Yi Yang

Nathalie Saffon-Merceron

Julien C Vantourout

Anis Tlili
email: anis.tlili@univ-lyon1.fr

Novel N(SCF 3 )(CF 3 )-amines: synthesis, scalability and stability †

We disclosed herein a straightforward strategy for the synthesis of unprecedented N-((trifluoromethyl)thio), N-(trifluoromethyl) amines using a combination of isothiocyanates with a fluoride source and an electrophilic trifluoromethylthiolation reagent. More interestingly, the scalability of the methodology has been demonstrated and the stability of the new motif has been studied.

Organouorine chemistry is by far one of the most active elds of research in modern organic chemistry. The unique properties induced by the uorine atom or uorinated motifs including high lipophilicity, increased solubility and metabolic stability have witnessed the efforts for extensive development during the last few years. 1 Nowadays, uorinated molecules are extensively used in agrochemicals 2 as well as for pharmaceutical 3 applications. In this span of time, several efficient procedures for the incorporation of triuoromethyl and triuoromethyl chalcogens have been reported in the literature through reagent and/ or catalyst design as well as methodology developments. 4 Nitrogen is also a predominant atom in life science technologies; 5 therefore the association of amines with uorinebased motifs such as triuoromethyl groups has been the quest of several research groups. For example, N-triuoromethyl azoles have demonstrated excellent in vitro aqueous stability which might improve metabolic stability and membrane permeability compared to their N-methyl counterparts. 6 In this context, several direct methodologies have been developed to access N-CF 3 amines making use of electrophilic tri-uoromethylation reagents, namely Umemoto 7 and Togni 8 reagents or radical triuoromethyl sources (Scheme 1A). 9,10 However, these strategies offer limited scope especially with regard to the amine starting material. A breakthrough was disclosed by the Schoenebeck group in 2017. In their study, the authors demonstrated that a wide range of triuoromethylamines could be accessed via in situ generation of thiocarbamoyl uoride using bench stable (Me 4 N)SCF 3 (Scheme 1A). 11 Aerwards, several groups designed new strategies to access the key thiocarbamoyl uoride intermediate. [12][13][14][15] Finally, the group of Xu recently reported an elegant oxidative approach for the synthesis of tri-uoromethyl amine reagents which have been used for the transfer of the N-CF 3 moiety. 16 Another way to access triuoromethylamines relies on the use of isothiocyanates. Indeed, in 1965, Shepard 17 initially reported that nucleophilic amines could be formed from isothiocyanates using mercury uoride. Inspired by this precedent, the group of Schoenebeck 18 elegantly demonstrated that silver uoride could efficiently replace the mercury-based reagent offering a practical and general way to synthesize N-tri-uoromethyl carbamoyl uoride (Scheme 1B). This procedure has been also adapted by the groups of Toste and Wilson 19 for the synthesis of N-triuoromethyl amides (Scheme 1B).

N,N-bis(triuoromethyl) amines represent another valuable motif due to their enhanced lipophilicity and stability in comparison to aliphatic and aromatic N-triuoromethylamines. 20,[START_REF] Hart | Halogenoamines have been also used, for a selected example please[END_REF] Despite these interesting properties, access to N-(CF 3 ) 2 amines remains very scarce with most promising synthesis employing a combination of N,N-bis(triuoromethyl)tri-uoromethanesulphonamide and a metal-based reagent (Scheme 1C). [START_REF]For selected references for the use of N,Nbis(triuoromethyl)triuoromethanesulphonamide please see[END_REF] Therefore, there is a clear need for developing new motifs that could be easily and robustly accessible while modulating the properties around the nitrogen atom such as the lipophilicity (Scheme 1D). 23 In this context, we report herein an unprecedented, mild and efficient protocol for accessing novel N-((triuoromethyl)thio)-N-(triuoromethylamines) starting with isothiocyanates and electrophilic triuoromethylthiolation reagents (Scheme 1E).

From a reaction design standpoint, inspired by the work of Schoenebeck, we envisioned that a triuoromethylamino nucleophile intermediate could be rst in situ generated by the reaction of isothiocyanate with silver uoride before subsequently reacting with an electrophilic triuoromethylthiolating source to furnish the desired compounds.

We initiated our study by using benzyl isothiocyanate 1a as a model substrate in the presence of three equivalents of silver uoride (Table 1). We found that the formed nucleophilic amine was able to react with the electrophilic Munavalli's 24 N-tri-uoromethylthiophthalimide 2a in MeCN at room temperature delivering the desired product 3a in 50% yield (Table 1, entry 1). This encouraging result decided us to further investigate parameters that could enhance the reaction outcome. We rst studied the impact of the solvent on the formation of the desired product.

THF and 1,4-dioxane as well as DCM were not suitable for the formation of 3a (Table 1, entries 2 &3). Lower yields were obtained when using DMSO and DMF, 30% and 40% respectively (Table 1, entries 2 and3). In addition, increasing the temperature was found to be detrimental since only 35% of 3a was obtained at 50 °C (Table 1,entry 7). Then, the impact of the triuoromethylthiolating reagent was investigated. Surprisingly, the attempt in switching to the more electrophilic Shen's reagent (N-tri-uoromethylthiosaccharin) 25 resulted in lower efficiency with compound 3a only obtained in 30% yield (Table 1, entry 8). To our delight, adding one equivalent of cesium uoride allowed for the formation of the desired product in 75% yield (Table 1,entry 9). Finally, potassium uoride did not improve the overall efficiency of the process (Table 1, entry 10).

With the best set of conditions in hand, we evaluated the effectiveness of the protocol for different isothiocyanate starting materials. Initial tests were devoted to subjecting benzylic isothiocyanate to our reaction conditions. The desired compounds were obtained from low to very good yields (Scheme 2, products 3a-c). Aerwards, aliphatic isothiocyanates were exposed to the reaction conditions and proved compatible with yields up to 67% (Scheme 2, products 3d-3i). Noteworthily, the melatonin precursor derivative (Scheme 2, compound 3d) was derivatized in a synthetically useful isolated yield of 35%. Several protected tertiary amines were also found to be effective under the reaction conditions (Scheme 2, products 3g-3i). Next, aromatic isothiocyanates were evaluated. Electron rich aryl starting materials were tolerated using our protocol and the desired products were obtained with yields up to 78% (Scheme 2, products 3j-3q). It should be mentioned that Scheme 1 (A-E) State of the art for the synthesis of trifluoromethylated amines and the need for accessing new motifs. a Reactions were performed with 1a (0.2 mmol, 1 equiv.), 2a (0.2 mmol, 1 equiv.), AgF (0.6 mmol, 3 equiv.) and solvent (1 mL) for 16 hours.

b Determined by 19 F NMR spectroscopy with PhCF 3 as an internal standard. Shen's reagent 2b (N-triuoromethylthiosaccharin).

Scheme 2 Substrate scope. Condition A: reactions were performed with 1 (0.2 mmol, 1 equiv.), 2a (0.2 mmol, 1 equiv.), AgF (0.6 mmol, 3 equiv.) and CsF (0.2 mmol, 1 equiv.) in MeCN (1 mL) Yields of isolated compounds. Yields of isolated compounds for 16 hours. a Yield determined by 19 F NMR spectroscopy with PhCF 3 as an internal standard. b Condition B: reactions were performed with chamber 1 (C1): 1 (0.2 mmol, 1 equiv.) and AgF (0.8 mmol, 4 equiv.) in MeCN (1 mL); chamber 2 (C2): CF 3 SO 2 Na (0.6 mmol, 3 equiv.) and Ph 2 PCl (0.6 mmol, 3 equiv.) in MeCN (1 mL) for 16 hours, yields of isolated compounds. c Reactions were performed with chamber 1 (C1): 1 (0.2 mmol, 1 equiv.) and AgF (0.8 mmol, 4 equiv.) in MeCN (1 mL); chamber 2 (C2): CF 3 SO 2 Na (0.6 mmol, 3 equiv.) and Ph 2 PCl (1.2 mmol, 6 equiv.) in MeCN (1 mL) for 16 hours, yields of isolated compounds. ortho, meta or para substituted isothiocyanates are suitable partners.

The para substituted phenylisothiocyanate with a phenyl ring furnishes the desired product in 67% yield (Scheme 2, 3r). Interestingly, the structure of 3m was unambiguously conrmed by Xray crystallographic analysis. 26 Aerwards, we evaluated the inuence of electron withdrawing substituents on the starting aryl isothiocyanate derivatives. Unfortunately, the presence of strong electron withdrawing groups including NO 2 , CN or uorine was detrimental to the reaction and no product formation was observed (Scheme 2, products 3s-3u) probably due to a decrease of the nucleophilicity of the resulting triuoromethyl amine anion intermediate. Knowing that Shen's reagent would be too electrophilic (vide supra) and based on the relative triuoromethylthio cation-donating scale, 27 we identied the triuoromethylthio dimer ((SCF 3 ) 2 ) as the most promising reagent to employ. In addition, the in situ generation of such a reactive species has been well documented in the literature. 4a Indeed, the Langlois reagent can react with phosphine derivatives to yield nucleophilic SCF 3 (ref. 28) which can easily be oxidized to the desired dimer. Disappointingly, our initial in situ test turned out to be ineffective. Being aware of the incompatibly issues that could arise from mixing together of all the reaction components, we decided to use a two-chamber reactor. In chamber 2, formation of the -SCF 3 anion was achieved by reacting chloro diphenylphosphine with the Langlois reagent.

This unstable anion readily collapses to afford the tri-uoromethylthio dimer ((SCF 3 ) 2 ) (see ESI for details †).The formation of nucleophilic triuoromethylamine through uorinative desulfurization with AgF also yield the Ag 2 S by-product that could potentially oxidize AgSCF 3 to afford the tri-uoromethylthio dimer ((SCF 3 ) 2 ). Our hypothesis turned out to be effective when isothiocyanate was mixed with silver uoride in the rst chamber while Langlois's reagent reacted with PPh 2 Cl in the second chamber. Under these conditions, electron poor arenes including NO 2 , CN, CF 3 , acetyl, and ester could be transformed into the desired products with isolated yields up to 80% (Scheme 2, products 3s-3r). Halogen substituted arenes including bromo and uoro derivatives were also obtained in excellent yields of 70% and 75%, respectively (Scheme 2, products 3z, 3u). Naphthalene derivative 3aa was obtained in 72% yield. Finally, we decided to assess this protocol for electron donating arene derivatives as well as for aliphatic compounds to offer a complementary approach to the original one (condition A) using commercially available reagents. It turns out that these new conditions are also effective with electron donating aryl isocyanate derivatives and the desired products are formed with very good yields up to 90% (Scheme 2, products 3ab, 3j-m). Herein also diarylether derivatives substituted with halogens, including uoro, chloro and bromo were tolerated and the desired products were obtained in an excellent yield up to 90% (Scheme 2, products 3ab, 3ac & 3ad). Moreover, aliphatic product 3g was also obtained in good yield (60%) while the penicillin core structure was derivatized in a synthetically useful yield of 33% (Scheme 2, product 3af). Finally, the robustness of our strategy was further demonstrated starting with other complex structures. Indeed, using DL-menthol derivatives allowed us to obtain the desired product 3ag in good isolated yield of 56%. Also, using the diacetonefructose derivatives allows the formation of the compound 3ah in very good yield. Finally, vitamin E derivative 3ai was obtained with an excellent yield of 83% when the reaction was performed in a mixture of ether/MeCN to increase the solubility of the starting 1ai.

The robustness of the second protocol was further demonstrated by performing a large-scale experiment. Starting with 10 mmol of isothiocyanate and using a 300 mL two-chamber reactor allowed both desired products 3m and 3r to be synthesized in very good yields of 60% and 59%, respectively (Scheme 3A).

