9, 123.6, 117.4, 113.8, 108.0, 93.0, 40.7, 34.9, 30.8, 30.6, 10.5 6, 156.8, 152.6, 142.1, 139.3, 134.9, 133.2, 129.6, 129.4, 126.6, 122.8, 121.1, 120.6, 93.1, 10.6 21, 154.96, 143.24, 143.04, 139.09, 136.54, 124.09, 122.97, 120.75, 118.10, 93.38, 22.12, 10.38, 1.17. 13 C NMR (126 MHz, CDCl3) δ 181. 18, 167.16, 154.93, 143.22, 143.01, 139.08, 136.54, 124.08, 122.96, 120.76, 118.11, 93.36, 22.13, 10.38 ). 13 C NMR (126 MHz, CDCl3) δ 184. 10, 166.10, 154.92, 144.21, 143.88, 136.78, 125.80, 124.07, 123.94, 121.52, 118.54, 93.58, 10.26 13 C NMR (126 MHz, CDCl3) δ 181. 93, 165.71, 155.20, 148.65, 138.28, 137.04, 130.04, 122.49, 122.31, 119.76, 119.35, 93.86, 10.36. 13 C NMR (126 MHz, CDCl3) δ 169. 83, 167.67, 157.17, 146.86, 144.25, 137.09, 129.44, 124.25, 123.28, 121.62, 119.03, 86.99 86, 166.31, 155.99, 146.77, 137.74, 136.29, 129.28,

Characterization

N Co Cp I 10a N Co Cp* N H O 1f
122. 96, 122.72, 120.87, 117.49, 93.57, 28.40, 9.41 13 C NMR (126 MHz, CDCl3) δ 175. 14, 166.79, 163.96, 153.82, 145.26, 136.39, 134.79, 130.36, 123.75, 121.79, 121.60, 118.08, 88.48, 26.69, 9.10 20, 139.47, 139.05, 135.19, 132.94, 131.32, 129.95, 129.38, 129.14, 126.07, 125.45, 124.84, 123.90, 123.45, 120.22, 117.86, 97.46, 9.64. 19 43, 162.04, 161.64, 161.25, 150.29, 148.75, 144.57, 141.09, 138.75, 135.37, 130.92, 129.49, 128.76, 127.87, 127.17, 125.94, 125.70, 123.54, 123.41, 122.54, 121.37, 117.65, 85.48, 53.28, 49.20, 19.84, 16.59, 13.52, 13.00, 9.71 43, 162.03, 161.64, 161.24, 150.27, 147.88, 144.83, 141.27, 140.61, 134.88, 132.96, 132.11, 131.01, 130.92, 129.24, 128.99, 128.40, 127.85, 126.28, 125.69, 123.52, 123.19, 121.45, 121.35, 117.67, 85.61, 53.15, 49.14, 19.89, 16.65, 13.48, 13.02, 9.81 43, 162.04, 161.65, 161.24, 150.54, 147.08, 145.25, 141.70, 139.85, 134.86, 131.00, 129.28, 129.01, 127.81, 127.17, 126.39, 125.67, 123.86, 123.51, 117.71, 85.98, 53.26, 49.14, 20.00, 16.68, 13.49, 13.06, 9.81. 19 ). 13 C NMR ( 126MHz, CDCl3) δ 162. 90, 162.50, 162.11, 161.71, 149.63, 148.79, 145.21, 141.00, 138.82, 135.36, 134.91, 133.33, 132.47, 130.34, 129.54, 129.30, 128.55, 128.39, 126.57, 126.23, 125.74, 124.24, 124.06, 118.03, 86.18, 82.57, 55.64, 22.27, 21.38, 21.01, 14.22, 11.54 69, 162.30, 161.90, 161.50, 149.61, 147.87, 145.42, 141.17, 137.81, 135.14, 134.69, 129.74, 129.59, 129.36, 129.34, 129.32, 129.29, 129.11, 129.09, 129.07, 129.04, 128.18, 127.71, 127.20, 126.58, 126.55, 126.01, 125.82, 125.79, 124.68, 123.85, 121.68, 117.88, 117.85, 117.81, 85.96, 82.60, 55.52, 21.99, 21.23, 20.79, 13.99, 11.34. 19 41, 162.02, 161.62, 161.23, 149.12, 148.74, 146.05, 145.93, 140.15, 139.67, 137.33, 135.62, 134.87, 131.30, 130.89, 130.38, 130.01, 129.70, 129.26, 128.99, 128.17, 127.83, 126.34, 125.66, 125.26, 124.45, 123.80, 123.49, 123.29, 122.53, 120.25, 117.68, 91.44, 85.17, 83.21, 82.47, 53.59, 49.67, 48.10. HRMS (ESI, m/z) calcd. for C27H21N2 + : 373.1699. Found: 373.17 6 eq), 1,3,5-trimethoxybenzene as internal inert reference and 5 mL of DCM were added. Upon sealing the vessel, the resulting suspension was vigorously stirred at 50 °C for 6 h and aliquots of both vessels were removed every hour, the solvent was evaporated and replaced by CD2Cl2 (0.3 mL) and the resulting solution analyzed by 1 H NMR spectroscopy for the determination of the yield in 1a and d4.1a. The isotopic effect at time t , i.e KIEt was determined by the ratio of the yield in 1a over the yield in d4.1a. 8.52 (td, J = 7.8, 3.7 Hz, 2H), 7.89 -7.84 (m, 1H), 7.62 -7.47 (m, 5H), 7.47 -7.33 (m, 5H). 13C NMR (126 MHz, DMSO-d6) δ 140.07, 138. 85, 136.48, 135.85, 134.40, 133.32, 132.76, 132.65, 131.17, 131.06, 130.69, 130.27, 130.23, 129.98, 129.60, 129.18, 128.85, 128.51, 128.43, 126.72, 125.31, 123.14, 118.42. 136.46, 135.76, 135.43, 134.55, 134.48, 133.19, 131.47, 131.16, 131.12, 131.01, 130.96, 130.26, 130.11, 129.99, 129.60, 128.79, 128.50, 128.42, 128.16, 126.50, 125.69, 125.42, 124.89, 124.74, 123.26, 117.97. with or without TEMPO.

Experiments related to

Noteworthy, during this reaction, without TEMPO, a large precipitate formed while with 1 equiv. TEMPO, only a small amount of precipitate was observed; with 4 equiv.

TEMPO, the solution remained homogenous. (The red stripe highlights proton H5.) Stacked 1 H NMR spectra of 1a and of the reaction mixture resulting from the reaction of 1a with triflic acid.

Experiment of 1a with

Reaction of 1a with AcOH

Under an argon atmosphere, 1a (12.8 mg, 0.026 mmol) was dissolved in ∼3 mL of DCM in a sealed Schlenk vessel, and then acetic acid (1.6 μL, 0.03 mmol) was added.

After 5 h and 24 h, the yields were calculated respectively by 1 H NMR with an internal reference.

Reaction of 5a with [Ph 3 C][BArF 24 ]

Under argon atmosphere, a mixture of 5a (1 equiv) and [Ph3C][BArF24] (1 equiv) was stirred overnight in ∼10-15 mL of CH2Cl2 at room temperature in a sealed Schlenk vessel. After reaction, the color changed from brown red to green, and the crude compound was analyzed by 1 H NMR with an internal reference. vessel. After reaction, the color changed from brown red to green, and the crude compound was analyzed by 1 H NMR with an internal reference.

Hydrosilylation of ketone via cobaltacycles 1b and 5b

Under argon atmosphere, to a solution of cobaltacycles (0.1 mol %) and ketone (0.1 mmol, 1 equiv) in ∼2 mL of DCM was added HSiEt3 (0.12 mmol, 1.2 equiv). The reaction mixture was stirred overnight at room temperature. After reaction, the crude compound was analyzed by 1 H NMR (1,3,5- (top: at 247 K; bottom: 298K).

Attempts for the cobalt hydride with additive

Under argon atmosphere, the compound 1a (10 mg, 0.021 mmol) was mixed with NaBHEt3 (0.032, mmol, 1.5 equiv) in J. Young valve NMR tube in THF-d8 at -40 °C, and the reaction was monitored by 1 H NMR spectroscopy.

Hydrosilylation of benzophenone with HSiEt 3

Under argon atmosphere, the Benzophenone (30.7 mg, 0.168 mmol) and cobaltacycles (0.008 mmol, 5 mol%) were dissolved in toluene (2 ml), and then, the HSiEt3 (0.08 ml, 0.505 mmol, 3 equiv.) was added, along with NaBHEt3 (10 mol%), and the mixture was stirred for 5 hours at room temperature. the crude compound was analyzed by 1 H NMR (1,3,5-trimethoxybenzene as internal reference). 13 C NMR (126 MHz, CDCl3) δ 182. 23, 166.83, 160.44, 153.72, 150.42, 135.50, 124.89, 123.64, 117.38, 113.79, 108.03, 93.01, 40.73, 34.87, 30.76, 30.64, 10.48, 1.17 13 C NMR (126 MHz, CDCl3) δ 175. 41, 167.58, 162.73, 162.33, 161.94, 161.54, 153.12, 147.07, 139.28 (d, J = 17.5 Hz), 135.18, 131.09, 129.62, 129.39, 129.13, 128.22, 126.06, 125.31, 124.66, 123.89, 123.36, 121.73, 120.04, 118.21 -117.25 (m), 96.88, 9.52, 4. 13 C NMR spectrum (126 MHz,CDCl3) 13 C NMR (126 MHz, CDCl3) δ 177. 99, 167.99, 161.82 (dd, J = 99.6, 49.8 Hz), 153.59, 145.12, 138.96, 137.11, 136.38, 134.93, 129.68 (d, J = 11.0 Hz), 129.18 (d, J = 3.2 Hz), 128.94, 128.40, 127.92, 125.76, 117.65 (d, J = 5.9 Hz), 96.94, 23.63, 9.22, 4.02. 13 C NMR spectrum (126 MHz,CDCl3) 13 C NMR (126 MHz, CDCl3) δ 176. 76, 167.22, 163.43, 162.41, 162.01, 161.61, 161.22, 151.34, 151.31, 134.92, 134.74, 129.40, 128.91, 128.66, 128.28, 127.93, 125.76, 125.04, 123.59, 121.43, 120.41, 118.76, 117.62, 114.84, 109.14, 96.08, 40.41, 35.23, 30.36, 9.36, 4. (metal), c) interaction energy between fragments 4 (2-phpy -) and 1 (metal), d) interation energy between fragments 5 (Cp* ligand) and 1 (metal), e) interaction energy between fragments 3 (auxiliary basis) and 2 (H + ), f) interaction energy between fragments 4 (2phpy -) and 2 (H + ), g) interaction energy between fragments 5 (Cp* ligand) and 2 (H + ), h) interaction energy between fragments 4 (2-phpy -) and 3 (auxiliary basis), i) interaction energy between fragments 5 (Cp* ligand) and 3 (auxiliary basis), j) interaction energy between fragments 5 (Cp* ligand) and 4 (2-phpy -). T9$M ! ' =' >DBGFAB@' >FG=EA@@' >FGDBAFC'

X-ray structure of 2c

NCMe NCMe

Me-Phpy

T9$M • ' C' >D=G@AH@' >DB=HA@C' >DBDDAFB' T9$MQ' =' >DEB=A@=' >D==FA@D' >D=DCAFH' T9$MO' =' >DCEHABH' >DBD?A@F' >DBG@A=G' F>3T9$M73MT9"7M%Q&' =' >=BFBDAB@' >=BBFFA@=' >=B=BCACB' F>3T9$M73MT9"7M%Q' MQ"M,"' =' >F@?AGB' >FD?AE=' >F@?AB@' ! ! !

Finally

  , I deeply appreciate the financial support provided by the China Scholarship Council (CSC), which gave me an opportunity to study abroad and gain insight. III IX Theoretical material for chapter 3 .................................................................................... 297 X List of tables

Figure 2 . 1 .

 21 Agostic intermediate in the CMD mechanism and summary of the effects governing the reactivity of this intermediate .

Figure 2 . 2 .

 22 Figure 2. 2. GGA-DFT-D energy profiles for the cyclometallation of 2-phpyH assisted by acetate (black lines) or by acetamidate (cyan lines) bases: Left) Cp*Co(III) system; Right) Cp*Ir(III) system. .

Figure 2 . 3 .

 23 Figure 2. 3. Scheme of the reactive site during the cyclocobaltation of 2-phpyH via the CMD

Figure 2 . 5 .

 25 Figure 2. 5. Evolution of the QTAIM/IQA ΔEint(Op-M) NHAc-OAc value (in kcal/mol) in the course of the CMD process where ΔEint(Op-M) NHAc-OAc = Eint(Op-M) NHAc -Eint(Op-M) OAc ..........................................

Figure 2 . 6 .

 26 Figure 2. 6. a) NCI surfaces (s=0.3, -0.03<sign(λ2)ρ<0.03) for the ag and Ir-NHAc-ag-col complexes (atom color code: light grey, C; dark blue, N; white, H; red, O; violet, Co; cyan, Ir): the circled NCI isosurface in Ir-NHAc-ag-col outlines a rather strong repulsive Nd-HAr interaction. b) geometries of TS-CH in the Co and Ir-based systems with the associated imaginary vibrational mode frequency as optimized in their singlet state at the COSMO(CH2Cl2)-ZORA-PBE-D3(BJ)/all electron TZP level. .....

Figure 2 . 7 .

 27 Figure 2. 7. s(r) diagrams for ag and Ir-NHAc-ag-col compounds. ....................................................

Figure 2 . 8 .

 28 Figure 2. 8. NCI peak densities for ag andIr-NHAc-ag-col complexes. ..............................................

Figure 2 . 11 .

 211 Figure 2. 11. Singlet geometries of Ir-NHAc-ag, Ir-NHAc-ag-col and Ir-NHAc-TS-CH with atom numbering, atomic QTAIM charges (blue colored numbers) main interatomic distances and the main QTAIM-IQA interatomic interaction energies Eint decomposed into covalent (green colored) and ionic (red colored) percentage of contribution. Positive and negative values of Eint indicate repulsive and attractive interactions respectively........................................................................................................

Figure 2 . 12 .

 212 Figure 2. 12. Singlet geometries of Co-NHAc-ag and Co-NHAc-TS-CH with atom numbering, atomic QTAIM charges (blue colored numbers) main interatomic distances (red colored numbers) and the main QTAIM-IQA interatomic interaction energies Eint decomposed into covalent (green colored) and ionic (red colored) percentage of contribution. Positive and negative values of Eint indicate repulsive and attractive interactions respectively.................................................................................................

Figure 2 . 13 .

 213 Figure 2. 13. Total electron energy profile for Co & Ir / -OAc and -NHAc systems computed in the gas phase at the DLPNO-CCSD(T)/def2-TZVPP level from geometries computed at the COSMO(CH2Cl2)-ZORA-PBE-D3(BJ)/all electronTZP level. ...............................................................

Figure 2 . 16 .

 216 Figure 2. 16. ORTEP diagram of the structure of [1e][I3] and [1e'][I3], ellipsoids displayed at 50%

Figure 2 . 18 .

 218 Figure 2. 18. ORTEP diagram of the structure of 2b and 1f, ellipsoids displayed at 50% probability.

Figure 2 . 19 .

 219 Figure 2. 19. ORTEP diagram of the structure of 2c, ellipsoids displayed at 50% probability.. ...........

Figure 2 . 20 .

 220 Figure 2. 20. Evolution of the KIE with error bars over 6 hours for independent cyclocobaltation

Figure 2 . 22 .

 222 Figure 2. 22. ORTEP diagram of the structure of (a) 4a and (b) 5a, ellipsoids displayed at 50%

Figure 2 . 23 .

 223 Figure 2. 23. ORTEP diagram of the structure of (a) 1b and (b) 3b , ellipsoids displayed at 50%

Figure 2 . 24 .

 224 Figure 2. 24. ORTEP diagram of the structure of (a) 4b and (b) 5b, ellipsoids displayed at 50%

Figure 2 . 25 .

 225 Figure 2. 25. ORTEP diagram of the structure of 1b', ellipsoids displayed at 50% probability ............

Figure 2 . 26 .

 226 Figure 2. 26. Left: Gibbs enthalpy profile (in kcal/mol at T= 298.15 K) computed at the COSMO(CH2Cl2)-ZORA-PBE-D3(BJ)/all electron TZP level for a model of the electrophilic activation of the CAr-HAr bond of 2-phpyH with the exogenous intervention of external 2-phpyH acting as proton acceptor in the EA-π-to-EA-MC process via dicationic reactive complex EA-pre-TS and transition state EA-TS. Right: CSD-Mercury drawings of geometries and selected interatomic distances (green colored fonts) are given in Å.................................................................................................................

Figure 3 . 1 .

 31 ORTEP diagram of the structure of {[Cp*Co]2(μ-I)3}[I3], ellipsoids displayed at 50%

Figure 3 . 14 .

 314 Figure 3. 14. Cyclic voltammograms of {[Cp*Co]2(μ-I3 + }[I3 -] (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1). v = 100 mV s-1 . .......................................

Figure 3 . 15 .

 315 Figure 3. 15. Cyclic voltammograms of 7a (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1). v = 100 mV s-1 . ......................................................................

Figure 3 . 23 .

 323 Figure 3. 23. Proposed computed Gibbs free energy profiles of the formation of [1c] + . ....................

Figure 3 . 24 .

 324 Figure 3. 24. Singlet and triplet state C-H•••Co agostic transient geometries computed at the (COSMO)-ZORA-PBE-D4(EEQ)/all-electron TZP level with selected interatomic distances.. ..........

Figure 4 . 1 .

 41 Standard stoichiometric reaction of 1b with HSiEt3 monitored by 1 H NMR. (top: at 247 K ; bottom : 298K) ....

Figure 4 . 2 .Figure 4 . 3 .

 4243 Figure 4. 2. ORTEP diagram of the structure of 1g, ellipsoids displayed at 50% probability.. 152 Figure 4. 3. ORTEP diagram of the preliminary structure of 1h, ellipsoids displayed at 50% probability.

Figure 5 . 3 .

 53 Figure 5. 3. NMR spectrum of the experiment of 1a with triflic acid (J-Young tube). Stacked 1 H NMR spectra of 1a and of the reaction mixture resulting from the reaction of 1a with triflic acid. ..................

Figure 5 . 4 .

 54 Figure 5. 4. 1 H NMR spectra of the reaction of 1a with acetic acid (top: 5 h; bottom: 24 h; blue point:

Figure 5 . 12 .

 512 Figure 5. 12. Standard stoichiometric reaction of 1a with NaBHEt3 monitored by 1 H NMR.. ...............

Figure

  Figure A. 1.1 H NMR spectrum (500 MHz, CDCl3) of 1a ............................................................................

Figure

  Figure A. 35. 1 H-1 H NOESY spectrum of [1c][BArF24] ...............................................................................

  Figure A. 63.13 C NMR spectrum (126 MHz, CD2Cl2) of [10c][BArF24] ....................................................

Figure A. 64 .

 64 Figure A. 64. 1 H-1 H COSY spectrum of [10c][BArF24] ................................................................................

Figure A. 65 .

 65 Figure A. 65. 1 H-1 H NOESY spectrum of [10c][BArF24] .............................................................................

Figure

  Figure A. 66. 1 H-13 C HSQC spectrum of [10c][BArF24] ..............................................................................

Figure A. 68 .

 68 Figure A. 68. Mass spectrum (ESI, negative mode) of the crude reaction mixture in negative mode. I3 - (m/z 380.7) and I -(m/z 126.9) were observed..............................................................................................

Figure A. 69 .

 69 Figure A. 69. Mass spectrum (ESI) overview of the crude mixture in positive mode. ...........................

Figure A. 70 .Figure A. 71 .

 7071 Figure A. 70. Zoomed mass spectrum of the crude residue, and simulation of protonated iodophenylpyridine. The protonated iodo 2-phenylpyridine and was observed at m/z 281. ..........................

Figure A. 72 .Figure A. 73 .Figure A. 74 .

 727374 Figure A. 72. Zoomed mass spectrum of the crude mixture, and simulation of {[Cp*Co]2(μ-I3)} + . {[Cp*Co]2(μ-I3)} + was observed at m/z 768.8 as well as Cp*CoI ("half" of this dimer) at m/z 320. ........ 278 Figure A. 73. Mass spectrum (ESI) overview of the crude compound in positive mode. ...................... 279 Figure A. 74. Zoomed mass spectrum (ESI) of the crude compound in positive mode. Phpy-Cp* was observed at m/z 290.19. .................................................................................................................................. 279

Figure A. 76 .Figure A. 77 .

 7677 Figure A. 76. Zoomed mass spectrum of the crude compound. Ph3C + was observed at m/z 243.12.280 Figure A. 77. Zoomed mass spectrum of the crude mixture. The Cp*Co-I fragment was observed at m/z 320.95. ........................................................................................................................................................ 281

Figure A. 80 .Figure A. 81 .

 8081 Figure A. 80. Mass spectrum overview of the crude mixture of the reaction between 1a and AgPF6 (positive mode). Protonated 2-phenylpyridine at m/z 156.08 was observed along [1c] + . ...................... 282 Figure A. 81. Zoomed mass spectrum of the crude mixture of the reaction between 1a and AgPF6

Figure A. 84 .

 84 Figure A. 84. Gibbs free energy (ZORA-PBE-D4(EEQ)/all electron TZP/COSMO(CH2Cl2) level) diagram of the considered pathways for the formation of [1c] + from 1a, considering the presence of a fictitious H• in the reactive medium. The energy of the abstraction of H• (e.g. +71.4 kcal/mol if H• originates from triphenylmethane) should be added to the energies represented by brown lines. (grey dotted lines) considered pathways, (blue dotted lines) proposed pathways............................................ 298

  . Crystal data and structure refinement for {[Cp*Co]2(μ-I3)}[I3] ......................................

  ce travail, une cyclométallation de la 2-phénylpyridine (2-phpyH) par Cp*Co(III) a été abordée suivant la procédure communément utilisée pour la cycloiridation et la cyclorhodation, favorisée par le mécanisme CMD (Métallation-Déprotonation Concertée) assisté par une base( Schéma R. 1). Le cobaltacycle [Cp*Co(2-phpy-κC,κN)I] peut être efficacement synthétisé à partir du [Cp*CoI2]2 stable à l'air et de la 2-phénylpyridine 2-phpyH, en présence de LiNHAc comme base, avec un rendement de 83%, alors qu'avec le NaOAc anhydre comme base, seul un rendement de 12% a été obtenu dans des conditions similaires. Parallèlement, une étude théorique systématique de ces réactions de cyclocobaltation assistées par une base a été menée. A l'aide de l'étude des profils d'énergie DFT et du rôle des interactions non covalentes, nous avons décrit les profils d'enthalpie de Gibbs pour la formation de l'intermédiaire agostique transitoire (Figure R. 1) et nous avons analysé également les contributions attractives et répulsives à la coupure de la liaison C-H (Figure R. 1). Les résultats montrent que la cyclométallation avec AcO -comme base auxiliaire est moins efficace que celle avec AcNH -sur la base de la thermochimie, ceci est principalement dû au fait que l'acétamidate réduit efficacement l'intéraction de chélation résiduelle avec le métal et par conséquent augmente la polarisation de la liaison C-H qui est déjà engagée dans une interaction agostique partiellement covalente partiellement non covalente avec le centre métallique chargé positivement. Différents cobaltacycles ont ensuite été synthétisés par cyclométallation favorisée par la [NHAc] -, caractérisés analytiquement et leurs structures ont été résolues par l'analyse structurale de diffraction des rayons X, confirmant l'importance de l'acétamidate dans la cyclométallation assistée par une base. En outre, l'effet de la base auxiliaire sur une réaction modèle de condensation alcyne-arène qui met en scène le [Cp*CoI2]2 comme catalyseur a été étudié. Schéma R. 1. Le mécanisme de CMD appliqué aux complexes Cp*M(III) de métaux de transition du groupe 9 : anag, le complexe réactif précurseur de l'intermédiaire agostique ag via TS-ag ; MCH, le produit de cyclométallation immédiat issu de la réaction de transfert de protons se produisant via TS-CH à partir de ag.

