Coralie Laborde

Muh-Mei Wei

Arie Van Der Lee

Éric Deydier

Jean-Claude Daran

Jean-Noël Null Volle

Rinaldo Poli

Jean-Luc Pirat

Eric Manoury

David Virieux

Eric Deydier

Jean-Noël Volle

Double [3 + 2]-dimerisation cascade synthesis of bis(triazolyl)bisphosphanes, a new scaffold for bidentate bisphosphanes

  L'archive ouverte pluridisciplinaire

Introduction

The development of innovative, efficient, cost-effective and environmental-friendly processes is essential for the manufacture of new chemical entities. 1 For this purpose, the processes involving the use of catalysis have clear advantages over those requiring stoichiometric amounts of reagents. 2 That is why catalysis has become one of the most practical methodologies to build organic molecules, including in enantioselective ways. Most impressive developments have led over the past two decades to numerous products of interest by connecting various building blocks using catalysed hydrogenation or coupling reactions (Heck, Kumada, Negishi, Sonogashira, Stille, Suzuki or Buchwald-Hartwig, etc). In this context, phosphane-based catalysts play an outstanding role because significant achievements have been made in achiral and chiral transition metal catalysed reactions or more recently in phosphane nucleophilic organocatalysed organic transformations. 3 The design of phosphane ligands has played a key role in the evolution of catalysis. [START_REF] Hartwig | Organotransition Metal Chemistry, from Bonding to Catalysis[END_REF] Fine tuning of the catalytic activity by modification of the electronic/steric properties of the ligand systems is far from trivial mainly because of the difficulty and cumbersome procedures for structural modification of the ligand scaffolds. Therefore, in spite of the large number of developed catalytic processes, much remains to be done in this field in order to develop applicable and highly productive catalysts. Bidentate phosphanes are currently used for their intrinsic chelation properties. Numerous bidentate bisphosphanes are C2-symmetric and DIOP [START_REF] Dang | [END_REF] or BINAP 6 are probably the most known archetypical ligands of this category (fig. 1). Phosphanes for which the phosphino group is directly connected to a heterocyclic ring can take advantage of both electronic and steric modulations induced by the presence of an extra heteroelement. 7 The dihedral angle in biaryl bisphosphanes has been shown to affect the catalytic properties. 8 The presence of heteroelements in this biaryl backbone, such as for instance oxygen atoms in SEGPHOS or SYNPHOS, induces stereoelectronic repulsions and consequently narrower dihedral angles. 9 In this context, still very few phosphanes involves a fivemembered ring as structural subunit. Then axially chiral bisphosphanes derived from 1,1'-naphthyl-benzimidazole core (BIMINAP 1 and BIMIONAP 2) were used as ligands. 10 Another relevant example, the 2,2'-bis(diphenylphosphanyl)-1,1'-bibenzimidazole (BIMIP 3) ligand is an electron-poor ligand derived from fivemembered bis-heteroaromatic diphosphanes which possess a hindered rotation on the N-N linkage. 11 By contrast, bis(thyenyl)bisphosphanes (BITIOP 4) is considered as electron rich bisphosphane.

Zhang

and coworkers introduced ClickPhos 5 (i.e. triazolylphosphanes) as potent heterocyclic phosphane ligands. 13 ClickPhos 5 were synthesized from a two-step procedure using phenyl azide and various aryl acetylenes. They revealed interesting ligand properties, particularly in Suzuki-Miyaura coupling reactions or in amination reactions of aryl halides. 14 In parallel, extensions of their synthesis and luminescence properties were studied by Bräse and coworkers. 15

Results and discussion

By contrast, the bis(triazole) backbone is an unprecedented scaffold for the development of new bisphosphane based ligands. We would like to report herein a new class of heterobisphosphanes. Their synthesis is straightforward by a tuneable and convergent methodology which involves the creation of 5 bonds in one chemical step from simple precursors available in large scale using a literature methodology developed with simple substrates. 16 This reaction was first observed by Sharpless in his early work on click chemistry and was considered at that time as an unwanted side process. 17 In order to avoid a possible Staudinger reaction, we decided to focus on the combination of diphenylethynylphosphane oxide 6 rather than the free phosphane with alkyl-or arylazides in a tandem coppermediated Huisgen reaction -oxidative coupling, forming bis(triazolylphosphane) oxides 8 (table 1). Diphenylethynylphosphane oxide 6 was synthesized in two steps from the reaction of chlorodiphenylphosphane and ethynylmagnesium bromide followed by oxidation of the resulting phosphane with hydrogen peroxide in 78% overall yield. 18 The conditions of the tandem [3+2] cyclisation/dimerization were optimized with diphenylethynylphosphane oxide 6 and benzylazide 7.1 (table 1, R = Bn). Representative assays of this optimization are listed in Table 1. The solvent appeared to have a deep effect on the formation of the desired product. When using a mixture of DMF and water (entries 1-3), only the 1,4-triazole 10 was formed whatever the carbonate base. THF/water (entries 4-6) gave better results, but the best solvent mixture was acetonitrile/water (entries 7-9). We also explored the effect of the copper catalyst nature. CuBr alone worked as well as the Cu 0 /CuSO4 mixture, even in submolar quantities (entry 8). However, the best results were obtained with 1 equivalent of CuBr (entry 9). Having these optimized conditions in hand, we then changed the nature of the R group linked to the azide reagents (Table 2). The best yields were obtained for the benzyl and n-butyl derivatives 8.1 and 8.2 with respectively 49% and 42%. The reaction tolerated the presence of functional groups such as esters or methylether functions but failed when the reactions were carried out with ketoazides (products 8.8 and 8.9) giving mainly the monotriazole 10 along with some degradation. Compounds 8.1 and 8.3 were crystallized in a form suitable for singlecrystal X-ray diffraction experiments, which confirmed the nature and the positions of the R group on the triazole ring (Fig. 2). The reduction of the phosphane oxides 8.1-8.3 was accomplished by the classical reaction with trichlorosilane in the presence of triethylamine (Scheme 1). 19 Under such conditions the resulting bisphosphanes 11 were isolated in almost quantitative yields. The ability of the new triazolylphosphanes to form complexes with different transition metals was also studied (scheme 2). In all cases, ligands 11 bind in the κ 2 -P,P' mode without any involvement of the triazole nitrogen atoms. The copper complex 15 was prepared upon reaction of stoichiometric amounts of 11.1 and 1,10-phenanthroline with [Cu(CH3CN)4]BF4 in dichloromethane. Similarly, the Pd II complexes 12.1-12.3 and 13 were obtained by coordination of ligands 11.1-11.3 to palladium dichloride or bis(acetonitrile) dichloropalladium(II). Platinum complex 14 was also synthesized from 11.1 and bis(acetonitrile)dichloroplatinum(II) and its structure was confirmed by X-ray diffraction (see Supporting Information). Finally, the addition of 11.1 to [IrCl(COD)]2 afforded either complex [IrCl(COD)(11.1)] 16 or the [Ir(COD)(11.1)] + [IrCl2(COD)] -salt 17 when using either a 1:1 or a 2:1 Ir/ligand ratio. The 5-coordinate geometry of 16 was confirmed by an X-ray diffraction study (Fig. 3); it is similar to that of other [IrCl(COD)L2] complexes. 20 As expected the Pd II -complex 12.1 showed a narrower dihedral angle of 48.4° compared to the BINAP-PdCl2 complex (71.5°) 21 , Synphos (73.6°) or difluorphos (73.0°) 9 and was a direct consequence of the 5-membered ring backbone rather than the 6-one.

The iridium complex 16 was tested as a precatalyst in the hydrogenation of N-(1-phenylethylidene)-aniline (see table 3). 22 Full conversion was achieved at RT under 30 bar hydrogen after 2 h with only 1% of complex 16. The in situ made precatalyst ( 11/[Ir(COD)Cl]2 = 1) was also effective, although slightly less than the complex 16 (table 3, entries 2-5).

Conclusions

In summary, the copper mediated [3+2]-cycloaddition/dimerization of diphenylethynylphosphane oxide with various alkyl azides readily allowed the highly convergent formation of bis(triazolylphosphane) oxides in a one-pot useful process. Reduction into bisphosphanes is very efficient, and coordination of the latter to various transition metals was demonstrated, introducing a new family of C2-symmetric bisphosphanes with a quite rare NCP backbone. Preliminary catalytic studies in imine hydrogenation have shown good catalytic activities with an iridium complex. The determination of configurational stability and the unusual heteroatom backbone could offer numerous perspectives for catalytic applications. This work was supported by Grants from the Ministère de l'Enseignement Supérieur et de la Recherche, the Centre National de la Recherche Scientifique (CNRS), the "Midi-Pyrénées" region, and the Institut Universitaire de France.

Experimental

General

All reactions were carried out under an argon or nitrogen atmosphere using standard Schlenk techniques otherwise stated. Solvents were carefully dried by conventional or were purified with an MBRAUN Solvent Purification System. 1 H, 13 C and 31 P NMR spectra were recorded with a Bruker Avance 500 FT-NMR or a bruker Avance 400 spectrometer. The resonances were calibrated relative to the residual solvent peaks and are reported with positive values downfield from TMS. NMR multiplicities are abbreviated as follows: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad signal. Chemical shifts (δ) and coupling constants (J) were expressed in ppm and Hz, respectively. For all characterized compounds, the peak assignments in the 1 H and 13 C NMR spectra were based on COSY, HSQC and HMBC 2D experiments. HRMS were obtained from dichloromethane solutions with a Xevo G2 Q TOF spectrometer by the electrospray method or with a LC-TOF spectrometer (Micromass).

Synthesis of bistriazolyl phosphane oxides

GENERAL PROCEDURE

To a mixture of bistriazole (1eq) and triethylamine (12 eq) in anhydrous toluene (0.15 mol.ml -1 ) was added dropwise trichlorosilane (10 eq) at room temperature under a nitrogen atmosphere. The mixture was stirred at reflux for 12 h. After complete reduction, observed by 31 P RMN, the reaction mixture was quenched with 2M NaOH aq and diluted with dichloromethane and water. The organic layer was separated, washed with water and dried over Na2SO4. After concentration under vacuum, the diphosphane was obtained.

4,4'-bis(diphenylphosphino)-

. The compound was isolated as a white solid after precipitation with diethylether and pentane; Yield: 98%;

HYDROGENATION OF N-(1-PHENYLETHYLIDENE)-ANILINE WITH COMPLEX (16

). The catalyst (6.4 mol: 6.5 mg of complex 16 or 4.4 mg of ligand 11b and 2.2 mg of [Ir(COD)Cl]2), N-(1phenylethylidene)-aniline (0.64 mmol, 125 mg) and I2 (19.2 mol, 4.9 mg) were placed in a vial which was placed into an autoclave. The autoclave was pressurized with H2 (30 bar) and the mixture was then stirred at room temperature. After the indicated time, the autoclave was vented and the recovered mixture was filtered through a short silica gel column before being analysed by GC.

Crystallographic studies

A single crystal of each compound was mounted under inert perfluoropolyether at the tip of a cryoloop and cooled in the cryostream of either an Oxford-Diffraction XCALIBUR SAPPHIRE-I CCD diffractometer or an Agilent Technologies GEMINI EOS CCD diffractometer. Data were collected using the monochromatic MoKa radiation (l= 0.71073). The structures were solved by direct methods (SIR97) 23 and refined by leastsquares procedures on F2 using SHELXL-97. [START_REF] Burnett | ORTEPIII, Report ORNL-6895[END_REF] All H atoms attached to carbon were introduced in idealised positions and treated as riding on their parent atoms in the calculations. The drawing of the molecules was realised with ORTEP3. [START_REF] Burnett | ORTEPIII, Report ORNL-6895[END_REF] CCDC reference numbers are 1031965-1031970.

Notes and references

12

 12

Fig. 1

 1 Fig. 1 Representative biaryl bisphosphanes 1-4 and ClickPhos 5.

Fig. 2 3 .

 23 Fig. 2 Views of the molecular geometries of compounds 8.1 and 8.3. The thermal ellipsoids are scaled to a 50% probability level.

Scheme 2 .