Unsurprisingly, product 3r turned out to be completely stable in CH 3 CN and DMSO as well as in water for more than 48 hours (Scheme 3B). This compound also demonstrated high stability under acidic conditions (HCl 1 M and pH 4) and in pH = 7 buffer with more than 90% recovery. Rapid degradation was observed under basic conditions (pH 10 and NaOH (1 M)). Interestingly, very high stability under saline conditions was also observed.

Scheme 3 (A) Scale-up experiments: a reactions were performed with chamber 1 (C1): 1 (10 mmol, 1 equiv.) and AgF (40 mmol, 4 equiv.) in MeCN (50 mL); chamber 2 (C2): CF 3 SO 2 Na (30 mmol, 3 equiv.) and Ph 2 PCl (60 mmol, 6 equiv.) in MeCN (50 mL) for 24 hours. b Reactions were performed with chamber 1 (C1): 1 (20 mmol, 1 equiv.) and AgF (80 mmol, 4 equiv.) in MeCN (100 mL); chamber 2 (C2): CF 3 SO 2 Na (60 mmol, 3 equiv.) and Ph 2 PCl (120 mmol, 6 equiv.) in MeCN (100 mL) for 24 hours yields of isolated compounds. (B) Stability of compound 3r in various media. (C) Proposed mechanism.

From a mechanistic standpoint, condition A proceeds via the generation of triuoromethyl amine anion I that subsequently reacts with the electrophilic triuoromethylthiolating reagent 2a yielding the desired product (Scheme 3C). On the other hand, for condition B, the key to success is the generation of the electrophilic CF 3 SSCF 3 dimer 2c. Dimer 2c nally reacts with nucleophilic amine I intermediate to deliver the desired product (Scheme 3C).

Conclusions

In summary, we reported the discovery of two efficient and complementary protocols for the synthesis of unprecedented N-((triuoromethyl)thio), N-(triuoromethyl) amines. While one uses a shelf-stable electrophilic triuoromethylthiolation reagent, the other employs a two-chamber reactor for the in situ generation of an electrophilic trilfuoromethylthiolating reagent. The desired products have been obtained in moderate to excellent yields. The scalability of the reaction was demonstrated through the preparation of more than 3.7 grams of the desired compounds. Importantly, N(SCF 3 )CF 3 shows high aqueous stability. We assume that this discovery will pave the way to future developments in this exciting eld of research.

  Scheme 2 Substrate scope. Condition A: reactions were performed with 1 (0.2 mmol, 1 equiv.), 2a (0.2 mmol, 1 equiv.), AgF (0.6 mmol, 3 equiv.) and CsF (0.2 mmol, 1 equiv.) in MeCN (1 mL) Yields of isolated compounds. Yields of isolated compounds for 16 hours. a Yield determined by19 F NMR spectroscopy with PhCF 3 as an internal standard. b Condition B: reactions were performed with chamber 1 (C1): 1 (0.2 mmol, 1 equiv.) and AgF (0.8 mmol, 4 equiv.) in MeCN (1 mL); chamber 2 (C2): CF 3 SO 2 Na (0.6 mmol, 3 equiv.) and Ph 2 PCl (0.6 mmol, 3 equiv.) in MeCN (1 mL) for 16 hours, yields of isolated compounds. c Reactions were performed with chamber 1 (C1): 1 (0.2 mmol, 1 equiv.) and AgF (0.8 mmol, 4 equiv.) in MeCN (1 mL); chamber 2 (C2): CF 3 SO 2 Na (0.6 mmol, 3 equiv.) and Ph 2 PCl (1.2 mmol, 6 equiv.) in MeCN (1 mL) for 16 hours, yields of isolated compounds. d 1.5 mL of ether and 0.5 mL of ACN as a solvent mixture in tube C1.

Table 1

 1 Optimization of the reaction

	Entry a	Deviation from standard conditions	Yield b (%)
	1	None	50
	2	THF or dioxane instead of MeCN	0
	3	DCM instead of MeCN	0
	4	PhMe instead of MeCN	5
	5	DMSO instead of MeCN	30
	6	DMF instead of MeCN	40
	7	50 °C instead of rt	35
	8	2b (Shen's reagent) instead of 2a	30
	9	With 1 equiv. of CsF	75
	10	With 1 equiv. of KF	40

© 2023 The Author(s). Published by the Royal Society of Chemistry

© 2023 The Author(s). Published by the Royal Society of Chemistry Chem.Sci., 2023, 14, 3893-3898 | 3897

| Chem. Sci., 2023, 14, 3893-3898 © 2023 The Author(s). Published by the Royal Society of Chemistry

Acknowledgements

Financial support from the CNRS and the Agence Nationale de la Recherche (ANR-JCJC-2020-CDI-DEOX) is gratefully acknowledged. Y. Y. thanks the CSC (China Scholarship Council) for a doctoral fellowship.

Notes and references

Data availability

Experimental data have been provided in the ESI. †

Author contributions

Y. Y. and A. T. conceived the project. J. C. V. and A. T. supervised the work and wrote the manuscript. N. S. M. performed the Xray analysis. All the co-authors contributed to the editing of the manuscript.

Conflicts of interest

There are no conicts to declare.


Yi Yang

Alexis Taponard

Julien C Vantourout
email: julien.vantourout@univ-lyon1.fr

Anis Tlili
email: anis.tlili@univ-lyon1.fr

Synthesis of Fluorinated Amines: a Personal Account

Keywords: Carbamoyl fluorides, CO 2 activation, Thiocarbamoyl fluorides, Trifluoromethylamines, Deoxyfluorination, SF 6 activation, Trifluoromethylthiolation, Organophotoredox catalysis

This account highlights the recent contributions made by our laboratory in the development of novel strategies to synthesize fluorinated amines. These strategies allow the practitioner to efficiently access carbamoyl fluorides, thiocarbamoyl fluorides as well as trifluoromethylamines using CO 2 or CS 2 as benign C1 sources. In addition, a novel N(SCF 3 )CF 3 moiety was synthesized. Noteworthy, we demonstrated that this reagent could also be used in radical-or electrophilic-based trifluoromethylthiolation reactions.

The synthesis of fluorinated compounds has attracted much attention these last years, and today a plethora of compounds bearing a fluorine atom have found a variety of applications in life sciences. [START_REF]Fluorine in Life Sciences: Pharmaceuticals, Medicinal Diagnostics, and Agrochemicals[END_REF][START_REF] Kirsch | Modern Fluoroorganic Chemistry[END_REF][START_REF] O'hagan | Understanding organofluorine chemistry. An introduction to the C-F bond[END_REF] The driving force for investigating the incorporation of fluorine moieties on several classes of molecules is due to the intrinsic physiochemical properties induced by the fluorine atom including high lipophilicity, high stability and better resistance toward oxidation. [START_REF] Leo | Partition coefficients and their uses[END_REF][START_REF] Linclau | Investigating the Influence of (Deoxy)fluorination on the Lipophilicity of Non-UV-Active Fluorinated Alkanols and Carbohydrates by a New log P Determination Method[END_REF][START_REF] Hagmann | The Many Roles for Fluorine in Medicinal Chemistry[END_REF] In addition to fluorine, the nitrogen atom is also ubiquitous in several valuable compounds. [START_REF] Vitaku | Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals[END_REF] Thus, the association of both of these atoms should clearly be attractive for several research domains.

In this context, we have recently established a research program aiming to develop new fluorinated amine derivatives. This account highlights the contributions made by our laboratory over the past few years.

SYNTHESIS OF CARBAMOYL FLUORIDES, THIOCARBAMOYL FLUORIDES AND TRIFLUROMETHYLAMINES

The synthesis of carbamoyl fluorides has attracted much attention these last five years due to the increased stability of such motif in comparison to other halogenated analogues. [START_REF] Kobayashi | Palladium-Catalyzed Intramolecular Cyanoamidation of Alkynyl and Alkenyl Cyanoformamides[END_REF][START_REF] Hande | Flexible Strategy for Syntheses of Spirooxindoles using Palladium-Catalyzed Carbosilylation and Sakurai-Type Cyclization[END_REF][START_REF] Eastwood | Synthesis of the Madangamine Alkaloid Core by a C-C Bond Activation Cascade[END_REF][START_REF] Wu | Pd-Catalyzed Regiodivergent Synthesis of Diverse Oxindoles Enabled by the Versatile Heck Reaction of Carbamoyl Chlorides[END_REF][START_REF] Fan | Nickel/Photo-Cocatalyzed Asymmetric Acyl-Carbamoylation of Alkenes[END_REF][START_REF] Liu | Atom-and Step-Economical Pathway to Chiral Benzobicyclo-[2.2.2octenones through Carbon-Carbon Bond Cleavage[END_REF][START_REF] Zhou | 4 + 1) vs (4 + 2): Catalytic Intramolecular Coupling between Cyclobutanones and Trisubstituted Allenes via C-C Activation[END_REF] However, historical synthetic strategies were mainly based on the use of toxic difluorophosgene derivatives. [START_REF] Pichette Drapeau | Modern synthesis of carbamoyl fluorides[END_REF][START_REF] Quan | Syntheses of isocyanates via amines and carbonyl fluoride[END_REF][START_REF] Liu | Recent Advances in the Synthesis and Transformation of Carbamoyl Fluorides, Fluoroformates, and Their Analogues[END_REF] More friendly alternatives were since developed relying on the in-situ generation of difluorophosgene from a trifluoromethoxy anion [START_REF] Song | Concise and Additive-Free Click Reactions between Amines and CF 3 SO 3 CF 3[END_REF][START_REF] Turksoy | Facile Access to AgOCF 3 and Its New Applications as a Reservoir for OCF 2 for the Direct Synthesis of N-CF 3, Aryl or Alkyl Carbamoyl Fluorides[END_REF][22][START_REF] Petzold | Visible-Light-Mediated Liberation and In Situ Conversion of Fluorophosgene[END_REF] or the use of PDFA [START_REF] Cadwallader | Synthesis of Carbamoyl Fluorides Using a Difluorophosgene Surrogate Derived from Difluorocarbene and Pyridine N-Oxides[END_REF] as a difluorocarbene source in the presence of an oxidant (Scheme 1). It should also be mentioned that other starting materials were used for the synthesis of carbamoyl fluoride including hydroxylamine derivatives. [START_REF] Baars | The Reactivity of Difluorocarbene with Hydroxylamines: Synthesis of Carbamoyl Fluorides[END_REF][START_REF] Song | Synthesis of Carbamoyl Fluorides via a Selective Fluorinative Beckmann Fragmentation[END_REF][START_REF] Lindley | Regulating to reduce emissions of fluorinated greenhouse gases[END_REF][28] Scheme 1. Current syntheses of carbamoyl fluorides starting with amines.