Figure R. 2 .Figure R. 3 .

 23 Figure R. 2. Profils d'énergie GGA-DFT-D pour les cyclométallations de 2-phpyH assistées par des bases acétate (lignes noires) ou acétamidate (lignes cyan); (gauche : Système Cp*Co(III) ; droite : système Cp*Ir(III)

Figure R. 4 .

 4 Figure R. 4. Diagramme ORTEP des structures de 4a (a), 5a (b) dessinées au niveau de probabilité de 50% avec numérotation partielle des atomes. Les atomes H et les molécules de solvant ont été omis pour des raisons de clarté.

Figure R. 5 .

 5 Figure R. 5. Diagramme ORTEP des structures de 1b (a), 3b (b) dessinées au niveau de probabilité de 50% avec numérotation partielle des atomes. Les atomes H et les molécules de solvant ont été omis pour des raisons de clarté.

Figure R. 6 .

 6 Figure R. 6. Diagramme ORTEP des structures de 4b (a), 5b (b) dessinées au niveau de probabilité de 50% avec numérotation partielle des atomes. Les atomes H et les molécules de solvant ont été omis pour des raisons de clarté.

Figure R. 7 .

 7 Figure R. 7. Diagramme ORTEP des structures de 1b' dessinées au niveau de probabilité de 50% avec numérotation partielle des atomes. Les atomes H et les molécules de solvant ont été omis pour des raisons de clarté.

Figure R. 8 .

 8 Figure R. 8. Diagramme ORTEP de la structure de [1c][I3] (condensation de Cp* sur phpy) dessiné avec une probabilité de 50%. Les atomes H et les molécules de solvant ont été omis pour des raisons de clarté.

Figure R. 9 .Figure R. 10 .

 910 Figure R. 9. Spectre RPE en bande X enregistré à 4,3 K après 5 min de réaction entre des solutions 40 mM de [Cp*Co(2-phpy-κC,κN)I] et [Ph3C][BArF24] dans DCM . Le spectre a été enregistré à une fréquence de 9,345 GHz;

Figure R. 11 .

 11 Figure R. 11. Schéma des voies proposées pour la condensation de Cp* sur phpy.

Figure R. 12 .

 12 Figure R. 12. Profils d'énergie libre de Gibbs calculés proposés. Les trois voies possibles sont matérialisées par des lignes de couleur solide (vert, bleu, rose). Profil d'énergie de Gibbs intrinsèque exergonique en considérant un H• fictif.

1 .

 1 cobaltacycles en tant qu'intermédiaires clé peuvent être facilement préparés avec de bons rendements via le mécanisme CMD (Métallation-Déprotonation Concertée) assisté par une base, et les avantages déduits de la théorie du sel d'acétamidate en tant que base ont été démontrés. La pertinence des intéractions non covalentes dans la cyclocobaltation promue par CMD (Métallation-Déprotonation Concertée) est évidente d'après l'évolution de ce qu'on dénomme le «site de réaction»: la contribution remarquable des interactions électrostatiques locales et donc de l'environnement multipolaire à la polarisation de la liaison CAr-HAr avant son activation par la carbométallation et le transfert de proton à la base voisine donne une raison valable pour l'optimisation non seulement de la cyclocobaltation et de la cyclonickelation mais aussi des cyclométallations utilisant d'autres métaux 3d. En outre, la cyclocondensation induite par l'oxydation des métallacycles Cp*Co(III) est un processus assez rapide induit par la formation d'un intermédiaire transitoire Co(IV), qui constitue un nouvel exemple de synthèse par effet " métal-template " centré sur le Co(IV) déclenché par oxydation mono-électronique, qui fournit également une nouvelle direction pour étudier de manière plus systématique et prédictive le mécanisme de fonctionnalisation des liaisonsC-H promues par les précatalyseurs à base d'entité « Cp*Co(III) ».D'une manière plus générale ces travaux fournissent des bases conceptuelles essentielles à la mise en oeuvre d'une nouvelle approche prédictive de l'ingénierie de la catalyse de fonctionnalisation des liaisons C-H par les complexes de métaux du bloc 3d des métaux de transition. Advantages and challenges of C-H activation In the last few decades, unprecedented developments have been made in the research of C-H bond activation, providing new disconnection tactics for the formation of C-C

Scheme 1 . 2 .

 12 Scheme 1. 2. Strategies of the selective for C-H functionalization (TM = transition metal; DG = directing group).

Scheme 1 . 3 .

 13 Scheme 1. 3. The approaches of transition metal-catalyzed C-H activation. (a) C-H functionalization assisted by DG; (b) C-H functionalization assisted by TDG; (c) C-H functionalization via noncovalent interaction strategy; (M = transition metal; DG = directing group; TDG = transient directing group; L = ligand).

  Notably, the Co(III) catalysts have been developed extremely rapidly in the last few years (Figure1.1 orange). Compared to the homologous rhodium and iridium, the cobalt is less electronegative, and Co-C bonds are usually more polarized than the corresponding Ir/Rh-C bonds, which permits conversion to organometallic cobalt complexes that are more nucleophilic, allowing for new reactivities and improving chemo-and regioselectivities. Therefore, this has led to increase the attention focused on this area, allowing researchers to develop novel, highly reactive cobalt complexes for the C-H bond activation.

Figure 1 . 1 .

 11 Figure 1. 1. Number of papers published per year on cobalt-catalyzed C-H activation. (In blue, cobalt-catalyst; in orange, Co(III) catalyst. Datas obtained from ISI Wos).

Figure 1 .

 1 2 summarizes the Cp*Co(III)-complexes and their synthetic routes that have been very common in C-H bond activation in recent years.

Figure 1 . 2 .

 12 Figure 1. 2. The Cp*Co(III)-catalyst precursors and their synthetic routes.

Scheme 1 . 8 .

 18 Scheme 1. 8. Addition reaction of 2-phenylpyridine.

Scheme 1 . 9 .

 19 Scheme 1. 9. Selected Cp*Co(III)-complex catalyzed C-H activation of Indoles based substrates (top) and 2-aryl N-containing heterocyclic substrates (bottom).

Scheme 1 . 11 .

 111 Scheme 1. 11. Selected Cp*Co(III)-catalyzed C(sp 3 )-H activation of 8-methylquinoline.

  Scheme 1.12.

Scheme 1 . 14 .

 114 Scheme 1. 14. Selected examples for the formation of heterocycles with alkynes via Cp*Co(III)-catalysts.

  Another example of isoquinoline derivatives was investigated by Pawar and coworkers (Scheme 1.14n)[START_REF] Pawar | Cp*Co(III)-Catalyzed C-H/N-N Functionalization of Arylhydrazones for the Synthesis of Isoquinolines[END_REF] , annulation of arylhydrazones with internal alkynes catalyzed by Cp*Co(CO)I2 via C-H/N-N bond functionalization with good yield, and the N-N bond also acted as an internal oxidant to facilitate this procedure. Most recently, Zhu and co-workers developed a novel method for the formation of 1aminoisoquinolines via directed C-H activation of oxadiazole with alkynes (Scheme 1.14o)[START_REF] Yang | Cobalt(III)-Catalyzed Oxadiazole-Directed C-H Activation for the Synthesis of 1-Aminoisoquinolines[END_REF] .

  Scheme 1. 16. Selected examples of Cp*Co(III)-catalyzed annulation of ioxazolones and diazo compounds.

1 .Scheme 1 . 17 .Scheme 1 . 18 .

 1117118 Scheme 1. 17. Selected examples of the synthesis of heterocyclics use other compounds as coupling partners.

Scheme 1 . 19 .

 119 Scheme 1. 19. General electrophilic bond activation mechanism of cyclometallation.

Agostic C -Scheme 1 . 20 .

 C120 Scheme 1. 20. Bond activation by electrophilic aromatic substitution and agostic C-H bond activation (E= donor atom, M=transition metal).

Scheme 1 . 21 .Scheme 1 . 23 .Scheme 1 . 24 .

 121123124 Scheme 1. 21. Oxidative addition mechanism for cyclometallation (E= donor atom, M=transition metal).

3 H 1 . 25 .Scheme 1 . 26 . 11 HScheme 1 . 27 . 28 .Scheme 1 . 29 .

 31251261112728129 Scheme 1. 25. The reactivity of metallacycles with the various of unsaturated molecules.

31 .

 31 Scheme 1. 31. Cp*Rh(III)-catalyzed ortho-C-H bond amidation.

[Scheme 1 . 33 . 1 (

 1331 Scheme 1. 33. The synthesis of Cr(CO) 3 -containing metallacycles.

Scheme 1 . 35 .

 135 Scheme 1. 35. The synthesis of cationic cyclometallated complex and catalyzed hydrosilylation of arylinitriles and ketones.

2 .Scheme 1 . 36 .

 2136 Scheme 1. 36. The first example for the synthesis of the Cp*Co(III)-metallacycle.

Figure 2 . 1 .

 21 Figure 2. 1. Agostic intermediate in the CMD mechanism and summary of the effects governing the reactivity of this intermediate. (N : blue; C : dark grey; H : light grey; O : red; Metals : magenta; Red arrows : electrostatic attraction; Blue arrows : electrostatic repulsive; Green arrows : charge density donation; Purple arrows : repulsion; The eggshaped orange-yellow area : the weak exchange CAr-HAr-metal interaction.)

  Scheme 2. 1. The CMD mechanism applied to group 9 transition metal Cp*M(III) complexes 179 : anag, the reactive complex precursor of the agostic intermediate ag, via TS-ag; MCH, the immediate cyclometallation product arising from the proton transfer reaction occurring via TS-CH from ag.

Figure 2 . 2 .

 22 Figure 2. 2. GGA-DFT-D energy profiles for the cyclometallation of 2-phpyH assisted by acetate (black lines) or by acetamidate (cyan lines) bases: Left) Cp*Co(III) system; Right) Cp*Ir(III) system.

(

  QTAIM)-based treatment of the electron density topology provides an intuitive spatial map of local repulsive, non-bonding and attractive NCI materialized by isosurfaces of the signed reduced density gradient. The QTAIM-Interacting Quantum Atoms (QTAIM-IQA) method computes and decomposes in a basis-set independent way interatomic interaction energies into covalent and ionic contributions.179,[218][219][220] Also relevant are the so-called QTAIM -or Bader-charges that have proven reliable in expressing the local charge density distribution.221 In this method, the analysis of NCI was essentially focused on the "reactive site" of the molecule where the C-H bond disruption occurs during the anag®TS-ag®ag®TS-CH®MCH sequence. This reactive site is the group of atoms comprising Co or Ir, CAr, HAr, Op (proximal to HAr), Od or Nd (distal to HAr), which undergoes various phenomena that are illustrated by Figure2.3 and were already outlined with the Ni/Pd dyad previously. Restricting our reasoning to this reactive site does not discard the role of the ligand retinue, i.e here the pentamethylcyclopentadienyl and the pyridyl fragment of 2-phpyH that respond in benign ways as the reactive site evolves (vide infra the DLPNO-CCSD(T)/LED analysis).

Figure 2 . 3 .

 23 Figure 2. 3. Scheme of the reactive site during the cyclocobaltation of 2-phpyH via the CMD mechanism.

  both Ir-OAc and Ir-NHAc systems the interaction is always repulsive and climbs to a maximum of repulsion at TS-CH. In Co-OAc and Co-NHAc the HAr-metal interaction is significantly attractive only in ag (Eint ~-9 kcal/mol) and becomes repulsive at TS-CH. In such a reduced space around the metal, the existence of a residual κ 2 chelation of the metal center by the base is evident from the values of the Eint for the Op-metal interaction that vary approximately from ~-220 kcal/mol in anag to ~-100 kcal/mol in TS-CH. For reference, the Eint value of the interaction of the distal heteroatom with the metal center, i.e. Od-M and Nd-M (where M= Co or Ir) is ~-200 kcal/mol throughout the anag -to-TS-CH process in all four systems, Co-OAc/NHAc and Ir-OAc/NHAc. The value of Eint (Op-metal) is higher than that of the H-bonding interaction Op-HAr (~-30 kcal/mol) in all stages of the reaction except TS-CH where Eint (Op-HAr) equals or slightly supersedes Eint (Op-metal) with values of ~100-120 kcal/mol. This residual chelation therefore contributes to the anag -to-ag barrier of activation. It is a challenger of the concerted carbometallation deprotonation when the strength of the chelation interaction prohibits the establishment of the Op-HAr interaction and a tighter interaction of CAr with the metal center. In all the four systems considered here the evolution of the Op-metal interaction shows that the covalent component of the interaction recedes to the ionic character to become residual at TS-CH (Figure 2.4).

Figure 2 . 4 .

 24 Figure 2. 4. Evolution of the ionic and covalent character of the Op-Co interaction in the course of the CMD process expressed as a percentage of the associated interatomic QTAIM-IQA energy of interaction Eint.

Figure 2 . 5 .

 25 Figure 2.5. It shows that the effect of the replacement of AcO -by AcNH -at each stage of the CMD mechanism is in fact the highest at the agostic intermediate ag were ΔEint(Op-M) NHAc-OAc amounts ~-11 kcal/mol, which in other terms means that the substitution of AcO -for AcNH -favors the access to ag by reducing significantly the residual chelation. Worthy to note the Eint value for the H-bonding interaction in the Op-HAr interactions displays a low sensitivity to the change of base in both Co and Ir systems.

Figure 2 . 5 .

 25 Figure 2. 5. Evolution of the QTAIM/IQA ΔEint(Op-M) NHAc-OAc value (in kcal/mol) in the course of the CMD process where ΔEint(Op-M) NHAc-OAc = Eint(Op-M) NHAc -Eint(Op-M) OAc .

Figure 2 .

 2 Figure 2.6 shows the results for the ag and Ir-NHAc-ag-col complexes in order to analyze the cleavage of the CAr-HAr bond. If one first looks at the interactions with the metal (M), one can easily see that Ir-NHAc-ag and Ir-NHAc-ag-col stand aside from the rest. Co-NHAc-ag, Co-OAc-ag and Ir-OAc-ag show strong interactions between the metal and the CAr-HAr bond which are the deep blue surfaces in Figure 2.6. Slightdifferences are observed though within the group. One interesting thing to note here is that whereas QTAIM would have identified M-HAr or M-CAr interactions, NCI clearly highlights the interaction with the full CAr-HAr fragment. This is specially so for the Ir-OAc-ag complex, where the blue region extends over a greater region of space (see that it is formed by two deep blue regions that have been highlighted by a discontinuous trace).

Figure 2 . 6 .

 26 Figure 2. 6. a) NCI surfaces (s=0.3, -0.03<sign(λ2)ρ<0.03) for the ag and Ir-NHAc-agcol complexes (atom color code: light grey, C; dark blue, N; white, H; red, O; violet, Co; cyan, Ir): the circled NCI isosurface in Ir-NHAc-ag-col outlines a rather strong repulsive Nd-HAr interaction. b) geometries of TS-CH in the Co and Ir-based systems with the associated imaginary vibrational mode frequency as optimized in their singlet state at the COSMO(CH2Cl2)-ZORA-PBE-D3(BJ)/all electron TZP level.

Figure 2 .

 2 Figure 2. 7. s(r) diagrams for ag and Ir-NHAc-ag-col compounds.

Figure 2 . 8 .

 28 Figure 2. 8. NCI peak densities for ag and Ir-NHAc-ag-col complexes.

Figure 2 . 9 .

 29 Figure 2. 9. NCI integrals for ag and Ir-NHAc-ag-col compounds.

Figure 2 . 10 .

 210 Figure 2. 10. Hag-Cag-Cb-Hb dihedral for ag and ag-col compounds.

Figure 2 .Figure 2 . 11 .

 2211 Figure 2.11 depicts Ir-NHAc-ag and Ir-NHAc-ag-col rotamers that differ by the orientation of the acetamidate ligand: in ag the carbonyl lies further away from the CAr-

Figure 2 . 12 .

 212 Figure 2. 12. Singlet geometries of Co-NHAc-ag and Co-NHAc-TS-CH with atom numbering, atomic QTAIM charges (blue colored numbers) main interatomic distances (red colored numbers) and the main QTAIM-IQA interatomic interaction energies Eint decomposed into covalent (green colored) and ionic (red colored) percentage of contribution. Positive and negative values of Eint indicate repulsive and attractive interactions respectively.

Figure 2 . 13 .

 213 Figure 2. 13. Total electron energy profile for Co & Ir / -OAc and -NHAc systems computed in the gas phase at the DLPNO-CCSD(T)/def2-TZVPP level from geometries computed at the COSMO(CH2Cl2)-ZORA-PBE-D3(BJ)/all electron TZP level.

Figure 2 .

 2 Figure 2.13 displays the gas phase DLPNO-CCSD(T) total electron energy profiles for the four systems, from the DFT-optimized structures, which illustrates in a qualitative

Figure 2 . 14 .

 214 Figure 2. 14. Local Energy Decomposition (LED) analysis for the Ir and Co systems along the reaction coordinates of the CMD mechanism with plots of the inter fragment interaction energies Ei-j, where i and j are the considered molecular fragment numbers:

Figure 2 .

 2 14a), and [2-phpy] -, i.e fragment 4, decreases by 20 to 45 kcal/mol for all four systems from anag to ag before increasing by ~500 kcal/mol from ag to MCH, while the interaction between fragment 2 and the auxiliary basis, fragment 3, decreases by ~30-40 kcal/mol during the formation of the agostic intermediate before decreasing again by ~400 kcal/mol along the proton abstraction, except for Ir-NHAc for which the interfragment 2-3 interaction energy increases by ~40 kcal/mol during the first step. The interaction between the fragment 2 and the superfragment "3+4", i.e. the sum of interactions between fragments 2 and 3 and between fragments 2 and 4, is shown in Figure2.8b.For both cobalt analogues and for Ir-OAc, this contribution stabilizes the system when forming the agostic intermediate, the stabilization being greater by ~30 kcal/mol in the cobalt cases, before becoming repulsive when the proton is transferred from fragment 3 to fragment 4. For Ir-NHAc, the contribution becomes repulsive when forming ag and attractive when forming ag-col. In both the cobalt and the iridium cases, concerning the (3+4)-2 interaction, no significant difference in stabilization of the agostic intermediate is observed when changing the auxiliary base. This difference in behavior enlightens the importance of the orientation of the base in the stabilization of the agostic intermediate. The total interaction around the reactive center, i.e. the sum of interaction energies between fragments 2, 3 and 4, still presents its minimum at ag, located ~20 kcal/mol lower for the cobalt analogues than for the iridium ones, thus defining the agostic intermediate as the optimal interaction situation within the reactive site.The interaction between fragment 2 and the "spectator" Cp* ligand, i.e fragment 5, is shown in Figure2.14c. This interaction energy decreases up to the ag stage and then increases towards an almost null final gain in energy (< 5 kcal/mol). The only variation to this trend happens for Ir-NHAc for which the interaction energy decreases from anag to TS-ag then increases to ag, decreases to ag-col before increasing again to MCH. When the auxiliary base is acetamidate instead of acetate, the stabilization of the agostic intermediate is lower in both the cobalt (~7 kcal/mol) and the iridium (~13 kcal/mol compared to the Ir-NHAc-ag-col) cases.

Figure 2 .

 2 Figure 2.14d. In the case of the cobalt analogues, in Ir-OAc, and in Ir-NHAc if considering only ag-col instead of ag, this repulsive interaction increases up to ag to decline subsequently, the interaction at the MCH stage being 20-40 kcal/mol more repulsive than the one at anag. The main reason for this behavior is the shortening of the metal-HAr distance at the ag step. In the case of Ir-NHAc, the repulsion at ag is not greater than the one at anag, due to a relatively similar metal-HAr distance which contrasts with Ir-NH-ag-col (Δdag-anag= 0.05 Å vs. Δdag-col-anag= 0.84 Å). Due to shorter metal-HAr distances for the cobalt analogues the maximum of repulsion is greater in the cobalt systems than in the iridium ones by more than 40 kcal/mol. In both cobalt and iridium systems, the metal-HAr repulsion is lower in the acetamidate case than in the acetate case by ~14 kcal/mol for Ir (compared to IrNH-ag-col) and by ~7 kcal/mol for Co, mainly due to a shorter distance in the acetate case than in the acetamidate one (ΔdAcO-AcNH(Co)=0.04 Å and ΔdAcO-AcNH(Ir)=0.21 Å). Overall, agostic intermediates

2 )Scheme 2 . 2 .Scheme 2 . 3 .

 22223 Scheme 2. 2. Example of the synthesis of iridacycle with [Cp*IrCl2]2.

  as an amide and a coordinatively noninterfering base are present in solution, the latter having putatively the role of deprotonating a transient Co-bound amide and generating in situ the amidate-Co species required for the metalation of the ligand via the CMD mechanism.

Figure 2 . 15 .

 215 Figure 2. 15. Effect of the solvent (THF vs DCM) on the yield in 1a upon cyclocobaltation of 2-phpyH by [Cp*CoI2]2 in the presence of various amounts of LiNHAc per Co atom(1, 3, 5, and 10 equiv)

Figure 2 . 16 .

 216 Figure 2. 16. ORTEP diagram of the structure of (a) [1e][I3] and (b) [1e'][I3], ellipsoids displayed at 50% probability. The hydrogen-atoms on the carbon, [I3] ─ and solvent molecules were omitted for clarity. (a) Selected bond distances [Å] and angles [°]: O1-Co2 1.9307(18), O2-Co1 1.9459(17), O2-Co2 1.9443(18), O3-Co1 1.9435(18), O3-Co2 1.9412(17), Co1-Co2 2.8926(5), N1-Co1 1.937(2), C21-O1 1.286(3), C21-N1 1.300(3); O2-Co2-Co1 41.98(5), O1-C21-N1 124.9(2), C21-N1-Co1 126.82(17), C21-O1-Co2 126.05(16), Co2-O2-Co1 96.07(8), Co2-O3-Co1 96.25(8). (b) Selected bond distances [Å] and angles [°]: N1-Co1 1.937(2), O1-Co2 1.935(2), O2-Co2 1.930(2), O2-Co1 1.940(2), Co1-I1 2.6415(4), Co2-I1 2.6384(4); Co2-O2-Co1 107.83(10), N1-Co1-O2 90.04(10), N1-Co1-I1 91.15(7), O2-Co1-I1 86.21(6), O2-Co2-O1 90.11(9), Co2-I1-Co1 72.650(13).

  the synthesis of [1c][I3] at a preparative scale, which will be discussed in detail later.