 2 Scheme 2. Synthesis of bis(triazolylphosphane) complexes 12-17.

Fig. 3 .

 3 Fig. 3. ORTEP view of the molecular geometry of 16. The thermal ellipsoids are scaled to a 50% probability level and the hydrogen atoms are omitted for clarity.

Table 1 Synthesis of bis(triazolylphosphane) dioxides 8. Entry Base 1 Eq. R-N3 2 Cosolvent 3 Copper catalysts 4 Product distribution 8/9/10 [%]

 1

	1	Na2CO3	1	DMF	Cu/CuSO4	0/0/100
	2	K2CO3	1	DMF	Cu/CuSO4	0/0/100
	3	Cs2CO3	1	DMF	Cu/CuSO4	0/0/100
	4	Cs2CO3	1	THF	Cu/CuSO4	16/74/10
	5	Cs2CO3	1	THF	Cu/CuSO4	10/71/19
	6	Cs2CO3	5	THF	CuBr (1 eq)	61/35/4
	7	Na2CO3	1	ACN	Cu/CuSO4	65/8/30
	8	Cs2CO3	5	ACN	CuBr (0.3 eq)	47/44/8
	9	Cs2CO3	5	ACN	CuBr (1 eq)	80/11/9
	1) 2 eq of base were used 2) R = benzyl. 3) 50/50 mixture of the indicated
	solvent with water. 4) 1eq / 0.3 eq for the Cu/CuSO4 mixtures.

Table 2

 2 Synthesis of bis(triazolylphosphane) dioxides

8.1-8.7

		R	Yield 1		R	Yield
	8.1	Bn	49	8.6	CH2CO2Me	20
	8.2	n-Bu	42	8.7	CH2OBn	12
	8.3	i-Bu	23	8.8	CH2C(O)Me	-
	8.4	c-Hex	6	8.9	CH2C(O)Ph	-
	8.5 CH2CO2Bn	29
	1) Isolated yield

.1- 8.3 to bisphosphanes 11.1-11.3.

	Scheme 1. Reduction of the bis(triazolylphosphane) oxides 8

Table 3

 3 Hydrogenation of N-(1-phenylethylidene)-aniline with iridium complex 16.

	Entry a	Catalyst	Time (h)	Yield of amine
	1	16	0.5	57%
	2	16	2	100%
	3	16	4	100%
	4	11

/[Ir(COD)Cl]2 (ligand/iridium ratio =1) 2 80% 5 11/[Ir(COD)Cl]2 (1/1) (ligand/iridium ratio =1) 4 100% a: 1% 16 , 3% I2, at RT in CH2Cl2.

4,4'-bis(diphenylphosphinoxy)-1,1'-diisobutyl-5,5'-bis-1,2,3- triazole dioxide (8.3). The

  by TLC, the solvent was removed under reduced pressure and the residue was dissolved in dichloromethane, washed with aqueous ammonia solution (10%, 3 x 10mL), brine, then dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The product was isolated as specified below.

	11.74 Hz,3.70 Hz, 2H), 2.53 -2.56 (m, 2H), 2.11 -2.02 (m, 2H), 1.91
	-1.83 (m, 2H), 1.75 -1.66 (m, 4H), 1.56 -1.48 (m, 4H), 1.18 -1.11
	(m, 2H), 0.99 -0.89 (m, 2H), 0,84 -0.74 (m, 2H); 13 C NMR (100,61
	MHz, CDCl3) δ 140.47 (d, J = 132.1 Hz), 133.13 (d, J = 40.3 Hz),
	132.23 (d, J = 2.9 Hz), 131.94 (d, J = 2.8 Hz), 131.79 (d, J = 10 Hz),
	131.56 (d, J = 11 Hz), 130.20 (d, J = 21.9 Hz), 128.62 (d, J = 12.6
	8.1-8.7 Hz), 128.40 (d, J = 13,0 Hz), 34.27 (s), 59.71 (s), 32.35 (s), 25.39 (s), 25.22 (s), 24.89 (s); 31 P NMR (161.97 MHz, CDCl3) δ 17,07 (s); HRMS (EI): m/z Calcd. for C40H42N6O2P2 [M+H] + :701.28; Found: 701.2908; mp: 282.4-283.0 °C. 4,4'-bis(diphenylphosphinoxy)-1,1'-bis(benzyloxyacetyl)-5,5'-bis-1,2,3-triazole dioxide (8.5). The compound was isolated as a white solid after purification by a chromatography column on silica gel with as eluent a mixture of dichloromethane-isopropanol (98/2); Yield: 28%; 1 H NMR (400,13 MHz, CDCl3) δ 7.97 -7.89 (m, 4H), 7,59 -7,52 (m, 2H), 7.51 -7.39 (m, 8H), 7.34 -7.28 (m, 8H), 7.25 -7.19 (m, 4H), 7.17 -7.09 (m, 4H), 5.40 (d, J = -17.8 Hz, 2H), 5.18 (d, J = -17.8 Hz, 2H), 5.05 (d, J = -12.1 Hz, 2H), 4.99 (d, J = -12.1 Hz, 2H); 13 C NMR (100,61 MHz, CDCl3) δ 165.89 (s), 141.10 (d, J = 129.7 Hz), 134.58 (s), 132.54 (a white solid after purification by a chromatography column on silica gel with as eluent a mixture of dichloromethane-isopropanol (98/2); Yield: 20%; 1 H NMR (400,13 MHz, CDCl3) δ 7.92 -7.84 (m, 4H), 7.50 -7.32 (m, 10H), 7.24 -7.18 (m, 2H), 7.09 -7.03 (m, 4H), 5.29 (d, J = -17.8 Hz, 2H), 5.06 (d, J = -17.8 Hz, 2H), 3.58 (s, 6H); 13 C NMR (100,61 MHz, CDCl3) δ 166.45 (s), 147.07 (d, J = 129.0 Hz), 132.57 (d, J = 2.78 Hz), 132.19 (d, J = 2.8 Hz), 131.82 (d, J = 10.9 Hz), 131.6 (dd, J = 23.4 Hz, J = 110.81 Hz), 131.17 (d, J = 10.9 Hz), 130.93 5 (s), 128,78 (d, J = 12.8 Hz), 128.5 (d, J = 13,0 Hz), 52.99 (s), 49.89 (s); 31 P NMR (161.97 MHz, CDCl3) δ 17.22 (s); HRMS (EI): m/z Calcd. for C34H30N6O6P2 [M+H] + :681.17; Found: 681.1790; mp: 211.7-212.1°C. 4,4'-bis(diphenylphosphinoxy)-1,1'-bis(benzyloxymethyl)-5,5'-bis-1,2,3-triazole dioxide (8.7). The compound was isolated as a white solid after purification by a chromatography column on silica gel with as eluent a mixture of dichloromethane-isopropanol (98/2); Yield: 12%; 1 H NMR (400,13 MHz, CDCl3) δ 8.04-7.89 (m, 4H), 7.64 -7.40 (m, 10H), 7.37 -7.11 (m, 16H), 5.87 (d, J = -11.2 Hz, 2H), 5.75 (d, J = -11.2 Hz, 2H), 4.42 (s, 4H); 13 C NMR (100,61 MHz, CDCl3) δ GENERAL 4,4'-bis(diphenylphosphinoxy)-1,1'-dibenzyl-5,5'-bis-1,2,3-triazole dioxide (8.1). The compound was isolated as a white solid after recrystallization from ethanol; Yield: 49%; 1 H NMR (400,13 MHz, CDCl3) δ 8.13 -7.97 (m, 4H), 7.65 -7.41 (m, 10H), 7.39 -7.08 (m, 12H), 6.91 -6.77 (m, 4H), 5.51 (d, J = -14.7 Hz, 2H), 4.70 (d, J = -14.7 Hz, 2H); 13 C NMR (100,61 MHz, CDCl3) δ 141.18 (d, J = 130.4 Hz), 132.88 (s), 132.36 (d, J = 2.8 Hz), 132.04 (d, J = 2.8 Hz), 131.65 (d, J = 10.0 Hz), 131.39 (dd, J = 55.3 Hz, J = 109.07 Hz), 131.23 (d, J = 10.9 Hz), 130.85 (d, J = 241.7 Hz), 128.92(s), 128.83 (s), 128.62 (d, J = 12.6 Hz), 128.54 (d, J = 12.8 Hz), 128.15 (s), 53.13 (s); 31 P NMR (161.97 MHz, CDCl3) δ 16.80 (s); HRMS (EI): m/z Calcd. for C42H34N6O2P2 [M+H] + :717.22; Found: 717.2306; mp: 224.5-227.4°C. compound was isolated as a white solid after purification by a chromatography column on silica gel with as eluent a mixture of dichloromethane-isopropanol (98/2); Yield: 23%; 1 H NMR (400,13 MHz, CDCl3) δ 8.05 -7.92 (m, 4H), 7.61 -7.44 (m, 10H), 7.38 -7.27 (m, 2H), 7.23 -7.14 (m, 4H), 4.20 (dd, J = 7.5 Hz, J = -13.9 Hz, 2H), 3.88 (dd, J = 7.4 Hz, J = -13.9 Hz, 2H), 2.10 (ht, J = 6.87 Hz, J = 6.87 Hz, 2H), 0.81 (d, J = 6.7 Hz, 6H), 0.73 (d, J = 6.6 Hz, 6H); 13 C NMR (100,61 MHz, CDCl3) δ 140.87 (d, J = 131.2 Hz), 133.26 (d, J = 41.9 Hz), 132.27 (d, J = 2.7 Hz), 132.00 (d, J = 2.8 Hz), 131.71 (d, J = 10.0 Hz), 131.22 (d, J = 10.8 Hz), 130.67 (d, J = 22 Hz), 128.58 (d, J = 12.6 Hz), 128.08 (d, J = 13.0 Hz), 56.97 (s), 28.02 (s), 20.16 (s), 20.03 (s); 31 P NMR (161.97 MHz, CDCl3) δ 16.5 (s); HRMS (EI): m/z Calcd. for C36H38N6O2P2 [M+H] + :649.25; Found: 141.51 (d, J = 129.5 Hz), 135.72 (s), 132.43 (d, J = 2.6 Hz), 132.07
	649.2618; mp: 237.1-238.0 °C.

PROCEDURE

In a round bottom flask, ethynyldiphenylphosphane oxide (250 mg, 1.1 mmol) was dissolved in acetonitrile

(3 mL)

. Then the corresponding azide (3.3 mmol) and aqueous cesium carbonate solution at 2 mol.L -1 (1.65 mL) were added followed by copper bromide (158 mg, 1 mmol). The resulting mixture was stirred at room temperature in an open vessel for 12 hours. After complete reaction as monitored 4,4'-bis(diphenylphosphinoxy)-1,1-dibutyl-5,5'-bis-1,2,3-triazole dioxide (8.2). The compound was isolated as a white solid after purification by a chromatography column on silica gel with as eluent a mixture of dichloromethane-isopropanol (98/2); Yield: 42%;

1

H NMR (400,13 MHz, CDCl3) δ7. 96 (dd, J = 7.6 Hz, J = 12.1 Hz, 4H), 7.61 -7.35(m, 10H), 7.33 -7.21 (m, 2H), 7.20 -7.08 (m, 4H), 4.23 -4.40 (m, 2H), 4.13 -4.01 (m, 2H), 1.92-1.78(m, 2H), 1.77 -1.64 (m, 2H), 1.22 -1.08 (m, 4H), 0.78 (t, J = 7.4 Hz, 6H); 13 C NMR (100,61 MHz, CDCl3) δ140.82 (d, J = 130,0 Hz), 133.27 (d, J = 2.7 Hz), 131.98 (d, J = 2.7 Hz), 131.66 (d, J = 10,0 Hz), 131.57 (dd, J = 29 Hz, J = 110.3 Hz), 131.27 (d, J = 10.9 Hz), 130.42 (d, J = 21.9 Hz), 129,57 (d, J = 12.7 Hz), 129.47 (d, J = 13,0 Hz), 49.40 (s), 31.07 (s), 19.84 (s), 13.31 (s); 31 P NMR (161.97 MHz, CDCl3) δ16,52 (s); HRMS (EI): m/z Calcd. for C36H38N6O2P2 [M+H] + :649.25; Found: 649.2607; mp: 172.2-172.7 °C.