Regarding our contribution for the synthesis of carbamoyl fluorides, we thought about intercepting the well-established reactivity of amines with atmospheric pressure of CO 2 yielding to carbamates. We wondered if deoxyfluorination reagents could react with carbamates to afford the desired carbamoyl fluorides. Thus, we could obtain these value-added products using inexpensive, safe, and abundant greenhouse gas CO 2 as a C1 source. Pleasingly, upon subjecting the amine to atmospheric pressure of CO 2 in the presence of DAST and DMAP as an external base, very good to excellent yields of the desired products 2a-2f were obtained (Scheme 2). [START_REF] Onida | Direct Synthesis of Carbamoyl Fluorides by CO 2 Deoxyfluorination[END_REF] It is worth noting that other deoxyfluorination reagents, including XtalFluor-E, XtalFluor-M and Fluolead, were competent under the reaction conditions albeit with lower reaction efficiency. Furthermore, labeled [START_REF] Liu | Atom-and Step-Economical Pathway to Chiral Benzobicyclo-[2.2.2octenones through Carbon-Carbon Bond Cleavage[END_REF] CO 2 could also be successfully used under our reaction conditions and the developed method allows for the direct formation of [START_REF] Liu | Atom-and Step-Economical Pathway to Chiral Benzobicyclo-[2.2.2octenones through Carbon-Carbon Bond Cleavage[END_REF] C labeled carbamoyl fluorides. With the idea of making the synthesis of carbamoyl fluorides greener and even more friendly, we then turned our attention to the development of more benign deoxyfluorination reagents. Indeed, we ambitioned to replace DAST by a more sustainable reagent. We identified the valorization of SF 6 , the most potent greenhouse gas [START_REF] Lindley | Regulating to reduce emissions of fluorinated greenhouse gases[END_REF] , as an attractive strategy. Indeed, given its high stability 28 , SF 6 is extensively applied as an insulating and arc-quenching gas in circuit breakers and electrical switchgears [START_REF] Okubo | Recent trend and future perspectives in electrical insulation techniques in relation to sulfur hexafluoride (SF 6 ) substitutes for high voltage electric power equipment[END_REF] , but its use as a reagent is currently limited. Recent studies reported the activation and the use of this gas as deoxyfluorination reagents. [START_REF] Mcteague | Photoredox Activation of SF 6 for Fluorination[END_REF][START_REF] Rueping | Metal-free reduction of the greenhouse gas sulfur hexafluoride, formation of SF 5 containing ion pairs and the application in fluorinations[END_REF][START_REF] Berg | Activation of SF 6 at Platinum Complexes: Formation of SF 3 Derivatives and Their Application in Deoxyfluorination Reactions Angew[END_REF][START_REF] Tomar | Photochemical activation of SF 6 by N-heterocyclic carbenes to provide a deoxyfluorinating reagent[END_REF][START_REF] Kim | Synthesis of Glycosyl Fluorides by Photochemical Fluorination with Sulfur(VI) Hexafluoride[END_REF][START_REF] Kim | Electrochemical Synthesis of Glycosyl Fluorides Using Sulfur(VI) Hexafluoride as the Fluorinating Agent[END_REF] We showed recently that the activation of atmospheric pressure of SF 6 could be achieved by using commercially available Tetrakis(dimethylamino)ethylene (TDAE) as a two-electron donor upon blue LED irradiation.

We succeeded to isolate an ion pair complex TDAE-SF 5 -F as a solid (Scheme 3). [START_REF] Taponard | Metal-Free SF 6 Activation: A New SF 5 -Based Reagent Enables Deoxyfluorination and Pentafluorosulfanylation Reactions[END_REF] Scheme 3. Synthesis of TDAE-SF 5 -F reagent.

With the solid in hand, we assume that such reagent could serve as a safe source of SF 4 , a strong deoxyfluorination reagent. In this context, we investigated its usefulness in the synthesis of carbamoyl fluorides under our previously reported CO 2 protocol to generate carbamoyl fluorides and valorize two greenhouse gases in the synthetic process. Herein, three equivalents of our SF 5based reagent in the presence of DMAP in MeCN provided the formation of the desired carbamoyl fluorides 2b, 2c and 2e-g in moderate to excellent isolated yields (Scheme 4). [START_REF] Taponard | Metal-Free SF 6 Activation: A New SF 5 -Based Reagent Enables Deoxyfluorination and Pentafluorosulfanylation Reactions[END_REF] Scheme 4. Synthesis of carbamoyl fluorides through deoxyfluorination of CO 2 with TDAE-SF 5 -F.

In parallel to carbamoyl fluorides, thiocarbamoyl fluorides are also an attractive class of compounds. [START_REF] Liu | Recent Advances in the Synthesis and Transformation of Carbamoyl Fluorides, Fluoroformates, and Their Analogues[END_REF][START_REF] Crousse | Recent Advances in the Syntheses of N-CF 3 Scaffolds up to Their Valorization[END_REF] The synthesis of these compounds has gained much attention these last years by using amines derivatives as starting materials and several complementary approaches have been developed [START_REF] Onida | Direct Synthesis of Thiocarbamoyl Fluorides and Trifluoromethylamines Through Fluorinative Desulfurization[END_REF] . It has been demonstrated that nucleophilic trifluoromethylthiolation reagents could be used in conjunction with amines to access the desired thiocarbamoyl fluorides (Scheme 5). [START_REF] Scattolin | Efficient Synthesis of Trifluoromethyl Amines through a Formal Umpolung Strategy from the Bench-Stable Precursor (Me 4 N)SCF 3[END_REF][START_REF] Zhen | Synthesis of Thiocarbamoyl Fluorides and Isothiocyanates Using CF 3 SiMe 3 and Elemental Sulfur or AgSCF 3 and KBr with Amines[END_REF][START_REF] Tyrra | Die Desulfonierung-Fluorierung von Thiuramdisulfiden, [R2NC(S)S]2 und Silberdithiocarbamaten, Ag[SC(S)NR 2 ] (R = CH 3 , CH 3 CH 2 , C 6 H 5 CH 2 ), mit Silber(I)fluorid[END_REF] Herein, the nucleophilic trifluoromethylthiolating reagent generates thiodifluorophosgene and fluoride anion, and the amine subsequently reacts with thiodifluorophosgene to generate the desired product. Other approaches consisted in the in-situ generation of thiodifluorophosgene by mixing the Langlois reagent or CF 3 SO 2 Cl with triphenylphosphine (Scheme 5) [START_REF] Zhen | Synthesis of Thiocarbamoyl Fluorides and Isothiocyanates Using CF 3 SiMe 3 and Elemental Sulfur or AgSCF 3 and KBr with Amines[END_REF][START_REF] Liang | One-pot synthesis of trifluoromethyl amines and perfluoroalkyl amines with CF 3 SO 2 Na and RfSO 2 Na[END_REF][START_REF] Wei | Synthesis of Thiocarbamoyl Fluorides and Isothiocyanates Using Amines with CF 3 SO 2 Cl[END_REF][45][START_REF] Xu | Synthetic Methods for Compounds Having CF 3 -S Units on Carbon by Trifluoromethylation, Trifluoromethylthiolation, Triflylation, and Related Reactions[END_REF][START_REF] Liao | Isothiocyanation of amines using the Langlois reagent[END_REF][START_REF] Liang | One-pot synthesis of trifluoromethyl amines and perfluoroalkyl amines with CF 3 SO 2 Na and R f SO 2 Na[END_REF][START_REF] Yang | Novel N(SCF 3 )(CF 3 )-amines: synthesis, scalability and stability[END_REF] Finally, the use of the Ruppert-Prakash reagent or any precursor of difluorocarbene in combination with elementary sulfur were also used for the synthesis of carbamoyl fluorides (Scheme 5). [START_REF] Zhen | Synthesis of Thiocarbamoyl Fluorides and Isothiocyanates Using CF 3 SiMe 3 and Elemental Sulfur or AgSCF 3 and KBr with Amines[END_REF][START_REF] Yu | Reaction of Thiocarbonyl Fluoride Generated from Difluorocarbene with Amines[END_REF] Scheme 5. Current syntheses of thiocarbamoyl fluorides starting with amines

The strategy we developed consisted of using CS 2 instead of CO 2 to translate our recently reported concept for the synthesis of carbamoyl fluoride to access the desired thiocarbamoyl fluorides (Scheme 6). [START_REF] Onida | Direct Synthesis of Thiocarbamoyl Fluorides and Trifluoromethylamines Through Fluorinative Desulfurization[END_REF] Subjecting amines to CS 2 in the presence of DAST and DIPEA in DCM at room temperature allows the formation of the desired thiocarbamoyl compounds 3a-f in moderate to excellent isolated yields. It has been shown that thiocarbamaoyl fluorides have interesting reactivity and they can be exploited for the direct access to trifluoromethyl amines through desulfurinative fluorination process. Indeed, inspired by Schoenebeck's procedure [START_REF] Scattolin | Efficient Synthesis of Trifluoromethyl Amines through a Formal Umpolung Strategy from the Bench-Stable Precursor (Me 4 N)SCF 3[END_REF] , we subjected the thiocarbamoyl fluorides to an excess of silver (I) fluoride in MeCN at 50 °C to afford the desired trifluormethylamines 4a-c in high yields (Scheme 7). [START_REF] Onida | Direct Synthesis of Thiocarbamoyl Fluorides and Trifluoromethylamines Through Fluorinative Desulfurization[END_REF] One of the major advantages of our procedure is the ease of purification as the desired products were obtained after simple filtration through a celite-pad. It should be mentioned that some of these trifluoromethylamines are highly water sensitive and thus degradation of the trifluoromethylamines is often observed upon aqueous workups.

Scheme 7. Synthesis of trifluoromethylamines from thiocarbamoyl fluorides.

As a greener alternative, we have also been able in this case to replace DAST by our SF 6derivated reagent TDAE-SF 5 -F for the synthesis of thiocarbamoyl fluorides. [START_REF] Taponard | Metal-Free SF 6 Activation: A New SF 5 -Based Reagent Enables Deoxyfluorination and Pentafluorosulfanylation Reactions[END_REF] It turns out that 3 equivalents of our deoxyfluorination reagent in conjunction with Et 3 N allows the formation of the targeted compounds 3a-c and 3g-i in good to excellent yields. The reaction was performed in DCM at room temperature for 2 hours (Scheme 8).

Scheme 8. Synthesis of thiocarbamoyl fluorides through fluorinative desulfurization of CS 2 with TDAE-SF 5 -F.

SYNTHESIS OF NOVEL N(SCF 3 )CF 3 COMPOUNDS AND THEIR APPLICATIONS

The stability of trifluromethylamines has been investigated by researchers from AstraZeneca. [START_REF]Trifluoromethyl Amines and Azoles: An Underexplored Functional Group in the Medicinal Chemist's Toolbox[END_REF] In their study, the authors demonstrated that several trifluoromethyamines were water sensitive. However, the study also highlighted that other classes of amines including trifluoromethylamides, trifluoromethylsulfonamides and bis(trifluoromethyl)amines derivatives offer greater stability. [START_REF] Yang | Novel N(SCF 3 )(CF 3 )-amines: synthesis, scalability and stability[END_REF] Thus, we were eager to develop new trifluoromethylated amines motifs that could be stable under aqueous conditions and to assess their potential applications in drug discovery. Herein, we identified N(SCF 3 )CF 3 as a viable and promising motif based on the properties of both the SCF 3 and CF 3 groups. From a retrosynthetic standpoint, we envisioned to in-situ generate trifluoromethylamino nucleophiles by reacting isothiocyanate derivatives with silver (I) fluoride following a procedure reported by the Schoenebeck group. This intermediate would then react with an electrophilic SCF 3 reagent to afford the targeted product. This hypothesis was tested by using the Munavalli's electrophilic trifluoromethylthiolating reagent.

Pleasingly, under the developed conditions, several aliphatic as well as aromatic N(SCF 3 )CF 3 groups were synthesized in moderate to very good yields (Scheme 9). However, anilines derivatives with electron withdrawing groups were not tolerated under our reaction conditions. Scheme 9. Synthesis of N(SCF 3 )CF 3 Munavalli's reagent.

To address this limitation, we investigated other SCF 3 electrophilic sources and were able to successfully couple electron-deficient anilines by reacting the nucleophilic trifluoromethylamines with (SCF 3 ) 2 dimer using a two-chamber reactor. Indeed, the use of Langlois's reagent (CF 3 SO 2 Na) with Ph 2 PCl allows the formation of the electrophilic dimer in chamber 2 (C2). Given the gaseous nature of this dimer at room temperature, it directly condenses into chamber 1 (C1) and reacts with the formed nucleophilic trifluoromethylamine anion. With this technology, we were able to convert several electron-deficient isothiocayanate derivatives to their corresponding N(SCF 3 )CF 3 analogues in moderate to excellent yields (Scheme 10). Interestingly, we demonstrated that the protocol was scalable with 3.74 g of p-Ph-C 6 H 4 N(SCF 3 )CF 3 obtained starting from a 20 mmol scale.