Figure 2 . 17 .

 217 Figure 2. 17. ORTEP diagram of the structure of (a) [1c][I3] and (b) [1c'][I3], ellipsoids displayed at 50% probability. The hydrogen-atoms on the carbon, [I3] ─ and solvent molecules were omitted for clarity. (a) Selected bond distances [Å] and angles [°]: C5-N1 1.359(5), C16-N1 1.544(5), C5-C6 1.470(6), C6-C11 1.399(6), C11-C12 1.513(6), C12-C16 1.557(6); N1-C16-C12 109.0(3), C5-N1-C16 122.0(3), C6-C11-C12 119.8(4), C11-C6-C5 120.0(4). (b) Selected bond distances [Å] and angles [°]: C12-C13 1.557(8), C13-C14 1.536(8), C13-N1 1.539(7), C14-C15 1.322(9), C15-C16 1.507(8), C16-O1 1.417(7), C16-O2 1.446(8), C5-N1 1.371(7), C11-C12 1.521(8), C12-O1 1.441(7); C11-C12-C13 109.9(5), O1-C12-C13 106.8(5), O1-C12-C11 102.6(4), C6-C11-C12 118.2(5), C6-C11-C12 118.2(5), C16-O11-C12 117.2(4), N1-C5-C6 119.1(5), O1-C16-C15 114.0(5), O1-C16-O2 108.9(5).

Scheme 2 . 4 .Scheme 2 . 5 .

 2425 Scheme 2. 4. Cyclocobalation and cycloiridation of 2-phpyH.

  is most probably precluded by amidate ligand's lability and by the higher affinity of the Co center for the iodo ligand. DFT modeling of acetamidate ligand displacement by I - and Cl -in 1f and 2b respectively, produced slightly endergonic processes, by only 1 kcal/mol more favorable to the Co system. Subsequently both compounds 2b and 1f were successfully isolated and fully characterized by spectroscopic and analytical methods, and their structures were established by X-ray diffraction analysis (Figure2.18).

Figure 2 . 18 .

 218 Figure 2. 18. ORTEP diagram of the structure of 2b and 1f, ellipsoids displayed at 50% probability. The hydrogen-atoms on the carbon were omitted for clarity. (a) Selected bond distances [Å] and angles [°]: C11-Ir1 2.033(2), C22-O1 1.255(3), C22-N2 1.314(3), N1-Ir1 2.0868(17), N2-Ir1 2.0656(18); C5-N1-Ir1 117.08(14), C11-Ir1-N282.72(8), C11-Ir1-N178.22(8), N2-Ir1-N1 87.45(7), C22-N2-Ir1 125.66(16). (b) Selected bond distances [Å] and angles [°]: N3-Co2 1.9673(15), N4-Co2 1.9286(16), C34-Co2 1.9215(17); C34-Co2-N3 83.11(7), N4-Co2-N3 92.85(7), C34-Co2-N4

Figure 2 . 19 .

 219 Figure 2. 19. ORTEP diagram of the structure of 2c, ellipsoids displayed at 50% probability. The hydrogen-atoms on the carbon, [I3] ─ and solvent molecules were omitted for clarity. Selected bond distances [Å] and angles [°]: N1-Ir2 2.1508(16), N1-Ir1 2.1525(16), N2-Ir1 2.1530(16), N2-Ir2 2.1536(15), O3-Ir1 2.0856(13), O3-Ir2 2.1035(13), Ir1-Ir2 3.05985(13); N2-Ir2-Ir1 44.72(4), Ir2-N1-Ir1 90.64(6), Ir1-N2-Ir2 90.55(6), Ir1-O3-Ir2 93.84(5), O3-Ir2-Ir1 42.85(4), N1-Ir2-Ir1 44.70(4).

Figure 2 . 20 .

 220 Figure 2. 20. Evolution of the KIE with error bars over 6 hours for independent cyclocobaltation reactions carried out under identical conditions in a sealed vessel in CH2Cl2 at 50°C with 2-phpyH and 2-(d5.ph)pyD.

  C NMR noise corrected spectrum of a raw reaction mixture gave a larger span or primary KIE values comprised between 1.7 and 2.0 that are most probably biased by different spin-lattice relaxation times T1 in 1a and d4-1a for the considered carbon nuclei (Figure 2.21) showing up at δ ~ 180.6 and 141.4 ppm.

Figure 2 . 21 .

 221 Figure 2. 21. Excerpts of the 1 H coupled 13 C NMR spectrum of the raw product displaying isotope shifts of resonances for the characteristic signals used for the estimation of the KIE from their integration.

Figure 2 . 22 .

 222 Figure 2. 22. ORTEP diagram of the structure of (a) 4a and (b) 5a, ellipsoids displayed at 50% probability. The hydrogen-atoms on the carbon were omitted for clarity. (a) Selected bond distances [Å] and angles [°]: N1-Co1 1.9439(16), Co1-I1 2.5738(3), C11-Co1 1.9313(19); C11-Co1-N1 82.44(7), C11-Co1-I1 91.70(6), N1-Co1-I1 92.98(5). (b) Selected bond distances [Å] and angles [°]: N1-Co1 1.9703(17), Co1-I1 2.5730(3), C1-Co1 1.9631(18), C1-Co1-N1 83.65(7), C1-Co1-I1 90.66(5), N1-Co1-I1 90.79(5).

Figure 2 . 23 .

 223 Figure 2. 23. ORTEP diagram of the structure of (a) 1b and (b) 3b, ellipsoids displayed at 50% probability. The hydrogen-atoms on the carbon and BArF24 ─ were omitted for clarity. (a) Selected bond distances [Å] and angles [°]: N1-Co1 1.964(3), N2-Co1 1.905(4), C11-Co1 1.949(4), N2-Co1-N1 90.11(16), N2-Co1-C11 94.82(16), C11-Co1-N1 82.48(16). (b) Selected bond distances [Å] and angles [°]: C1-Co1 1.927(3), N1-Co1 1.942(2), N2-Co1 1.906(3), C1-Co1-N1 82.06(12), N2-Co1-C1 94.30(11), N2-Co1-N1 90.85(11).

Figure 2 . 24 .

 224 Figure 2. 24. ORTEP diagram of the structure of (a) 4b and (b) 5b, ellipsoids displayed at 50% probability. The hydrogen-atoms on the carbon and BArF24 ─ were omitted for clarity. (a) Selected bond distances [Å] and angles [°]: N1-Co1 1.974(2), N3-Co1 1.907(2), C11-Co1 1.944(2), N3-Co1-C11 90.03(10), N3-Co1-N1 93.72(9), C11-Co1-N1 82.94(10). (b) Selected bond distances [Å] and angles [°]: N1-Co1 1.977(3), N2-Co1 1.910(3), C1-Co1 1.958(3), N2-Co1-C1 91.92(11), N2-Co1-N1 95.47(12), C1-Co1-N1 83.89(13).

Figure 2 . 25 .

 225 Figure 2. 25. ORTEP diagram of the structure of 1b', ellipsoids displayed at 50% probability. The hydrogen-atoms on the carbon and BArF24 ─ were omitted for clarity. (a) Selected bond distances [Å] and angles [°]: N1-Co1 1.966(5), N2-Co1 1.895(5), C11-Co1 1.943(6); C11-Co1-N1 82.2(2), N2-Co1-C11 89.0(2), N2-Co1-N1 94.1(2).

  General conditions: substrates (0.1 mmol, 1 equiv), diphenylacetylene (0.15 mmol, 1.5 equiv), [Cp*CoI2]2 (0.005 mmol, 5 mol %), LiNHAc (0.03 mmol, 30 mol %), AgBF4 (0.2 mmol, 2 equiv), DCE (5 mL), at 130 °C for 24 h. Trimethoxy benzene was used as internal 1 H NMR reference.

Figure 2 . 26 .

 226 Figure 2. 26. Left: Gibbs enthalpy profile (in kcal/mol at T= 298.15 K) computed at the COSMO(CH2Cl2)-ZORA-PBE-D3(BJ)/all electron TZP level for a model of the electrophilic activation of the CAr-HAr bond of 2-phpyH with the exogenous intervention of external 2-phpyH acting as proton acceptor in the EA-π-to-EA-MC process via dicationic reactive complex EA-pre-TS and transition state EA-TS. Right: CSD-Mercury drawings of geometries and selected interatomic distances (green colored fonts) are given in Å.

protonated 2 -

 2 phenylpyridine, i.e [H(2-phpyH)] + . This scenario is slightly different from the one privileged by Qu and Cramer 190 for a Cp*Rh(III) electrophilic C-H bond activation mechanism which considered the preliminary Rh binding of the second 2-phpyH ligand prior to its migration to abstract the proton of the C-H bond, resulting in a large activation barrier of ca. 16 kcal/mol. The theoretical KIE → (4.6) and KIE ← (6.3) values (Scheme 2.10) were computed by applying the simplified Bigeleisen method, 243

  good yields via the base assisted CMD mechanism provided that the proper base is chosen to optimize the formation of the transient agostic intermediate. This choice of base can be greatly enlightened by theory like shown in this study, which considered necessary to approach the C-H bond activation mechanism by focusing attention on the role of the noncovalent interactions. The relevance of noncovalent interactions in the CMD-promoted cyclocobaltation is evident from the evolution of the so-called reaction site along reaction coordinates: the remarkable contribution of local electrostatic interactions and of the multipolar environment to the polarization of the CAr-HAr bond prior to its activation by carbometallation and proton transfer to the neighboring base gives a valid rationale for the optimization not only of cyclocobaltation but also of cyclometallations using other 3d metals. This account of NCI constitutes in our view the cornerstone to the effective use of 3d metal complexes in C-H bond activation be it via the CMD or the EA mechanism. In this study, like in the previous

Scheme 3 . 2 .Scheme 3 . 3 .

 3233 Scheme 3. 2. The example of Cp* ligand protonation.

Scheme 3 . 4 .

 34 Scheme 3. 4. The example of collapse of a metallacycle of a CpNi (II) complex.

1 HScheme 3 . 5 .

 135 Scheme 3. 5. The reaction of 1a with I2.

Figure 3 . 1 .

 31 Figure 3.1. ORTEP diagram of the structure of {[Cp*Co]2(μ-I)3}[I3], ellipsoids displayed at 50% probability. The hydrogen-atoms, [I3] ─ and solvent molecules were omitted for clarity. Selected bond distances [Å] and angles [°]: Co1-I1 2.5873(5), Co1-I2 2.6123(5), Co1-I3 2.6320(5), Co2-I1 2.5847(5), Co2-I2 2.6300(5), Co2-I3 2.6242(5), I1-Co1-I2 86.677(15), I1-Co1-I3 87.706(15), I2-Co1-I3 86.301(15), I1-Co2-I286.363(15), I1-Co2-I3 87.927(15), I3-Co2-I2 86.099(14), Co2-I1-Co1 75.791(14), Co1-I2-Co2 74.599(14), Co2-I3-Co1 74.370(14).

Figure 3 . 2 .

 32 Figure 3. 2. ORTEP-type drawings of the structures of [1c][BArF24] at 50% probability with partial atom numbering. The [BArF24] anion and lattice solvent were omitted for clarity. Selected bond distances [Å] and angles [°]: C1-C12 1.528(3), C13-N1 1.552(3), C12-C13 1.545(3), C13-C14 1.521(3), C14-C15 1.335(4), C15-C16 1.513(4), C12-C16 1.556(3), C1-C12-C13 113.23(19), C14-C13-N1 108.51(19), C12-C13-N1 108.84(18), C15-C14-C13 110.0(2), C15-C16-C12 101.1(2).

Scheme 3 . 6 .

 36 Scheme 3. 6. The Co-templated oxidative cyclocondensation of different Cp*-bound cobaltacycles.

  under argon atmosphere, cobaltacycles (0.1 mmol, 1 eq),[Ph3C][BArF24] (0.1 mmol, 1 eq), DCM (5 mL), 25°C, 16 h. a 1 H NMR yield in the presence of 1,3,5-trimethoxybenzene as an internal standard. b isolated yield.

Figure 3 . 3 .

 33 Figure 3.3. ORTEP-type drawings of the structures of (a) 7a and (b) 8a at 50% probability with partial atom numbering. The hydrogen-atoms on the carbon were omitted for clarity. (a) Selected bond distances [Å] and angles [°]: C1-Co1 1.917(5), N1-Co1 1.957(4), I1-Co1 2.5633(7), C1-Co1-I1 88.76(14), N1-Co1-I1 92.37(13), C1-Co1-N1 82.63(18). (b) Selected bond distances [Å] and angles [°]: N1-Co1 1.9546(14), Co1-I1 2.5625(2), C1-Co1 1.9204(15), C1-Co1-N1 82.77(6), C1-Co1-I1 90.54(4), N1-Co1-I1 94.78(4).

[

  7c] + and [8c] + were both established by X-ray diffraction analysis (Figure3.4), which revealed features akin to those of [1c] + .

Figure 3 . 4 .

 34 Figure 3. 4. ORTEP-type drawings of the structures of (a) [7c] + and (b) [8c] + at 50% probability with partial atom numbering. The [BArF24] anion and lattice solvent were omitted for clarity. (a) Selected bond distances [Å] and angles [°]: C1-C16 1.516(3), C12-N1 1.546(3), C12-C13 1.521(4), C13-C14 1.345(4), C14-C15 1.499(4), C15-C16 1.556(4), N1-C12-C16 109.33(19), C14-C13-C12 109.7(2), C13-C14-C15 111.5(2), C14-C15-C16 102.5(2), C1-C16-C15 113.2(2), C12-C16-C15 101.5(2), N1-C12-C16 109.33(19). (b) Selected bond distances [Å] and angles [°]: C16-N1 1.550(2), C11-C12 1.512(3), C12-C13 1.562(3), C13-C14 1.519(3), C14-C15 1.329(3), C15-C16 1.525(3), C12-C16 1.555(2), C11-C12-C16 113.19(15), C11-C12-C13 113.44(15), N1-C16-C12

[Scheme 3 . 7 .Figure 3 . 5 .

 3735 Scheme 3. 7. The cyclocondensation reaction of 5a with [Ph3C][BArF24]

Figure 3 . 6 .

 36 Figure 3. 6. ORTEP-type drawings of the structures of (a) [7d][BArF24], and (b) [8d][BArF24] at 50% probability with partial atom numbering. The [BArF24] anion and lattice solvent were omitted for clarity. (a) Selected bond distances [Å] and angles [°]:

Scheme 3 . 8 .Scheme 3 . 9 .

 3839 Scheme 3. 8. Synthesis of 9a and its reaction with [Ph3C][BArF24].

Figure 3 . 7 .

 37 Figure 3. 7. ORTEP-type drawing of the structure of (a) 10a and (b) [10c][BArF24] at 50% probability with partial atom numbering. The [BArF24] -anion and solvent were omitted for clarity. (a) Selected bond distances [Å] and angles [°]: I1-Co1 2.5767(3), Co1-N1 1.9355(19), Co1-C16 1.934(2), N1-Co1-I1 90.25(6), C16-Co1-I1 92.10(6), C16-Co1-N1 83.13(8). (b) Selected bond distances [Å] and angles [°]: C1-C12 1.494(3), C1-C16 1.510(3), C1-N1 1.523(3), C1-C13 1.554(3), C13-C14 1.548(3), C14-C15 1.507(4), C15-C16 1.318(4), C14-C17 1.519(3), C12-C1-C16 116.6(2), C12-C1-N1

Figure 3 . 8 .

 38 Figure 3. 8. Instrumentation of the typical isothermal titration calorimetry.

1 ,Figure 3 . 9 .

 139 Figure 3. 9. Thermographic trace of the isotherm calorimetric titration of a solution of 1a (0.94 mM) by sequential addition of 2 μL of a solution of [Ph3C][BArF24] (19.6 mM) in DCE at 25°C in an argon-filled glovebox. Individual heat flow peaks correspond to the response of the cell containing 1a after the addition of portions of a solution of [Ph3C][BArF24]. The inflexion point considered at the 29 th peak (at ca. 55000 s) corresponds to a n=1:1 stoichiometry.

Scheme 3 . 12 .

 312 Scheme 3. 11. Use of CD2Cl2 and/or [d15-Ph3C][BArF24] that does not result in the incorporation of 2 H at the C 5 position in [1c][BArF24].

3. 13 )Scheme 3 . 13 .

 13313 Scheme 3. 13. Treatment with acid that results in hydrodemetalation.

  3):when the atmosphere is disregarded, with D2O an 1 H NMR analysis of the reaction mixture revealed no incorporation of deuterium at the C5 position of[1c][BArF24].The formation of the latter in the presence of water occurred with a lower yield when the reaction was run under argon(∼10%) in comparison to that run under air (∼80%). This result suggests that the combination of water contamination with oxidizing conditions (one-electron oxidant + air) favors the formation of [1c] + .It is worth noting that [Cp*Co]2(μ-I)3 + , i.e. the main side product of the collapse of 1a, fully decomposes in the reaction carried out in the presence of water under air.

  hexafluorophosphate ([NBu4][PF6]) in dry distilled 1,2-C2H4Cl2.The reference electrode was the Ag/AgCl electrode, which was electrically connected to the solution by a junction bridge filled with 5 mL of anhydrous CH3CN + 0.1 M [NBu4][PF6]. The working electrode was a platinum-disk electrode (d = 3 mm in diameter). All potentials are given vs Ag/AgCl used as an external reference and are uncorrected for Ohmic drop. The electrochemical behavior of the compounds involved in the cyclocondensation of 1a was studied by cyclic voltammetry under argon with solutions in the moderately volatile 1,2-dichloroethane using [N(nBu)4][PF6] (0.1 mol L -1 ) as background electrolyte (Figure 3.10 and Table

Figure 3 . 10 .

 310 Figure 3. 10. Cyclic voltammograms of {[Cp*Co]2(μ-I)3}[I3], TEAI, 1a and [1c][BArF24] (0.4 mmol L -1 ) on Pt electrode in a DCE solution in the presence of [N(nBu)4][PF6] (0.1 mol L -1 ). v = 100 mV s -1 .

  V) vs. Ag/AgCl were obtained from cyclic voltammetry in DCE with 0.1 mol L -1 [N(nBu)4][PF6]. Scan rate = 100 mV s -1 . Working electrode: Pt, d= 3 mm in diameter. The given half-wave potentials are equal to E1/2 = (Epa+ Epc)/2. Under bracket: △Ep = |Epa-Epc|. irr : Irreversible peak potential. a Slow process: couple I3 -/I -or I2/I3 -. Cyclic voltammogram of {[Cp*Co]2(μ-I)3}[I3] (Figure 3.10 black curve and Figure 3.11)shows the presence of three successive oxidation processes at -0.02 V, 0.36 V and 1.25 V vs. Ag/AgCl. The last oxidation at 1.25 V is irreversible and may correspond to the oxidation of the cobalt center, while the two first oxidations are similar to the redox behavior of tetraethylammonium iodide (abbr. TEAI)(Figure 3.12). It corresponds to the redox properties of the triiodide I3 -counter-anion. In fact, at the potential applied 123 at the start of the sweep; I3 -is first reduced to I -, redox behavior similar to that of TEAI is observed.

Figure 3 . 11 .

 311 Figure 3. 11. Cyclic voltammograms of {[Cp*Co]2(μ-I)3}[I3] (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s -1 .

Figure 3 . 12 .

 312 Figure 3. 12. Cyclic voltammograms of {[Cp*Co]2(μ-I)3}[I3] and of TEAI (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s -1 .

  52 and 1.11 V vs. Ag/AgCl (Figure 3.10, red curve). The first oxidation corresponds to the oxidation of Co(III) to Co(IV). Note that the intensity of the peak current of the second irreversible oxidation at 1.11 V is a little less than half of the intensity of the first oxidation. It may corresponds to the oxidation of the intermediate of the reaction giving [1c] + (Figure 3.13) or may be related to the oxidation of {[Cp*Co(III)]2(μ-I)3} + (Figure 3.14).

Figure 3 . 13 .

 313 Figure 3. 13. Cyclic voltammograms of [1c][BArF24] (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s -1 .

Figure 3 . 14 .126

 314 Figure 3. 14. Cyclic voltammograms of {[Cp*Co]2(μ-I)3}[I3] (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s -1 .

  oxidation of the Co(III) is little affected by the nature of substituent R (R = H, Br or CF3) or by substitution of Cp* by Cp in cobaltacycles. However, the redox behavior is dissimilar in the case of 9a by changing I by Cl substituent where only one irreversible oxidation and two irreversible reductions are detected at 0.80 V, -1.21 V and -1.76 V respectively.

Figure 3 . 15 .

 315 Figure 3. 15. Cyclic voltammograms of 7a (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s -1 .

Figure 3 . 16 .

 316 Figure 3. 16. Cyclic voltammograms of 8a (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s -1 .

Figure 3 . 17 .

 317 Figure 3. 17. Cyclic voltammograms of 9a (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s -1 .

Figure 3 . 18 .

 318 Figure 3. 18. Cyclic voltammograms of 1a and 10a (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s -1 .

Figure 3 . 19 .

 319 Figure 3. 19. Cyclic voltammograms of 10a (0.4 mmol L -1 ) on Pt electrode in a 1,2-C2H4Cl2 solution in the presence of NBu4PF6 (0.1 mol L -1 ). v = 100 mV s -1 .

  EPR spectra were recorded on a continuous wave X-band EMX-plus instrument equipped with a TE102 rectangular cavity (ER 4102ST, Bruker) and an ESR900 continuous flow cryostat controlled with an Oxford ITC503S apparatus. EPR spectra were recorded with the following parameters: a microwave power of 1 mW, a modulation frequency and amplitude of respectively 100 kHz and 0.4 mT, a conversion time of 300 ms, and a time constant of 20.48 ms. A second-order polynomial baseline was subtracted from the spectra recorded between 0 and 450 mT. The simulation was done using the Easyspin 63 toolbox working under MatLab (MathWorks).The mixture produced by the reaction of 40 mM 1a and [Ph3C][BArF24] was analyzed by EPR spectroscopy at low temperature in frozen DCM. The EPR spectrum (Figure3.20) recorded after 5 minutes of reaction at 4 K shows the superposition of the signatures of two species. One intense is centered at g~2.003 (ΔHpp=1.25 mT) and supports the presence of an organic radical[323][324][325][326][327][328][329][330] in frozen solution. The second signal of lower intensity displays a distorted axial pattern with broad resonances and effective g values at g~ 4.80 and g~ 2.02 similar to that already reported byWang et al. 331 These main peaks point to high-spin Co(IV) species 331, 332 (S= 3/2 or S= 5/2) as a result of the 1h = Cp*CoPhPyCl (1,2-EtCl 2 + 0.1 M TBAPF 6 , WE: Pt, v = 0and in agreement with their disappearance at higher temperature in frozen solution, i.e from 30 K. 332 After 1 hour of reaction of the molten mixture, both signals disappeared when the sample was frozen back to 4 K and analyzed.