4,4'-bis(diphenylphosphinoxy)-1,1'-dicyclohexyl-5,5'-bis-1,2,3triazole dioxide (8.4).

The compound was isolated as a white solid after sublimation; Yield: 6%;

1

H NMR (400,13 MHz, CDCl3) δ7.95 -7.89 (qt, 3H), 7.51 -7.38 (m, 11H), 7.27 -7.21 (m, 6H), 3.70 (tt, J = d, J = 2.7 Hz), 132.3 (dd, J = 20.8 Hz, J = 110.9 Hz), 132.19 (d, J = 2.7 Hz), 131.83 (d, J = 10.2 Hz), 131.82 (d, J = 21.7 Hz), 131.21 (d, J = 10.9 Hz), 128,77 (d, J = 12.6 Hz), 128.75 (s), 128,72 (s), 128.55 (s), 128.5 (d, J = 13.0 Hz), 68.04 (s), 50.11 (s); 31 P NMR (161.97 MHz, CDCl3) δ 17,36 (s); HRMS (EI): m/z Calcd. for C46H38N6O6P2 [M+H] + :833.23; Found: 833.2400; mp: 157.4-157.9 °C. 4,4'-bis(diphenylphosphinoxy)-1,1'-bis(methoxyacetyl) -5,5'-bis-1,2,3-triazole dioxide (8.6). The compound was isolated as (d, J = 2.7 Hz), 131.84 (dd, J = 31.1 Hz, J = 111 Hz), 131.78 (d, J = 10.2 Hz), 131.22 (d, J = 10.9 Hz), 130.84 (dd, J = 21.3 Hz), 128.64 (d, J = 12.8 Hz), 128.50 (s), 128.42 (d, J = 12.9 Hz), 128.36 (s), 128.26 (s), 76.79 (s), 71.29 (s); 31 P NMR (161.97 MHz, CDCl3) δ 17,34 (s); HRMS (EI): m/z Calcd. for C36H38N6O2P2 [M+H] + :777.24; Found: 777.25183; mp: 154.0-154.8 °C.

  JCP = 70.2 Hz, PCN), 137.4 (JCP = 13.6 Hz, PPh2), 133.5 (quat, Ph/Bn), 132.6 (JCP = 9.0 Hz, PPh2), 132.0 (PPh2), 130.1 (PPh2), 128.3 (Ph/Bn), 128.2 (JCP = 11.2 Hz, PPh2), 127.7 (JCP = 10.8 Hz, PPh2), 127.6 (Ph/Bn), 127.3 (Ph/Bn), 127.1 (quat, JCP = 11.0 Hz, PCCN), 125.3 (quat, JCP = 53.9 Hz, PPh2), 94.8 (JCP = 13.4 Hz, COD), 94.3 (JCP = 16.1 Hz, COD), 55.4 (COD), 53.2 (COD), 51.7 (NCPh), 34.3 (COD), 32.1 (COD), 29.9 (COD), 29.1 (COD). 31 P{ 1 H} NMR (500 MHz, CDCl3) δ (ppm): 8.7. HR/MS (ES+) m/e: 985.2916 (M of cation, 100%) (calc. M: 985.2888).

	dichloromethane solution. 1 H{ 31 P} NMR (500 MHz, CDCl3) δ	Synthesis of complexes 12-17
	(ppm): 7.75 (4H, m, PPh2), 7.57 (4H, m, PPh2), 7.44 (6H, m, PPh2), 7.33 (2H, m, PPh2), 7.25 (4H, m, PPh2), 7.17 (2H, m, Ph/Bn), 7.07 (4H, m, Ph/Bn), 6.77 (4H, m, Ph/Bn), 4.65 (2H, d, J = 15.3 Hz, NCH2), 4.58 (2H, d, J = 15.3 Hz, NCH2), 3.67 (2H, m, COD), 3.13 (2H, m, COD), 2.00 (2H, m, COD), 1.74 (2H, m, COD), 1.69 (2H, m, COD), 1.53 (2H, m, COD). 13 C{ 1 H} NMR (500 MHz, CDCl3) δ (ppm): 144.9 (quat, JCP = 49.1 Hz, PCN), 135.3 (JCP = 11.7 Hz, PPh2), 133.1 (JCP = 9.4 Hz, PPh2), 132.8 (quat, Ph/Bn), 132.6 (quat, PPh2), 132.0 (quat, PPh2), 130.3 (PPh2), 129.4 (PPh2), 128.8 (Ph/Bn), 128.4 (Ph/Bn), 128.3 (quat, JCP = 26 Hz, PCCN)128.0 (PPh2), 127.6 (PPh2), 127.4 (Ph/Bn), 68.7 (JCP = 7.9 Hz, COD), 67.0 (JCP = 6.8 Hz, COD), 52.5 (NCPh), 32.9 (COD), 32.1 (COD). 31 P{ 1 H} NMR (500 MHz, CDCl3) δ (ppm): -17.8. HR/MS (ES+) m/e: 985.2919 (M-Cl, 80%) (calc. M: 985.2888).	SYNTHESIS OF THE PALLADIUM COMPLEX (13). In a Schlenk tube under argon, a mixture of compound 11.1 (20 mg, 0.029 mmol) and bis(acetonitrile)dibromopalladium (10.1mg, 0.029 mmol) was dissolved in dry chloroform (2 ml). The reaction was carried out at room temperature for 2 hours. The solvent was evaporated and the resulting orange solid was washed by dry pentane. After evaporation of the solvent, 22.1 mg of 12.1 were obtained (80% yield). 1 H{ 31 P} NMR (500 MHz, CDCl3) δ (ppm): 7.98 (4H, m, PPh2), 7.63 (4H, m, PPh2), 7.52 (2H, m, PPh2), 7.49 (2H, m, PPh2), 7.46 (4H, m, PPh2), 7.36 (4H, m, PPh2), 7.32 (2H, m, Ph/Bn), 7.25 (4H, m, Ph/Bn), 6.77 (4H, m, Ph/Bn), 4.69 (2H, d, J = 15.7 Hz, NCH2), 4.49 (2H, d, J = 15.7 Hz, NCH2). 13 C{ 1 H} NMR (500 MHz, CDCl3) δ (ppm): 141.7 (JCP = 61.1 Hz, quat, PCN), 135.8 (JCP = 6.5 Hz, PPh2), 133.9 (JCP =5.0 Hz, PPh2), 132.9 (PPh2), 132.1 (quat, Ph/Bn), 131.2 (PPh2), 129.2 (JCP = 6.3
	SYNTHESIS OF THE IRIDIUM COMPLEX (17). In a Schlenk tube under argon, a mixture of compound 11.1 (20 mg, 0.029 mmol) and [Ir(COD)Cl]2 (19.6 mg, 0.029 mmol) was dissolved in dry dichloromethane (4 ml). The mixture was stirred at room temperature for 45 minutes. The solvent was then evaporated and	Hz, PPh2), 129.2 (Ph/Bn), 129.0 (Ph/Bn), 128.2 (quat, JCP = 19.9 Hz, PPh2), 127.7 (JCP = 6.0 Hz, PPh2), 127.6 (quat, PCCN)127.1 (Ph/Bn), 125.8 (quat, JCP = 40.8 Hz, PPh2), 52.5 (NCPh). 31 P{ 1 H} NMR (500 MHz, CDCl3) δ (ppm): 8.4. HR/MS (ES+) m/e: 871.0541 (M-Br, 100%) (calc. M: 871.0311).
	1 H NMR (400,13 MHz, CDCl3) δ 7.48 -7.58 (m, 4H), 7.30 -7.22 (m, 6H), 7.21 -7.06 (m, 10H), 3.96 -3.78 (m, 4H), 1.63 -1.50 (m, 4H), 1.08 -0.89 (m, 4H), 0.63 (t, J = 7.4 Hz, 6H); 13 C NMR (100,61 MHz, CDCl3) δ 144.02 -145.96 (m (ABX)), 144.88 -144.82 m (ABX)), 135.51 -135.46 (m C36H38N6P2 [M+H] + : 617.26; Found: 617.2715; mp: 154.1-155.0 °C. (161.97 MHz, CDCl3) δ -37.75 (s); HRMS (EI): m/z Calcd. for 49.07 ( m (ABX)), 31.72 (m (ABX)), 19.81 (s), 13.30 (s); 31 P NMR 53.3 Hz), 128.71 -128.59 (m (ABX)), 128.44 -128.32 (m (ABX)), 133.48 -133.24 (m (ABX)), 130.64 (d, J = 44.9 Hz), 129.11 (d, J = (ABX)), 135.08 -135.04 (m (ABX)), 134,37 -134.14 (m (ABX)), the resulting yellow solid was washed by dry pentane. After evaporation of the solvent, 35.4 mg of 17.1 were obtained (90% yield). 1 H{ 31 P} NMR (500 MHz, CDCl3) δ (ppm): 7.67 (4H, m, PPh2), 7.50 (4H, m, PPh2), 7.50 (2H, m, PPh2), 7.31 (2H, m, PPh2), 7.30 (4H, m, PPh2), 7.24 (4H, m, PPh2), 6.97 (2H, m, Ph/Bn), 6.91 (4H, m, Ph/Bn), 6.63 (4H, m, Ph/Bn), 5.26 (2H,m, COD), 5.17 (2H, m, COD), 4.92 (2H, d, J = 15.6 Hz, NCH2), 4.26 (2H, d, J = 15.6 Hz,NCH2), 2.68 (2H, m, COD), 2.48 (2H, m, COD), 2.37 (2H, m, COD), 2.15 (4H, m, COD), 2.14 (2H, m, COD), 1.98 (2H, m, COD), 1.76 (2H, m, COD), 1.67 (2H, m, COD), 1.45 (2H, m, COD). 13 C{ 1 H} NMR (500 MHz, CDCl3) δ (ppm): 140.5 (quat,	(Ph/Bn), 129.0 (PPh2), 129.0 (Ph/Bn), 127.7 (JCP = 6.0 Hz, PPh2), Hz,PPh2), 132.8 (PPh2), 132.2 (quat, Ph/Bn), 131.4 (PPh2), 129.2 82 Hz, quat, PCN), 135.4 (JCP = 6.5 Hz, PPh2), 134.2 (JCP = 4.9 NCH2). 13 C{ 1 H} NMR (500 MHz, CDCl3) δ (ppm): 140.4 (JCP = 4.74 (2H, d, J = 15.3 Hz, NCH2), 4.60 (2H, d, J = 15.3 Hz, 7.33 (2H, m, Ph/Bn), 7.25 (4H, m, Ph/Bn), 6.77 (4H, m, Ph/Bn), SYNTHESIS OF THE PLATINUM COMPLEX (14). In a Schlenk tube, under argon, a mixture of ligand 11.1 (20 mg, 0.029 mmol) and bis(benzonitrile)dichloroplatinum (13.7 mg, 0.029 mmol) was dissolved in dry chloroform (2 ml). The reaction was carried out at reflux for 2 hours. The solvent was evaporated and the resulting white solid was washed by dry pentane. After evaporation of the solvent, 19.3 mg of 14.1 were obtained (70% yield). A single crystal of 14 suitable for X-ray diffraction analysis was obtained by slow diffusion of pentane in a dichloromethane solution. 1 H{ 31 P} NMR (500 MHz, CDCl3) δ (ppm): 7.93 (4H, m, PPh2), 7.63 (4H, m, , PPh2), 7.50 (2H, m, , PPh2), 7.48 (2H, m, , PPh2), 7.45 (4H, m, , PPh2), 7.34 (4H, m,),
	4,4'bis(diphenylphosphino)-1,1'-diisobutyl-5,5'-bis-1,2,3-triazole	127.6 (JCP = 6.4 Hz, quat, PCCN), 127.0 (Ph/Bn), 125.5 (quat,
	(11-.3). The compound was isolated as a white solid after precipitation	JCP = 29.8 Hz, PPh2), 125.1 (quat, JCP = 41.2 Hz PPh2), 52.6
	with diethylether and pentane; Yield: 98%; 1 H NMR (400,13 MHz,	(NCPh). 31 P{ 1 H} NMR (500 MHz, CDCl3) δ (ppm): -5.1.
	CDCl3) δ 7.99 -7.49 (m, 4H), 7.28 -7.23 (m, 6H), 7.22 -7.16 (m,	HR/MS (ES+) m/e: 915.1645 (M-Cl, 100%) (calc. M:
	4H), 7.16 -7.07 (m, 6H), 3.79 (dd, J = 7.6 Hz, J = 13.6 Hz, 2H), 3.67	915.2381).
	(dd, J = 7.6 Hz, J = 13.6 Hz, 2H), 1.99 -1.75 (m, 2H), 0.61 (d, J = 6.7
	Hz, 6H), 0.58 (d, J = 6.7 Hz, 6H); 13 C NMR (100,61 MHz, CDCl3) δ	SYNTHESIS OF THE IRIDIUM COMPLEX (16). In a Schlenk tube
	145.15 -145.06 (m (ABX)), 144.96 -144.91 (m (ABX)), 135.71 -	under argon, a mixture of compound 11.1 (20 mg, 0.029 mmol)
	135.67 (m (ABX)), 135.05 -135.00 (m (ABX)), 133.56 -133.29 (m	and [Ir(cod)Cl]2 (9.8 mg, 0.015 mmol) was dissolved in dry
	(ABX)), 133.13 -133.14 (m (ABX)), 131.20 (d, J = 1.20 Hz), 130.74	dichloromethane (2 ml). The reaction was carried out at room
		temperature for 45 minutes. The solvent was evaporated and the
		resulting yellow solid was washed by dry pentane. After
		evaporation of the solvent, 29.3 mg of 16 were obtained (99%
		yield). A single crystal of 16 suitable for X-ray diffraction
		analysis has been obtained by slow diffusion of pentane in a