Scheme 10. Synthesis of N(SCF 3 )CF 3 using (SCF 3 ) 2 dimer.

Afterwards, we studied the overall stability of this new motif by subjecting p-Ph-C 6 H 4 N(SCF 3 )CF 3 , 6m to various media. Although this compound demonstrated excellent stability in aqueous and other physiological media, it turns out that the degradation of this product was observed under basic conditions. Under this line, we wanted to evaluate the ability of this compound to be used as a shelf-stable reagent for the incorporation of fluorinated motifs. trifluoromethylthiolated products could be obtained in excellent yields with several aromatic and aliphatic Grignard starting materials at room temperature in THF (Scheme 11). 51

Scheme 11. Trifluoromethylthiolation of Grignard with reagent 6m.

Afterwards, we were eager to test the reactivity of this new shelf-stable trifluoromethylthiolating reagent with other nucleophiles. We were able to demonstrate that indole derivatives could be used as nucleophilic partners for the synthesis of trifluoromethylthiolated compounds in very good to excellent yields. The reaction was performed in DMF at 90 °C in the presence of catalytic amount of NaCl (5 mol%) for 24 hours (Scheme 12). 52

Scheme 12. Trifluoromethylthiolation of indole derivatives with reagent 6m.

Then, we turned our attention to study the usefulness of reagent 6m in trifluoromethylthiolation of styrene under photochemical conditions. Vinyl-SCF 3 compounds were successfully synthesized using PC1 (4CzIPN) as organophotocalyst under blue LED irradiation (Scheme 13). [START_REF] Yang | Organophotocatalyzed Synthesis of Vinyl-SCF 3 and Benzoyl-SCF 3 Using a New Shelf-Stable PhPh-N-(SCF 3 )(CF 3 ) Reagent[END_REF] The use of stoichiometric amount of sodium bromide as an activator is mandatory as already reported by Hopkinson, Glorius and co-workers. [START_REF] Honeker | Visible-Light-Promoted Trifluoromethylthiolation of Styrenes by Dual Photoredox/Halide Catalysis[END_REF] Scheme 13. Synthesis of vinyl-SCF 3 under organophotocatalyzed conditions with reagent 6m.

Moreover, by using the same organophotocatalyst we were able to synthesize aroyl-SCF 3 derivatives starting from the corresponding aldehydes. [START_REF] Yang | Organophotocatalyzed Synthesis of Vinyl-SCF 3 and Benzoyl-SCF 3 Using a New Shelf-Stable PhPh-N-(SCF 3 )(CF 3 ) Reagent[END_REF] The key to success is the use of catalytic amount of sodium benzoate as a HAT catalyst. The desired aroyl-SCF 3 were obtained in very good to excellent yields (Scheme 14).

Scheme 14. Synthesis of aroyl-SCF 3 under organophotocatalyzed conditions with reagent 6m.

In conclusion, we have been able to design new routes to access carbamoyl fluorides, thiocarbamoyl fluorides as well as trifluoromethylamines by activating small molecules including CO 2 and CS 2 and starting with widely available amines derivatives. While initial methods were based on the use of commercially available DAST as deoxyfluorination reagent,

we have been able to propose an alternative by developing a new stable deoxyfluorination reagent through the activation of the most potent greenhouse gas, SF 6 . Moreover, the synthesis of new N(SCF 3 )CF 3 ) motifs has been developed in our laboratory by using two complementary approaches which are based on the in-situ generation of the nucleophilic trifluoromethyl anion.

While the first one uses the Munavalli's reagent as an electrophilic source of SCF 3 to trap the CF 3 anion, the second makes use of a two-chamber reactor for the safe generation of the electrophilic (SCF 3 ) 2 dimer. Finally, we demonstrated that p-Ph-C 6 H 4 N(SCF 3 )CF 3 could be used as a shelf-stable reagent for trifluoromethylthiolation reactions. Future directions in our laboratory are dedicated to the development of other classes of fluorinated amines.

• Data Availability Statement

The data underlying this study are available in the published article.

-

Scheme 2 .

 2 Scheme 2. Synthesis of carbamoyl fluorides through deoxyfluorination of CO 2 .

Scheme 6 .

 6 Scheme 6. Synthesis of carbamoyl fluorides through fluorinative desulfurization of CS 2 with DAST.

  NC(S)F. J. Fluorine.Chem. 2001, 109, 189-194.

	ein	einfacher	Zugang	zu	Diorgano(trifluormethyl)aminen,	R 2 NCF 3 ,	und
	Thiocarbamoylfluoriden, R 2

ACKNOWLEDGMENT

Financial support from the CNRS, the University Lyon 1, the Agence Nationale de la Recherche (Grant to AT, ANR-JCJC-2020-CDI-DEOX) and la Région Auvergne-Rhône-Alpes (GES-MEDOC, Grant to AT) are gratefully acknowledged. Y.Y thanks the CSC (China Scholarship Council) for a doctoral fellowship.


Dr Seifallah Abid

Kevin P Quirion

Yi Yang

Dr Renhe Tang

] Binh

Khanh Mai

Peng Liu
email: pengliu@pitt.edu

Anis Tlili
email: anis.tlili@univ-lyon1.fr

Prof B K P Mai

Liu

Photochemically Driven Nickel-Catalyzed Carboxylative Buchwald Hartwig Amination: Scope and Mechanism

Herein we disclosed an unprecedented photochemically driven nickel-catalyzed carboxylative Buchwald Hartwig amination to access a wide range of aryl carbamate derivatives. This reaction is performed under mild condition of temperature and atmospheric pressure of CO2 starting from commercially available (hetero)aryl iodides/bromides derivatives and alkyl amines preventing the formation of hazardous and/or toxic waste. Moreover, preliminary mechanistic investigation including stochiometric experiments as well as DFT calculations allows us to shed the light on the reaction mechanism.

Introduction

Transition-metal (TM) catalyzed cross-coupling reactions between aryl (pseudo)halides and carbon or heteroatom nucleophiles have revolutionized the way new bonds are assembled. [START_REF]Transition Metals for Organic Synthesis: Building Blocks and Fine Chemicals[END_REF] The robustness of this technology to forge C-C and C-heteroatom bonds is routinely demonstrated in academia and in large scale industrial applications. [START_REF]Transition Metals for Organic Synthesis: Building Blocks and Fine Chemicals[END_REF]2] In addition to classical cross-coupling reactions, three-component transition metalcatalyzed carbonylative methodologies using carbon monoxide are another efficient approach to construct complex molecules. [3] For such processes, the key to success is the insertion of carbon monoxide into the metal-aryl bond due to its high reactivity. For example, direct access to valuable amides could be achieved through the cross-coupling of aryl halides and amines in the presence of carbon monoxide under transition metal catalysis. [4] On the other hand, carbon dioxide is the most important greenhouse gas on Earth. Its concentration has exceeded the 400-ppm level in the atmosphere and to date only few industrial processes enable CO2-based transformations due to its thermodynamic and kinetic stability. [START_REF] Topham | Ullmann's Encyclopedia[END_REF] Complementary to the chemistry of carbon monoxide, the design of three-component reactions making use of CO2 will allow the formation of highly complex scaffolds. As an example, aryl carbamate derivatives are valuable compounds that are usually obtained from hazardous chemicals while generating highly toxic waste. [ 6 ] A threecomponent reaction with carbon dioxide would offer a more effective route to access aryl carbamates. Surprisingly, while from a simple retrosynthetic analysis, the reductive elimination from [TM](OC(O)NR 1 R 2 )Ar may lead to the formation of the desired aryl carbamate (ArOC(O)NR 1 R 2 ) product, to date, no example of metal-catalyzed carboxylative crosscoupling of aryl halides with amines have been reported. This is certainly due to two mechanistic questions that have to be considered: i) Although amine reacts with atmospheric pressure of CO2 to generate carbamate, [7] the reactivity of such species with transition metal has not been reported yet; ii) The C-O reductive elimination of [TM](OC(O)NR 1 R 2 )Ar to forge C(sp 2 )-OC(O)NR 1 R 2 is also an unknown fundamental step.

Unlocking these critical steps of the catalytic cycle will pave the way to the development of a robust carboxylative process to easily access aryl carbamate derivatives. Recent results by the Macmillan group demonstrated that the reductive elimination of [Ni](OC(O)R)Ar for the synthesis of esters could take place under energy transfer (EnT) catalysis with an [Ir] photocatalyst. [ 8 ] In addition, a similar strategy was developed by the groups of Li, Huang and Zhang where the authors successfully replaced the [Ir] catalyst with a cyanoarene organophotocatalyst. [ 9 ] These examples highlight that a combination of a photocatalyst with transition metal catalysis can promote challenging reductive elimination. [ 10 ] Based on this principle, we report herein an unprecedented photochemically driven nickel-catalyzed carboxylative Buchwald Hartwig amination to access a wide range of aryl carbamate derivatives. [11]

Results and Discussion

To confirm the feasibility of this concept we selected piodobenzotrifluoride as model substrate with diethyl amine as coupling partner under atmospheric pressure of CO2 and white light irradiation (2*27 W CFL). To our delight 80% of the desired product was obtained by using 5 mol% of air stable NiBr2.diglyme in conjunction with 5 mol% 4,4'-dtbbpy as ligand and Cs2CO3 as base using PC1 (5CzBN, 1 mol%) as photocatalyst. Herein, the choice of this photocatalyst was guided by the triplet energy (ET, 2.68 eV) [9] higher than that of Ir(ppy)3 (2.33 eV) used in the Macmillan system. [8a] Table 1. Optimization of nickel/ligand precursors.

Entry [a] Deviation from Standard conditions Yield [%] [b] 1 With this proof of concept in hand, initial focus was devoted to the optimization of the nickel/ligand catalytic system. NiBr2.DME shows higher reactivity in comparison to NiCl2.DME (Table 1, entries 2&4). Ni(acac)2 was also effective under our reaction conditions albeit in low yield of 34% (Table 1, entries 4). The use of air sensitive Ni(COD)2 allow the formation of the desired product in an excellent yield of 80% (Table 1,entries 5). Afterwards, bipyridine type ligands were investigated. While simple bipyridine afforded lower reactivity of 60%, the use of electron rich 4,4-diMeObpy furnished the desired product in 76% yield. The presence of di-Me group in 6,6' position is detrimental to the reaction since only 29% of the desired product was observed (Table1, entry 8).