Figure 3 .

 3 Figure 3. 20. X-band EPR spectrum recorded at 4.3 K after 5 min of reaction between 40 mM solutions of 1a and [Ph3C][BArF24] in DCM . The spectrum was recorded at a frequency of 9.345 GHz.

  Recent reports281, 334 have indeed stressed the assisting effect of local attractive NCI interactions in the reactant complexes of base assisted aromatic C-H bond activation by Pd(II), Ni(II), Co(III) and Ir(III) centers. NCI plots are particularly informative of the

  21 and Figure 3.22 display the isosurfaces of attractive domains (red colored isosurfaces) and repulsive or non-bonding ones (blue colored isosurfaces) in various singlet and doublet state geometries of complexes relevant to this report. NCIs are materialized by reduced density gradient isosurfaces (cut-off value s = 0.5 au, ρ =0.02 au.) colored according to the sign of the signed density i.e. in red for attractive NCI domains and in blue for repulsive (or non-bonding) NCI domains. Specific NCI attraction domains between the Cp* and the phpy ligand are circled in green.

Figure 3 . 21 .

 321 Figure 3. 21. NCI plots 25, 336 from ADFview2019 for optimized geometries of a) singlet ground state 1a, b) its singlet ground state Ir analogue Ir-1a, c) doublet ground state [1a'] + , d) doublet ground state [Ir-1a'] + (SCM-ADF2019 339 ZORA 340 -PBE 202 -D4(EEQ) 341 / all electron TZP / COSMO 342 (CH2Cl2) level). Color code for atoms: dark blue, N; gray, C; white, H; organe, Ir; purple, I; indigo, Co. NCIs are materialized by reduced density gradient isosurfaces (cut-off value s = 0.5 au, ρ =0.02 au.) colored according to the sign of the signed density i.e. in red for attractive NCI domains and in blue for repulsive (or non-bonding) NCI domains. Specific NCI attraction domains between the Cp* and the phpy ligand are circled in green.

Figure 3 . 22 .

 322 Figure 3. 22. NCI plots 25, 336 from ADFview2019 for optimized geometries of a) doublet ground state [9a'] + and b) doublet ground state [Cp*Co(SCF3)(phpy)] + (SCM-ADF2019 339 ZORA 340 -PBE 202 -D4(EEQ) 341 / all electron TZP / COSMO 342 (CH2Cl2) level). Color code for atoms: dark blue, N; gray, C; white, H; yellow, S; light green, F; indigo, Co; green, Cl. NCIs are materialized by reduced density gradient isosurfaces (cut-off value s = 0.5 au, ρ =0.02 au.) colored according to the sign of the signed density i.e. in red for attractive NCI domains and in blue for repulsive (or non-bonding) NCI domains. Specific NCI attraction domains between the Cp* and the phpy ligand are circled in green.

2 .Scheme 3 . 15 .Pathway 1 :Pathway 2 :Pathway 3 :

 2315123 Scheme 3. 15. Proposed pathways for the condensation of Cp* on phpy. Pathway1 (light pink): 1a → [1a'] + → [IntC'] + → [IntCH] → [pre-1c] + → [pre-1c-sol] + → [1c] + . Pathway 2 (light blue): 1a → [1a'] + → [IntC'] + → [pre-1c'] + → [pre-1c] + → [pre-1c-sol] + → [1c] + . Pathway 3 (light green): 1a → [1a'] + → [1aH] + → [IntCH] → [pre-1c] + → [pre-1c-sol] + → [1c] + .

Figure 3 . 23 .

 323 Figure 3. 23. Proposed computed Gibbs free energy profiles of the formation of [1c] + . The three possible pathways are materialized by solid-colored lines (green, blue, pink). a) Exergonic intrinsic Gibbs energy profile considering a fictitious H. b) Endergonic intrinsic Gibbs energy profile considering Ph3CH as the source of H. c) Endergonic intrinsic Gibbs energy profile considering Ph3C-C6H5C(Ph2) as the source of H.

  8 kcal/mol for the triplet, and ΔG= + 69 kcal/mol for the quintet). It was therefore inferred that the "CoI" moiety might undergo the oxidative-addition of a solvent molecule. Insertion of the Co(I) of CoI in the C-Cl bond of a solvent molecule after the release of [1c] + was found highly stabilizing (ΔG= -48 kcal/mol). The addition of a solvent molecule before the release of [1c] + was also considered. The insertion of the Co in the C-Cl bond is endergonic (ΔG= + 4 kcal/mol) in the triplet state (lowest spin state). From there, the release of [1c] + , generating a [Co(Cl)(I)(CH2Cl)] complex, becomes exergonic (ΔG= -8 kcal/mol).

Scheme 4 . 2 .Scheme 4 . 3 .

 4243 Scheme 4. 1. The synthesis of iridacycles and the reaction of iridacycles with HSiEt3.

Figure 4 . 1 )

 41 , which is consistent with the result of the catalytic experiment we first performed with cobaltacycles.

Figure 4 . 1 .

 41 Figure 4. 1. Standard stoichiometric reaction of 1b with HSiEt3 monitored by 1 H NMR.

(

  top: at 247 K ; bottom : 298K) Based on our theoretical studies of the Cp*Ir(III)-metallacycles catalyzed hydrosilylation of ketones, the crucial elements of this reaction were the activation of

Figure 4 . 2 .

 42 Figure 4. 2. ORTEP diagram of the structure of 1g, ellipsoids displayed at 50% probability. The hydrogen-atoms on the carbon and BArF24 ─ were omitted for clarity. Selected bond distances [Å] and angles [°]: Co1-S1 2.2309(8), N1-Co1 1.944(2), C11-Co1 1.955(2); C11-Co1-S1 94.99(7), N1-Co1-S1 90.98(7), N1-Co1-C11

Figure 4 . 3 .

 43 Figure 4. 3. ORTEP diagram of the preliminary structure of 1h, ellipsoids displayed at 50% probability. The hydrogen-atoms on the carbon and BArF24 ─ were omitted for clarity.

Figure 4 . 4 .

 44 Figure 4. 4. Variable-temperature 1 H NMR spectra of the reaction of 1b with ethyl diazoacetate (600 MHz, THF-d8).

  All experiments were conducted under a dry argon atmosphere using standard Schlenk lines and dry glovebox techniques. All glassware was cleaned and oven-dried prior to use. All organic chemicals were purchased from Sigma Aldrich, TCI Chemicals and Alfa Aesar. Co2(CO)8 was purchased from Pressure Chemical Co. The compound4-tertiobutyl,2-(4-N,N-dimethylaminophenylene)-pyridine (abbr. 2-anpyH), 2,3-Diphenylquinoxaline, chloro(2-phenylpyridine-k 2 -C,N)(pentamethylcyclopentadienyl)iridium(III) (2a) and the cobalt(III) complexes [Cp*Co(μ-I)I]2 were prepared as reported in the literature.147, 356, 357 All solvents were distilled over sodium or CaH2 under argon before use. Deuterated solvents were dried over sodium or CaH2, filtered over activated neutral alumina, and stored under argon before use. 1 H (300, 400, 500, and 600 MHz), 11 B (128 MHz),13 C (75 and 126 MHz), and 19 F (282 MHz) NMR spectra were measured on Bruker DPX 300 and 400, Avance I 500, and Avance III 600 spectrometers. Chemical shifts (expressed in parts per million) were referenced against solvent peaks or external reference standards (CF3C6H5 in CDCl3 for19 F, and NaBH4 in D2O for 11 B). Mass spectra were run on a MicroTOF Bruker Daltonics spectrometer, using a TOF-ESI coupling analysis system. Elemental analyses were achieved with Thermo Scientific FLASH 2000 CHNS/O analyzers.

  fibre and placed in a low-temperature N2 stream. For complexes [1b][I3], [1b'][I3], [1c][I3], [1c'][I3], 4a and 5a, X-Ray diffraction data collection was carried out on a Bruker APEX II DUO Kappa-CCD diffractometer equipped with an Oxford Cryosystem liquid N2 device, using Mo-Kα radiation (λ = 0.71073 Å). The crystal-detector distance was 38 mm. The cell parameters were determined (APEX3 software) 358 from reflections taken from three sets of 12 frames, each at 10 s exposure. The structures were solved using the program SHELXT-2014

  ][BArF24] and [8d][BArF24], X-ray diffraction data collection was carried out on a Bruker PHOTON III DUO CPAD diffractometer equipped with an Oxford Cryosystem liquid N2 device, using Mo-Kα radiation (λ= 0.71073 Å). The crystal-detector distance was 37 mm. The cell parameters were determined (APEX3 software) 358 from reflections taken from 1 set of 180 frames at 1 s exposure. The structures were solved using the program SHELXT-2014.359 The refinement and all further calculations were carried out using SHELXL-2014 or SHELXL-2018. 360 For complexes 1f, 2b and 2c the hydrogen atoms of the NH groups, OH groups and of the water molecules were located from Fourier difference. For complexes 4b and 5b, the SQUEEZE instruction in PLATON 361 was applied. A semi-empirical absorption correction was applied using SADABS in APEX3 358 . For compound [8c][BArF24], the hydrogen atom of the OH group was located from Fourier difference. The other H-atoms were included in calculated positions and treated as riding atoms using SHELXL default parameters.

  Voltammetry was conducted under the supervision of Prof. Laurent RUHLMANN (Laboratoire d'Electrochimie et Chimie Physique du Corps Solide, Institut de Chimie de Strasbourg). All glassware was dried for 24 hours at 90°C prior to use. Voltammetric data were recorded using an Autolab PGSTAT30 potentiostat (Eco Chemie, Holland) driven by the GPSE software with a standard three-electrode system flushed with a gentle stream of argon. The electrolyte was a solution of 0.1 mol L -1 of anhydrous tetrabutylammonium hexafluorophosphate ([NBu4][PF6]) in dry distilled 1,2-C2H4Cl2. The reference electrode was the Ag/AgCl electrode, which was electrically connected to the solution by a junction bridge filled with 5 mL of anhydrous CH3CN + 0.1 M [NBu4][PF6]. The working electrode was a platinum disk electrode (d = 3 mm in diameter). All potentials are given vs. Ag/AgCl used as external reference and are uncorrected from ohmic drop. recorded by Sylvie CHOUA and Nolwenn LE BRETON (Laboratoire Propriétés Optiques et Magnétiques des Architectures Moléculaires, Institut de Chimie de Strasbourg) on a continuous-wave X-band EMX-plus equipped with TE102 rectangular cavity (ER 4102ST, Bruker) and an ESR900 continuous flow cryostat controlled with an Oxford ITC503S. EPR spectra were recorded with the following parameters: microwave power of 1 mW, a modulation frequency and amplitude of respectively 100 kHz and 0.4 mT, a conversion time of 300 ms and a time constant of 20.48 ms. Isothermal titration calorimetry (ITC) experiments were carried out on a Waters-SAS nano-ITC device (TA Instruments®) equipped with two stainless steel Hastelloy cells of 1 mL volume each) and housed in an argon-filled glovebox. Auto equilibration of the ITC was performed before every experiment to reach an acceptable baseline. The solutions of reactants were prepared in the same glovebox by dissolving a mass of substrate placed in a volumetric flask in pure, freshly distilled and degassed 1,2dichloroethane. The ITC experiments were performed by sequential injection at 25.00⁰C with a stirring rate of 300 rpm. The solution of tritylium salt was placed in the injection syringe and the solution of compound 1a in the measure cell. Three thermograms were acquired by sequential injection of 2-3 μL with a delay between two injections not exceeding 900 s, and the raw enthalpy of the reaction was inferred by summing up the heat flow released from which was deduced the residual heat flow after the thermal inflexion point.Geometry optimizations of reactants, intermediates, transitions states and products were performed with the methods of density functional theory using the SCM-ADF2019.01 package, 363 considering the molecules in the gas phase at the singlet state. The PBE 202 functional augmented with Grimme's DFT-D3(BJ) implementation of dispersion364, 365 with a Becke-Johnson (BJ) damping function[203][204][205] was used in all geometry optimizations. All geometry computations were carried out using scalar relativistic corrections within the zeroth order regular approximation for relativistic effects with ad hoc all-electron (abbr. ae) single polarization function triple-ζ Slater type basis sets (TZP).[366][367][368] Solvation was treated by the COSMO 199-201 procedure assuming CH2Cl2 (ε= 8.93) as the solvent. Geometry optimizations by energy gradient minimization were carried out in all cases with integration grid accuracy comprised between 4.5 and 6.5, an energy gradient convergence criterion of 10 -3 au, and tight to very tight SCF convergence criteria. All transition states were submitted to the Intrinsic Reaction Coordinate (IRC) procedure to verify the connection to their reactive complexes and products. Counterpoise correction for basis set superposition error (BSSE) was neglected throughout this study. Vibrational modes were analytically computed to verify that the optimized geometries were related to energy minima or to transition states. Bader (QTAIM) charges 221 and Interacting Quantum Atoms218, 220

  It is based on two simple considerations to define all possible NCIs: i) given the fact that the density decays exponentially with distance from the nuclear position, the regions of space involved in NCIs have low density, and ii) in the NCI regions the reduced density gradient approaches zero, leading to a local minimum. Combining these two criteria, one can detect NCIs over a three-dimensional grid looking for the low ρ(r) and low s(r) regions of space of a given system. Three-dimensional visualization of NCIs can be obtained by representing isosurfaces of s(r) surrounding the local minimum of s(r). Qualitative information on the strength and sign of the NCI can be obtained from the electron density and the sign of the second eigenvalue of its Hessian matrix, sign(λ2), which is negative for attractive interactions and positive for repulsive ones. NCIs are normally associated to density values between 0.00 and 0.1, the weakest interactions, e.g. dispersion, being close to zero and the strongest interactions, e.g. hydrogen bonds, shifted towards larger density values. When sign(λ2) is taken into account, the range of sign(λ2) ρ(r) spanned by NCIs extends from -0.1 to 0.1 a.u. It is known that different types of weak interactions decay differently with distance, with the electrostatic terms decaying slower than van der Waals. To mirror this behavior, the volume and ρ(r) were integrated over the volume of NCIs according to two ranges: i) -0.05<sign(λ2)<0.00 corresponding to attractive interactions (attr), ii) 0.00< sign(λ2)<0.05, corresponding to repulsive interactions (rep).222, 223 These values have been chosen to include the interactions around the hydrogen atom. As can be seen in FigureS56, H interactions cover up to ρ=0.05 a.u.

  Under the argon atmosphere, in a Schlenk flask an equimolar mixture of [κ 2 -(C,N)-(L)CoI] and Na[BArF24] was dissolved in acetonitrile (~7-10mL). The resulting mixture was vigorously stirred at room temperature within a period not exceeding 6h, unless otherwise stated. The solution was subsequently filtrated through a pad of celite, and the solvent was removed from the filtrate under reduced pressure. The solid was either recrystallized in a mixture of CH2Cl2 and n-pentane or washed with n-pentane, to afford an analytically pure compound.Under argon atmosphere, a mixture of 1a (95 mg, 0.2 mmol) and dry tetrabutylammonium chloride (100 mg, 0.35 mmol) was stirred overnight in ∼10-15 mL

  .

  and 2-(d5.ph)pyD (0.10 mmol, 2 eq) were placed in two separate Schlenk vessels to which identical amounts of [Cp*CoI2]2 (0.05 mmol, 1 eq), LiNHAc (0.3 mmol,

  Under argon atmosphere, a mixture of 1a (4.7 mg, 0.01 mmol) and [Ph3C][BArF24] (10 mg, 0.01 mmol) was added in three sealed Schlenk vessels, one Schlenk vessel acting as a "blank" reference was exempt of TEMPO. In two of them, TEMPO (1.5 mg, 0.01 , 0.04 mmol) was added in different amounts in ∼1 mL of deuterated DCM, and the three resulting solutions were stirred at room temperature overnight.

Figure 5 . 1 .

 51 Figure 5. 1. Comparison of 1 H NMR spectra for the reaction of 1a with [Ph3C][BArF24]

6 ]

 6 AgPF 6 or [Ph 3 C][PF Under argon atmosphere, a mixture of 1a (1 equiv., 0.02 mmol) and [Ph3C][PF6] (1 equiv.) or AgPF6 (2 equiv.) was stirred overnight in ∼10-15 mL of CH2Cl2 at room temperature in a sealed Schlenk vessel. After the reaction, the crude compound was analyzed by 1 H NMR.

Figure 5 . 2 . 1 H 1 .

 5211 Figure 5. 2. 1 H NMR spectra of 1a with [Ph3C][PF6] (top) or AgPF6 (bottom). The red stripe highlights the resonance of H5.

Figure 5 . 3 .

 53 Figure 5. 3. NMR spectrum of the experiment of 1a with triflic acid (J-Young tube).

Figure 5 . 4 . 1 H

 541 Figure 5. 4. 1 H NMR spectra of the reaction of 1a with acetic acid (top: 5 h; bottom: 24 h; blue point: starting materiel; red point: final product). In this reaction, the color slowly changed from red-brown to green.

Figure 5 . 5 . 1 H

 551 Figure 5. 5. 1 H NMR spectrum of the reaction of 1a with acetic acid after 24 h.

Figure 5 . 6 . 1 H

 561 Figure 5. 6. 1 H NMR spectra of the reaction of 1a with [Ph3C][BArF24] under argon (top) or air (bottom). After the reaction mixture was filtrated over Celite followed by removal of the solvent. The resulting residue was purified by column chromatography and then recrystallized with CH2Cl2/n-pentane and/or washed with n-pentane to obtain a white powder. The red stripe highlights H5 in [1c] + and the blue stripe highlights [1d] + . The n point the salient signals of [1c] + . The * point the signals of [1d] + , which was derived by comparing the 7d and 8d NMR spectra).

Figure 5 . 7 . 1 H 24 ]

 57124 Figure 5. 7. 1 H NMR spectrum of the reaction mixture (bottom) resulting from the reaction of 5a (top) with [Ph3C][BArF24].

Figure 5 . 8 . 1 H 24 ]

 58124 Figure 5. 8. 1 H NMR spectrum of the reaction mixture (bottom) resulting from the reaction of 9a (top) or 1a (bottom) with [Ph3C][BArF24].

Figure 5 . 9 . 1 HFigure 5 . 10 . 1 H

 5915101 Figure 5. 9. 1 H NMR spectrum of the reaction mixture produced by the reaction of 1b with [Ph3C][BArF24] after 17 h and 48 h.

3

 3 Under argon atmosphere, the cationic cobaltacycle 1b (0.02 mmol) was mixed with HSiEt3 (0.02 mmol) in J. Young valve NMR tube in DCM-d2 at 298 K or 247 K, and the reaction was monitored by 1 H NMR spectroscopy.

Figure 5 . 11 .

 511 Figure 5. 11. Standard stoichiometric reaction of 1b with HSiEt3 monitored by 1 H NMR.

Figure 5 . 12 .

 512 Figure 5. 12. Standard stoichiometric reaction of 1a with NaBHEt3 monitored by 1 H NMR. A hydride peak signature was observed at -15.07 ppm, however this signal disappearing progressively.

  In the context of the catalysis, the cyclocondensative collapse of cobaltacycles represents an irreversible destructive deactivation pathway, which further confirms that establishing the whereabouts of the Cp(*)Co(III)-based catalysts after catalysis is an imperious need.From the view point of metal mediated synthesis, the oxidation-induced cyclocondensation of Cp*Co(III) metallacycles in this thesis is a new example of oxidation triggered Co(IV)-centred "metal-templated" 398-401 synthesis of valuable threedimensional alkaloids of the Berberine 362 class, the hydroxylation reaction of which deserves further investigations. In addition, the application of these new Cp*Co(III)metallacycles will continued to be investigated, such as in hydrosilylation and hydroboration catalysis mentioned in chapter 4. Overall, the Cp*Co(III)-complexes are promising catalysts and catalysis intermediates.

  Final R indexes [I>=2σ (I)] R1 = 0.0532, wR2 = 0.1357 Final R indexes [all data] R1 = 0.0679, wR2 = 0.1484 Largest diff. peak/hole / e Å -3 1.80/-1.36

  Final R indexes [all data] R1 = 0.0730, wR2 = 0.1416 Largest diff. peak/hole / e Å -3 0.87/-0.66 Table A. 21. Crystal data and structure refinement for [7d][BArF24]. Final R indexes [all data] R1 = 0.1021, wR2 = 0.1961 Largest diff. peak/hole / e Å -3 2.05/-1.31

CFigure A. 3 . 1 HFigure A. 5 . 1 H

 3151 Figure A. 1. 1 H NMR spectrum (500 MHz, CDCl3) of 1a

  .

Figure A. 9 . 1 HFigure A. 18 . 1 H

 91181 Figure A. 9. 1 H NMR spectrum (500 MHz, CDCl3) of 6a

  Figure A. 22. 1 H NMR spectrum (500 MHz, CDCl3) of 3b

CH 2 2 4b

 22 Figure A. 24. 1 H NMR spectrum (500 MHz, CDCl3) of 4b

  Figure A. 26. 1 H NMR spectrum (500 MHz, CDCl3) of 5b

Figure A. 34 .

 34 Figure A. 34. 1 H-1 H COSY spectrum of [1c][BArF24]

Figure A. 36 .

 36 Figure A. 36. 1 H-13 C HSQC spectrum of [1c][BArF24]

Figure A. 37 .

 37 Figure A. 37. 1 H-13 C HMBC spectrum of [1c][BArF24]

Figure A. 38 . 1 H

 381 Figure A. 38. 1 H NMR spectrum (500 MHz, CDCl3) of [7c][BArF24]

Figure A. 40 .

 40 Figure A. 40. 1 H-1 H COSY spectrum of [7c][BArF24]

Figure A. 42 .

 42 Figure A. 42. 1 H-13 C HSQC spectrum of [7c][BArF24]

Figure A. 44 . 1 H

 441 Figure A. 44. 1 H NMR spectrum (500 MHz, CDCl3) of [8c][BArF24]

Figure A. 46 .

 46 Figure A. 46. 1 H-1 H COSY spectrum of [8c][BArF24]

Figure A. 48 .

 48 Figure A. 48. 1 H-13 C HSQC spectrum of [8c][BArF24]

Figure A. 50 . 1 H

 501 Figure A. 50. 1 H NMR spectrum (500 MHz, CD2Cl2) of [7d][BArF24]

Figure A. 52 .

 52 Figure A. 52. 1 H-1 H COSY spectrum of [7d][BArF24]

Figure A. 54 .