(d, J = 1.37 Hz), 129.06 (d, J = 66.8 Hz), 128.68 -128.50 (m (ABX)), 128.42 -128.24 (m (ABX)), 56.45 -56.6 (m (ABX)), 45.85 (s), 28.68 (s), 19.88 (s); 31 P NMR (161.97 MHz, CDCl3) δ -38.08 (s) ; HRMS (EI): m/z Calcd. for C36H38N6P2 [M+H] + : 617.26 ; Found: 617.2714; mp: 154.2-154.8 °C.

  Institut Charles Gerhardt / UMR 5253 / AM2N, Ecole Nationale Supérieur de Chimie de Montpellier, 8, Rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France. b CNRS, LCC (Laboratoire de Chimie de Coordination) -Université de Toulouse, UPS, INPT -205 route de Narbonne, BP 44099, F-31077 Toulouse Cedex 4, France. c Institut Européen des Membranes, CNRS -UMR 5635, Université de Montpellier II -Case Courrier 047 Place E. Bataillon, F-34095 MONTPELLIER Cedex 5, France.

a d Institut Universitaire de France, 103 bd Saint-Michel, F-75005 Paris, France.

J. Name., 2012, 00, 1-3 | 5Reduction of bistriazolylphosphane oxides 8 into bisphosphanes


Steven J Schwartz
email: s.schwartz@imperial.ac.uk

Timothy Horbury

Christopher Owen

Wolfgang Baumjohann

Rumi Nakamura

Patrick Canu

Alain Roux

Fouad Sahraoui

Philippe Louarn

Jean- André Sauvaud

Jean-Louis Pinçon

Andris Vaivads

Maria Federica Marcucci

Anastasios Anastasiadis

Masaki Fujimoto

Philippe Escoubet

Matt Taylor

Steven Eckersley

Elie Allouis

Marie-Claire Perkinson

J.-A Sauvaud

M.-C Perkinson

Cross-scale: multi

Keywords: scale coupling in space plasmas Cross-scale, Cosmic Vision, Multi-scale coupling in plasmas, Space plasmas PACS 90.05-a, 94.80.+g, 95.40.+s, 52.27.-h 1

Three fundamental physical processes operate to bring about the universal collisionless plasma coupling in physical environments where momentum and energy transfer is important.

Shock waves guide strong flows around obstacles or at interfaces between two flow regimes. They are important locations for the transfer of directed bulk flow energy into heat, with an attendant acceleration of energetic particles (see Fig. 1).

Magnetic reconnection releases stored magnetic energy to the plasma, and allows for exchange of material between previously isolated regions. Moreover, the consequent change in magnetic topologies provides a coupling between plasma regions which often drives the global scale dynamics of the system (see Fig. 2).

Turbulence transports energy from large scales at which it is input to small scales where it is dissipated. In the process, it interacts strongly, and often selectively, with plasma particle populations as either a source or sink (or both) of energy (see Fig. 3). Near-Earth space is a unique laboratory for quantifying the physics of these three processes. Breakthroughs have arisen due to the high quality of data that, unlike more distant regimes, is sampled directly by plasma and fields experiments on satellites.

To date, in situ measurements have focused on terrestrial phenomena, such as the mechanisms that populate the van Allen radiation belts. Dual spacecraft studies during the 1980s began to address the real microphysics. Present generation missions (Cluster and MMS) utilise four spacecraft to sample a specific volume, and hence characterise the physics operating on the single scale corresponding to the spacecraft separation. By the time MMS has flown, we shall have a catalogue of behaviour that ranges from the smallest, electron scale, to the largest fluid-like phenomena.

That knowledge is incomplete due to the ambiguity and uncertainty about the dynamics and variability of the larger contextual scales (for the electron and ion scales) and of the internal micro-processes that mediate the energy exchange (for the larger scales). The complex, dynamic nonlinear coupling of scales and physical mechanisms can not be quantified without simultaneous information on all scales. Further details of the Science Objectives can be found in the full proposal [START_REF]The Cross-Scale Team: Cross-scale: multi-scale coupling in space plasmas[END_REF] and in earlier mission publications [e.g., [START_REF] Horbury | Cross-scale: a multi-spacecraft mission to study cross-scale coupling in space plasmas[END_REF][START_REF] Owen | Multi-point, multi-scale investigations of fundamental plasma processes in the Earth's magnetosphere[END_REF] and in the description of the Japanese SCOPE mission provided by Fujimoto et al. [START_REF] Fujimoto | The SCOPE mission[END_REF].

Science questions

Cross-Scale will target compelling and fundamental questions, such as:

-How do shocks accelerate and heat particles? -How are particles accelerated in and around shocks? -How is the energy incident on a shock partitioned? -How do shock variability and reformation influence the acceleration process? -How does reconnection convert magnetic energy? -What initiates magnetic reconnection? -How does the magnetic topology evolve? -How does reconnection accelerate particles and heat plasma? -How does turbulence control transport in plasmas? -How does the turbulence cascade transfer energy across physical scales? -How does the magnetic field break the symmetry of plasma turbulence? -How does turbulence generate coherent structures?

These address directly the Cosmic Vision question "How does the Solar System work?" by studying basic processes occurring "From the Sun to the edge of the Solar System." By quantifying the fundamental processes involved, the advances made by the mission will extend beyond the Solar System to plasmas elsewhere in the Universe.

Mission strategy

Cross-Scale will meets its scientific objectives by employing 3D concepts and techniques, pioneered by Cluster, simultaneously on three logarithmically spaced scales. Focused instrumentation on each scale then enables the dynamic coupling across those key scales to be measured.

Mission profile

Cross-Scale will employ 10 spacecraft which will fly with two highly complementary spacecraft from its sister mission SCOPE provided by JAXA. Together, they will form three nested tetrahedra, as shown in Fig. 4, to separate spatial and temporal variations simultaneously on the three key scales for the first time. In near-Earth space, the electron physics occurs on scales ∼2-100 km, the ion physics on scales ∼50-2,000 km, and the macroscopic fluid scales are typically ∼3,000-15,000 km. Over the two year mission in a highly eccentric orbit the spacecraft will encounter various collisionless shocks, explore regions of both spontaneous and strongly driven reconnection, and investigate both nascent and highly evolved plasma turbulence.

Fig. 4 The orbit of Cross-Scale (left) is designed to traverse the dayside solar wind, bow shock and magnetosheath, and 6 months later the nightside in the "tailbox" region. These provide examples under a variety of physical conditions of shock waves, magnetic reconnection, and turbulence. The nested configuration of spacecraft (right) are actually logarithmically spaced from 2-100 km at the smallest separations up to 15,000 km at the largest to measure simultaneously the 3 key scales: electron, ion, and fluid

Spacecraft

The spacecraft will be identical in bus design (for economy) with modular bays that can accommodate instrument suites tailored to the relevant scale. The two JAXA SCOPE spacecraft complete the instrumentation and locations needed to meet the requirements. Dedicated hardware will determine the inter-satellite ranges at the smaller scales.

While some aspects of the spacecraft are challenging (X-band communica-tions, large onboard memory, centralised processing, autonomous operation and data retrieval), there are no new technologies that must be established. The ten spacecraft will be dispensed by a vehicle with commercial heritage. Construction and calibration of the instruments is a large task (a factor ∼2 larger than previous missions) but builds, together with the operation of a fleet of spacecraft, on recent European experience and success.

Payload

The payload consists almost entirely of proven technology, with heritage in recent missions (e.g., Cluster, Polar, Themis, STEREO) and well-advanced concepts (e.g., MMS). Although the spacecraft bus and subsystems are identi-cal, spacecraft devoted to different scales need different payload in terms of, e.g., time resolution, particle distributions vs. gross characteristics, and DC/AC fields. The largest demands come from the smallest scale (electron) spacecraft, with those at the fluid scale more modest.

To achieve this while benefiting from the economies of identical bus sys-tems, the payload can be accommodated in universal mountings, such as modular bays or simple mounting plates. These plates present a common mechanical and electrical interface to the spacecraft, and are arranged on a single instrument shelf located at the top of the spacecraft. Figure 5 illustrates the concept, which provides ease of assembly, integration, and verification and facilitates replacement of faulty instruments. A thermal and electrical cover of some kind is needed, which could be a full or partial top to the entire spacecraft or specific to the individual bay.

Table 1 provides an overview of the instrument complement on each space-craft, shown pictorially in Fig. 6. The main spacecraft resources are provided in Table 2.

The instrument complement on each spacecraft is targetted in terms of type of measurement, time resolution, and level of detail to match the highest science priorities (see [START_REF]The Cross-Scale Team: Cross-scale science priority document[END_REF] for details). The overall characteristics are shown in Table 3 with the deployment on the various spacecraft encapsulated in Table 1 and Fig. 6.

DC magnetometers (dual-sensors) will be deployed on all spacecraft, re-turning field vectors sampled at up to ∼100 Hz on the electron scale, and 1-10 Hz on the ion scale spacecraft. This data provides a robust roadmap of the 3D multi-scale morphology/connectivity, fundamental components of the Fig. 5 Instruments mounted on universal plates [START_REF]Cross-Scale[END_REF]. For reasons of economy, Cross-Scale will utilise a single spacecraft bus design. Since the science payload is not identical for all spacecraft, a modular approach is adopted to accommodate different instruments in the same position. For ease of assembly, integration, and verification, a universal plate will be provided to instrument teams. Intrument mounting (left) and testing (middle) can be performed independently before the bays are then integrated, connected, and tested on the spacecraft (right). Plate locations used in Table 1 are lettered for convenience overall turbulence spectrum, and specific fluctuations responsible for particle scattering and energisation.

AC coil magnetometers extend waveform measurements up to ∼500,Hz and spectral information up to several kilohertz. These complete the characterisation of waves responsible for particle scattering and extend the turbulence analysis into the electron dissipation range.

Electric field antennae will be used to cover the range from DC to 100 kHz on the inner spacecraft, where wave scattering and energisation of ions and electrons is a key priority for shocks and reconnection, and for the dissipation . Table 1 identifies the instruments and bay locations, which are lettered in Fig. 5 of turbulence. Electric measurements complement the magnetic ones to iden-tify the electrostatic components of the waves and turbulence. The antennae will also be employed to measure the ambient DC electric field and the spacecraft floating potential. These, together with an electron density sounder, provide a high time resolution, high quality total electron density measurement that is central to the shock and reconnection science objectives, and that underpins the calibration of the particle instruments. Apart from the fluid-scale spacecraft, all satellites will carry a crossed pair of wire boom antennae. At the electron scale all three components of the crucial reconnection electric field and the cross-shock electric fields will be completely characterised by the addition of rigid, dual-axial booms.