Table 2. Reaction optimization

Entry [a] Deviation from Standard conditions Yield [%] [b] 1 No PC1 0 17 0.1 mol% of PC1 instead of 1 mol% 85 (83%) [c] 18 pCF3PhBr instead of pCF3PhI 74 (69%) [c] [a] Reactions were performed with 1a (0.2 mmol, 1 equiv), HNEt2 (0.4 mmol, 2 equiv), CO2 (1 atm), PC1 (1 mol%), NiBr2.diglyme (5 mol%), L3 (5 mol%), Cs2CO3 (0.4 mmol, 2 equiv) and DMF (2 mL). The reaction mixture was stirred at RT for 16 hours under 2*27W CFL unless otherwise noted [b] Determined by Then, we investigated other reaction parameters (Table 2). First, the impact of several bases on the reaction outcome was assessed. To some extent, K2CO3 showed interesting reactivity and 65% yield of 2a was obtained. Lower product formation was observed with K3PO4 (table 2, entry 3). Interestingly, the use of CsF provided good reactivity and the desired product 2a was obtained in 71% yield (table 2, entry 4). The use of organic bases was also investigated. While NEt3 furnishes the desired product in only very low yield of 15%, DBU showed good compatibility and 60% of 2a was obtained (table 2, entries 15&16). Regarding the solvent, similar reactivity was observed in DMA but very low amount or traces of product were observed in DMSO and MeCN, respectively (Table 1, entries 7-9). Several photocatalysts were also investigated. Cyanoarenes PC2-PC4 were effective and yields up to 74% were obtained (table 1, entries 10-14). Similarly, [Ir] based photocatalyst showed interesting reactivity although with lower efficiency than PC1 (Table 1, entries 13&14). Control experiments without light or without PC1 demonstrated the importance of both the light and the presence of the organophotocatalyst since no product formation was observed (table 2, entries 15&16). To our delight, decreasing the organophotocatalyst loading to 0.1 mol% afforded product 2a in 85% yield (Table 1, entry 17). Finally, the use of pbromobenzotrifluoride was also effective under our reaction conditions and the corresponding product 2a was obtained in very good yield of 74% (Table 2,entry18). Scheme 2. Substrate scope: [a] Reactions were performed with 1 (0.2 mmol, 1 equiv.), amine (0.4 mmol, 2 equiv.), CO2 (1 atm), PC1 (0.1 mol%), NiBr2.diglyme (5 mol%), L3 (5 mol%), Cs2CO3 (0.4 mmol, 2 equiv) and DMF (2 mL). The reaction mixture was stirred at RT for 16 hours unless otherwise noted. Yield of isolated products. [b] Determined by [START_REF] Maity | [END_REF] F NMR spectroscopy with PhOCF3 as an internal standard. [c] Determined by 1 H NMR spectroscopy with 1,3,5-trimehtoxybenzene as an internal standard With the optimized set of conditions in hand, we turned our attention to studying the scope of the carboxylative Buchwald-Hartwig amination. The use of several (hetero)aryl iodides and bromides was first investigated. Trifluoromethyl substituted iodoas well as bromoarene were converted with low to very good yield (products 2a-c up to 77%). Arenes substituted with cyano groups were successfully employed under the reaction conditions and the desired products were obtained in excellent yields up to 87% (products 2d & 2e). The presence of ester groups either in the para or meta position was also tolerated under our protocol and the corresponding products were obtained in excellent yields either by starting from the iodo-or bromoaryl derivatives (products 2f & 2g). Moreover, the use of sensitive functional groups toward basic conditions including acetyl and aldehyde were successfully converted to the desired product with moderate to very good yields (products 2f & 2i). Simple naphthalene and biphenyl starting material were smoothly converted to the desired carbamate derivatives with yields up to 82% (products 2i & 2j). Afterwards, pharmaceutically relevant heterocyclic pyridinebased iodo and bromo derivatives were subjected to our protocol. The presence of methyl as an electron donating group allows the formation of the desired product in synthetically useful yield of 53% (product 2l). Iodo-and bromopyridines substituted with CF3 group are also tolerated under this protocol and the desired trifluoromethylpyridine carbamate were obtained in excellent yields up to 90% (products 2m-2o). Finally, the use of iodoaryl substituted either with boronic acid pinacol ester or bromo groups were converted to the desired corresponding aryl carbamate with yields up to 80% (products 2p-2q). Herein, post functionalization under cross-coupling reaction conditions is envisioned as a follow-up reaction. After observing good reactivity with different aryl iodides and bromide, we decided to investigate the scope of different amines derivatives. Other dialkylamine derivatives also showed excellent compatibility with our protocol including bulky di-iPr-and di-tBu-amines and the corresponding aryl carbamate were obtained in very good yields up to 75% (product 2fa and 2fb). Benzyilic amines were also tolerated under our reaction conditions and the desired aryl carbamates were obtained in excellent yields (2fc, 2fd and 2fe). The use of cyclic amine was also successfully investigated. Indeed, piperidine and morpholine turned out to be good amines coupling partners under our protocol (product 2ff and 2fg). Similarly, piperazine derivatives turned out to be effective for the synthesis of aryl carbamates (product 2fh and 2fi). Moreover, an excellent yield of 90% for aryl carbamate 2fm was achieved starting from pyrrolidine as amine coupling partner. Finally, the use of pharmaceutically relevant amines was also investigated. Desipramine, Nortriptyline as well as Maprotiline were successfully coupled for the synthesis of aryl carbamates and the corresponding desired products were obtained in excellent yields up to 91% (products 2fk, 2fl and 2fm).

After observing general reactivity with (hetero)aryl iodide and bromide as well as different amines coupling partners, we turned our attention to the investigation of the reaction mechanism by performing several control experiments. As observed in the optimization of the reaction, Ni(COD)2 is an active precatalyst for the carboxylative Buchwald-Hartwig amination (Table 1, entry 5). Herein, we envisioned that the oxidative addition of the aryl halide is a plausible first step for the catalytic cycle. In this context, we synthesized the Ni-I complex resulting from the oxidative addition of the tBubpy nickel(0) complex and the 4-bromobenzotrifluoride. this complex was then stoichiometrically submitted to the reaction conditions in the presence of 1 mol% of PC1. Surprisingly, no desired product was observed. Instead, 60% of the reduced product PhCF3 was detected in [START_REF] Maity | [END_REF] F NMR (Scheme 3, 1). Herein, the photochemical homolysis of the Ni-C6H4CF3 bond could occur as already reported by Doyle [12] and Hadt [13] followed by HAT to form the reduced PhCF3. Although this Ni(II) complex is not effective for the synthesis of aryl carbamate under stochiometric conditions, it turned out to be catalytically active for the formation of the desired product 2a in 80% yield by [START_REF] Maity | [END_REF] F NMR (Scheme 3, 2). The photodegradation of complex Ni-I was confirmed in the presence of 1 mol% of PC1 under irradiation to give PhCF3. (Scheme 3, 3). As previously reported, the photolysis of the Ni(II)-PhCF3 bond is expected to lead to a Ni(I) species that may be active for the desired cross-coupling reaction. Indeed, when the photolysis reaction is carried out in the presence of an external aryl iodide 1f in the reduced PhCF3 is formed along with the formation of compound 2f in 99% yield indicating the formation of an active nickel precatalyst in situ (Scheme 3, 3).

Scheme 3. Preliminary mechanistic investigations

In order to get more insights into the reaction mechanism, we performed density functional theory (DFT) calculations to investigate the Ni(4,4'-dtbbpy)-catalyzed carboxylative amination of aryl iodide 1a with dimethyl amine as the model substrate. [START_REF])/SMD(DMF)//B3LYP-D3/SDD-6-31G(d) level of theory. TD-DFT calculations were performed at the B3[END_REF] We first examined the Ni(0)-Ni(II) pathway [8] that initiates from a nickel(0) active catalyst 1 6 (Figure 1). A three-centered oxidative addition ( 1 TS1) of aryl iodide 1a forms an arylnickel(II) iodide ( 1 7), which then proceeds through ligand exchange with cesium carbamate 4 to form 1 9. The formation of cesium carbamate [START_REF] Said | mechanism of carbamate formation[END_REF] 4 from CO2, amine, and Cs2CO3•(DMF)2 (ΔG = -17.8 kcal/mol, Figure 1a), the aryl iodide oxidative addition (ΔG = -46.1 kcal/mol), and the ligand exchange with cesium carbamate (ΔG = -15.1 kcal/mol) are all exergonic, the resulting nickel(II) carbamate 1 9 is highly thermodynamically stable. The direct C-O reductive elimination (RE) from 1 9 requires an insurmountable barrier of 43.4 kcal/mol (TS2) and is endergonic by 29.4 kcal/mol. This is consistent with previous computational studies that indicate the Ni(II)-Ni(0) C-O reductive elimination is challenging [16] whereas the reverse reaction-Ni(0)-Ni(II) oxidative addition of aryl carbamates-was exergonic by more than 25 kcal/mol. [17] Based on previous computational studies by Chen [16a] and Guan [16b] and experimental studies by MacMillan and Scholes [8b] that suggested the C-O(carboxylate) RE of Ni(II)(aryl) acetate complexes can be promoted by an energy transfer (EnT) process with iridium photocatalysts, we performed TD-DFT calculations to study the excitation-promoted C-O RE pathway to form aryl carbamate. Our calculations indicated that the adiabatic excitation of arylnickel(II) carbamate 1 9 leads to a metal-to-ligand charge transfer (MLCT) complex3 9 (MLCT) [START_REF] Alternatively | excited to a triplet d-d state. However, previous computational studies suggested that the excitation-promoted C-O RE involves the MLCT state[END_REF] with an adiabatic excitation energy of 34.0 kcal/mol. This MLCT complex involves singleelectron excitation from a metal d orbital to the π* orbital on the ligand (see Figure S1 Next, we considered an alternative mechanism with nickel(I) iodide 2 10 as the active catalyst (Figure 2). The nickel(I) species may be formed via either SET from the photocatalyst to NiBr2 precatalyst, [16] or photochemical homolysis of arylnickel(II) halide [12,13,[START_REF] Maity | [END_REF] (see Scheme 3). Because the ligand exchange to afford nickel(I) carbamate 2 11 is exergonic by 10.6 kcal/mol, the aryliodide oxidative addition ( 2 TS3) occurs with 2 11 to form an octahedral nickel(III) intermediate

Conclusion

We demonstrated that the carboxylative Buchwald-Hartwig amination could be performed under dual approach using an organophotocatalyst and an air stable Ni(II) precatalyst. The aryl carbamate derivatives have been synthesized under mild conditions of temperature and atmospheric pressure of CO2 tolerating a wide range of commercially available (hetero)aryl iodides and bromides, and amines. Moreover, preliminary mechanistic investigations including stoichiometric reactions as well as DFT calculations have been performed to discriminate between two plausible catalytic cycles: a Ni( 0

Scheme 1 .

 1 Scheme 1. State of the art on the Buchwald-Hartwig amination, carbonylative amination and introduction of the new concept.

19 F

 19 NMR spectroscopy with PhOCF3 as an internal standard.[c] Isolated Yield.

  ), thus leading to nickel(III) character that promotes C-O RE. The computed barrier for C-O RE from the MLCT complex 3 9 (MLCT) is 24.8 kcal/mol, which is substantially lower than the C-O RE from ground state nickel(II) 1 9. The MLCT C-O RE transition state ( 3 TS2 (MLCT) ) and the corresponding singlet 1 TS2 are both square planar, although the former has a significantly longer forming C-O bond (1.97 Å compared to 1.72 Å in 1 TS2), indicating an earlier TS consistent with the Hammond postulate.

Figure 1 .

 1 Figure 1. Computed reaction energy profile of the Ni(0)/Ni(II) pathway.

2 12 .

 12 In sharp contrast to the highly endergonic Ni(0)-Ni(II) oxidative addition, the Ni(III) intermediate 2 12 is only 6.3 kcal/mol more stable than 2 11. Complex 2 12 undergoes facile C-O reductive elimination via a five-membered cyclic TS (TS4). The Ni(III)-Ni(I) C-O RE requires a low barrier of 13.3 kcal/mol and is exergonic by 14.9 kcal/mol. The three-membered reductive elimination (TS4') is 10.4 kcal/mol less stable than TS4 (see Figure S4 for an even less favorable outer-sphere C-O RE involving a dissociated carbamate radical). Although the energy transfer-promoted C-O RE pathway via MLCT complex cannot be completely ruled out based on the computed barrier (ΔG ‡ = 24.8 kcal/mol, vide supra), the Ni(I)-Ni(III) pathway was found to require lower barriers in both Ar-I oxidative addition and C-O RE steps. Therefore, the DFT calculations indicate that the Ni(I)-Ni(III) pathway is kinetically feasible once the catalytically active Ni(I) or Ni(III) species is generated.

Figure 2 .

 2 Figure 2. Computed reaction energy profile of the Ni(I)-Ni(III) pathway.

  )-Ni(II) catalytic cycle under EnT catalysis and a Ni(I)-Ni(III) catalytic cycle through SET. Experimental data indicates the reduction of Ni(II) to generate an active Ni(I) catalyst as key step for the initiation of the catalytic cycle. Also, low barriers were required for both oxidative addition and C-O reductive elimination steps in the Ni(I)-Ni(III) cycle. Thus, these experimental and computational studies support a Ni(I)-Ni(III) pathway as a more likely route for the synthesis of aryl carbamate.