 54 Figure A. 54. 1 H-13 C HMBC spectrum of [7d][BArF24]

Figure A. 56 . 1 H

 561 Figure A. 56. 1 H NMR spectrum (500 MHz, CD2Cl2) of [8d][BArF24]

Figure A. 58 .

 58 Figure A. 58. 1 H-1 H COSY spectrum of [8d][BArF24]

Figure A. 60 .

 60 Figure A. 60. 1 H-13 C HMBC spectrum of [8d][BArF24]

Figure A. 62 . 1 H

 621 Figure A. 62. 1 H NMR spectrum (300 MHz, CD2Cl2) of [10c][BArF24]

Figure A. 64 .

 64 Figure A. 64. 1 H-1 H COSY spectrum of [10c][BArF24]

Figure A. 66 .

 66 Figure A. 66. 1 H-13 C HSQC spectrum of [10c][BArF24]

Figure A. 69 .

 69 Figure A. 69. Mass spectrum (ESI) overview of the crude mixture in positive mode.

Figure A. 70 .Figure A. 71 .

 7071 Figure A. 70. Zoomed mass spectrum of the crude residue, and simulation of protonated iodo-phenylpyridine. The protonated iodo 2-phenylpyridine and was observed at m/z 281.

Figure A. 72 .

 72 Figure A. 72. Zoomed mass spectrum of the crude mixture, and simulation of {[Cp*Co]2(μ-I3)} + . {[Cp*Co]2(μ-I3)} + was observed at m/z 768.8 as well as Cp*CoI ("half" of this dimer) at m/z 320.

Figure A. 77 .

 77 Figure A. 77. Zoomed mass spectrum of the crude mixture. The Cp*Co-I fragment was observed at m/z 320.95.

Figure A. 78 .

 78 Figure A. 78. Zoomed mass spectrum of the crude compound. The Cp*Co(phpy)fragment was observed at m/z 348.12.

Figure A. 81 .

 81 Figure A. 81. Zoomed mass spectrum of the crude mixture of the reaction between 1a and AgPF6 (positive mode). [1c] + at m/z 290.19 was observed. A dimer of protonated 2-phenylpyridine resulting from an homocoupling is observed at m/z 309.14.

Figure A. 83 .

 83 Figure A. 83. LED analysis for Co-OAc (red lines), Co-NHAc (green lines), Ir-OAc (blue lines) and Ir-NHAc (brown lines) systems along the reaction coordinates of the CMD mechanism with plots of inter-fragment interaction energies Ei-j, where i and j are the considered molecular fragment numbers : a) interaction energy between fragments 2 (H + ) and 1 (metal), b) interaction energy between fragments 3 (auxiliary basis) and 1

Table 2 . 1 .

 21 Performance of the cyclocobaltation of 2-phpyH by [Cp*CoI2]2 under various conditions ...

Table 2 . 2 .

 22 Performance of the catalyzed condensation 1,2-diphenylacetylene with2-phpyH ...............

Table 2 . 3 .

 23 Catalyzed condensation of various aromatic substrates with1,2-diphenylacetylenea. .......

Table 3 . 1 .

 31 Reaction of 1a with [Ph3C][BArF24] in various conditions. .......................................................

Table 3 . 2. Reaction of

 3

Table A . 1. Crystal data and structure refinement for 1a.

 A

Table A . 14. Crystal data and structure refinement for [1c][I3]

 A . ..........................................................

Table A . 15. Crystal data and structure refinement for [1c'][I3] .

 A

Table A . 18. Crystal data and structure refinement for [1c][BArF24

 A

]. ................................................

Table A . 19. Crystal data and structure refinement for [7c][BArF24

 A

]. ................................................

Table A . 20. Crystal data and structure refinement for [8c][BArF24]

 A

. ................................................

Table A . 21. Crystal data and structure refinement for [7d][BArF24]

 A

. ................................................

Table A . 22. Crystal data and structure refinement for [8d][BArF24]

 A

. ................................................

Table A . 23. Crystal data and structure refinement for [10c][BArF24].

 A

. Crystal data and structure refinement for [1e][I3].

Table A . 26. Crystal data and structure refinement for [1e'][I3].

 A

Table A . 27 .

 A27 DLPNO-CCSD(T)/LED results forCo-OAc (All energies in kcal/mol) ................................

Table A . 28 .

 A28 DLPNO-CCSD(T)/LED results for Co-NHAc (All energies in kcal/mol) .............................

Table A . 29 .

 A29 DLPNO-CCSD(T)/LED results forIr-OAc (All energies in kcal/mol) ..................................

Table A . 30 .

 A30 DLPNO-CCSD(T)/LED results forIr-NHAc (All energies in kcal/mol) ................................

	Table A. 31. Energies of optimized geometries at the ZORA-PBE-D4(EEQ)/all electron
	TZP/

  ..

	Aabbreviations Résumé
	Dichloromethane Introduction	DCM
	1,2-Dichloroethane	DCE
	2-Phenylpyridine Au cours des dernières décennies, l'activation de la liaison C-H a connu des avancées 2-phpyH
	Benzo[h]quinoline majeures grâce aux catalyseurs à base de métaux de transition et cette approche bzqH
	Dibenzo[f,h]quinoline catalytique moderne s'est progressivement imposée comme un outil précieux pour la bzbzqH
	2-(o-tolyl)pyridine synthèse organique. Au stade initial de l'activation C-H, la plupart des réalisations dans 2-tolpyH
	2-(p-tolyl)pyridine	4-tolpyH
	2-[4-(trifluoromethyl)phenyl]pyridine	4-tfmphpyH
	1,2,3,4,5-Pentamethylcyclopentadiene	Cp*
	Cyclopentadiene	Cp
	Tetrakis[3,5-bis(trifluoromethyl)phenyl]borate	NaBArF24
	Anhydrous sodium acetate	NaOAc
	4-tertiobutyl,2-(4-N,N-dimethylaminophenylene)pyridine	2-anpyH
	2-(4-bromophenyl)pyridine	Br-phpyH
	2-[4-(trifluoromethyl)phenyl]pyridine	CF3-phpyH
	Lithium Acetamidate	LiNHAc
	(2,2,6,6-tetramethylpiperidin-1-yl)oxy	TEMPO
	Density functional theory	DFT
	Noncovalent interactions	NCIs
	Noncovalent interactions plots	NCI plots
	Interacting quantum atoms	IQA
	Local energy decomposition	LED
	Quantum Theory of Atoms in Molecules	QTAIM
	Domain-based local pair natural orbital coupled cluster method DLPNO-CCSD(T)
	Concerted Metalation-Deprotonation	CMD
	Ambiphilic Metal Ligand Activation	AMLA
	Electrophilic aromatic substitution	S E Ar
	Interacting Quantum Atoms	IQA
	Oak Ridge Thermal Ellipsoid Plot	ORTEP
	1

ce domaine ont été accomplies avec les métaux de transition de deuxième et troisième rangées tels que Pd, Pt, Rh, Ru et Ir. Cependant, le clivage des liaisons C-H à l'aide des métaux de transition de la troisième rangée, peu coûteux et abondants dans le monde, a pris un essor considérable récemment, car il s'agit d'une alternative beaucoup plus respectueuse de l'environnement et économiquement attrayante, qui permet en outre une sélectivité et des schémas de réactivité uniques, en raison de leurs propriétés électroniques. À cet égard, les complexes de cobalt sont apparus comme des catalyseurs efficaces et polyvalents pour l'activation C-H, comme en témoigne le nombre croissant de publications sur l'activation C-H catalysée par le cobalt qui ont été récemment divulguées. Malgré d'excellents travaux réalisés avec des complexes de cobalt à basse valence, qui ont permis d'améliorer le statut du cobalt dans le domaine de l'activation C-H, et d'étendre considérablement l'application de l'activation C-H en synthèse organique, certains défis restent à relever. Contrairement à la prévalence de l'activation C-H catalysée par le cobalt de basse valence, l'activation C-H catalysée par le cobalt de haute valence a progressivement attiré l'attention ces dernières années. Malheureusement, la compréhension mécanistique du fonctionnement de ces nouveaux protocoles catalysés par le cobalt de haute valence est très peu développée. Ceci est probablement une conséquence de l'instabilité des intermédiaires clés, bien qu'il y ait un intérêt croissant pour leur détection et leur isolement. Ainsi, l'objectif principal de cette thèse de doctorat est la synthèse et la caractérisation de métallacycles de cobalt, et nous nous concentrerons sur l'étape d'activation C-H pour élucider le mécanisme de fonctionnement dans le clivage des liaisons C-H médié par le cobalt de haute valence.

.1. Low-valent cobalt-catalyzed C-H activation

	The active cobalt complexes used in C-H bond activation have two different oxidation a) Murahashi 1955
	states, low-valent and high-valent. The so-called low-valent cobalt-catalyzed C-H activation involves the addition of Grignard's reagent as a base and reductants to N Ph Co 2 (CO) 8 CO (100-200 atm) N Ph
	produce an active cobalt species from pre-catalysts. The low-valent cobalt catalysts H Benzene, 220-230 ºC 5 h O
	most commonly used in C-H activation are [CoH(PMe3)4], [CoMe(PMe3)4],
	[CoH(H2)(PPh3)3], [CoH(N2)(PPh3)3], and some Cp*Co(I) complexes. Whereas the high-valent cobalt complexes normally are Co(III) complexes that can switch between b) Kisch 1994 Scheme 1. 5. Hydroarylation by low-valent cobalt complex.
	Ph Co(II) and Co(III) oxidation states during C-H activation, such as Cp*Co(III)-complexes. Ph N N Ph N N Ph Ph CoH(N 2 )(PPh 3 ) 3 Thereafter, this type of low-valent cobalt catalyzed C-H bond activation has been
	H Cl rapidly developed by Yoshikai 32 , Ackermann 33, 34 , Matsunaga 35 , etc.. Despite these H Ph Ph neat, 85 ºC, 2 h Ph Cl Cl Cl c) Brookhart, 1997 excellent works which have improved the status of cobalt in C-H activation and have 1.2The use of low-valent cobalt in C-H activation arguably dates back to 1955. Murahashi greatly expanded the application of C-H activation in organic synthesis, it is still subject
	first reported the use of Co2(CO)8 to catalyze the ortho-carbonylation reaction of to some limitations. In the vast majority of low-valent cobalt-catalyzed C-H activation,
	aromatic imine under harsh CO pressure to afford an isoindolinone derivative in yield of 80%, which involves cobalt-mediated activation (cyclometallation) of the ortho C-H H O SiMe 3 Co relatively large amounts of Grignard reagents are required, mainly because the active SiMe 3 O SiMe 3 Me 3 Si cobalt species are difficult to form in situ.
	bond (Scheme 1.4a) 27 . Since then, the development of low-valent cobalt catalyzed C-toluene, 35 ºC
	H activation has been dormant. It was only in 1994 that the low-valent cobalt catalyst Scheme 1. 4. Pioneering examples of cobalt-catalyzed C-H activation.
	was further developed by Kisch and co-workers, using the cobalt(I) complex
	([CoH(N2)(PPh3)3]) to catalyze hydroarylations of alkynes (Scheme 1.4b) 28 . In this
	reaction, diphenylacetylene reacts with azobenzenes via anti-addition to afford the In these pioneering examples of cobalt-catalyzed C-H activation, where the catalysts
	desired product in 70-80% yields. In addition, [CoH(H2)(PPh3)3] was successfully used used are what we call well-defined low-valent cobalt complexes. Another low-valent
	as a catalyst. Those low-valent cobalt catalysts have high reactivity, but the C-H cobalt complex used in C-H bond activation is typically a complex generated in situ by
	activation required harsh reaction conditions and was limited by the range of substrates. reaction of simple cobalt(II) salt with Grignard reagents, such as CoBr2 salt.
	Later, Brookhart and coworkers reported a low-valent Cp*Co(I) complex catalyzed Based on Kisch's seminal work, the cobalt catalyzed C-H bond hydroarylation regained
	hydroacylation interest. In 2010, an efficient hydroarylation reaction of alkynes via directed C-H in 1997 (Scheme 1.4c) 29, 30 . The Cp*Co(VTMS)2
	(VTMS=Vinyltrimethylsilane) can be used as a pre-catalyst for both intra-and inter-activation was reported by Yoshikai and co-workers, by using a ternary catalytic system,
	molecular hydroacylation of aromatic aldehydes with olefins under mild conditions. which consists of CoBr2, a phosphine ligand (PMePh2 or P(pMeOC6H4)3), and a
	Grignard reagent (MeMgCl or tBuCH2MgBr) as reductant (Scheme 1.5) 31 . After this
	work, the application of Co(II) salt to catalyze C-H functionalization has witnessed a
	strong development.

1.2.2.1.1. C-C bond formation

	As stated previously, the formation of C-C bond is one of the most fundamental
	reactions in synthetic organic chemistry. The development and improvement of current
	approaches for the efficient construction of C-C bonds have been emphasized with C-
	H activation, both from an academic and industrial application perspective. In terms of
	the number of articles published currently, the construction of C-C bonds via high-
	valent cobalt-catalyzed C-H activation is now the most widely studied. For better
	discussion, these examples of C-C bond formation are grouped by substrate type,
	mainly because in many cases this reaction is found to be substrate type-specific, such
	as indoles-based substrates, 2-aryl-N-containing heterocyclic substrates and other
	type substrates.
	As mentioned previously, Matsunaga and Kanai first reported the use of
	[Cp*Co(C6H6)](PF6)2 as a catalyst to catalyze C2-selective addition of indoles in 2013 40 .
	Further, they also found that the use of [Cp*Co(CO)I2] can promote direct dehydrative
	C-H allylation of non-activated allyl alcohols, thus giving C2-allylated indoles, phenyl-
	pyrazole, and pyrrole in good yields, whereas analogous Cp*Rh(III) catalyst was
	ineffective (Scheme 1.9a) 42 . Shortly afterward, the scope of this allylation protocol was
	extended by Glorius and co-workers, the allyl carbonates can be used as coupling
	partners (Scheme 1.9b) 43 .
	Furthermore, an example of alkylation was published by Wang and co-workers,
	Cp*Co(III)-catalyzed C-H coupling reaction of indoles with α-diazomalonates (Scheme
	1.9c) 44 , which proceeds under relatively mild reaction conditions. In this protocol, α-
	diazomalonates, the most commonly used carbene precursor, can be reacted with
	metal to give a highly reactive metal-carbene intermediate and promote the alkylation
	of indoles. With an optimized catalytic system based on previous work, the group of

  [START_REF] Sen | Cobalt(III)-Catalyzed Dehydrative [4+2] Annulation of Oxime with Alkyne by C-H and N-OH Activation[END_REF] , and Scheme 1.15 shows the proposed pathway for the synthesis of indoles and quinolines. The electrophilicity of the carbonyl group can be improved

	by the coordination of Cp*Co(III) and Lewis acids, and the nucleophilic addition
	process was further promoted (Scheme 1.15, cycle A). In contrast, changing the steric
	and electronic properties of the directing group will inhibit nucleophilic attack, allow the
	dehydrogenation process (Scheme 1.15, cycle B), which leads to the generation of two
	different heterocycles. Prior to this work, the analogous quinolines could be
	synthesized by using unsymmetrical alkynes, which was reported by Li and coworkers
	(Scheme 1.14h) 80 , with good functional group tolerance and relatively high
	regioselectivity.
	Scheme 1. 15. Two pathways for the synthesis of quinolines (cycle A) and indoles
	(cycle B).
	In 2015, Sundararaju and co-workers successfully synthesized isoquinolines for the
	first time via Cp*Co(III)-catalyzed C-H functionalization (Scheme 1.14j) 81 ,
	[Cp*Co(CO)I2

Table 2 . 1 .

 21 [Cp*CoI2]2 as the metal source. The performance of the cyclocobaltation of 2-phpyH with [Cp*CoI2]2 assisted by various carboxy bases (3:1 base/Co ratio) is shown in table 2.1. Performance of the cyclocobaltation of 2-phpyH by [Cp*CoI2]2 underAs shown in table 2.1, in the absence of base no trace of the desired complex 1a was observed in 1 H NMR after 17 h (Table2.1, entry 1). The first base probed for the cyclocobaltation was NaOAc, which performed well in the iridium case, affording 2a in ~93 % yield for an overnight reaction(17 h). 230 In the case of cobalt, a maximum yield of 12 % in the brown-red-colored 1a complex was achieved after 2 days of reaction (Table2.1, entry 2) in the presence of dry NaOAc. Like suggested by theory (Figure 2.2), the C-H activation in the presence of NaOAc with [Cp*CoI2]2 is much less favorable than with the [Cp*IrCl2]2.

	various conditions

mmol, 6 eq), DCM (5 mL), 50°C. a at room temperature. b with 4 eq of 2-phpyH. c with 8 eq of 2-phpy. d at room temperature and 2 eq of Na2CO3. 1,3,5-Trimethoxybenzene was used as internal 1 H NMR reference.

  Notably, while no trace of a similar Co acetamidate complex, i.e. 1f, was ever detected at the end of the cyclocobaltation reaction, this complex could be easily synthesized in ca. 48% yield (NMR yield) from 1a by reaction with a large excess (>10-fold) of LiNHAc (Scheme 2.5 bottom). Reaction of 1f with excess amounts of either NaI or [nBu4N]I in CH2Cl2 at 50°C in a sealed Schlenk vessel for over 17 h produced complex 1a in ~50% yield, thus suggesting that the formation of 1f under the conditions of cyclocobaltation

		[Cp*CoI 2 ] 2	LiNHAc 6 eq DCM, 50°C, 17 h	N Co 1a I Cp* 68%
	N	sealed Schlenck vessel
	2-phpyH	[Cp*IrCl 2 ] 2	DCM, 50°C, 17 h LiNHAc 6 eq	N	Cl Ir Cp* 20%	and	N	Ir H N Cp*	O	29%
					2a		2b

  Furthermore the KIE ¬ value is consistent with a strengthening of the C-H(D) bond more favorable to the deuterated isomer in the backward ag-to-TS-ag path corresponding to the dismantlement of the agostic C-H…Co interaction. Also important is the fact that KIE CH holds the highest value, which is consistent with the quasi-linearity of the key bonds being disrupted and formed in TS-CH according to Westheimer's model.246

					N	Co	Cp*			NCMe, NaBArF 24 room temp.	N	Co	Cp*	NCPh, NaBArF 24 DCM, room temp.	N	Co	Cp*
								NCMe				I	NCPh
						1b (80%)	Cp* BArF 24	1a (83%) kinetic determining step	Cp*	1b' (64%)	BArF 24
													LiNHAc,
					HN	O	Co	D/H	N	H/D	KIE = 1.2 H N DCM, 50 ºC	HN	O	H/D Co	N	H/D
										D/H		H/D	D/H	H/D
								anag	H/D	TS-ag	H/D
	2.2.3. N	Co	N The synthesis of cobaltacycles assisted by acetamidate H N H I KIE = 0.8 T=333.15 K [Cp*CoI 2 ] 2 Cp* LiNHAc, LiNHAc, DCM, 50 ºC DCM, 50 ºC	N	Co	I Cp*
	N Afterwards, the cyclocobaltation of other ligands assisted by LiNHAc was also H/D H/D Co HN Cp* N H H/D H/D N HN N Co 3a (81%) 5a (30%) Cp* KIE CH = 7.1 bond breaking step investigated, by using the optimization conditions for the 2-phpyH descried above NCMe, NaBArF 24 room temp. NCMe, NaBArF 24 room temp.
	N	Co	NCMe Cp*		D/H TS-CH O	H/D	H/D	LiNHAc, DCM, 50 ºC	O	D/H ag	H/D	H/D N Co	NCMe Cp*
					BArF 24						N	Cp*	BArF 24
													Co
	5b (79%)									I	3b (85%)
													N
													4a (82%)
													N	Cp*
													Co
													NCMe
													BArF 24
													4b (80%)
	analytically computed for the considered stationary points at the COSMO (CH2Cl2)-Scheme 2. 8. Cyclocobaltation of 2-tolpyH, 2-anpyH, and bzqH and the conversion of
	ZORA-PBE-D3(BJ)/ all electron TZP level. This provided values of KIE ® and KIE ¬ of the resulting iodo cobaltacycles into the ionic cobaltacyles.
	1.2 and 0.8 respectively, and 8.9 for KIE CH at T= 298.15 K. The values slightly changed
	at T= 333.15 K (Scheme 2.7) to KIE ® = 1.2, KIE ¬ = 0.8 and KIE CH = 7.1. In spite of the All complexes were fully characterized by 1 H and 13 C NMR, ESI mass spectroscopy,
	physical limitations of the Bigeleisen equation, those values of KIE are consistent with and elemental analysis. And the structures of 4a, 5a, 1b, 1b', 3b, 4b, and 5b were
	the experimental primary KIE of the cyclocobaltation reaction if one considers the determined by X-ray diffraction analysis from suitable single crystals (Figures 2.22-
	formation of the agostic intermediate as being the kinetic determining step. Quite 2.25).
	interestingly the computed KIE 233

240, 241

Scheme 2. 7. Kinetic isotope effect computed from DFT-computed vibrational frequencies with the Bigeleisen equation for key steps in the cyclocobaltation of 2-phpyH and 2-(d5.ph)pyD according to the CMD mechanism.

In this study, KIEs were determined using solely harmonic vibrational frequencies that were readily calculated by DFT routines assuming the Born-Oppenheimer approximation. 243 Forward KIE ® and backward KIE ¬ for the anag-ag step and KIE CH for the forward ag-to-TS-CH step were determined with the vibrational frequencies ® values indicate that the formation of ag is not marked with an "inverse" KIE value typical of formally non-bond-breaking steps (i.e KIE < 1). (Scheme 2.8). 7,8-benzo[h]quinoline (abbr. bzqH), 4-[4-(t-butyl)pyridin-2-yl]-N,Ndimethylaniline 132 (abbr. 2-anpyH) and the 2-(2-methylphenyl)pyridine (abbr. 2-tolpyH)

were successfully used allowing the formation of the corresponding complexes 3a, 4a and 5a in 81%, 82% and 30% isolated yield respectively. But all attempts to cyclometallation of 1,2-diphenylquinoxaline or N,N-dimethylbenzylamine failed to produce any traceable organometallic complex. Moreover, the unique stabilizing ability of MeCN is also utilized to synthesize cationic Cp*Co(III)-complexes (1b, 3b, 4b, and 5b) by displacing the iodo ligand by acetonitrile in the presence of 1 equiv of NaBArF24 at room temperature over 1 h. Similarly, benzonitrile can also use to synthesize the corresponding cationic compound 1b'.

  [248][249][250][251][252] is a well-established process that has recently been ported to Cp*Co(III) catalysis by the groups of Zhu, 253 Cheng 176 and

Perez-Temprano

141, 143, 144, 185

. In the latter's reports particularly, the outlying feature of this catalytic process is the putative electrophilic activation of the C-H bond of the main heterocyclic substrate by [Cp*Co(MeCN)3] + .