Electrostatic particle detectors of various designs will be carried on all spacecraft. These provide not only the basic plasma parameters (density, velocity, temperature, etc.) but also the full 3D velocity distribution functions. Collisionless plasma processes are driven by particle beams, temperature anisotropies, and other features that are not accessible to the low-order moments. Energy partition (heating and acceleration) amongst the various ion components requires some massresolving capability employing time-of-flight techniques in concert with the basic electrostatic design that is utilised for electrons. The comprehensive instrument suite on the SCOPE mother spacecraft enables Cross-Scale to deploy a small number of core instruments to address the multi-scale aspects.

Modern analysers utilise a top-hat design which has a narrow field of view in one dimension. Full 3D velocity measurements require a full satellite spin period for a single sensor, which is adequate at the fluid scale. Multiple sensors, as either dual-heads within a single unit or multiple units, are deployed on the ion and electron scale spacecraft to increase the resolution and provide full 3D capability at the corresponding ion or electron time scales demanded by the science objectives. Additionally, deflector plates can be employed to increase the field of view for subspin resolution and reduce the number of sensors required. A combined electron/ion electrostatic analyser would greatly enhance the science return within payload mass restrictions by avoiding separate instruments for each species.

Energetic ion and electron detectors are required to investigate acceleration processes. The larger gyroradii and scales associated with these particles im-plies that not all spacecraft need to be so equipped, and the deployment 1 represents a minimal configuration at each scale in a way which returns essential information on energetic ions, electrons, 3D ion velocity distributions, and ionic species.

Centralised onboard processing represents an attractive means of coor-dinating the payload, sharing (and hence reducing) resources. A dedicated wave processor has been successfully used in the past to coordinate common commanding, data taking, signal processing, and telemetry for electric and AC magnetic field instruments. A similar approach to particle instruments may be adopted. Alternatively, a distributed system taking advantage of modern communication and computing capabilities, such as SPACEWIRE, will be studied during the assessment phase. There are obvious and significant mass savings to be gained by reducing or eliminating one or several instrument-dedicated data processing units. This strategy needs to be developed in tandem with the multi-instrument bays in the current spacecraft design.

Active spacecraft potential control will be flown on the electron scale. This limits the contamination of the electron measurements by photoelectrons of spacecraft origin, and enables the low energy population to be resolved without large and sometimes uncertain corrections.

The basic characteristics of the instruments are described in Table 3. All instruments have recent flight heritage. Ongoing developments in mass, power, and science performance will be utilised to optimise the actual mission hardware.

Data rates

The science requirements met by the payload complement on the various spacecraft lead to a substantial data volume. That volume is estimated in Table 4, and used to allocate adequate spacecraft resources, telemetry, and ground station support. The total mission data rate is 1.6 M-science words per second. A 16-bit science word (generous for the particle instruments) and a compression ratio of 10 (conservative given modern compression techniques for particle data, which dominates the data volume) would imply a mission data-rate of 2.6 Mbps of which 31% can be accommodated in a nominal total downlink capability of 800 kbs. The actual downlink budget is driven by the subset of the orbit corresponding to the key target regions and boundary layers, so the full science objectives can be comfortably accommodated by this data rate. In fact, the majority of the data volume is generated by the electron scale spacecraft. Based on Table 4, these accumulate roughly 61 Gbytes of compressed data in two orbits (6 days). If adequate centralised onboard storage is not available for these spacecraft, a number of strategies exist to avoid compromising the science, including internal instrument memory, autonomous or predicted event triggers, higher compression, and downsampling in energy-angle-time resolution.

Operations

Limited instrument modes and minimal station-keeping are planned to restrict the ground segment resources required by the mission. A data segment is planned to ensure that the data are processed and calibrated, with high-quality science data made available in a timely fashion for the widest possible community.

Current status

Cross-Scale has been selected by ESA to proceed to an Assessment Phase commencing late 2007. A Science Study Team will refine the mission and payload, which will be the subject of two parallel industrial studies that will be completed in 2009. Toward the end of 2009, ESA will make a further set of selections into a formal Definition Phase, from which two missions will be selected in 2011 for launch in 2017/2018.

Conclusion

Cross-Scale is an innovative next-generation mission with high-quality science objectives that attack fundamental physical phenomena in collisionless plas-mas. It taps directly into European leadership in multi-point in situ space plasmas, and is built around flight-proven technologies. The mission has been selected by ESA to proceed to the Assessment Phase of Cosmic Vision mis-sions. Further details and the mission proposal can be found on the community web-site at http://www.crossscale.org.

Fig. 1

 1 Fig. 1 Sketch of a collisionless shock under quasi-parallel conditions, in which the magnetic field threads the shock layer allowing the escape of particles into the oncoming flow. The resulting patchwork of field enhancements, shown as ovals, result in a configuration that is dramatically different to the traditional view of a shock as a 1-D planar transition from the incident, fast unshocked material on the left to the decelerated and "heated" plasma on the right. Such shocks are efficient accelerators of particles, and require simultaneous measurements at the largest fluid scales, intermediate patchwork scales, and smallest electron scales (at which there is locally steepening indicated by the black bars) [after 6]

Fig. 2

 2 Fig. 2 Magnetic reconnection at a convoluted shear boundary, showing the deployment of nested observations necessary to unravel the dynamic coupling that changes the magnetic topology and accererates particles [see, e.g., 7]

Fig. 3 A

 3 Fig.3A computer simulation of 2D electron MHD turbulence, showing how plasma currents are spatially localised into thin sheets and whorls. Many-point measurements, such as those from Cross-Scale, are required to measure such structures in 3D in space plasmas over a range of scales not accessible in simulations[after 4]

Fig. 6

 6 Fig.[START_REF] Schwartz | Quasi-parallel shocks-a patchwork of three-dimensional struc-tures[END_REF] Accommodation and fields of view of the scientific payload on the electron (left), ion (two middle), and fluid-scale (right) spacecraft[START_REF]Cross-Scale[END_REF]. Table1identifies the instruments and bay locations, which are lettered in Fig.5

Table 1

 1 Cross-Scale payload by spacecraft

		Instr	Spacecraft/location on which deployed
			Electron	Ion		Fluid
			e 1-2	i 1	i 2-4	f 1-4
		MAG	F	F	F	F
		ACB	B	B	B	B
		E2D	ACEG	ACEG	ACEG
		E3D	O
		EDEN	Z	Z	Z
		ACDPU	Z	Z	Z
	Instrument locations are given by lettered bays, and shown in Fig. 5; blanks indicate instruments not flown on that particular spacecraft; location Z refers to internal electronics	EESA CESA ICA ECA HEP ASP CPP	BDFH O Z	BF DH Z	BDFH AE CG Z	D H Z

Table 2

 2 Mass and power requirements of the payload complements on the different spacecraft, excluding margin

		Mass	Power	e 1-2			i 1			i 2-4			fluid
		(kg)	(W)	no.	Mass	Power	no.	Mass	Power	no.	Mass	Power	no.	Mass	Power
	MAG	1.5	1	1	1.5	1	1	1.5	1	1	1.5	1	1	1.5	1
	ACB	1.75	0.1	1	1.75	0.1	1	1.75	0.1	1	1.75	0.1	1	1.75	0.1
	E2D	8	3	1	8	3	1	8	3	1	8	3	0	0	0
	E3D	4	2	1	4	2	0	0	0	0	0	0	0	0	0
	EDEN	0.2	0.25	1	0.2	0.25	1	0.2	0.25	1	0.2	0.25	0	0	0
	ACDPU	1.5	2	1	1.5	2	1	1.5	2	1	1.5	2	1	1.5	2
	EESA	2	5.5	4	8	22	0	0	0	0	0	0	0	0	0
	IESA	1.5	2	0	0	0	0	0	0	0	0	0	0	0	0
	CESA	2.5	2	0	0	0	2	5	4	4	10	8	1	2.5	2
	ICA	5	6	0	0	0	2	10	12	0	0	0	0	0	0
	ECA	1	0.5	0	0	0	0	0	0	2	2	1	0	0	0
	HEP	1.2	1	0	0	0	0	0	0	2	2.4	2	1	1.2	1
	CPP	3	2	1	3	2	1	3	2	1	3	2	1	3	2
	ASP Ranging	1.9 5	2.7 -a	1 1	1.9 5	2.7 -a	0 1	0 5	0 -a	0 1	0 5	0 -a	0 0	0 0	0 0
	Totals			13	34.85	35.05	11	35.95	24.35	15	35.35	19.35	6	11.45	8.1
	a Included in spacecraft system power budget

Table 3

 3 Cross-Scale instruments-see Table1for key to the subset of these deployed on the different spacecraft

	Instr	Mass (kg)	a	Power (W)	a	Volume (cm 3 )	b	Measurement	Recent heritage	TRL
	MAG	1.5		1.0		11 × 5 × 5 (×2 units)	Boom-mounted DC vector magnetic field	VEX, Double Star	9
	ACB	1.75		0.1		10 ×10×10	Boom-mounted AC vector magnetic field 1Hz-2kHz	Themis, Demeter	9
									(spectra + waveform)
	E2D	8.0		3.0		20	× 30 × 15 (×4 units)	30-50m wire double probe 2D electric field (DC + spectra)	Themis, MMS, Demeter	8
									0-100kHz (DC + spectra)
	E3D	4.0		2.0		10 cm dia.	Dual axial 5m antennae; (DC + spectra)	Polar, Themis	7
	EDEN ACDPU	0.2 1.5		0.25 2.0		-23	×19×6	Electron density sounder Common processor & electronics for ACB, E2D, E3D, EDEN	Cluster Cluster	9 7
	EESA	2.0		3.0		26 ×15×26	Dual-head thermal 3D electron electrostatic analyser 3eV-30keV	MMS	6
	CESA	2.5		2.0		15 ×20×15	Combined 3D ion/electron electrostatic analyser 3eV-30keV	Medusa, Astrid	6
									ions, electrons
	ICA	5		6		25	×45×25	3D ion composition <40 keV	Cluster	8
	ECA	1		0.5		10 ×15×15	3D energetic multi-species ion analyser 100 keV-1 MeV	STEREO	8
	HEP	1.2		1		15 ×5×15	Solid-state high energy particle detector >30 keV	Themis, Demeter	9
	CPP	3.0		2.0		10 ×20×5	Centralised payload processor	Themis, SpaceWire	5
	ASP	1.9		2.7		19 ×16×17	Active potential control	Cluster, MMS	8
	a Total (all units); excluding most margins; excludes booms
	b Sensor volume only for MAG, ACB; MAG electronics 19 × 16 × 10

Acknowledgements

The EADS Astrium UK Ltd. study was funded by the Science and Technol-ogy Facilities Council of the UK. We wish to record here our appreciation to Marcel van den Berg for the tireless, thorough and good-humoured manner in which he liaised with utmost integrity between the community and the ESA-funded Technology Reference Study, and our deepest sadness at his untimely death.