TS2 (MLCT) ΔG ‡ (9→TS2) = 24.8

Acknowledgements

1

TS2 ΔG ‡ (9→TS2) = 43.4 This work was supported by the EMERGENCE@INC2022 action and the National Science Foundation (CHE-2247505). AT is deeply thankful to the INC-CNRS for their kind support. DFT calculations were carried out at the University of Pittsburgh Center for Research Computing and the Advanced Cyberinfrastructure Coordination Ecosystem: Services & Support (ACCESS) program, supported by NSF award numbers OAC-2117681 and OAC-2138259. Y.Y and R. T thanks the the CSC (China Scholarship Council) for a doctoral fellowship. AT is thankful to Prof. Abderrahmane Amgoune and Dr. Julien. C. Vantourout (ICBMS Lyon) for fruitful discussions. Keywords: Carboxylation • Dual catalysis • Buchwald-Hartwig • Photochemistry • Density functional theory

The carboxylative Buchwald-Hartwig amination is disclosed herein under mild conditions of temperature and under atmospheric pressure of CO2. The key to success is the use of a dual strategy organophotocatalysis/nickel catalysis under visible light irradiation. The developed conditions demonstrated high functional group tolerance toward (hetero)aryl iodide and bromide. Furthermore, preliminary mechanistic investigations including stoichiometric reactions and DFT calculations shed light on the reaction mechanism.


Asma Fatnassi

Claudia Cammarano

Erwan Oliviero

Vasile Hulea

Nicolas Brun
email: nicolas.brun@enscm.fr

Carbon Aerogel-Supported Noble Metal Nanoparticles as Hydrogenation Catalysts

Keywords: Hydrothermal carbonization, atom economy, nanocomposite, ruthenium, platinum, 4-chloronitrobenzene, 4-chloroaniline

We report a one-pot hydrothermal route for the atom-economical biosynthesis of carbon aerogel-supported noble metal nanoparticles. A simple sugar derived from hemicellulose, e.g., xylose, and a natural phenol produced by brown algae, e.g., phloroglucinol, were used as renewable and abundant precursors. We demonstrated the versatility of the one-pot hydrothermal route to prepare Pt/C and Ru/C nanocomposites with tuneable properties of both the carbonaceous support and the supported metal nanoparticles. We obtained ruthenium nanoparticles with an unusual facecentered-cubic structure. The Pt/C aerogel nanocomposites showed competitive properties as catalysts for a model hydrogenation reaction as compared with analogous metal/carbon catalysts.

TEXT

Supported metal nanoparticles (SMNPs) onto porous materials have been widely studied and employed in heterogeneous catalysis processes, especially in the fine chemicals industry. [START_REF] Campelo | Sustainable Preparation of Supported Metal Nanoparticles and Their Applications in Catalysis[END_REF][START_REF] White | Supported metal nanoparticles on porous materials. Methods and applications[END_REF][START_REF] Ndolomingo | Review of supported metal nanoparticles: synthesis methodologies, advantages and application as catalysts[END_REF][START_REF] Anderson | Supported metals in catalysis[END_REF] In particular, supported noble metal nanoparticles such as platinum, palladium and ruthenium have been reported for a wide range of catalytic reactions, including oxidations [START_REF] Herves | Catalysis by metallic nanoparticles in aqueous solution: model reactions[END_REF] and hydrogenations of a large diversity of organic molecules. [START_REF] Zhang | Selective hydrogenation over supported metal catalysts: from nanoparticles to single atoms[END_REF] The use of porous supports to immobilize metal nanoparticles displays many advantages in terms of stability, processability and cost, especially when dealing with expensive noble metal catalysts. First, SMNPs enable easier recycling of the metal catalysts and can slow down the leaching of metal species, providing better reusability and long term stability. [START_REF] Ndolomingo | Review of supported metal nanoparticles: synthesis methodologies, advantages and application as catalysts[END_REF] Second, the support can avoid metal nanoparticles' aggregation and give better metal dispersion. [START_REF] Ndolomingo | Review of supported metal nanoparticles: synthesis methodologies, advantages and application as catalysts[END_REF] On the other hand, specific metal-support interactions can significantly modify the structure of the metal nanoparticles at the atomic level together with its catalytic properties, in terms of activity and selectivity. [START_REF] Zhang | Probing the Metal-Support Interaction in Carbon-Supported Catalysts by using Electron Microscopy[END_REF] Supported metal catalysts are usually prepared by procedures involving multi-steps including: (i) synthesis of the porous support; (ii) impregnation of the as-prepared support with one or several metal precursors (usually metal salts); and (iii) reduction of the metal salts using either molecular hydrogen at high temperature or chemical reducing agents in solution. [START_REF] Pinna | Supported metal catalysts preparation[END_REF] Such multi-step procedures are inefficient in terms of duration and energy consumption [START_REF] Huang | Fabrication of reduced graphene oxide/metal (Cu, Ni, Co) nanoparticle hybrid composites via a facile thermal reduction method[END_REF] and lead to relatively weak interactions between the metal nanoparticle and the support. [START_REF] Su | Thermally reduced ruthenium nanoparticles as a highly active heterogeneous catalyst for hydrogenation of monoaromatics[END_REF] To overcome these drawbacks, simpler one-pot synthetic routes need to be developed.

Due to their high thermal and chemical stabilities together with their relative abundance and low cost, porous carbon materials have been among the most commonly employed supports for metal nanoparticles. [START_REF] Pérez-Mayoral | Metal-supported carbon-based materials: opportunities and challenges in the synthesis of valuable products[END_REF] Carbon materials can be prepared from a large variety of renewable and abundant organic resources, such as lignocellulosic material and its derivatives. [START_REF] Titirici | Sustainable carbon materials[END_REF] One of the most powerful approach to synthetize biosourced carbons is the hydrothermal carbonization (HTC), [START_REF] Nicolae | Recent advances in hydrothermal carbonisation: from tailored carbon materials and biochemicals to applications and bioenergy[END_REF] also known as wet pyrolysis or wet torrefaction. HTC is a thermochemical process that occurs in subcritical water and converts organic compounds into carbonaceous materials, known as hydrochars. Usually, HTC is conducted in autoclaves at moderate temperature (typically between 120 and 250°C) and under autogenous pressure (typically below 10 bars). When applied to monosaccharides or their furan derivatives (i.e., furfural or hydroxymethylfurfural), HTC yields monodisperse microspheres with a mean diameter between 100 nm and 5 µm. [START_REF] Zhang | Hydrophobic precipitation of carbonaceous spheres from fructose by a hydrothermal process[END_REF] Interestingly, HTC is also a simple and sustainable route for the one-pot synthesis of carbonaceous SMNPs. [START_REF] Sun | Colloidal carbon spheres and their core/shell structures with noble-metal nanoparticles[END_REF] In 2008, Titirici et al. [START_REF] Makowski | Selective partial hydrogenation of hydroxy aromatic derivatives with palladium nanoparticles supported on hydrophilic carbon[END_REF] demonstrated the effective reduction of a water soluble palladium salt (i.e., palladium acetylacetonate) during the HTC of furfural at 190°C. The authors reported core-shell microspheres with a mean diameter of ca. 200 nm made of a Pd 0 core and a hydrophilic carbonaceous shell. These metal@hydrochar nanocomposites showed high selectivity towards partial hydrogenation products of various phenolic compounds. [START_REF] Makowski | Selective partial hydrogenation of hydroxy aromatic derivatives with palladium nanoparticles supported on hydrophilic carbon[END_REF] However, since first described in the literature, [START_REF] Sun | Colloidal carbon spheres and their core/shell structures with noble-metal nanoparticles[END_REF] the one-pot HTC approach has hardly ever been reported to prepare hydrothermal carbon-supported noble metal nanoparticles for heterogeneous catalysis. [START_REF] Matos | Methane conversion on Pt-Ru nanoparticles alloy supported on hydrothermal carbon[END_REF] So far, the preparation of porous HTC supports for noble metal nanoparticles has been mainly limited to multi-step procedures using incipient wetness impregnation [START_REF] Bosilj | Directing nitrogen-doped carbon support chemistry for improved aqueous phase hydrogenation catalysis[END_REF] or to atom inefficient one-pot procedures, which involve sacrificial soft-templates that ultimately become chemical wastes. [START_REF] Liu | Biomass-derived ordered mesoporous carbon nano-ellipsoid encapsulated metal nanoparticles inside: ideal nanoreactors for shape-selective catalysis[END_REF] Here, we report a one-pot, atom-economical, hydrothermal route for the biosynthesis of carbon aerogel-supported noble metal nanoparticles for hydrogenation catalysis. A simple sugar derived from hemicellulose, e.g., xylose, and a natural phenol produced by brown algae, e.g., phloroglucinol, were used as renewable and abundant precursors. [START_REF] Brun | Hydrothermal synthesis of highly porous carbon monoliths from carbohydrates and phloroglucinol[END_REF] We already showed that, using this simple hydrothermal route, we could produce stable hydrogels made of the aggregation of small carbonaceous nanoparticles. [START_REF] Brun | Hydrothermal synthesis of highly porous carbon monoliths from carbohydrates and phloroglucinol[END_REF] After solvent exchange, freeze-drying and pyrolysis, carbon aerogels with a high specific surface area, a high meso-macropore volume (so-called external volume) and a multi-scale porosity could be prepared. As meso-and macropores are essential for the diffusion of reagents and products during catalytic reactions, [START_REF] Coasne | Multiscale adsorption and transport in hierarchical porous materials[END_REF] we believe that these aerogels have a great potential as supports for heterogeneous catalysis. Analogous N-doped carbons aerogels already demonstrated promising properties as metal-free electrocatalysts for the oxygen reduction reaction. [START_REF] Brun | Original design of nitrogen-doped carbon aerogels from sustainable precursors: application as metal-free oxygen reduction catalysts[END_REF] In the present study, we propose to extend this simple hydrothermal route to the synthesis of Pt/C and Ru/C aerogel nanocomposites (Figure 1). Water soluble salts, e.g., ruthenium(III) nitrosylnitrate and hexachloroplatinic(IV) acid hydrate, were used as noble metal precursors. Various theoretical metal loadings were applied, from 0.4 to 10 wt.%, yielding RuX/C and PtX/C samples with X corresponding to the theoretical metal loading in percentage by mass (see Table 1). Aerogels with high theoretical metal loadings (i.e., 10 wt.%) were prepared to provide insights into the fate of metal species after HTC and subsequent pyrolysis. Both incipient wetness impregnation followed by reduction (ImR) and one-pot (OP) routes were used to prepare Pt/C and Ru/C nanocomposites (Figure 1). Besides porous carbon aerogels, lab-made microporous microspheres (Pt0.4/C-OP00) and ordered mesoporous carbons (Pt0.4/C-OMC) were prepared starting from similar precursors. An analogous commercial catalyst (Pt0.5/C-com) was also studied and characterized to provide further insights into the potential of the one-pot hydrothermal route reported herein. The experimental metal loadings for all the samples were determined by ICP-OES and compared with the theoretical expected values, as reported in Table 1. At low metal loading, i.e., at 0.4 wt.%, the experimental values were really close to the theoretical ones, especially for the Ru0.4/C-OP sample (0.48 vs 0.4 wt.%). Interestingly, the OP process allowed reaching reasonable loadings with moderate metal leaching despite solvent exchange and thermal treatment at high temperature. Thus, Pt0.4/C-OP and Pt0.4/C-ImR samples displayed metal loadings of 0.25 and 0.37 wt.%, respectively.