  Table 2, entry 7) did not improve the yield in condensation product. However, the use of molar 30 % of LiNHAc raised the yield up to 71 % (Table 2.2, entry 8).

	Table 2. 2. Performance of the catalyzed condensation 1,2-diphenylacetylene with 2-
	phpyH
	Entry	Base	Additive	Yield
	1	no base	AgBF4 (2 equiv)	49%
	2	LiNHAc	NaBF4 (2 equiv)	8%
	3	LiNHAc	NaBF4 (2 equiv) + Cu(OAc)2 (2 equiv)	0%
	4	LiNHAc	NaBF4 (2 equiv) + CuCl2 (2 equiv)	0%
	5	LiNHAc	AgBF4 (10 mol %) + NaBF4 (1.9 equiv)	10%
	6	no base	AgBF4 (10 mol %) + NaBF4 (1.9 equiv)	9%
	7	NaOAc	AgBF4 (2 equiv)	48%
	8	LiNHAc	AgBF4 (2 equiv)	71%
	9	no base	AgBF4 (2 equiv) no [Cp*CoI2]2	0%
	General conditions: 2-phpyH (0.1 mmol, 1 equiv), diphenylacetylene (0.15 mmol, 1.5
	equiv), [Cp*CoI2]2 (0.005 mmol, 5 mol %), with or without LiNHAc (0.03 mmol, 30
	mol %), DCE (5 mL), and additive, at 130 °C for 24 h. Trimethoxy benzene was used
	as internal 1 H NMR reference.

for the purpose of comparison. Quite expectedly blank experiments in the presence of the sole AgBF4 and excluding [Cp*CoI2]2 led to no conversion (Table

2

.2, entry 9). The contribution of the electrophilic activation pathway was confirmed by performing the condensation reaction with 2 eq. of AgBF4 relative to 2-phpyH and no base, which provided a yield in the condensation product of 49 % (Table

2

.2, entry 1). Under identical conditions the addition of molar 30 % of NaOAc (Other variants entail the use of a preformed cobalt(III) solvato-metallacycle of 2-phpy as the catalyst. In almost all cases reported to date with Cp*Co catalysts the effective assistance of an auxiliary base was either not considered or not established.

253

Table 2

 2

	.2,

concurrent CMD mechanism cannot be ruled out when LiNHAc is present. Worthy to note, in the case of a domino catalysis promoted by Cp*Co(III), Ackermann et al.

254

Table 2 . 3

 23 .2, entry 2).

	Situations where two mechanisms might coexist are not specific to Co though and have
	been considered earlier by Davies, Macgregor et al. for the condensation of alkynes
	with 3-arylpyrazoles catalyzed by either [Cp*Rh(MeCN)3][PF6]2 or [(p-
	cymene)RuCl2]2. 250 Another example addressed by Qu and Cramer 190 for the C-H
	bond functionalization with diazo compounds catalyzed by Cp*Co(III)/Rh(III)
	complexes tends to suggest the possible coexistence of two mechanisms of C-H bond
	activation. On the basis of the data collected in the present study the KIE might be a
	good indication of the nature of the dominating mechanism : an electrophilic activation
	(abbr. EA) of a C-H bond being expected to produce a much higher KIE than that of a

reaction governed by the CMD mechanism 122 for which the kinetic determining step is the formation of the agostic intermediate ag. This assumption is supported by the data published by Cheng et al. 174 for the annulation reaction of 2-phpyH with 1,2-diphenylacetylene promoted by the [Cp*RhCl2]2/Cu[BF4]2/O2 mixture in 1,2dimethoxyethane, which showed KIE values spanning 2.03 -2.84. . Catalyzed condensation of various aromatic substrates with 1,2diphenylacetylenea.

The oxidative collapse of cobaltacycles

  255, 256 Cp*Co(III) catalysis257 since it has been recently reported that amide-based enantiopure ligands224, 258, 259 may not only assist C-H bond activation via the CMD mechanism but also induce stereo-discrimination at the level of the agostic transient in Pd(II)-promoted catalysis. By extension to Co(III) stereocenters the same concept could lead to effective stereo-differentiation in the proton transfercarbometallation step and consequently initiate chiral induction in further steps, a feature that the herein merely addressed EA mechanism is less prone to achieve.

	Chapter 3. The most relevant results of this chapter have been already published [reprinted with
	permission from J.P. DJUKIC et al. Fate of Cobaltacycles in Cp*Co-Mediated C-H
	Bond Functionalization Catalysis: Cobaltacycles May Collapse upon Oxidation via
	Co(IV) Species. Organometallics 2021, 40, 15, 2624-2642. Copyright © 2021
	American Chemical Society]. The theoretical aspects were done with the help of Yann
	CORNATON and Jean-Pierre DJUKIC.

Table 3 . 2

 32

	Entry Complex Solvent (atm.)	Product(s) (yield)
	1	4a	DCM (Ar)	[4c][BArF24] (0%)
	2	6a	DCM (Ar)	[6c][BArF24] (0%)
	3	7a	DCM (Ar)	[7c][BArF24] (57% a )
	4	7a	DCM (ambient air)	[7c][BArF24] (84% a , 37% b )
	5	7a	DCM (Ar) and CDCl3 (air)	[7d][BArF24] (21% b )
	6	8a	DCM (Ar)	[8c][BArF24] (63% a )
	7	8a	DCM (ambient air)	[8c][BArF24] (88% a , 35% b

. Reaction of Co(III) cobaltacycles with [Ph3C][BArF24] in DCM

  anion, 1a or any of the products of its degradation such as 2-phenylpyridine, {[Cp*Co]2(μ-I)3}[BArF24]. To eventually rule out [BArF24] --anion as a potential source of H atom, the reaction of 1a with [Ph3C][PF6] 314, 315 was undertaken, which led to the formation of [1c] + in yields similar to that obtained with the tritylium BArF24 salt.Whether the H atom is captured directly from 1a by an oxidized form of 1a or from an organic source such as Ph3CH, was not elucidated experimentally. Triphenylmethane could indeed arise from an hydride abstraction from the Cp* ligand of 1a by [Ph3C] + if one refers to the work of Tilley et al.316 that was originally carried out with a tetraphenyl borate salt. However, the presence of Ph3CH was not overwhelming in all analyzed reaction media. Furthermore, like shown below in the theoretical investigation, Ph3CH is a very unlikely source of H radical for thermochemical reasons.

Table 3 . 3 .

 33 Treatment with D2O/H2O that promotes the formation of [1c][BArF24] under an atmosphere of Air or Argon

	Entry	H2O or D2O	Atmosphere	Yield
	1	H2O	Argon	13%
	2	D2O	Argon	8%
	3	H2O	Air	87%
	4	D2O	Air	77%

Table 3 .

 3

	1. Electrochemical data for 1a, 7a, 8a, 9a, 10a, {[Cp*Co]2(μ-I)3}[I3], [1c] + , and
	TEAI.
	Compounds			E1/2
	1a		1.11 irr	0.52 irr
	7a		1.19 irr	0.59 irr	-1.60
	8a		1.23 irr	0.61 irr
	9a			0.80 irr	-1.21 irr	-1.76 irr
	10a		1.11 irr	0.49 irr
	{[Cp*Co]2(μ-I)3}[I3]	1.25 irr	0.36 (168)	-0.02 a (293) -0.51 (120) -1.76 irr
	[1c][ BArF24]				-1.39 irr

Table 3 . 2 .

 32 Interatomic "Intrinsic Bond Strength Indexes" (IBSI) 285 and the integrated difference between the density gradients with and without interference IGM283, 284 : Δg inter computed for 1a and [1a'] + , Ir-1a[Ir-1a] + , 9a, [9a'] + , [Cp*Co(SCF3)(phpy)] and [Cp*Co(SCF3)(phpy)] + .

		1a	Ir-1a	[1a'] + [Ir-1a'] +	9a	[9a'] + [Cp*Co(SCF3)(phpy)]	[Cp*Co(SCF3)( phpy)] +
				IBSI Atom-Pair Interactions (au)
	C4-C2'	0.047	0.038 0.052	0.020 0.044 0.053	0.038	0.048
	C3-N	0.026	0.012 0.048	0.009 0.026 0.027	0.021	0.029
	C4-Co/Ir	0.253	0.274 0.232	0.248 0.244 0.203	0.242	0.192
	C3-Co/Ir	0.259	0.301 0.213	0.247 0.250 0.223	0.235	0.204
	C2'-Co/Ir 0.479	0.488 0.469	0.498 0.497 0.460	0.485	0.459
	N-Co/Ir	0.385	0.402 0.376	0.410 0.385 0.378	0.392	0.391
	C2'-X	0.026 a 0.024 a 0.024 a 0.020 a 0.030 b 0.027 b	0.046 c	0.032

c

Interacting Fragments Δg inter

  The deferred capture of H by intermediate [IntC'] + was considered by attempting the optimization of a hydrido Co(III) species, which eventually ended up in the migration of H to C5, thus yielding the triplet state intermediate [IntCH] + , which undergoes the N-C coupling as mentioned for the pathway 1. From [IntC'] + , the formation of the C-N bond is also endergonic (ΔG= + 20 kcal/mol) and barrierless. Tentative optimization of a Co(III) hydride species accounting for the capture of H eventually ended up in the migration of H to C5, yielding [pre-1c] + .

	3.2.6.2.6.	Capture of H in pathway 2
	3.2.6.2.7.	N-C coupling followed by H capture in pathway 3
	3.2.6.2.8.	Fate of "CoI"

C-C bond in intermediate [IntC']

+ from [1a'] + is endergonic with a ΔG of + 12 kcal/mol.

Table 4 . 1 .

 41 Chalk-Harrod mechanism Modified Chalk-Harrod mechanism as reducing agent and 0.1 mol% of catalyst) as reported by our group 133 . Unfortunately, the hydrosilylation of ketones catalyzed by cobaltacycles 1b and 5b did not produce the desired product, as shown in table 4.1. Hydrosilylation of ketone via cobaltacycles 1b and 5b

	Entry	Ketone	Catalyst	Yield
	1	Acetophenone	1b	0%
	2	Benzophenone	1b	0%
	3	Acetophenone	5b	0%
	4	Benzophenone	5b	0%

Table 4 . 2 .

 42 Hydrosilylation of benzophenone with HSiEt3. with Cp instead of Cp*, gave us no hope as new catalyst (Table 4.2, entry 8) proving again the importance of the Cp* ligand in catalysis. None of the blank reactions

	Entry 1 2 a 3 4 5 6 7 8 9 10 11 12 13 14 15 Reaction conditions: benzophenone (1 mmol), catalyst (5 mol%), HSiEt3(3 mmol), Catatalyst Additive Conv. to A (B) (%) Total Conv. (%) NMR* Yield (%) 1b -0 0 0 1b -5.5 (1.6) 7.1 7 1a -0 (0) 0 0 1a NaBHEt3 78.6 (18.1) 96.7 83 1a Red-Al 9 (33.9) 42.8 9 5a NaBHEt3 55.9 (17.3) 73.3 58 9a NaBHEt3 75.6 (21.7) 97.3 74 10a NaBHEt3 3.4 (11.9) 15.2 6 [Cp*CoI2]2 NaBHEt3 61 (-) 61 70 [Co2(CO)8] NaBHEt3 0 (17) 17 0 [CoCp*(CO)I2] NaBHEt3 18 (18) 36 19 [CoCl2] NaBHEt3 0 (21) 21 0 [Co(acac)2] NaBHEt3 3 (16) 19 3 -NaBHEt3 0 (23) 23 0 --0 (0) 0 0 toluene (2 mL); a same condition in DCM. 1,3,5-trimethoxybenzene as internal reference. None of the simple starting Co complexes such as [Co2(CO)8], [Cp*CoI2]2, [CoCp*(CO)I2], [CoCl2], [Co(acac)2] presented similar activity (Table 4.2, entries 9-13). Moreover, the cobaltacyle 9a with chloride instead of iodine, shown a lower activity as contrary to the previous results with the homologous Ir complexes. The cobaltacycle HSiEt 3 O catalyst (5 mol %) addiitive (10 mol %) SiEt 3 H Toluene room temp. O H 10a, O (1 equiv.) (3 equiv.) A B

Preparation of the tritylium tetrakis[3,5-bis(trifluoromethyl)- phenyl]borate ([Ph 3 C][BArF 24 ])

  The resulting suspension was filtrated and the collected solid was washed with dry n-pentane and dried under reduced pressure (77% yield). IR (ATR, neat): δ 1588 (m, C=O stretching) cm -1 . 1 H NMR (400

	5.2.3.	Preparation of the d 15 -trityl chloride
		O	n-BuLi		O
		H 2 N	THF, -80 ºC to room temp.	Li	H N
	d15-Tritylium chloride was prepared according to a literature procedure with minor
	modification 391 . Under argon atmosphere, a mixture of d6-benzene (5.0 mL, 0.05 mmol)
	and carbon tetrachloride (1.0 mL, 0.01 mmol) was dissolved in 20 mL of 1,1,2,2-
	tetrachloroethane in a sealed Schlenk vessel, and cooled down to 0 °C. Aluminium
	trichloride (1.6 g, 0.01 mmol) was then added slowly during stirring. After 15 min of
	stirring, the solution was refluxed for 90 min and then cooled down to room temperature.
	The solution was quenched with 1 M HCl, and the organic phase was extracted with
	DCM and dried over Mg2SO4. After removal of the solvent under vaccum, the crude
	MHz, CDCl3) δ 7.27 (d, J = 1.6 Hz, 1H), 2.02 (d, J = 2.9 Hz, 3H). solid was purified by column chromatography (hexanes/ethyl acetate = 9:1) to afford
	5.2.2. d15-tritylium chloride (1.2 g, 37%).
	5.2.4.
					F 3 C	CF 3
				F 3 C	CF 3
		Cl	NaBArF 24		B
			CH 2 Cl 2	F 3 C	CF 3
					F 3 C	CF 3
	[Ph3C][BArF24] was prepared according to a literature procedure with minor
	modification. 390 Under argon atmosphere, a mixture NaBArF24 (886.2 mg, 1 mmol) and
	tritylium chloride (278.1 mg, 1 mmol) was stirred overnight in ~20 mL of CH2Cl2 at room
	temperature in a sealed Schlenk vessel. The reaction mixture was then filtrated through
	Celite, the filtrate was evaporated under reduced pressure. The resulting solid was first
	washed with n-pentane and then purified by recrystallization with CH2Cl2/n-pentane to
	afford bright yellow microcrystals (973 mg, 88% yield). 1 H NMR (300 MHz, CDCl3) δ
	8.15 (ddt, J = 8.8, 7.3, 1.3 Hz, 3H), 7.80 -7.73 (m, 6H), 7.68 (p, J = 2.1 Hz, 8H), 7.59
	-7.54 (m, 6H), 7.48 (s, 4H).

Synthesis of CpCo(CO)I 2 and [CpCoI 2 ] 2

  50 mL of distilled heptane. The solution was stirred and refluxed during 2 days. After reaction, the solid was filtrated and washed 3 times with distilled pentane. [CpCoI2] was insoluble in most solvents, but slightly soluble in coordinating solvents such as CH3CN and THF giving rise to quite air and light sensitive solutions.

	1) CCl 4 C 2 H 2 Cl 4, 0 ºC 2) AlCl 3 150 ºC to room temp. were introduced with All analytical data were in accord with data published in literature. 393-396 Cl d 6 d 5 d 5 d 5
	5.2.5.	General procedure for the synthesis of iodocobaltacycles
	Under the argon atmosphere, a mixture of [Cp*CoI2]2 (1 equiv), LiNHAc (6 equiv.), and
	2-arylpyridine ligand (2 equiv.) were stirred in ∼10-15 mL of CH2Cl2 at 50 °C for 48 h
	in a sealed Schlenk vessel. The reaction mixture was filtrated over Celite and followed
	by the removal of the solvent. The resulting residue was then purified by column
	chromatography (DCM/n-pentane= 4/1) and recrystallization with CH2Cl2/n-pentane
	and/or washing with n-pentane.
		CpCo(CO) 2	I 2 , Et 2 O room temp.	CpCo(CO)I 2	heptane reflux	[CpCoI 2 ] 2
			I		II
	Procedure I: In a Schlenk tube, CpCo(CO)2 (1 mL, 7.5 mmol) and 20 mL of distilled
	Et2O were introduced under argon atmosphere. I2 (2 g, 7.9 mmol) dissolved in distilled
	Et2O was added to the Schlenk tube with a cannula. The reaction was stirred overnight
	at room temperature. At the end of the reaction, the solvent was removed under
	reduced pressure and the residual solid washed 4 times with distilled pentane. 1 H NMR
	analysis in CDCl3 revealed the disappearance of the signal of the starting compound
	at 5.06 ppm that was replaced by a new Cp singlet at 5.68 ppm. Analytical data were
	in accord with those reported in the literature. 392, 393
	Procedure II: The synthesis of the [CpCoI2]2 was carried out by applying the
	methodology reported for [Cp*CoI2]2. 281 In a round bottom flask, 1 g of [CpCo(CO)I2]
				164

phenylenepyridine-κ 2 -C,N) cobalt (III) (1a)

	5.3.1.	Iodo(pentamethylcyclopentadienyl)(2-[Cp*CoI2]2 (448 mg, 0.5 mmol), LiNHAc (195.1 mg, 3 mmol), and 2-
		phenylpyridine (155.2 mg, 1mmol) in 10 mL of CH2Cl2, yield is 78 %
		(370 mg). Anal. calcd for C21H23NICo•CH2Cl2: C, 52.72; H, 5.03; N,
		2.79. Found: C, 52.51; H, 4.91; N, 3.19. 1 H NMR (500 MHz, CDCl3) δ
	9.20 (dt, J = 5.6, 1.2 Hz, 1H), 8.27 (dd, J = 7.7, 1.1 Hz, 1H), 7.66 -7.58 (m, 2H), 7.56
	(dd, J = 7.6, 1.5 Hz, 1H), 7.30 -7.26 (m, 1H), 7.04 (td, J = 6.2, 2.1 Hz, 2H), 1.49 (s,
	15H);

  . MS-ESI (m/z): [M+Na] + calcd for C22H25NINaCo, 512.03; Found, 512.03; [M-I] + calcd forC22H25CoN, 362.13; Found, 362.13.

	[Cp*CoI2]2 (225 mg, 0.25 mmol), LiNHAc (97.58 mg, 1.5 mmol), and
	4-(4-(tert-butyl)pyridin-2-yl)-N,N-dimethyl-aniline (127.18 mg, 0.5
	mmol) in 10 mL of CH2Cl2, yield was 82% (239 mg). Anal. calcd for
	C27H36 N2ICo•CH2Cl2: C, 55.72; H, 6.35; N, 4.63. Found: C, 55.54; H,
	6.36; N, 4.92. 1 H NMR (500 MHz, CDCl3) δ 8.91 (d, J = 6.2 Hz, 1H),
	7.62 (d, J = 2.5 Hz, 1H), 7.42 (d, J = 8.5 Hz, 1H), 7.37 (d, J = 2.2 Hz, 1H), 6.89 (dd, J
	= 6.2, 2.2 Hz, 1H), 6.45 (dd, J = 8.5, 2.4 Hz, 1H), 3.12 (s, 6H), 1.50 (s, 15H), 1.30 (s,
	9H

5.3.3. Iodo(pentamethylcyclopentadienyl)[4-tertiobutyl,2-(4-N,Ndimethylaminophenylene)pyridine-κ 2 -C,N]cobalt (III) (4a)

(4-bromophenyl)pyridine-κ 2 - C,N](pentamethylcyclopentadienyl)cobalt(III) (7a)

  . HRMS (ESI, m/z) calcd. for C22H25CoN + : 362.1319. Found: 362.13.

	5.3.6.	Iodo[2-[Cp*CoI2]2 (448 mg, 0.5 mmol), LiNHAc (195 mg, 3 mmol), and 2-(4-
	N	Cp*	bromophenyl)pyridine (235 mg, 1 mmol) in 20 mL of CH2Cl2 afforded
		Co	a yield of 71% (393 mg). Anal. calcd for C21H22BrCoIN: C,45.52, H
		I	4.00, N 2.53. Found: C 45.33, H 4.05, N 2.62. 1 H NMR (500 MHz,
	5a		CDCl3) δ 9.16 (ddd, J = 5.7, 1.5, 0.8 Hz, 1H), 8.34 (d, J = 1.9 Hz, 1H),
	7.63 (ddd, J = 8.0, 7.1, 1.5 Hz, 1H), 7.59 (ddd, J = 8.2, 1.8, 0.8 Hz, 1H), 7.40 (d, J =
	8.2 Hz, 1H), 7.17 (dd, J = 8.2, 1.9 Hz, 1H), 7.08 (ddd, J = 7.3, 5.7, 1.7 Hz, 1H), 1.50 (s,
	15H
	N	Cp*
	Co
		I
	6a
			168

  . HRMS (ESI, m/z) calcd. for C21H22BrCoN + : 426.0268. Found: 426.0262.

	[Cp*CoI2]2 (448 mg, 0.5 mmol), LiNHAc (195 mg, 3 mmol), and 2-(4-
	(trifluoromethyl)phenyl)pyridine (224 mg, 1 mmol) in 10 mL of CH2Cl2
	afforded 8a in 62% yield (335 mg). Anal. calcd for C53H36BF24N:
	C,48.64; H,4.08; N,2.58. Found: C, 48.55; H, 4.04; N, 2.64. 1 H NMR
	(500 MHz, CDCl3) δ 9.25 -9.20 (m, 1H), 8.50 (dd, J = 1.8, 0.9 Hz, 1H),
	7.72 -7.66 (m, 2H), 7.63 (dd, J = 8.1, 0.9 Hz, 1H), 7.29 -7.26 (m, 1H), 7.14 (ddd, J =
	6.6, 5.7, 2.2 Hz, 1H), 1.50 (s, 15H).

5.3.7.

Iodo[2-(4-(trifluoromethyl)phenyl)pyridine-κ 2 -

C,N](pentamethylcyclopentadienyl)cobalt(III) (8a)

-phenylpyridine-κ 2 -C,N](cyclopentadienyl)cobalt(III) (10a).