Joseph M Hayes

Éric Deydier

Gregori Ujaque

Agusti Lledos

Raluca Malacea-Kabbara

Eric Manoury

Sandrine Vincendeau

Rinaldo Poli

Eric Deydier

Agustí Lledós

Raluca Malacea

Ketone hydrogenation with iridium complexes with "non N-H" ligands: The key role of the strong base

Keywords: Catalyzed ketone hydrogenation, Catalyzed transfer hydrogenation, Iridium, Bifunctional ligands, Asymmetric catalysis, Effect of strong base

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

The reduction of carbonyl compounds and particularly the enantioselective reduction of prochiral ketones, leading to optically pure secondary alcohols, has been the topic of a considerable number of studies because of its significance for the manufacture of pharmaceuticals and advanced materials. [START_REF] Collins | Chirality in Industry: The commercial Manufacture and Applications of Optically Active Compounds[END_REF][START_REF] Shimizu | [END_REF][START_REF] Blaser | Asymmetric Hydrogenation[END_REF][START_REF] Magano | [END_REF] Remarkable efforts have been devoted to the development of this method by using organometallic complexes as catalysts. The majority of the work carried out in this area has employed ruthenium-based pre-catalysts in combination with a variety of phosphine and amine ligands. [5][6][7][8][9][10] Of these, the family of [RuCl2(diphosphine)(diamine)] molecules developed by Noyori, Ikariya, Ohkuma and coworkers stands out. [11][12][13][14] Efficient enantioselective catalysts based on rhodium, [15][16][17] iridium, [18][19][20][21][22][23][24][25][26] and iron 27- 36 have also been reported in the literature. Interest in iridium as a catalytic metal is sparked by the observation that it outperforms rhodium for the ionic hydrogenation of particularly difficult substrates such as imines and industrial processes based on Ir-catalyzed ketone hydrogenation have been implemented. [37][START_REF] Bianchini | Iridium-catalyzed C=O hydrogenation[END_REF][START_REF] Malacea | [END_REF][40] Contrary to olefins, unsaturated oxygenated substrates may be hydrogenated by the outer sphere mechanism, 41,42 without substrate coordination. These processes are also characterized by the need of a strong base co-catalyst in order to function. In the generally accepted view, a proton from a metal coordinated XH function (typically an amine) is transferred to the O atom and a hydride is transferred to the C atom (Scheme 1, I  II). 43 The invoked role of the base in Noyori's systems is to allow the catalyst to remain in a more active neutral form (cycle B), whereas only the slower cycle A via the protonated form III would occur without base. 44 Indeed, certain isolated amido systems (e.g. complexes of type II) are active catalysts in the absence of added base. 43 Computational explorations of this mechanism, mostly carried out in the gas phase, have analyzed the neutral cycle (B) but have not addressed the role of the base, 43, except for occasionally verifying that the base-promoted HCl removal from a chloride complex pre-catalyst is exothermic. 67 Only one recent study has addressed the role of the base, using a solvent model, for the further deprotonation of the NH donor function in the neutral hydride complex with generation of a more active anionic complex. 68 Scheme 1. "Classical" outer sphere mechanism for the hydrogenation of ketones.

There are, however, efficient systems that do not contain active protons and yet a strong base is crucial. For instance, the iridium complexes [Ir(COD)(1 R )Cl] (2 R where 1 R = {CpFe[1,2-C5H3(PPh2)(CH2SR)}, Scheme 2) 69 are good pre-catalysts for aromatic ketone hydrogenation in alcohol solvents, 70 although only in the presence of a strong base such as MeONa or tBuOK. No significant activity was observed in the absence of H2 or when a weaker base such as NEt3 was used. This behavior is shared by many other catalysts that are devoid of active protons, whether they are used in hydrogenation 20 or transfer hydrogenation. [71][72][73][74][75][76][77][78][79][80] The common view is that the base is needed to eliminate the acidity generated during the catalyst activation step. Contrary to other compounds described in the literature, such as [Ir(BINAP){1,2-c-C6H10(NH2)2}(H)(Cl)] + and [Ir(COD){Ph2PhCH(Ph)CH(Me)NHMe}] + , 20,22 complexes 2 R also function quite well in aprotic solvents such as benzene or acetonitrile (so long as a strong base and H2 are present), 70 demonstrating that hydrogenation, rather than transfer hydrogenation, takes place at least under these conditions. Scheme 2. Ligand and pre-catalyst object of this study.

In pursuit of further mechanistic information on the catalytic action of 2 R , we have tested a pre-catalyst that internally contains the needed methoxide base as a ligand, [Ir(OMe)(COD)]2, leading to the conclusion that the active catalyst cannot be a neutral complex. We have also carried out additional experiments on non-enolizable substrates. Finally, a DFT analysis provided a rationalization of the experimental observations. The key result is that the hydrogenation cycle requires the generation of anionic species. This constitutes a new paradigm in the hydrogenation of carbonyl compounds, where access to an efficient outer sphere mechanism does not require the presence of deprotonatable ligands on the catalytic metal.

Results and Discussion

Experimental studies

Chloride vs. methoxide

In order to probe the effect of the strong base, we have now tested a pre-catalyst that internally contains the needed strong base for the generation of neutral chloride-free species. As previously reported, 70 compounds 2 R (R = Et, Ph, tBu, Bz) display high activity in the hydrogenation of substituted acetophenones when used in iPrOH in combination with a strong base (NaOMe, KOH or KOtBu) under an H2 atmosphere (30 bars) at room temperature or below (e.g. see run 1

in Table 1). Run 2 shows that the in situ generated chloride precatalyst yields the same activity as the isolated complex 2 Et , 70 thus it is not necessary to isolate compounds 2 R . Runs 3-5 confirm the need of both the ligand and a strong base for activity. Hence, the methoxide analogue was also generated in situ from [Ir(OMe)(COD)]2 and 1 Et , without attempting the isolation of putative [Ir(OMe)(COD)(1 Et )]. Contrary to our expectations, the [Ir(OMe)(COD)]2/1 Et catalyst showed only very small activity (run 6), comparable to that of the corresponding chlorido system (run 4)

and no activity was recorded in the absence of ligand (run 7). However, full activity was restored in the presence of both the ligand and the external base (run 8). When the enantiomerically pure ligand was used (run 9), the enantiomeric excess of the hydrogenation product (67%) was identical to that observed for the reaction catalyzed by 2 Et /NaOMe under the same conditions, 70 suggesting generation of the same active species. Hence, the chlorido ligand in [IrCl(COD)]2/1 Et or 2 Et has no active role in catalysis. This conclusion matches with that of another recent study 81 of the related Rh I complexes, where complexes [Rh(COD)(1 tBu )] + BF4 -and [RhCl(COD)(1 tBu )] whereas shown to feature the same catalytic behavior. 70 . d Enantiomerically pure ligand (S); e ee = 67% (S).

Non enolizable substrates

For certain hydrogenation catalysts, evidence has been advanced in favor of a mechanism proceeding through a metal-assisted enolization of the ketone, followed by hydrogenation of the enol C=C unsaturation. 82,83 Two non-enolizable ketones, PhCOR with R = CF3 and tBu, have therefore been used as substrates for the hydrogenation catalyzed by [IrCl(COD)]2/1 Et (runs 10 and 11, respectively). Although the catalytic activity is reduced for these systems, probably because of electronic effects in the former case and steric hindrance in the latter one, hydrogenation does take place. Hence, a hydrogenation mechanism without the need of tautomerization is energetically viable, at least for these two substrates.

Fate of the cyclooctadiene

Additional information on the nature of the catalyst activation process was sought by treating the [IrCl(COD)]2/1 Et mixture with H2 in the absence of substrate. This reaction results in COD elimination selectively as cyclooctene (observed by gas-chromatography), with no detectable trace of cyclooctane. Thus, hydrogenation of the COD ligand takes place at the initial stages of the hydrogenation catalysis and the cyclooctene product does not have sufficient binding affinity with the Ir center under these conditions to be further hydrogenated.

Mechanistic considerations

In sphere, although the vacant position can then be saturated by the ketone substrate or by the alcohol product. This would well rationalize the observation of catalytic activity even in a noncoordinating solvent. However, this neutral system cannot be the catalytically active species, because it should be equally accessible also from the [Ir(OMe)(COD)]2/1 Et mixture. The need of additional base to promote the catalytic activity points to further deprotonation with the generation of anionic species.

Numerous attempts have been made to identify the nature of the catalytically active species in solution by generation from [Ir(OMe)(COD)]2/1 Et and strong base in the absence of substrate, under a variety of different conditions and in different solvents and notably to find supporting evidence for its anionic nature, using NMR spectroscopic and mass spectrometric methods.

Because of the compounds extreme sensitivity, we have so far been unable to isolate or spectroscopically identify this species. Therefore, we have used computational chemistry to explore the likely nature and structure of a putative anionic catalyst.

DFT computational study

Cationic vs. neutral vs. anionic systems.

Exploratory investigations used a simpler model of 1, henceforth abbreviated as (PS), generated by replacing the ferrocene linker with a -CH=CH-linker and the phenyl groups by H atoms (see Scheme 3), but relevant systems were subsequently calculated with the real ligand.

The calculations included the effect of solvation by optimization in a polarizable continuum (methanol being used as the solvent) and the base was modelled by [MeO(MeOH)n-1] -clusters, yielding [(MeOH)n], 85 with n up to 6. The proton transfer Gibbs energies are greatly dependent on n for small n values but then converge, remaining essentially unchanged on going from 5 to 6 (see details in the SI). Only the values for n = 6 will be presented. Views of all calculated structures are in the SI and the energy results are presented in Figure 1. Note that these computational investigations are only meant to assess the relative stability of various species and do not intend to suggest the mechanism leading from the pre-catalyst to the most stable species.

Scheme 3. Ligand simplification used for the initial computational investigations. oxidative addition to 15 or by deprotonation of 10. Wherever there are isomeric possibilities, as noted above for the cationic and for the neutral systems, the most stable isomer is always the one placing the stronger σ donor ligand trans to S and the weaker one trans to P. Also parallel to the trends already noted for the cationic and neutral manifolds, the H2 oxidative addition processes are exoergic and the iPrOH reductive elimination processes are endoergic, though by a lesser amount. This phenomenon yields a trend of decreasing energy upon substitution of OiPr ligands with hydrides by the H2 oxidative addition -iPrOH reductive elimination sequence.

The most important energetic result, however, concerns the deprotonation. While for certain stoichiometries the most stable system is the neutral one (e.g. 6a vs. 4 and 11; 7b vs. 5b and 12b; 9 vs. 14) and the deprotonation of 8b to 13b is nearly thermoneutral, the tetrahydrido system 16 is much more stabilized than the protonated neutral version 10 and is by far the most stabilized species overall. It is therefore likely to correspond to the catalyst resting state. Note that 16 is isoelectronic with the [IrH4(PR3)2] -(R = iPr, Ph) anions, 86,87 which were isolated and fully characterized as salts of crown-ether-stabilized alkali metals. 86,88 After obtaining preliminary indications of the likely identity of the most stable solution species from the above exploratory investigations, selected calculations were carried out on the full system in order to assess the importance of electronic and steric effects associated to the ligand simplification. The calculations were carried out using 1 Ph as ligand at the full quantum mechanical level. The relative energies for all systems investigated did not greatly vary relative to those of the simpler model: cationic 5b Ph is at -1. . [89][90][91][92] However, detailed investigations by Halpern et al. subsequently demonstrated that the Pez complex, which yields [RuH3(PPh3)3] -under H2, 93,94 is reversibly protonated to [RuH2(H2)(PPh3)3] in alcohol solvents and that the latter "tetrahydride" complex is the real catalyst. 95 It seems that, after these debated contributions, the catalytic activity of anionic hydride complexes has no longer been considered.

Relevance of anionic hydrides in hydrogenation catalysis.

This Pez/Halpern contribution on the protonation state of the ruthenium-phosphine-hydride catalyst gives us the opportunity to benchmark our computational system. We have therefore computed the [RuH3(PPh3)3] -/[RuH2(H2)(PPh3)3] system using the same base and solvent models and level of theory as for the above iridium study. Three isomeric structures were optimized for the neutral system, one non-classical ruthenium(II) complex with a dihydrogen ligand, [RuH2(H2)(PPh3)3], and two classical ruthenium(IV) tetrahydride complexes (see Figure 3). The lowest energy isomer is the non-classical one, in agreement with NMR evidence 96,97 and with the solid state structure of a related complex. 98 The next lowest isomer has a 1:3:3 (capped octahedron) geometry, an H atom capping the fac (PPh3)3 face (3.2 kcal/mol higher than the nonclassical minimum). The less stable geometry can be described as a pentagonal bipyramid with two axial and one equatorial PPh3 ligands (4.3 kcal/mol higher than the minimum). The Using the same base and conjugate acid models also employed to calculate the deprotonation energetics of the iridium system, namely the [MeO(MeOH)5] -and (MeOH)6 clusters, the deprotonation of the tetrahydride complex was found nearly thermoneutral (-0.7 kcal/mol). This result is in good agreement with the experimental evidence of an equilibrated process for the [RuH3(PPh3)3] -/[RuH2(H2)(PPh3)3] system (the experimental study used cyclohexanol in THF-D8) 95 and confirms that the Ir system has greater tendency to be anionic in basic alcohol relative to the Pez/Halpern Ru system.