When increasing the metal loading from 0.4 to 10 wt.%, the experimental metal loadings diverged significantly from the theoretical loadings with an estimated leaching of ca. 50 and 60 wt.% for Ru10/C-OP and Pt10/C-OP, respectively. We believe that the leaching occurred during the washing steps in water/tert-butanol mixtures and involved the bigger metal aggregates which were weakly bound to the carbon support. Despite metal loss, the OP method offered a good control over metal loading.

Besides, the addition of the metal salts before HTC (OP method) did not disturb the gelation process. As shown in Figure 1C, stable hydrogels were systematically obtained. After freeze-drying and subsequent pyrolysis, the textural properties were not significantly affected by the presence of the metal, whatever the metal loading (see Table 1). Both SEM (Figure 1D) and TEM micrographs (Figure 1E) showed highly porous frameworks made of the aggregation of small carbon nanoparticles. At low metal loading, i.e., for Ru0.4/C-OP and Pt0.4/C-OP samples, both the BET equivalent specific surface areas (SSABET, ca. 760 m 2 g -1 ) and pore volumes (Vtotal, ca. 1.5 cm 3 g -1 )

were close to the ones obtained for the metal-free carbon aerogel, i.e., C-OP (796 m 2 g -1 and 1.56 cm 3 g -1 , respectively). When increasing the metal loading from 0.4 to 1 wt.%, both SSABET and pore volumes slightly increased, while a further increase in the metal loading from 1 to 10 wt.% yielded a decrease in both SSABET and pore volumes (see Table 1). One may assume that the metal salts acted as catalysts for the dehydration and polycondensation reactions occurring during HTC, which might cause structural and textural changes at intermediate to high loadings. Nevertheless, no clear difference could be seen by FTIR on aerogels before pyrolysis (Figure S1). Moreover, all the aerogels prepared by the one-pot method displayed hybrid type I/II nitrogen sorption isotherms with H3 hysteresis loops (see for instance Pt0.4/C-OP in Figure 1E). These isotherms are related to multiscale porous materials with both micro-and macropores which were not completely filled with nitrogen condensate. [START_REF] Thommes | Physisorption of gases, with special reference to the evaluation of surface area and pore size distribution (IUPAC Technical Report)[END_REF] Interestingly, at similar metal loading, the ImR method gave lower SSABET and pore volumes than the OP method (see Table 1). This feature suggests pore clogging by the metal salts and metal nanoparticles during impregnation and subsequent reduction. Besides OP and ImR aerogels, three other samples with different textural properties were studied: Pt0.4/C-OP00, Pt0.4/C-OMC, and an analogous commercial catalyst (Pt0.5/C-com). Pt0.4/C-OP00 and Pt0.5/C-com displayed type-I isotherms typical of microporous materials, while Pt0.4/C-OMC displayed a type IV isotherm with H1 hysteresis loop, typical of ordered mesoporous materials. The nitrogen sorption isotherms (Figure S2), SEM (Figure S3) and TEM micrographs (Figure S4) of all the samples reported herein are available in supporting information. 2B). No such observation could be made in Ru0.4/C-OP (Figure 2F). When increasing the metal loading, no metal nanoparticle aggregates were observed for the PtX/C-OP series (Figure 2C). However, small metal clusters were observed by STEM-HAADF (Figure 2D). Unlike Pt, Ru aggregates of ca. 50 nm were observed for Ru1/C-OP (Figure 2G) and Ru10/C-OP (Figure 2H). Such aggregates were also observed before pyrolysis (see Ru10H in ESI, Figure S6), suggesting that metal nanoparticles already formed during HTC. To assess the nature of the metal species after HTC and pyrolysis, X-ray diffraction (XRD, Figure 3 and Figure S7), X-ray photoelectron spectroscopy (XPS, Figure 3) and hydrogen temperature programmed reduction (H2-TPR, Figure S8) were performed. As for platinum at high metal loading, the XRD patterns showed three main peaks at 2θ= 39.8°, 46.3° and 67.5°, corresponding to the (111), (200), and (220) crystallographic planes of metallic Pt 0 , respectively (Figure 3A). These three diffractions peaks were observed both before (Pt10/H) and after pyrolysis (Pt10/C-OP), confirming that platinum was already reduced during HTC. The peaks are narrower and more intense after pyrolysis, suggesting a sintering of the platinum particles. The crystallite size of the Pt nanoparticles determined by the Scherrer equation (Table 1) increased from 5 nm for Pt10/H to 22 nm for Pt10/C-OP, which is inconsistent with electron microscopy observations that only showed platinum clusters smaller than 2 nm (Figure 2 C-D). This feature suggests some heterogeneity in the sample. At low metal loadings, these three diffractions peaks vanished, which is consistent with the very low concentration of platinum (below 0.5 wt%) and suggests the presence of eV which is attributed to metallic Pt 0 . After pyrolysis (Pt10/C-OP, Figure 3B, bottom), a shift to higher binding energies was noted for the Pt 0 doublet (Pt4f7/2 and Pt4f5/2 centered at 71.7 and 75.1 eV, respectively) as compared with the ones observed before pyrolysis. This positive shift in binding energies corresponds to a decrease in the electronic charge density on the platinum atoms present in the material. It might be due to electrons transfer from Pt nanoparticles to the carbon support, transfer that is most probably favored after pyrolysis. [START_REF] Sen | Different sized platinum nanoparticles supported on carbon: An XPS study on these methanol oxidation catalysts[END_REF] This feature suggests strong interaction between Pt nanoparticles and the carbon support. A second set of doublet observed at binding energy of 72.6 and 76.5 eV after pyrolysis (72.1 and 75.6 eV before pyrolysis) can be assigned to platinum oxide states (PtO and Pt(OH)2). [START_REF] Zhang | Water-in-oil microemulsion synthesis of platinum-ruthenium nanoparticles, their characterization and electrocatalytic properties[END_REF] The percentage of Pt 2+ was estimated at ca. 40 and 26 % before and after pyrolysis, respectively. This feature is at variance with H2-TPR. One may consider that XPS is a surface characterization technique that may significantly overestimate the amount of surface metal oxide species.

As known for the metallic ruthenium, the XRD pattern of Ru10/C-OP showed several peaks at 2θ= 38.5°, 42.4°, 44.4°, 58.6°, 69.7° and 78.7°, corresponding to the (100), (002), ( 101), ( 102), (110), and

(103) crystallographic planes, respectively (Figure 3C), of metallic Ru 0 with a hexagonal closepacked (hcp) structure. At low metal loadings, these diffractions peaks vanished, in the same way as observed for the PtX/C-OP series, suggesting the presence of very small amorphous metal clusters together with larger nanoparticles. Besides, the crystallite size of the Ru nanoparticles determined by the Scherrer equation (Table 1) increased after pyrolysis, from 5 nm for Ru10/H to 13 nm for Ru10/C-OP. Interestingly, before pyrolysis, an unexpected phase was evidenced for ruthenium with diffraction peaks at 2θ= 41.0°, 47.4° and 69.7°. These peaks can be indexed as the ( 111), (200), and

(220) planes of face-centered-cubic (fcc) Ru (JCPDS card No. 01-088-2333), as reported in a few recent articles. [START_REF] Kusada | Discovery of Face-Centered-Cubic Ruthenium Nanoparticles: Facile Size-Controlled Synthesis Using the Chemical Reduction Method[END_REF][START_REF] Pang | Solvents-dependent selective fabrication of face-centered cubic and hexagonal close-packed structured ruthenium nanoparticles during liquid-phase laser ablation[END_REF] While the hcp structure is the thermodynamically stable phase of Ru, the fcc structure is rather unusual and was hardly ever reported in the literature. According to Zhao et al., [START_REF] Zhao | Carbon coated face-centered cubic Ru-C nanoalloys[END_REF] the fcc phase can be stabilized by the dissolution of carbon and the formation of Ru-C nanoalloys.

These features were supported by XPS. Before pyrolysis six peaks centered at 461.8, 463.5, 465.2, 483.9, 485.5 and 487.3 eV were observed (Ru10/H, Figure 3D, top). These six peaks correspond to three Ru3p3/2 and Ru3p1/2 doublets. The doublet at 461.8 and 483.9 eV can be assigned as Ru 0 metal (Ru3p3/2 and Ru3p1/2, respectively), [START_REF] Morgan | Resolving ruthenium: XPS studies of common ruthenium materials[END_REF] while the doublet at 465.2 and 487.3 eV could be attributed to ruthenium oxide. The assignation of the third doublet at 463.5 and 485.5 eV is not straightforward but it can be attributed to ruthenium carbide species. After pyrolysis, the contribution of this doublet significantly decreased, from ca. 42 to 17 % (Ru10/C-OP, Figure 3D, bottom). This feature confirms the formation of Ru-C nanoalloys during HTC, which is expected to favor the formation of the unusual fcc structure. It also supports the subsequent removal of carbon atoms from the solid solution during pyrolysis. After pyrolysis, the Ru3p spectrum shows the same six peaks. The percentage of Ru 0 increased from ca. 32 to 61 %, while the percentage of ruthenium oxide decreased from ca. 26 to 22 %. The presence of ruthenium oxide in Ru10/C-OP was also confirmed by H2-TPR analysis and was estimated at ca. 6 % (Figure S8). The deviation between the two techniques suggests that ruthenium oxide species are mainly located at the very surface of ruthenium particles, as mentioned previously for Pt10/C-OP. Interestingly, H2-TPR analysis of Ru10/C-OP displayed two reduction peaks related to hydrogen consumption centered at ca. 100 and 250°C (Figure S8). The significant interval between these two reduction peaks suggests the presence of two different sets of ruthenium oxide species. The first peak can be related to the reduction of ruthenium species having weak interaction with the carbon support, while the second peak can be assigned to ruthenium species strongly embedded in the carbon matrix. This last feature might be related to the presence of Ru-C nanoalloys before pyrolysis and demonstrates that the OP approach provides close interaction between metal nanoparticles and the carbon support.