	5.3.8.	Iodo[2The synthesis of 10a was performed similarly to the one of 1a
				published recently. 2 Under argon atmosphere, [CpCoI2]2 (40 mg, 0.053
	N		Cp*	mmol), 2-phenylpridine (15.1 µL, 0.106 mmol) and LiNHAc (20 mg,
	Co	I	0.307 mmol) were introduced in a Schlenk tube. 5 mL of distilled
	CH2Cl2 were added. The reaction was stirred two days at 50°C. The reaction was
	filtrated and the solvent removed under reduced pressure. The resulting solid was Br 7a washed 3 times with distilled pentane. The solid was then purified by chromatography
	column. 100% of pentane was first used, and then 100% of CH2Cl2 allowed the
	migration of the desired purple compound. The compound was obtained in 40% yield
	(17 mg). Anal. calcd. for C16H13CoIN•1/2 H2O: C 46.40, H 3.41, N 3.38. Found: C 46.26,
	H 3.24, N 3.29. 1 H NMR (500 MHz, CDCl3) δ 9.69 -9.63 (dd, 1H), 8.48 (dd, J = 7.7,
	1.1 Hz, 1H), 7.70 -7.60 (m, 3H), 7.31 (td, J = 7.4, 1.5 Hz, 1H), 7.14 -7.02 (2dd, 2H),
	5.15 (s, 5H).
	N		Cp*
	Co
		I
	CF 3
	8a
	19 F NMR (282 MHz, CDCl3): δ -62.1 ppm. HRMS (ESI, m/z) calcd. for C22H22CoF3N + :
	416.1036. Found: 416.1035.
				169

  . MS-ESI (m/z): [M-NHAc] + calcd forC21H23NCo, 348.12; Found, 348.12.

	5.3.10. Acetamidato[2-phenylenepyridine-κ 2 -C,N](pentamethyl-
	cyclopentadienyl)iridium (III) (2b)
	Under an argon atmosphere, 2a (26.6 mg, 0.0514 mmol) and excess
	of LiNHAc (33.4 mg, 0.514 mmol) were dissolved in CH2Cl2 (~7-10
	mL) in a Schlenk flask. The resulting suspension was vigorously
	stirred at room temperature overnight and the reaction mixture
	filtrated through celite. The filtrate was stripped of solvents under reduced pressure to
	afford a solid residue that displayed some reactivity with SiO2, which prevented
	chromatographic separation. The residue was therefore redissolved in CH2Cl2 and the
	resulting solution was swiftly filtered through dry SiO2. The filtrate was stripped of
	solvent and recrystallized from CH2Cl2 and pentane to afford 2b slightly contaminated
	with acetamide (9.05 mg, yield: 32,6%). Anal. calcd for C23H27IrN2O•1/3 CH2Cl2•4/3
	NH2COCH3: C, 48.46; H, 5.35; N, 7.2. Found: C, 48.09; H, 5.71; N, 6.99. 1 H NMR
	(500 MHz, CDCl3) δ 9.14 -9.11 (m, 1H), 7.79 (dd, J = 7.5, 1.2 Hz, 1H), 7.74 -7.71 (m,
	1H), 7.66 (dd, J = 7.7, 1.5 Hz, 1H), 7.57 (td, J = 7.7, 1.6 Hz, 1H), 7.19 (td, J = 7.3, 1.4
	Hz, 1H), 7.09 (td, J = 7.4, 1.2 Hz, 1H), 7.01 (ddd, J = 7.3, 5.8, 1.5 Hz, 1H), 3.47 (s, 1H),
	1.71 (s, 15H), 1.70 (s, 3H).

3.11. Acetonitrilo(pentamethylcyclopentadienyl)(2-phenylenepyridine-κ 2 - C,N) cobalt (III) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (1b)

	5.3
	N	Ir	Cp*
			N
		H		O
		2b
				1a (47.5 mg, 0.1 mmol) and NaBArF24 (88.6 mg, 0.1 mmol)
		N		Cp*	in 10 mL of acetonitrile, yield is 80 % (100.2 mg). Anal. calcd
		Co	NCMe	for C55H38 N2BF24Co • 3/2CH2Cl2: C, 51.25; H, 3.13; N, 2.11.
				,BArF 24	Found: C, 51.34; H, 2.97; N, 2.14. 1 H NMR (500 MHz,
		1b

. MS-ESI (m/z): [M-NHAc] + calcd for

C21H23NIr, 482.15; Found, 482.15

.

5.

CD2Cl2) δ 8.92

(d, J = 5.7 Hz, 1H), 8.09 -8.04 (m, 1H), 7.90 -7.78 (m, 2H)

, 7.72 (p, J = 2.4 Hz, 8H), 7.65 (dd, J = 7.6, 1.

5 Hz, 1H), 7.56 (s, 4H), 7.40 (td, J = 7.4, 1.5 Hz, 1H), 7.31 -7.22 (m, 2H), 2.14 (s, 3H), 1.31 (s, 15H)

.

13 C NMR (126 MHz, CD2Cl2) δ 175.4,

.15. Benzonitrilo(pentamethylcyclopentadienyl)(2-phenylenepyridine-κ 2 - C,N) cobalt (III) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (1b')

	1a (50 mg, 0.1 mmol), benzonitrile(1mL) and NaBArF24
	(88.6 mg, 0.1 mmol) in 10 mL of DCM, yield was 64 %
	(88.5 mg). Anal. calcd for C60H40N2BF24Co • 0.25 CH2Cl2
	• 0.1 C5H12: C, 54.33; H, 3.13; N, 2.09. Found: C, 54.35;
	H, 3.13; N, 2.06. 1 H NMR (500 MHz, CD2Cl2) δ 8.98 (d, J
	= 5.8 Hz, 1H), 8.10 (d, J = 7.8 Hz, 1H), 7.88 (t, J = 7.6 Hz, 1H), 7.84 (d, J = 8.1 Hz,
	1H), 7.71 (s, 8H), 7.68 (s, 1H), 7.64 (dd, J = 9.2, 4.7 Hz, 2H), 7.55 (s, 4H), 7.44 (d, J =
	4.7 Hz, 4H), 7.29 (dt, J = 14.4, 7.1 Hz, 2H). 13 C NMR (126 MHz, CD2Cl2) δ 153.

16. [1c][BArF 24 ]

	F NMR (471 MHz, CD2Cl2) δ -
	62.87. 11 B NMR (96 MHz, CD2Cl2) δ -6.6 (dq, J = 5.4, 2.8 Hz). MS-ESI (m/z): [M-NCPh-
	BArF24] Under argon atmosphere, 1a (48 mg, 0.1 mmol) and
	[Ph3C][BArF24] (111 mg, 0.1 mmol) in 10 mL of CH2Cl2, isolated
	yield: 29% (33 mg). Anal. Calcd for C53H36BF24N: C 55.18, H 3.15,
	N 1.21. Found: C 55.21, H 3.34, N 1.21. 1 H NMR (500 MHz,
	CDCl3) δ 8.30 (dd, J = 6.5, 1.5 Hz, 1H), 8.06 (dd, J = 8.4, 1.6 Hz, 1H), 7.97 (ddd, J =
	8.5, 7.3, 1.4 Hz, 1H), 7.87 (dd, J = 8.0, 1.3 Hz, 1H), 7.73 (td, J = 7.7, 1.3 Hz, 1H), 7.70
	(dt, J = 5.2, 2.3 Hz, 8H), 7.59 -7.51 (m, 2H), 7.50 (s, 4H), 7.45 (ddd, J = 7.8, 6.6, 1.6
	Hz, 1H), 2.42 -2.36 (m, 1H), 2.09 (dq, J = 2.7, 1.3 Hz, 3H), 1.70 (p, J = 1.3 Hz, 3H),
	1.40 (s, 3H), 1.29 (s, 3H), 0.96 (d, J = 7.2 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ
	162.

+ calcd for C21H23CoN

+ , 348.12; Found, 348.11; [BArF24]

-calcd for C32H12F24B -, 863.07; Found, 863.06.

5.3.

.17. [7c][BArF 24 ]

	5.3Under argon atmosphere, 7a (27 mg, 0.05 mmol) and
			[Ph3C][BArF24] (55 mg, 0.1 mmol) in 10 mL of CH2Cl2, the NMR
	N	Cp*	yield: 57%; under air, NMR yield : 84%, isolated yield : 37% (22
	Co		mg). Anal. calcd for C53H35BBrF24N•0.15 CH2Cl2: C 51.26, H
		NCPh	2.86, N 1.12. Found: C 51.24, H 2.95, N 1.26. 1 H NMR (500
	BArF 24 MHz, CDCl3) δ 8.29 (dd, J = 6.6, 1.4 Hz, 1H), 7.98 (dd, J = 8.5, 1.7 Hz, 1H), 7.90 (ddd,
	J = 8.4, 7.3, 1.4 Hz, 1H), 7.71 (s, 3H), 7.69 (dd, J = 5.1, 2.7 Hz, 8H), 7.50 (s, 4H), 7.45
	-7.38 (m, 1H), 2.42 -2.37 (m, 1H), 2.08 (dd, J = 2.8, 1.4 Hz, 3H), 1.72 -1.68 (m, 3H),
	1.40 (s, 3H), 1.30 (s, 3H), 0.98 (d, J = 7.2 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ
	162.
	N
		,BArF 24

. HRMS (ESI, m/z) calcd. for C21H24N

+ : 290.1903+ : 290. . Found: 290.1897. .

.19. [7d][BArF 24 ].

	5.37a (16 mg, 0.03 mmol) and [Ph3C][BArF24] (30 mg, 0.03 mmol)
	N	in 10 mL CH2Cl2, isolated yield: 21% (8 mg). Anal. Calcd for
		C53H35BBrF24NO: C,50.99; H,2.83; N, 1.12. Found: C 50.69, H
	,BArF 24	2.76, N 1.18. 1 H NMR (500 MHz, CDCl3) δ 8.46 (dd, J = 6.6,
	Br	1.4 Hz, 1H), 8.28 (ddd, J = 8.7, 7.4, 1.4 Hz, 1H), 8.18 (dd, J =
	8.3, 1.6 Hz, 1H), 7.91 (d, J = 8.5 Hz, 1H), 7.85 -7.77 (m, 2H), 7.73 (d, J = 6.4 Hz, 1H),
	7.73 -7.70 (m, 8H), 7.56 (s, 4H), 5.34 -5.30 (m, 7H), 2.21 (q, J = 1.3 Hz, 3H), 1.80
	(q, J = 1.3 Hz, 3H), 1.51 (s, 3H), 1.40 (s, 3H), 1.32 (s, 3H), 1.06 (s, 1H
	N
	,BArF 24
	CF 3
		F NMR (282
	MHz, CDCl3): δ -62.4 ppm. HRMS (ESI, m/z) calcd. for C22H23F3N + : 358.1777. Found:
	358.18.

.21. [10c][BArF 24 ].

	5.310a (15 mg, 0.03 mmol) and [Ph3C][BArF24] (30 mg,
	N	0.03 mmol) in 10 mL CH2Cl2, isolated yield: 17% (6 mg).
	OH	Anal. calcd for C59H33BF24N2•1.1 CH2Cl2: C 54.27, H
	,BArF 24	2.67, N 2.11. Found: C 54.15, H 2.80, N 2.04. 1 H NMR
	Br (300 MHz, CDCl3) δ 8.52 (d, J = 5.4 Hz, 1H), 8.25 (d, J = 6.2 Hz, 1H), 8.01 -7.89 (m,
	2H), 7.89 -7.75 (m, 3H), 7.69 (d, J = 4.2 Hz, 8H), 7.67 -7.60 (m, 2H), 7.58 -7.50 (m,
	2H), 7.48 (d, J = 1.3 Hz, 4H), 7.47 -7.38 (m, 3H), 7.26 -7.17 (m, 1H), 6.83 (dd, J =
	5.4, 2.0 Hz, 1H), 5.75 (dd, J = 5.4, 2.7 Hz, 1H), 5.30 (s, 1H), 5.08 (d, J = 7.5 Hz, 1H),
	3.06 (dd, J = 15.9, 8.0 Hz, 1H), 2.80 (dd, J = 15.9, 6.7 Hz, 1H). 13 C NMR (126 MHz,
	CDCl3) δ 162.
	N
	OH
	,BArF 24
	CF 3
		F NMR (282 MHz, CDCl3): δ -62.8 ppm. HRMS (ESI, m/z) calcd.
	for C22H23F3NO + : 374.1726. Found: 374.1700.

Table 5 . 1 .

 51 The yields of 1a or d4-1a in 6 hours.

		Entry	1h	2h	3h	4h	5h	6h
		1	12.65	28.92	39.31	43.37	46.09	50.16
	1a	2	12.95	31.34	40.81	46.7	49.44	51.8
		average 12.8	30.13	40.06	45.035 47.765 50.98
		1	10.4	21.22	27.89	33.29	37.46	41.62
	d4-1a	2	9.99	18.55	25.42	28.54	30.68	32.82
		average 10.195 19.885 26.655 30.915 34.07	37.22

5.4.1.2. Intermolecular competitive reaction

[Cp*CoI2]2 (0.05 mmol) and LiNHAc (0.15 mmol) were mixed in 5 mL of distilled DCM.

2-phpyH (0.05 mmol) and 2-(d5.ph)pyD (0.05 mmol) were added to the suspension.

The reaction was stirred vigorously at 50°C during 17 hours in a sealed Schlenk vessel.

5.4.2.2. 5,6-diphenylbenzo[de]pyrido[3,2,1-ij]quinolin-4-ium tetrafluoroborate

	Yellow solid; 1 H NMR (500 MHz, DMSO-d6) δ 9.47 (d, J =
	7.9 Hz, 1H), 9.21 (dd, J = 6.6, 1.0 Hz, 1H), 8.83 (d, J = 7.8
	Hz, 1H), 8.77 (d, J = 9.2 Hz, 1H), 8.67 (d, J = 9.2 Hz, 1H),

5.4.2.3. 5,6-diphenyldibenzo[de,g]pyrido[3,2,1-ij]quinolin-4-ium tetrafluoroborate

	Yellow solid; 1 H NMR (500 MHz, DMSO-d6) δ 10.20
	(d, J = 7.6 Hz, 1H), 9.56 (d, J = 7.6 Hz, 1H), 9.25 (dt, J
	= 7.8, 1.7 Hz, 2H), 9.19 (d, J = 6.7 Hz, 1H), 8.57 -8.49
	(m, 2H), 8.15 -8.05 (m, 2H), 7.83 (d, J = 7.9 Hz, 1H),
	7.62 -7.49 (m, 5H), 7.46 -7.35 (m, 5H). 13C NMR (126 MHz, DMSO-d6) δ 138.72,

Table A . 5. Crystal data and structure refinement for 8a.

 A Largest diff. peak/hole / e Å -3 0.37/-0.29

	Identification code	8a
	Empirical formula	C22H22NF3CoI
	Formula weight	543.23
	Temperature/K	120(2)
	Crystal system	monoclinic
	Space group	P21/c
	a/Å	17.0641(6)
	b/Å	14.0385(5)
	c/Å	8.7326(3)
	α/°	90
	β/°	91.7390(10)
	γ/°	90
	Volume/Å 3	2090.97(13)
	Z	4
	ρcalcg/cm 3	1.726
	μ/mm -1	2.330
	F(000)	1072.0
	Crystal size/mm 3	0.220 × 0.140 × 0.120
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 4.776 to 55.814
	Index ranges	-22 ≤ h ≤ 22, -18 ≤ k ≤ 16, -11 ≤ l ≤ 11
	Reflections collected	71245
	Independent reflections	5006 [Rint = 0.0350, Rsigma = 0.0131]
	Data/restraints/parameters 5006/0/258
	Goodness-of-fit on F 2	1.093
	Final R indexes [I>=2σ (I)]	R1 = 0.0173, wR2 = 0.0372
	Final R indexes [all data]	R1 = 0.0206, wR2 = 0.0389

Table A . 6. Crystal data and structure refinement for 10a.

 A Largest diff. peak/hole / e Å -3 0.84/-0.55

	Identification code	10a
	Empirical formula	C16H13CoIN
	Formula weight	405.10
	Temperature/K	120(2)
	Crystal system	monoclinic
	Space group	P21/c
	a/Å	10.2517(3)
	b/Å	8.4219(3)
	c/Å	16.2038(5)
	α/°	90
	β/°	97.8910(10)
	γ/°	90
	Volume/Å 3	1385.77(8)
	Z	4
	ρcalcg/cm 3	1.942
	μ/mm -1	3.450
	F(000)	784.0
	Crystal size/mm 3	0.120 × 0.100 × 0.080
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 4.01 to 58.052
	Index ranges	-13 ≤ h ≤ 13, -11 ≤ k ≤ 11, -22 ≤ l ≤ 22
	Reflections collected	42371
	Independent reflections	3676 [Rint = 0.0371, Rsigma = 0.0164]
	Data/restraints/parameters 3676/0/172
	Goodness-of-fit on F 2	1.117
	Final R indexes [I>=2σ (I)]	R1 = 0.0214, wR2 = 0.0445
	Final R indexes [all data]	R1 = 0.0268, wR2 = 0.0468

Table A . 7. Crystal data and structure refinement for 1b.

 A Largest diff. peak/hole / e Å -3 1.47/-1.05

	Identification code	1b
	Empirical formula	C55H38BCoF24N2
	Formula weight	1252.61
	Temperature/K	173(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	12.5894(6)
	b/Å	13.1911(6)
	c/Å	17.0725(8)
	α/°	91.818(2)
	β/°	97.890(2)
	γ/°	107.1210(10)
	Volume/Å 3	2676.1(2)
	Z	2
	ρcalcg/cm 3	1.555
	μ/mm -1	0.445
	F(000)	1260.0
	Crystal size/mm 3	0.35 × 0.25 × 0.12
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 3.24 to 55.968
	Index ranges	-16 ≤ h ≤ 16, -17 ≤ k ≤ 17, -22 ≤ l ≤ 22
	Reflections collected	114918
	Independent reflections	12762 [Rint = 0.0643, Rsigma = 0.0532]
	Data/restraints/parameters	12762/0/751
	Goodness-of-fit on F 2	1.017
	Final R indexes [I>=2σ (I)]	R1 = 0.0938, wR2 = 0.1985
	Final R indexes [all data]	R1 = 0.1313, wR2 = 0.2194

Table A . 8. Crystal data and structure refinement for 3b.

 A Largest diff. peak/hole / e Å -3 2.17/-1.57

	Identification code	3b
	Empirical formula	C56H40BCoF24N2
	Formula weight	1266.64
	Temperature/K	120(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	12.5987(5)
	b/Å	13.3136(5)
	c/Å	17.2460(7)
	α/°	93.019(2)
	β/°	97.6630(10)
	γ/°	106.9780(10)
	Volume/Å 3	2729.12(19)
	Z	2
	ρcalcg/cm 3	1.541
	μ/mm -1	0.437
	F(000)	1276.0
	Crystal size/mm 3	0.200 × 0.150 × 0.100
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 3.858 to 55.86
	Index ranges	-16 ≤ h ≤ 16, -17 ≤ k ≤ 17, -22 ≤ l ≤ 22
	Reflections collected	139336
	Independent reflections	13075 [Rint = 0.0385, Rsigma = 0.0168]
	Data/restraints/parameters	13075/0/758
	Goodness-of-fit on F 2	1.040
	Final R indexes [I>=2σ (I)]	R1 = 0.0700, wR2 = 0.1824
	Final R indexes [all data]	R1 = 0.0768, wR2 = 0.1894

Table A . 9. Crystal data and structure refinement for 4b.

 A Largest diff. peak/hole / e Å -3 1.71/-1.95

	Identification code	4b
	Empirical formula	C61H51BCoF24N3
	Formula weight	1351.79
	Temperature/K	120(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	14.6865(7)
	b/Å	15.3384(8)
	c/Å	16.6795(8)
	α/°	99.496(2)
	β/°	98.116(2)
	γ/°	109.430(2)
	Volume/Å 3	3416.3(3)
	Z	2
	ρcalcg/cm 3	1.314
	μ/mm -1	0.354
	F(000)	1372.0
	Crystal size/mm 3	0.180 × 0.100 × 0.080
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 4.168 to 64.096
	Index ranges	-21 ≤ h ≤ 21, -22 ≤ k ≤ 22, -24 ≤ l ≤ 24
	Reflections collected	143751
	Independent reflections	23751 [Rint = 0.0473, Rsigma = 0.0363]
	Data/restraints/parameters 23751/0/777
	Goodness-of-fit on F 2	1.060
	Final R indexes [I>=2σ (I)]	R1 = 0.0823, wR2 = 0.2268
	Final R indexes [all data]	R1 = 0.1100, wR2 = 0.2521

Table A . 13. Crystal data and structure refinement for 2b.

 A Largest diff. peak/hole / e Å -3 1.51/-1.90

	Identification code	2b
	Empirical formula	C23H29IrN2O2
	Formula weight	557.68
	Temperature/K	120(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	10.9189(5)
	b/Å	12.9178(5)
	c/Å	16.1472(7)
	α/°	98.7820(10)
	β/°	107.051(2)
	γ/°	93.859(2)
	Volume/Å 3	2136.70(16)
	Z	4
	ρcalcg/cm 3	1.734
	μ/mm -1	6.269
	F(000)	1096.0
	Crystal size/mm 3	0.120 × 0.100 × 0.080
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 4.542 to 60.112
	Index ranges	-15 ≤ h ≤ 15, -18 ≤ k ≤ 15, -22 ≤ l ≤ 22
	Reflections collected	81688
	Independent reflections	12491 [Rint = 0.0345, Rsigma = 0.0220]
	Data/restraints/parameters 12491/0/543
	Goodness-of-fit on F 2	1.039
	Final R indexes [I>=2σ (I)]	R1 = 0.0197, wR2 = 0.0341
	Final R indexes [all data]	R1 = 0.0260, wR2 = 0.0364

Table A . 14. Crystal data and structure refinement for [1c][I3].

 A Largest diff. peak/hole / e Å -3 3.06/-2.25

	Identification code	[1c][I3]
	Empirical formula	C21H24I3N
	Formula weight	671.11
	Temperature/K	173(2)
	Crystal system	monoclinic
	Space group	P21/c
	a/Å	10.3746(4)
	b/Å	13.0748(6)
	c/Å	16.9157(7)
	α/°	90.00
	β/°	95.694(2)
	γ/°	90.00
	Volume/Å 3	2283.22(17)
	Z	4
	ρcalcg/cm 3	1.952
	μ/mm -1	4.111
	F(000)	1264.0
	Crystal size/mm 3	0.2 × 0.16 × 0.14
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 3.94 to 60.1
	Index ranges	-12 ≤ h ≤ 14, -18 ≤ k ≤ 18, -23 ≤ l ≤ 23
	Reflections collected	42452
	Independent reflections	6692 [Rint = 0.0374, Rsigma = 0.0231]
	Data/restraints/parameters 6692/0/231
	Goodness-of-fit on F 2	1.061
	Final R indexes [I>=2σ (I)]	R1 = 0.0435, wR2 = 0.0834
	Final R indexes [all data]	R1 = 0.0652, wR2 = 0.0938

Table A . 16. Crystal data and structure refinement for 2c.

 A Largest diff. peak/hole / e Å -3 1.29/-1.46

	Identification code	2c
	Empirical formula	C24H43ClIr2N2O5
	Formula weight	859.45
	Temperature/K	120(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	8.4469(4)
	b/Å	10.0791(4)
	c/Å	17.3569(8)
	α/°	93.5250(10)
	β/°	95.071(2)
	γ/°	111.9100(10)
	Volume/Å 3	1358.46(11)
	Z	2
	ρcalcg/cm 3	2.101
	μ/mm -1	9.920
	F(000)	824.0
	Crystal size/mm 3	0.250 × 0.200 × 0.120
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 4.378 to 64.142
	Index ranges	-12 ≤ h ≤ 12, -14 ≤ k ≤ 15, -25 ≤ l ≤ 25
	Reflections collected	100357
	Independent reflections	9439 [Rint = 0.0331, Rsigma = 0.0168]
	Data/restraints/parameters 9439/0/347
	Goodness-of-fit on F 2	1.118
	Final R indexes [I>=2σ (I)] R1 = 0.0150, wR2 = 0.0379
	Final R indexes [all data]	R1 = 0.0158, wR2 = 0.0384

Table A . 18. Crystal data and structure refinement for [1c][BArF24].