Exploration of the hydrogenation mechanism from the anionic complex 16.

The hydrogenation of polar substrates may in principle occur by several different mechanisms.

The most common ones are the inner-sphere, or coordination/insertion mechanism, which can be further classified into monohydride and dihydride mechanisms depending on the number of available hydrides on the catalytic metal and on the order of the insertion/H2 activation/reductive elimination events, and an outer-sphere mechanism where the catalyst provides a hydride and a proton to the substrate without the need of substrate coordination, either concertedly (e.g. as in Scheme 1) or stepwise. The fundamental problem of system 16 is that neither a coordination site Exploratory calculations (see Figure 4) where initially run on the simpler model and then repeated for the best cycle on the full system. Only the energies related to the full system are presented in Figure 4; once again, they do not substantially differ from those of the simpler model (see SI for the details). In addition, single-point calculations on all fixed optimized geometries were also repeated with a larger basis set (BS2, see Computational Details). The calculations used acetone as model substrate, methanol as model solvent and Na(MeOH)n + (n =

3) as counterion, while using cation models with n > 3 yielded higher G values for all systems.

The cycle starts with a [Na + (MeOH)3 Ph , corresponds to the isopropoxide substitution by H2. Therefore, the hydrogenation is in essence an outer sphere process with stepwise H -/H + transfer to the sodium-activated ketone, but the proton is not initially present on the catalyst; it is only provided in a later step after H2 activation. The cycle energy span is 18.2 kcal/mol (or 17.3

kcal/mol at the BS2 level), in good agreement with the observed high TOF at room temperature. 70 Indeed, for a TON of 500 in 2 h at 298K, a span of 19.0 kcal/mol can be calculated using the Eyring equation, but the initial TOF is greater for an estimated span closer to the computed value. Note that the alkali metal cation plays a crucial role in this mechanism, (17 Ph ). For each species the Gibbs energies (optimized geometry with BS1/fixed geometry with BS2) in kcal/mol are given in parentheses below the compound symbol.

It is of interest to compare the energy profile of this cycle with that recently presented by Dub et al. for the related [K] + [RuH2(BINAP)(NHCHPhCHPhNH2)] -species. 68 For the deprotonated Noyori catalyst, where a naked K + cation was used as opposed to our more realistic MeOHsolvated Na + cation, the calculated rate-determining transition state was the ketone insertion step.

This step yields an intermediate where the alkoxide ligand is not coordinated to the alkali metal but rather forms a hydrogen bond with the N-H group and a very weak σ C-H coordination to the Ru center. In this way, there is no need to displace a strongly bonded anionic ligand to coordinate H2, as opposed to our calculated cycle in which the alkoxide rearranges to bridge the Ir and Na metals.

Exploration of the hydrogenation mechanism from the neutral complex 9.

The next question to be addressed is why catalysis is not efficient in the absence of a strong base. This means that the best available cycle from a neutral iridium complex must have a higher energy span than the anionic system presented above. The lowest energy species calculated within the neutral manifold (which is accessed from [Ir(OMe)(COD)]2/1 Et when no strong base is added) is the trihydride complex 9. Therefore, this species is likely the resting state of any putative operating cycle under base-free conditions. Species 9 has an easily accessible vacant position for a coordination/insertion mechanism, made available by isopropanol dissociation, and also a proton (on the coordinated alcohol) for an outer sphere pathway.

Here, again, initial explorations were run on the simpler model system. Figure 5 shows the best cycle, while full details are provided in the SI. The first step is dissociative replacement of the isopropanol ligand to yield the acetone complex 25 via the coordinatively unsaturated trihydride complex 24. Isopropanol dissociation has a very small energy cost (3.8 kcal/mol) because of the strong trans labilizing effect of the hydride ligand. The next step is hydride insertion to yield the alkoxide complex 26, of which two isomers are possible (26a with the alkoxide trans to S, represented in Figure 5, and 26b with the alkoxide trans to P). Isomer 26b is actually lower in energy (at 3.8 kcal/mol relative to 9) because the two strongest trans labilizing ligands (the hydride and the P donor) are not mutually trans. However, isomer 26a leads to the lowest span cycle. Note that the isopropoxide ligand in 26a occupies the same equatorial position previously occupied by the hydride ligand: the axial ketone moves toward the equatorial plane concertedly with the insertion process. Therefore, this is an example of a real insertion, as opposed to a migratory insertion which characterizes the alkyl migration toward carbonyl groups in carbonylation processes or toward coordinated olefins in coordination polymerization processes.

The catalytic cycle is then closed by H2 coordination yielding the adduct 27a' and heterolytic activation, to transfer a proton to the coordinated isopropoxide and regenerate the hydride ligand via the rate-determining transition state TS(27a'-9). This pathway involves coordination of H2 to the equatorial position with concomitant rearrangement of the isopropoxide ligand, which migrates toward the axial position. The alternative H2 coordination to the vacant axial site trans to the hydride ligand in 26a, while yielding a lower energy dihydrogen complex 27a, leads to a higher energy TS for the final heterolytic activation step. It is also possible to envisage an alternative outer sphere pathway for the concerted transfer of a proton from the coordinated isopropanol and a hydride ligand from 9 to the outer sphere acetone (indicated as the dashed pathway in Figure 5). This, however, would generate the same dihydro-isopropoxide complex

26.

The coordination/insertion pathway that has already been found for this transformation is not the cycle rate-determining process. Therefore, even if the outer sphere H + /H -transfer were competitive with the coordination/insertion pathway, the cycle would remain limited by the rate of H2 activation and catalyst regeneration and the cycle energy span would not change. The catalyst regeneration step from 26 to 9 can also be envisaged in another way, by inverting the H2 addition and iPrOH formation steps. Isopropoxide-hydride coupling could take place first, to generate the [IrH(PS)(iPrOH)] system (8), followed by H2 oxidative addition. Thus, the mechanism would operationally become a "dihydride coordination/insertion" mechanism, as opposed to that shown in Figure 5 which is operationally a "monohydride coordination/insertion" mechanism. This possibility has also been explored on the model system, as shown in Figure 6.

In this case, the best pathway involves the lower energy isomer 26b. A direct transfer of the axial H atom from Ir to the isopropoxide ligand requires a very high activation barrier, but the involvement of an additional solvent molecule, modelled with methanol, makes the process easier through a proton shuttle mechanism. 26b forms an H-bonded adduct with MeOH, 26b•MeOH, which leads to 8b•MeOH via TS(26b-8b)•MeOH. While this TS is at lower energy relative to the non-MeOH assisted mechanism, it still remains at higher energy than the alternative rate-determining TS for the monohydride mechanism in Figure 5. Once arrived at the Ir I hydride complex 8b, the cycle is completed by H2 oxidative addition. The TS of this final step was not calculated since the high energy of TS(26b-8b)•MeOH already makes this pathway less viable than the monohydride coordination/insertion mechanism of Figure 5. Following this preliminary exploration and given the general fidelity of the relative energies found for the real system to those of the simpler model (vide supra), the cycle energy span for 4 the trans influence of these two ligands is alleviated by the alkoxide coordination to sodium and by the incipient substitution with H2.

Conclusion

We have experimentally demonstrated that the Ir ketone hydrogenation catalyst generated by activation of 2 cannot be a neutral iridium complex; the need of additional strong base suggests the generation of an anionic active complex. Calculations with the inclusion of implicit and explicit solvation effects and of the Na(MeOH)3 + counterion suggest that the contact ion pair [Na + (MeOH)3•••Ir -H4(PS)], containing an anionic tetrahydride complex similar to already described bis(phosphine) systems, is the catalyst resting state and yield a cycle with an energy span consistent with the observed catalytic activity. The base has the dual role of generating the anionic complex and providing the Lewis acid co-catalyst for ketone activation. The cycle is similar to that recently presented by Dub et al. for the Noyori catalyst. 68 However, we have demonstrated here for the first time that an outer sphere mechanism for ketone hydrogenation can be accessed also in the presence of "non-deprotonatable" supporting ligands, with the strong base playing a crucial role in the generation of anionic species through a sequence of H2 addition and deprotonation steps. Current work aims at studying the catalyst resting state by experimental methods. The role of the cation in the ketone activation will also be investigated in further combined experimental and computational work.

Experimental Section

All operations were carried out under an atmosphere of argon under standard glove-box and Schlenk-line techniques. Isopropanol was purified by distillation over CaH2. Ligand 1 Et and complex 2 Et were prepared as previously described. 69,104 Compounds [Ir(OMe)(COD)]2 (Strem), acetophenone (Aldrich, 99%), 2,2,2-trifluoroacetophenone (Lancaster, 98%) and phenyl tertbutyl ketone (Alfa Aesar, 98%) were used as received.

General procedure for asymmetric hydrogenation. In a glove box, a solution of 6.4•10 -3 mmol of catalyst (6.4•10 -3 mmol of 2 Et or 6.4•10 -3 mmol of 1 Et and 6.4•10 -3 mmol of metallic precursor), 3.2•10 -2 mmol of NaOMe (5 equiv, if appropriate) and 0.37 mL of acetophenone (381 mg, 3.2 mmol, 500 equiv) in 2 mL of iPrOH was transferred into a 5 mL glass ampoule which was then placed into a stainless steel autoclave. The reaction vessel was pressurized to the required H2 pressure (30 bars) and stirred with a magnetic bar for the desired time at 27 °C). The reaction was stopped by release of pressure and quenching of the solution with CH2Cl2 at room temperature. The crude materials were obtained by evaporation of the solvent on rotavapor. The product was finally analysed by chiral GC (Supelco BETA DEX 225).

Computational Details. The calculations were carried out within the DFT approach with the M06 functional, 105 including an ultrafine integration grid, as implemented in Gaussian 09. 106 All geometry optimizations were carried out using a basis set BS1, which consisted of the SDD basis

Figure 1 .

 1 Figure 1. Relative energy in methanol solution (ΔGMeOH in kcal/mol) of various species generated from [Ir(COD)(PS)] + /H2/[MeO(MeOH)5] -). Only the structures of the lowest energy

  5 kcal/mol relative to 6a Ph (vs. -5.2 kcal/mol for the model system), neutral 7b Ph , 9 Ph and 10 Ph are respectively at -11.9, -20.4 and -18.0 kcal/mol (vs. -13.5, -21.9 and -19.3 kcal/mol for the model system) and anionic 12 Ph , 14' Ph and 16 Ph are respectively at -7.8, -16.2 and -25.8 kcal/mol (vs. -9.1, -17.4 and -28.3 for the model system) showing a limited effect of the ligand backbone and substituents. The deprotonation from 10 Ph to 16 Ph is exoergic by -7.8 kcal/mol (cf. -9.0 kcal/mol for the model system). The geometry of 16 Ph , the lowest energy system calculated by this study, is depicted in Figure2. To conclude, the DFT calculations suggests a thermodynamically favorable transformation of the iridium precatalysts 2 R to the octahedral anionic tetrahydride complex 16 R in the presence of H2 and a strong base in alcohol solvents.

Figure 2 .

 2 Figure 2. View of the optimized geometry for the anionic complex [IrH4(1 Ph )] -(16 Ph ).

  Quite some time ago, Pez et al. proposed the role of anionic hydride species in the catalytic hydrogenation of several oxygenated substrates, following the isolation and characterization of ortho-metallated [K(Ln)][RuH2(κ 2 :C,P-o-C6H4PPh2)(PPh3)2] salts (Ln = solvent or crown

  anionic trihydride complex [RuH3(PPh3)3] -has a regular octahedral geometry with a fac arrangement of the hydrides and PPh3 ligands, as in the experimentally determined structures of [K(18-crown-6)][RuH3(PPh3)3] 99 and [Li(THF)3][RuH3(PPh3)3]. 100

Figure 3 .