Carbon and carbon precursors, such as sucrose, [START_REF] Su | Thermally reduced ruthenium nanoparticles as a highly active heterogeneous catalyst for hydrogenation of monoaromatics[END_REF] have been reported in the literature as reducing agents of metal salts at high temperatures, typically above 700°C. The use of HTC and reducing sugars, especially aldoses and xylose, or sugar-derived aldehydes, such as furfural, [START_REF] Makowski | Selective partial hydrogenation of hydroxy aromatic derivatives with palladium nanoparticles supported on hydrophilic carbon[END_REF] allowed working at lower temperatures, typically below 200°C. While this feature was confirmed herein, our study also demonstrated the versatility of the one-pot hydrothermal route to design carbonaceous-SMNPs with tuneable textural and structural properties of both the carbonaceous support and the supported metal nanoparticles. Considering both textural and structural properties, the metal/C-OP carbon aerogels reported herein show great promise as catalysts for hydrogenation reactions. To support this assumption, we used these nanocomposites as catalysts for a model reaction, i.e., the selective hydrogenation reaction of 4-chloronitrobenzene (CNB) into 4-chloroaniline (CAN). The production of halogenated aromatic amines by heterogeneous catalysis has received much attention for industry. [START_REF] Serna | Transforming nano metal nonselective particulates into chemoselective catalysts for hydrogenation of substituted nitrobenzenes[END_REF] In particular, the selective hydrogenation of CNB into CAN is an industrially important process, as chloroanilines are important intermediates in the chemistry of dyes, drugs, pesticides and herbicides. Conventionally, the chloroanilines are produced from the corresponding halonitrobenzene with stoichiometric reductants or hydride reagents. However, due to the discovery of promising catalytic systems for this reaction, based on platinum, palladium, rhodium, ruthenium, nickel, gold, iridium, etc., hydrogenation of halogenated nitroarenes with molecular hydrogen has received more attention during the last decades. [START_REF] Oubenali | Hydrogenation of p-Chloronitrobenzene over Nanostructured-Carbon-Supported Ruthenium Catalysts[END_REF] Various co-products can be obtained during this reaction such as chlorobenzene, aniline (AN), 4nitrosochlorobenzene (CNSB) or 4-chlorophenylhydroxylamine (Figure S9). While CAN is the desired main product, CNSB is an intermediate of the reaction and AN is a co-product to avoid. In other words, we aim to promote the hydrogenation of nitro group and to avoid the dehalogenation of CAN. In our study, CAN was systematically the main product of the reaction and AN was below 1.5 % (Figure S10), demonstrating the high selectivity of our catalysts. However, significant differences were observed regarding the initial rate of the reaction (r0, Table 2). While Pt0.4/C-OP was highly active at 70°C and 10 bars, Ru0.4/C-OP was not and higher temperature (140°C) and pressure (20 bars) must be applied to reach comparable catalytic properties (Figure 4A). Overall, RuX/C were less active than PtX/C catalysts. Interestingly, the Pt/C catalysts prepared through the OP hydrothermal route showed competitive catalytic properties as compared with the ones prepared via the conventional ImR route (Figure 4). Thus, Pt0.4/C-OP showed a slightly higher initial rate and selectivity than Pt0.4/C-ImR (Table 2). Moreover, at similar Pt loading (ca. 0.5 wt%), Pt1/C-OP showed higher initial rate as the one obtained for the commercial catalyst (Pt0.5/C-com, Figure 4B), more evidence of the attractiveness of the OP hydrothermal route. Finally, yet importantly, an extra reduction with molecular hydrogen before catalysis did not improve the catalytic properties of two OP samples, i.e., Ru0.4/C-OP and Pt1/C-OP (Table S11). Such post-treatment proved to be detrimental for the Pt/C catalyst, with a decrease in the initial rate from 530 mmolCNB/h.gcatalyst for Pt1/C-OP to 443 for Pt1/C-OPR (Table S11). This feature confirms that, following the OP hydrothermal route, no extra reduction is necessary.

As mentioned above, two other Pt0.4/C materials were prepared through the OP hydrothermal route with similar precursors: microporous microspheres (Pt0.4/C-OP00) and ordered mesoporous carbons with a pore size distribution centered at 5 nm (Pt0.4/C-OMC, Figures S2 andS4). Despite similar platinum loading of ca. 0.3 wt%, the three materials showed significant differences in terms of catalytic properties (Figure 4C). A clear correlation was made between the external pore volume, where diffusivity of large molecules is enhanced, and the initial rates (Figure 4D). Moreover, smaller carbon nanoparticles in Pt0.4/C-OP might favor the nucleation and stabilization of smaller Pt nanoparticles during HTC, as suggested by XRD and determined by the Scherrer equation (Figure S7 and Table 1). In conclusion, we developed a one-pot, atom-economical, hydrothermal route for the biosynthesis of carbon aerogel-supported noble metal nanoparticles. We demonstrated the versatility of the one-pot hydrothermal route with tuneable textural and structural properties of both the carbonaceous support and the supported metal nanoparticles. Carbon aerogels with high specific surface area (ca. 800 m 2 g -1 ), high pore volume (> 1.5 cm 3 g -1 ) and well-dispersed metal clusters were obtained. Interestingly, our approach allowed synthesizing an unusual fcc metallic ruthenium structure and might be used in the future for the preparation of other thermodynamically unstable metal and nanoalloy phases. Besides, the Pt/C aerogel nanocomposites showed competitive properties as catalysts for a model reaction, i.e., the selective hydrogenation reaction of CNB into CAN. A comparison with analogous metal/carbon catalysts showed a clear correlation between the external pore volume, where diffusivity of large molecules is enhanced, and the initial rate of the reaction.

While full of promise, the OP HTC route is still a young topic with a limitless variety of sugars and metal precursors to combine and to investigate. We are currently studying other metal salts and mixtures, especially to design supported bimetallic clusters and nanoparticles. Furthermore, other hydrogenation reactions, especially dealing with biorefinery schemes, are currently under study.

Besides, the aerogel-supported Ru-C nanoalloys described herein might be promising catalysts for CO2 hydrogenation reactions at low temperatures. [START_REF] Cored | Hydrothermal Synthesis of Ruthenium Nanoparticles with a Metallic Core and a Ruthenium Carbide Shell for Low-Temperature Activation of CO2 to Methane[END_REF] Overall, we believe that the OP HTC route will open new perspectives for the design of carbonaceous-based SMNPs not only for thermochemical catalysis, but also for photocatalysis, electrocatalysis, sensors and energy storage.

SUPPORTING INFORMATION

Experimental section; procedures and analytical methods; FTIR spectra of organic aerogels before

Figure 1 .

 1 Figure 1. Schematic representations of the two synthetic procedures employed to prepare carbon aerogel-supported noble metal nanoparticles. (A) One-pot method (OP), and (B) impregnationreduction method (ImR). (C) Picture of a gel before freeze-drying. (D) Scanning electron micrograph (SEM), (E) transmission electron micrograph (TEM), and (F) nitrogen sorption isotherm at 77 K of Pt0.4/C-OP.

Figure 2

 2 Figure 2 shows TEM and HR-TEM micrographs of the PtX/C-OP (Figure 2A-D) and the RuX/C-

Figure 2 .

 2 Figure 2. TEM micrographs of (A) Pt0.4/C-OP (and (B) HR-TEM micrograph), (C) Pt10/C-OP (and (D) STEM-HAADF micrograph), (E) Ru0.4/C-OP (and (F) HR-TEM micrograph), (G) Ru1/C-OP and (H) Ru10/C-OP.

  metal clusters, as shown by TEM and HR-TEM micrographs. The H2-TPR analysis performed on Pt10/C-OP confirmed the reduction of platinum during HTC since no clear reduction peak related to hydrogen consumption was observed (FigureS8). These features were also confirmed by XPS. Before pyrolysis (Pt10/H, Figure3B, top), the XPS spectrum shows a doublet containing a low energy band (Pt4f7/2) at 70.9 eV and a high energy band (Pt4f5/2) centered at 74.4

Figure 3 .

 3 Figure 3. (A) XRD patterns of platinum based catalysts, (B) Fitted XPS spectrum of Pt4f signal for Pt10/C-OP (top) before and (bottom) after pyrolysis, (C) XRD patterns of ruthenium based catalysts, (D) Fitted XPS spectrum of Ru3p signal Ru10/C-OP (top) before and (bottom) after pyrolysis.

Figure 4 .

 4 Figure 4. Catalytic properties of different carbon-SMNPs over the hydrogenation reaction of 4chloronitrobenzene (CNB) into 4-chloroaniline (CAN). (A) Comparison between Pt0.4/C-OP and Ru0.4/C-OP at various temperatures and pressures. (B) Comparison between Pt0.4/C-OP, Pt1/C-OP, Pt0.4/C-ImR and Pt0.5/C-com at 70 °C and 10 bars. (C-D) Influence of the textural properties of the carbon support for three materials prepared by the one-pot HTC route with a similar metal loading: Pt0.4/C-OP, Pt0.4/C-OMC and Pt0.4/C-OP00. Experimental conditions: 10 bars, 50°C.

Pt0. 4

 4 C-OP, 70°C 10 bars R u0.4/C-OP, 140°C 10 bars R u0.4/C-OP, 70°C 20 bars R u0.4/C-OP, 70°C 10 bars

  pyrolysis with and without metal; nitrogen sorption isotherms; SEM and TEM micrographs; STEM-EDX mapping of Ru0.4/C-OP, Ru10/C-OP, Pt0.4/C-OP and Pt10/C-OP; XRD spectra of Pt0.4/C-OP00 and Pt0.4/C-ImR; H2-TPR curves of C-OP, Ru10/C-OP and Pt10/C-OP; catalytic properties of Pt1/C-OPR and Ru0.4/C-OPR.

Table 1 .

 1 Textural properties, metal loading, elemental composition and crystallite size of the different RuX/C and PtX/C materials.

	Sample	SSABET	Vtotal a	Vinterp b	Metal loading c	Mass ratio e Lc f
		(m 2 .g -1 )	(cm 3 .g -1 )	(cm 3 .g -1 )	(wt%)	O/C M/C	(nm)
	C-OP	796	1.56	1.38	0 (0)	0.06	0	n/a
	Ru0.4/C-OP	760	1.45	1.27	0.48 (0.4)	0.06 0.005 n/a
	Ru1/C-OP	814	1.56	1.36	0.85 (1)	n/a	n/a	n/a
	Ru10/C-OP	644	1.05	0.87	5.27 (10)	0.09 0.066 13
	Ru10H	270	0.87	0.85	n/a	0.46 n/a	5
	Pt0.4/C-OP	763	1.49	1.32	0.25 (0.4)	0.06 0.003 n/a
	Pt1/C-OP	832	1.91	1.74	0.49 (1)	n/a	n/a	31
	Pt10/C-OP	757	1.63	1.46	4.14 (10)	0.04 0.045 22
	Pt10H	684	1.80	1.70	n/a	0.42 n/a	5
	Pt0.4/C-ImR	640	1.38	1.24	0.37 (0.4)	n/a	n/a	n/a
	Pt0.4/C-OP00	656	0.30	0.05	0.28 (0.4)	n/a	n/a	11
	Pt0.4/C-OMC	686	0.36	0.13	0.28 (0.4)	n/a	n/a	n/a
	Pt0.5/C-com	1115	0.46	0.03	0.5 d	n/a	n/a	5

a Total pore volume determined at p/p 0 0.99 on the desorption branch. b Vinterp = Interparticle volume. c Experimental values obtained by ICP-OES versus theoretical expected values (in brackets). d Value provided by the supplier. e Experimental values obtained by elemental analyses. f Crystallite size determined by the Scherrer equation (spherical crystallites were considered; thus, a shape factor, K, of 0.94 was used in the Scherrer equation).

Table 2 .

 2 Catalytic properties of the different RuX/C and PtX/C materials over the hydrogenation reaction of 4-chloronitrobenzene (CNB) into 4-chloroaniline (CAN).

	Catalyst	P (bars)	T (°C)	r0 (mmolCNB/h.gcatalyst) a	t95(min) b	SAN (%) b
	C-OP			0	n/a	0
	Pt0.4/C-OP			497	10	1.5
	Pt0.4/C-ImR	10	70	444	10	1.3
	Pt0.5/C-com			374	16	1.4
	Pt1/C-OP			530	5	1.3
	Ru0.4/C-OP			0	n/a	0
	Pt0.4/C-OP00			72	131	1.5
	Pt0.4/C-OMC Pt0.4/C-OP	10	50	157 422	77 12	1.4 1.5
	Pt0.5/C-com			365	13	1.4

a : initial reaction rate; b : values are determined at 95% CNB conversion

ACKNOWLEDGMENT

AF is grateful to ANR I-Site MUSE ("Montpellier Université d'excellence", ANR-IDEX-006) for financial support [agreement number: 170544IA]. The authors are thankful to all the people who contributed to this work. They would thank specially Didier Cot (IEM, Montpellier, France) for scanning electron microscopy (SEM) analyses, Franck Godiard (MEA Platform, Univ. Montpellier, Montpellier, France) for transmission electron microscopy (TEM, HR-TEM and STEM-EDX) analyses, Lucie Koeller (AETE-ISO Platform, Montpellier, France) for ICP-OES analyses and all the staff of the Platform of Analysis and Characterisation (PAC) of the Pôle chimie Balard Institutes in Montpellier that contributed to XPS (Valérie Flaud), XRD (Bernard Fraisse) and elemental analyses (Magalie Lefeuvre).

Synopsis

We report the atom-economical biosynthesis of carbon aerogel-supported noble metal nanoparticles with competitive properties as hydrogenation catalysts.