 A Largest diff. peak/hole / e Å -3 1.49/-1.38

	Identification code	[1c][BArF24]
	Empirical formula	C53H36BNF24
	Formula weight	1153.64
	Temperature/K	120(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	12.1615(5)
	b/Å	12.7457(5)
	c/Å	17.5248(7)
	α/°	78.947(2)
	β/°	70.2900(10)
	γ/°	72.4030(10)
	Volume/Å 3	2425.42(17)
	Z	2
	ρcalcg/cm 3	1.580
	μ/mm -1	0.156
	F(000)	1164.0
	Crystal size/mm 3	0.300 × 0.200 × 0.150
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 4.19 to 55.854
	Index ranges	-16 ≤ h ≤ 15, -16 ≤ k ≤ 16, -23 ≤ l ≤ 23
	Reflections collected	171592
	Independent reflections	11602 [Rint = 0.0286, Rsigma = 0.0123]
	Data/restraints/parameters	11602/0/723
	Goodness-of-fit on F 2	1.034
	Final R indexes [I>=2σ (I)]	R1 = 0.0670, wR2 = 0.1722
	Final R indexes [all data]	R1 = 0.0714, wR2 = 0.1761

Table A . 19. Crystal data and structure refinement for [7c][BArF24].

 A

	Identification code	[7c][BArF24]
	Empirical formula	C53H35NBF24Br
	Formula weight	1232.54
	Temperature/K	120(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	12.5126(7)
	b/Å	12.9558(9)
	c/Å	17.5115(12)
	α/°	77.264(2)
	β/°	69.227(2)
	γ/°	69.990(2)
	Volume/Å

Table A . 20. Crystal data and structure refinement for [8c][BArF24].

 A

	Identification code	[8c][BArF24]
	Empirical formula	C54H35NBF27
	Formula weight	1221.64
	Temperature/K	120(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	12.8233(6)
	b/Å	12.8600(6)
	c/Å	17.6228(8)
	α/°	77.166(2)
	β/°	69.467(2)
	γ/°	69.564(2)
	Volume/Å 3	2533.7(2)
	Z	2
	ρcalcg/cm 3	1.601
	μ/mm -1	0.163
	F(000)	1228.0
	Crystal size/mm 3	0.220 × 0.180 × 0.120
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 3.978 to 58.12
	Index ranges	-17 ≤ h ≤ 17, -17 ≤ k ≤ 17, -24 ≤ l ≤ 24
	Reflections collected	130182
	Independent reflections	13524 [Rint = 0.0436, Rsigma = 0.0218]
	Data/restraints/parameters	13524/0/777
	Goodness-of-fit on F 2

Table A . 22. Crystal data and structure refinement for [8d][BArF24].

 A Largest diff. peak/hole / e Å -3 0.77/-0.75

	Identification code	[8d][BArF24]
	Empirical formula	C54H35NBF27O
	Formula weight	1237.64
	Temperature/K	120(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	12.7809(5)
	b/Å	12.9782(6)
	c/Å	17.3787(8)
	α/°	76.563(2)
	β/°	70.971(2)
	γ/°	70.330(2)
	Volume/Å 3	2541.6(2)
	Z	2
	ρcalcg/cm 3	1.617
	μ/mm -1	0.165
	F(000)	1244.0
	Crystal size/mm 3	0.200 × 0.140 × 0.120
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 3.908 to 58.12
	Index ranges	-17 ≤ h ≤ 17, -17 ≤ k ≤ 17, -23 ≤ l ≤ 23
	Reflections collected	192638
	Independent reflections	13577 [Rint = 0.0340, Rsigma = 0.0140]
	Data/restraints/parameters	13577/0/784
	Goodness-of-fit on F 2	1.047
	Final R indexes [I>=2σ (I)]	R1 = 0.0490, wR2 = 0.1194
	Final R indexes [all data]	R1 = 0.0560, wR2 = 0.1258

Table A . 23. Crystal data and structure refinement for [10c][BArF24].

 A Largest diff. peak/hole / e Å -3 1.17/-1.24

	Identification code	[10c][BArF24]
	Empirical formula	C119H68B2F48N4Cl2
	Formula weight	2558.29
	Temperature/K	120(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	12.6465(4)
	b/Å	14.4270(4)
	c/Å	16.3560(5)
	α/°	79.6400(10)
	β/°	70.3980(10)
	γ/°	77.4660(10)
	Volume/Å 3	2725.58(14)
	Z	1
	ρcalcg/cm 3	1.559
	μ/mm -1	0.196
	F(000)	1286.0
	Crystal size/mm 3	0.120 × 0.100 × 0.090
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 4.084 to 55.834
	Index ranges	-16 ≤ h ≤ 16, -18 ≤ k ≤ 18, -21 ≤ l ≤ 21
	Reflections collected	57228
	Independent reflections	12991 [Rint = 0.0307, Rsigma = 0.0259]
	Data/restraints/parameters	12991/0/781
	Goodness-of-fit on F 2	1.022
	Final R indexes [I>=2σ (I)]	R1 = 0.0711, wR2 = 0.1943
	Final R indexes [all data]	R1 = 0.0811, wR2 = 0.2054

X-ray structure of [5a'][BArF 24 ] Table A. 24. Crystal data and structure refinement for [5a'][BArF24].

  Largest diff. peak/hole / e Å -3 0.74/-0.62

	Identification code	[5a'][BArF24]
	Empirical formula	C45H22BNF24
	Formula weight	1043.44
	Temperature/K	120(2)
	Crystal system	monoclinic
	Space group	C2/c
	a/Å	38.276(2)
	b/Å	12.9570(8)
	c/Å	17.4202(11)
	α/°	90
	β/°	105.898(2)
	γ/°	90
	Volume/Å 3	8309.0(9)
	Z	8
	ρcalcg/cm 3	1.668
	μ/mm -1	0.173
	F(000)	4160.0
	Crystal size/mm 3	0.15 × 0.12 × 0.1
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 3.942 to 55.858
	Index ranges	-50 ≤ h ≤ 48, -17 ≤ k ≤ 17, -22 ≤ l ≤ 22
	Reflections collected	111016
	Independent reflections	9950 [Rint = 0.0641, Rsigma = 0.0279]
	Data/restraints/parameters	9950/0/640
	Goodness-of-fit on F 2	1.021
	Final R indexes [I>=2σ (I)]	R1 = 0.0523, wR2 = 0.1191
	Final R indexes [all data]	R1 = 0.0772, wR2 = 0.1353

Table A . 25. Crystal data and structure refinement for [1e][I3].

 A Largest diff. peak/hole / e Å -3 1.31/-1.53

	Identification code	[1e][I3]
	Empirical formula	C22H36Co2I3NO3
	Formula weight	861.08
	Temperature/K	120(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	8.5835(6)
	b/Å	9.9507(7)
	c/Å	17.0139(12)
	α/°	93.269(3)
	β/°	100.004(3)
	γ/°	93.577(3)
	Volume/Å 3	1424.90(17)
	Z	2
	ρcalcg/cm 3	2.007
	μ/mm -1	4.436
	F(000)	824.0
	Crystal size/mm 3	0.350 × 0.150 × 0.120
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 4.112 to 60.254
	Index ranges	-12 ≤ h ≤ 12, -14 ≤ k ≤ 14, -23 ≤ l ≤ 23
	Reflections collected	81284
	Independent reflections	8340 [Rint = 0.0382, Rsigma = 0.0195]
	Data/restraints/parameters 8340/0/299
	Goodness-of-fit on F 2	1.073
	Final R indexes [I>=2σ (I)]	R1 = 0.0259, wR2 = 0.0526
	Final R indexes [all data]	R1 = 0.0338, wR2 = 0.0567

Table A . 26. Crystal data and structure refinement for [1e'][I3].

 A

	Identification code	[1e'][I3]
	Empirical formula	C22H35NO2Co2I4
	Formula weight	970.97
	Temperature/K	120(2)
	Crystal system	triclinic
	Space group	P-1
	a/Å	7.5349(4)
	b/Å	12.6023(7)
	c/Å	15.8053(9)
	α/°	100.869(2)
	β/°	92.059(2)
	γ/°	90.909(2)
	Volume/Å 3	1472.56(14)
	Z	2
	ρcalcg/cm 3	2.190
	μ/mm -1	5.338
	F(000)	912.0
	Crystal size/mm 3	0.2 × 0.18 × 0.15
	Radiation	MoKα (λ = 0.71073)
	2Θ range for data collection/° 3.802 to 64.198
	Index ranges	-11 ≤ h ≤ 11, -18 ≤ k ≤ 18, -23 ≤ l ≤ 23
	Reflections collected	132549
	Independent reflections	10273 [Rint = 0.0298, Rsigma = 0.0129]
	Data/restraints/parameters 10273/0/295
	Goodness-of-fit on F 2

  13 C NMR spectrum (126 MHz, CDCl3) of 1a

	182.23	166.83	160.44	153.72	150.42	135.50	124.89	123.64	117.38	113.79	108.03	93.01		77.41 CDCl3	77.16 CDCl3	77.16 CDCl3	76.91 CDCl3			40.73	34.87	30.76	30.64	10.48	1.17
			C (s)		E (s)		H (s)		J (s)											N (s)
			160.44		150.42		123.64	113.79											34.87
	A (s)	B (s)		D (s)	F (s)	G (s)	I (s)		K (s)	L (s)							M (s)		O (s)	Q (s)	R (s)
	182.23	166.83		153.72	135.50	124.89	117.38	108.03	93.01							40.73	30.76	10.48	1.17
																						P (s)
																					30.64
	180	170	160		150	140	130	120	110	100	90	80			70	60	50	40		30	20	10	0	-10
													f1 (ppm)

  of 3b

	p6-49-200113.11.fid 177.99	167.99	162.41	162.01	161.62	161.22	153.59	145.12	138.96	137.11	136.38	134.93	129.73	129.64	129.19	129.17	128.94	128.40	127.92	125.76	123.59	123.29	122.03	121.42	117.68	117.63	96.94		77.41 CDCl3	77.16 CDCl3	77.16 CDCl3	76.91 CDCl3	53.58		23.63	9.22	4.02
		N		Cp*
		Co
			NCMe
																		Q (s)
								,BArF 24									125.76
		3b									K (s) 136.38	N (s) 128.94
					F (dd)			I (s)					L (d)																			U (s)
					161.82			138.96			129.68																		4.02
	D (s)	E (s)					G (s)	H (s)			A (s)			P (s)				B (d)			R (s)								T (s)	C (s)
	177.99	167.99				153.59	145.12		134.93	127.92				117.65			96.94								23.63	9.22
											J (s)			M (d)
											137.11		129.18
																O (s)
																128.40
	180	170				160	150		140					130				120				110	100	90	80			70	60	50	40	30	20	10	0
																													f1 (ppm)

  of 4b

	p6-28-191105-corrige.12.fid 161.61 162.01 162.41 163.43 167.22 176.76	161.22	151.34	151.31	134.92	134.74	129.40	129.15	128.91	128.66	128.28	127.93	125.76	125.04	123.59	121.43	120.41	118.76	117.62	114.84	109.14	96.08		77.41 CDCl3	77.16 CDCl3	77.16 CDCl3	76.91 CDCl3			40.41	35.23	30.36	9.36	4.14
		N	Cp*
		Co
			NCMe
														T (s)
													123.59
		N	G (s)	,BArF 24					P (s)
		4b	161.22							128.28
			E (s)							N (s)					X (s)
			162.01						128.91				117.62
		C (s)		I (s)	K (s)				R (s)		W (s)													C1 (s)	F1 (s)
		163.43		151.31	134.74		125.76		118.76												35.23	4.14
	A (s)	B (s)			H (s)	J (s)		Q (s)			V (s)					Z (s)	A1 (s)								B1 (s)	D1 (s)	E1 (s)
	176.76	167.22			151.34	134.92		127.93		120.41				109.14	96.08								40.41	30.36	9.36
			D (s)								L (s)			U (s)
		162.41						129.40		121.43
			F (s)							O (s)							Y (s)
			161.61						128.66						114.84
													S (s)
													125.04
	180	170	160		150	140			130					120				110	100	90	80			70	60	50	40	30	20	10	0
																									f1 (ppm)

Table A .

 A 31. Energies of optimized geometries at the ZORA-PBE-D4(EEQ)/all electron TZP/COSMO(CH2Cl2) level

	I(1%>=->#/,K ! '	='	>@=HEABH'	>?GBCAGF'	>?GDHACE'
	M/OM,3MQ"M,7'	='	>?@BADH'	>?F@ACB'	>?@DA=='
	M/OM,3MQCM,7'	E'	>?HBAFC'	>?D?AG?'	>?HDA@D'
	I=5SOK ! '		='	>?DGFACG'	>?EF?A@@'	>?EG=AG='
	I=5SOK ! '		E'	>?DHDAEH''	>?EE@AD='	>?EHDA=E''
	O1>=5'	!"#$%&'	!()*'&+,$)(,)-)$"' ./*0'%*%12"'34-5,6&/,7' 8*$95,("'34-5,6&/,7' :);;#'<1%%'%*%12"'34-5,6&/,7' =' >?@@FAEB' >?DCDAEB' >?D@FADB'
	O1>=5'		E'	>?@EBACH'	>?FHCAEF'	>?DEFADB'
	=5'		='	>?@?=ABC'	>?D==ACE'	>?D?=AB@'
	IO1>=5JK ! '		C'	>???BA=C'	>?F=BA@@'	>?F?BA=?'
	M/O'		='	>==FAHG'	>==CA=F'	>=EBAEC'
	M/O'		E'	>=F?A?G'	>=FEAG?'	>=?CACC'
	M/O'		D'	>=C?AFF'	>=CEA@E'	>=FCA=?'
	I=-K ! '		='	>?D=EADD'	>?CDHA@B'	>?EBCABD'

NCMe, NaBArF 24 room temp.

Annexes I

Remerciements

=5' E' >?@FBACF' >?FG=ABH' >?DFCAGF' I=5JK ! ' C' >??FHA=@' >?EGHA?H' >?FF?AGB' I=5JK ! ' F' >??CCAEG'' >?E@EAB@''' '>?FCFAG?'' I=5JK ! ' ?' >?DHGAHH'' >?EF=AF?' >?EGDA=D'

I=5JJK "! ' =' >?FGHAE@' >?CDBA=?' >?CG@AD='

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

O*$MQ' E' >?@C=A?=' >?F?EA?C' >?D=EAEE' I(1%>=-K ! ' E' >?@=HA@B' >?F?BAF@' >?DB@A@G' I(1%>=-K ! ' =' >?@=CAD=' >?FDEAG=' >?DBBA@D' IL!=MJK !# 3=J5NO*$MJ7' C' >??CHADB' >?E@GA=B' >?FC@A@B' IL!=PJK !# 3=J5NO*$PJ7' C' >??BDA@@' >?ED?ADD' >?FBDA=G' IL!=MPJK !# 3=J5N(1%>=-J7' C' >?DGHADD' >?EFGADB' >?EGHA@B' IO*$MJK ! ' C' >??EDADD' >?EHDA=C' >?FEFA?G' I(1%>=-JK ! ' C' >??=@AHH' >?E?@A=?' >?F=FADC' I(1%>=->#/,K ! ' E' >@CBEA@B' >?GCFAEB' >?GHBA=H'

My study at the LCSOM (Laboratoire de

Theoretical material for chapter 3

Scheme A. 1. Theoretically considered structures and pathways for the formation of [1c] + from 1a. (black arrows) considered pathways, (blue arrows) proposed pathways, (gray arrow) pathways not explored in this study.

Research objectives of this thesis

Despite the rapid development of approaches for the cobalt-catalyzed C-H bond functionalization, the attention seemed to be directed to the application of cobaltcatalysts in various reactions, e.g., the range of reactions, catalyst activity, selectivity and reaction efficiency, as in the various examples mentioned previously. One of most important stages in transition metal-catalyzed C-H activation is constantly overlooked.

Therefore, one of the main objectives of this thesis was to get a better understanding of the mechanism of the cobalt-base catalytic system and the role of noncovalent interactions. On the other hand, considering the huge potential application of cyclometalated Cp*Co(III)-complexes, as well as the uncertainty remaining on the mechanistic details, a thorough study of this reactivity by combined experimental and theoretical approaches was systematically undertaken. General conditions: under argon atmosphere, 1a (0.1 mmol, 1 eq), [Ph3C][BArF24] (0.1 mmol, 1 eq) or AgPF6 (0.2 mmol, 2 eq), DCM (5 mL), 25°C, 16 h. a 1 H NMR yield in the presence of 1,3,5-trimethoxybenzene as an internal standard. b isolated yield.

Compound [1c][BArF24] was isolated pure by repeated recrystallization with a major loss of material due to the difficulty that arose in the separation of this salt from other polar Co-containing residues (isolated yield: 29 %). The structure of the cation of [1c][BArF24] obtained by X-ray diffraction analysis is in all aspects identical (Figure 3. between the ligands and the metal center. This analysis suggests that the condensation of the phpy ligand with the Cp* moiety could be somewhat encoded in the favorable IBSI and NCI signatures observed in 1a and its oxidized Co(IV) form

The general qualitative behavior of the Δg inter interaction score and of the IBSI remains the same when replacing the iodo ligand by a chloro one in the Co complex (Table 3.5).

The main difference lies in the Δg inter between phpy and the halido ligand which is lower in the chloro analogue than in the iodo at the +III formal oxidation state, while it is higher at the +IV formal oxidation state.

When comparing 1a to [Cp*Co(SCF3)(phpy)], 140,333 the general quantitative behavior of the Δg inter interaction score between Cp* and phpy, and of the IBSI remain the same (Table 3.5). However, the Δg inter interaction score between phpy and the X ligand is higher when X= SCF3 than when X= I : while it decreased in the latter case, it increases in the former, seemingly explaining the possibility of the C-S bond formation. 140 . More important is the fact the the Δg inter for the Cp*-phpy interaction in almost identical in Overall, this unexpected result draws some light on the widely accepted catalytic systems, thus questioning its robustness.

5.1.7.

Computational details for chapter 3

DFD-D computations

Geometry optimization of the reactants, intermediates, transition states, and products were performed using the SCM-ADF2019.01 package 371 , at the Density Functional

Theory (DFT) level in the gas phase. The Perdew-Burke-Ernzerhof (PBE) 372 functional augmented with Grimme's dispersion corrections with the electronegativity equilibrium model (DFT-D4(EEQ)) 373 was used in all geometry optimizations. All geometry computations were carried out using scalar relativistic effects with ad hoc all-electron (abbr. ae) single polarization functions triple-ζ Slater-type basis set (TZP) [374][375][376] .

Solvation was treated by the Conductor-like Screening Model (COSMO) [377][378][379] procedure assuming CH2Cl2 (ε=8.9, r=2.94 Å) as a solvent. Geometry optimization by energy gradient minimization were carried out in all cases with integration grid accuracy "Normal" 380 . All transition states were found using the Nudged Elastic Band (NEB) 381 procedure and submitted to the Intrinsic Reaction Coordinate (IRC) 382,383 procedure to verify the connection to their reactive complexes and products.

Vibrational modes were analytically computed to verify that the optimized geometries were related to energy minima or to transition states. For the monoatomic systems that were considered (H -and I -), as the enthalpy and entropy corrections to the energy are usually computed from the vibrational energies, these contributions were neglected and the Gibbs free energy was approximated as the bond energy.

IBSI computations

Intrinsic Bond Strength Index (IBSI) of the key atom pairs were computed using the IGMPLOT program At the end of the reaction, the solution was filtrated through Celite and the solvent was removed under reduced pressure. The resulting solid residue was washed with distilled pentane to remove the soluble components of the mixture to afford a solid composed of a mixture of the desired cobaltacycles 1a and d4-1a in proportion estimated by 1 H-coupled 13 C NMR. Two signals typical of 1a and d4-1a were readily discriminated by their isotope shifts. The KIE was determined by comparing the integrations of 13 and LiNHAc (30 mol %) were added to a Schlenk vessel. Then, the tube was moved to an Ar-filled glove box and 2-arylpyridines (0.10 mmol), AgBF4 (0.20 mmol) were added to the load of the vessel. DCE (2 mL) was added to the solid mixture, the Schlenk vessel was sealed and the suspension was stirred at 130 °C for 24 h. The reaction vessel was hence cooled to room temperature and the suspension diluted with DCM (10 mL). The mixture was filtered through a Celite pad and the Celite pad was washed with DCM (30 mL). The filtrate was concentrated and purified by silica gel column chromatography using DCM/MeOH (95:5) as eluent to deliver the desired annulation product.

General conclusions and perspectives

In this thesis, we have synthesized and characterized a serie of cobaltacycles where "redox" co-catalysts are commonly used on a trial-and-error basis. 333,397 Single crystal X-ray diffraction X-ray structure of 1a --------------------------------------------------- ---------------------------------------------------Bond Energy:

X-ray structure of 4a

X-ray structure of 5a

X-ray structure of 7a

X-ray structure of 5b

X-ray structure of 1b'

X-ray structure of 1f

TS-ag

- ---------------------------------------------------Bond Energy:

- ---------------------------------------------------Bond Energy:

TS-CH

- ---------------------------------------------------Bond Energy:

Co-NHAc anag

- ---------------------------------------------------Bond Energy:

TS-ag

- -------------------------------------------------- ---------------------------------------------------Bond Energy:

TS-CH

- ---------------------------------------------------Bond Energy:

Ir-OAc anag

- -------------------------------------------------- ---------------------------------------------------Bond Energy:

TS-ag

- ---------------------------------------------------Bond Energy:

TS-CH

- ---------------------------------------------------Bond Energy:

- ---------------------------------------------------Bond Energy:

Ir-NHAc anag

TS-ag

- ------------------------- ---------------------------------------------------Bond Energy:

- ---------------------------------------------------Bond Energy:

- --------------------------------------------------- ---------------------------------------------------Bond Energy:

LED analysis of the DLPNO-CCS(D)T computations

- EA-pre-TS (2+)

Summary of energy terms hartree eV kcal/mol kJ/mol ----------------------------------------------------Bond Energy:

- --------------------------------------------------- EA-MCH (2+)

Summary of energy terms hartree eV kcal/mol kJ/mol ----------------------------------------------------Bond Energy:

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Résumé en anglais

The Key word : Cobaltacycles, acetamidate-assisted CMD mechanism, homogeneous catalysis, collapse, oxidative, cationic alkaloids.