 3 Figure 3. Relative energy in methanol solution (ΔGMeOH in kcal/mol) of three "RuH4(PPh3)3"

3 (

 3 PPh 3 ) 3 ] - for a ketone coordination/insertion pathway nor a transferrable proton for the outer sphere pathway are available. A possible pathway, however, follows that recently presented by Dub et al. to reappraise the hydrogenation mechanism in the presence of Noyori's catalyst, 68 concluding that the base (tBuOK) serves to deprotonate the amine in [RuH2(BINAP)(NH2CHPhCHPhNH2)].The operating cycle occurs on a [K] + [RuH2(BINAP)(NHCHPhCHPhNH2)] -system with stepwise hydride transfer, H2 coordination and proton transfer, whereas II (Scheme 1) is only an off-loop species.

insuring the ketone activation in intermediate 18 .

 18 Evidence in favor of an active role played by the alkali cation has been documented for Ru II -diamine-based hydrogenation catalyst.102, 103

Figure 4 .

 4 Figure 4. Computed cycle for acetone hydrogenation catalyzed by [Na(MeOH)3][IrH4(1 Ph )]

Figure 5 .

 5 Figure 5. Best cycle for acetone hydrogenation catalyzed by [IrH4(1 Ph )(iPrOH)] (9). For each

Figure 6 .

 6 Figure 6. Alternative O-H coupling/H2 oxidative addition pathway for the regeneration of the

  set and ECP for the Ir and Fe atoms, 107 augmented with f polarization functions (α = 0.938 and 2.462, respectively), 108 the 6-31G(d) basis set for all other heavy atoms, and the 6-31G(d,p) basis set for all H atoms.109 All molecules involved in the best catalytic cycle (see Results and Discussion) were also recalculated at their fixed geometries with a more extended basis set BS2 (same SDD functions for Ir and Fe, plus the 6-311++G(d,p) functions for all other atoms). The effect of the solvent was included by the SMD polarizable continuum110 in methanol (ε=35.688) during the geometry optimizations with BS1 and single point calculations with BS2. All of the energies presented in the text are Gibbs energies in methanol (ΔGMeOH). A correction of 1.95 kcal/mol was applied to all G values to change the standard state from the gas phase (1 atm) to solution (1 M). 111 Synopsis Activation of [IrCl(COD)(PS)], [IrCl(COD)]2/PS or [Ir(OMe)(COD)]2/PS (PS = ferrocenyl phosphine thioether) under H2 requires the presence of a strong base such as MeONa in order to yield an efficient ketone hydrogenation catalyst. A computational investigation using [MeO(MeOH)n] -as a model base for deprotonation yields anionic [IrH4(PS)] -as the lowest energy species. A catalytic cycle starting from the [Na + (MeOH)3•••Ir -H4(PS)] contact ion pair yields an energy span in agreement with the experimentally observed efficiency.

Table 1 .

 1 Results of catalytic runs for the hydrogenation of PhCOR to PhCH(R)OH. a

run catalyst ligand Additive R Time (h) Conv.(%) b

	1 c	2 Et	-	NaOMe	CH3	5	>99
	2	[Ir(COD)Cl]2	1 Et	NaOMe	CH3	5	>99
	3 c	2 Et	-	-	CH3	5	0
	4	[Ir(COD)Cl]2	1 Et	-	CH3	5	7
	5	[Ir(COD)Cl]2	-	-	CH3	5	0
	6	[Ir(COD)(OMe)]2 1 Et	-	CH3	5	7
	7	[Ir(COD)(OMe)]2 -	-	CH3	5	0
	8	[Ir(COD)(OMe)]2 1 Et	NaOMe	CH3	5	98
	9	[Ir(COD)(OMe)]2 1 Et d	NaOMe	CH3	5	81 e
	10	[Ir(COD)Cl]2	1 Et	NaOMe	CF3	2	42
	11	[Ir(COD)Cl]2	1 Et	NaOMe	tBu	5	25
	a Reaction conditions: racemic catalyst, 6.4•10 -3 mmol ; additive, 3.2•10 -2 mmol ;
	acetophenone, 3.2 mmol; under 30 bars at 27°C in 2 mL of isopropanol. b Conversions
	determined by GC; 100% selectivity in (R/S)-PhCH(R)OH.

c

From ref.

4, -0.3 12a, 12a'

	3.2
	11
	0.1
	-6.8
	12b'
	H 2
	H 2

13a 13b -4.5 14' -17.4 iPrOH 15 -7.7

  examined above. The lowest energy isomer (7b) features the strongest donor ligand (hydride) trans to S. These four compounds can also be generated by deprotonation of the corresponding isomers of 5. It now possible to envisage iPrOH reductive elimination from 7 to yield two isomers of [IrH(PS)(iPrOH)] (8a and 8b), which may also be generated by deprotonation of 5 at the metal with concomitant iPrOH release. Isomer 8b with the hydride ligand trans to S is the more stable one. The iPrOH reductive elimination process is endoergic by ca. 7 kcal/mol. It is then possible to oxidatively add H2 to 8a/b to give [IrH3(PS)(iPrOH)] with [IrH3(OiPr)(PS)] -(14, two isomers) by H2 oxidative addition to 13 or by deprotonation of 9, [IrH2(PS)] -(15) by iPrOH reductive elimination from 14, and finally [IrH4(PS)] -(16) by H2

				9.3	cationic
				4	4.0, 5.1
			ΔG solv		5a, 5a' -5.2 -1.1 5b'
			H 2	5b
		4.0 6b		2.7 8a	neutral
		0.0 6a	-4.8 7a	-4.7 8b
	ΔG solv	H 2	7b, 7b' -12.3, -13.4 -7.5 7a'		-21.5
					9'	-19.3
			iPrOH	-21.9	10
				H 2	9
					H 2
	ΔG solv		14 -17.0		iPrOH anionic
					H 2	-28.3
				iPrOH	16
		Hydrogenation
	Concerning the anionic species, [Ir(OiPr)2(PS)] -(11) is obtained by deprotonation of 6a or 6b,
	[IrH2(OiPr)2(PS)] -(12, four isomers) by H2 oxidative addition to 11 or by deprotonation of 7,

isomers, H trans to S); blue (numbers with no letter, primed numbers for isomers), symmetric systems.

Starting from the cationic [Ir(PS)(COD)] + (3), COD removal by hydrogenation coupled to isopropanol coordination yields [Ir(PS)(iPrOH)2] + (4). This process is undoubtedly exothermic and the formation of cyclooctene has been experimentally demonstrated, therefore no calculations were carried out on this step. Complex 4 is 9.3 kcal/mol higher than the neutral system [Ir(OiPr)(PS)(iPrOH)] (iPrOH trans to P, isomer 6a), which is taken as the reference point on the G scale. H2 oxidative addition to 4 to yield [IrH2(PS)(iPrOH)2] + (5) can occur in 4 different ways, each one leading to a different stereoisomer. Indeed, H2 may add along the P-Ir-O or the S-Ir-O' vector and in each case the additions either above or below the coordination plane are diastereotopically related because of the ligand chirality. Of the four possible isomers, 5a and 5a' with a hydride ligand trans to P and 5b and 5b' with a hydride ligand trans to S, the two latter ones have lower energy because the strongest trans labilizing ligand (hydride) is located trans to the less strongly bonded donor atom (S). Figure

1

illustrates the energy of all isomers but details only the geometry of the lowest energy one. All chemical drawings are provided in the SI.

Neutral and anionic systems can be obtained by single and double deprotonation. In the neutral manifold, two isomers of [Ir(OiPr)(PS)(iPrOH)] (6a and 6b) are generated by deprotonation of 4, involving either the isopropanol ligand located trans to S (isomer 6a) or that trans to P (6b). The deprotonation process is energetically favorable and the lowest energy isomer is 6a where the isopropoxide, which is a stronger donor than isopropanol, is located trans to the weaker donor S atom. H2 oxidative addition to 6 to generate [IrH2(OiPr)(PS)(iPrOH)] (

7

) is also energetically favorable and may occur in four different ways, by analogy to the H2 oxidative addition to the protonated analogue 4 three fac H ligands (9 and 9', both generated from either 8a or 8b). This process is very exothermic, even when starting from the most stable isomer 8b (ΔG = -17.2 kcal/mol). The two products have a symmetric substitution pattern trans to the PS ligand, therefore only two isomers are possible, differing by the placement of the axial H and iPrOH ligands above and below the enantiomeric equatorial plane. Putative mer isomers of 9 would be disfavored because of strong trans influence of the mutually trans H atoms and have not been considered. Another possible tautomer, the 7-coordinate [IrH4(OiPr)(PS)] of formally Ir V , converged to a nonclassical octahedral isomer of Ir III , [IrH2(OiPr)(H2)(PS)] (9"), at much higher energy and is not included in Figure

1

. Substitution of iPrOH with H2 in 9 or 9' leads to [IrH3(H2)(PS)], 10. A classical pentahydride tautomer of this compound (10') was found higher in energy (see SI). Hence, the lowest energy species in the neutral manifold is the trihydride complex 9. This will be considered as the putative catalyst resting state in hydrogenation cycles carried out in the absence of base (vide infra).

[IrH(OiPr)(PS)] -(13, two isomers) by iPrOH reductive elimination from 12 or by deprotonation of 8,

(21-22)

  The acetone adduct 18Ph is only slightly more stable, by 0.4 kcal/mol, than the precursor 17Ph , but becomes less stable after recalculation with BS2. Hydride transfer follows to generate a Na + -anchored alkoxide (19 Ph ) held in the Ir coordination sphere by σ C-H coordination, which then rearranges to a more stable µ2-O isomer (20 Ph ). In the next step, H2 displaces OiPr from the Ir coordination sphere to yield 22 Ph through a van der Waals adduct (21 Ph ) as a local minimum. The H2 ligand in 22 Ph then delivers a proton to the Na + -bonded OiPr ligand to yield an isopropanol adduct 23 Ph and the cycle is completed by product expulsion. The resting state is the acetone adduct 18 Ph (or the tetrahydrido complex 17 Ph at the BS2 level) and the rate determining transition state, TS

•••16 Ph ] ion pair

(17 Ph

). The Na + cation anchors the ketone substrate in the first step (17 Ph -18 Ph ). A very recent paper has also highlighted the role of the alkali metal cation, modeled as [Na(H2O)6] + , in the formate decarboxylation catalyzed by an iron pincer complex.

101

  the real system was assessed by calculating only the resting state 9 Ph , the key intermediate 27a'Ph , which was found at 26.3 kcal/mol from 9Ph . The energy span of this cycle is therefore 26.3 kcal/mol, i.e. 8.1 kcal/mol higher than that afforded by the anionic hydride 17Ph . This result agrees with the experimental evidence that hydrogenation is efficient only when a strong base in present. The rate determining transition state for the neutral cycle is unfavorable because it involves heterolytic H2 activation in a structure with two mutually trans strong ligands (H and OiPr), whereas in the anionic cycle of Figure

	TS(27a'-9)
		(32.9)
		TS(26b-8b)
		(25.0)
		(14.0) TS(26b-8b)•MeOH
				(11.4)
	(3.8)	(2.7)	8b•MeOH	8b
	26b			9
		26b•MeOH		(-5.8)

Ph

for the best cycle (found at 19.6 kcal/mol from 9 Ph ), and the rate determining transition state

ACKNOWLEDGMENT

We thank the European Commission through the HYDROCHEM program (contract HPRN-CT-2002-00176) for support of this work. Additional bilateral support (LEA, Toulouse-Barcelona) and National support from the CNRS (France), from the Institut Universitaire de France, and from the MINECO (project CTQ2014-54071-P, Spain) is also gratefully acknowledged.

ASSOCIATED CONTENT

Supporting Information. Additional details of the DFT calculations, Cartesian coordinates and views of the optimized geometries. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION

Corresponding Author

* Agustí Lledós: fax. +34-935912477 E-mail agusti@klingon.uab.es. * Rinaldo Poli: fax. +33-561553003; E-mail rinaldo.poli@lcc-toulouse.fr.

Present Addresses

Author Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Notes

The authors declare no competing financial interest.