Photochemically Driven Palladium- Phosphinoacridine Catalysis: A Carboxylative Approach for Arylcarbamate Synthesis.

In this study, we demonstrate that phosphinoacridines are efficient bidentate ligands for palladium-catalyzed carboxylative C-N coupling reactions under blue LED irradiation. This method facilitates the direct synthesis of arylcarbamates using a range of non-activated aryl halides, such as iodides and bromides, with various amines under atmospheric pressure of CO2. The optimized conditions exhibit high tolerance to sensitive functional groups, resulting in very good to excellent yields of the desired products.

Formate Salt as a Bifunctional Reagent for Hydroxylation and Carbonylation Reactions Under Photochemically Driven Nickel Catalysis.

In this study, we disclose for the first time that formate salt can be used as a bifunctional reagent for the synthesis of phenol derivatives and as a CO source for carbonylative cross-coupling processes using the COware gas reactor under activation free conditions. Key to this success is the in-situ synthesis of aryl formate via an unprecedented nickel/organophotocatalyst system under blue LED irradiation. This developed system demonstrated high applicability to various aryl iodide substrates for synthesizing phenol derivatives.

Synthesis of Fluorinated Amines: A Personal Account.

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 or CS as benign C1 sources. In addition, a novel N(SCF)CF moiety was synthesized.

Photochemically Driven Nickel-Catalyzed Carboxylative C-N Coupling: 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 CO starting from commercially available (hetero)aryl iodides/bromides derivatives and alkyl amines preventing the formation of hazardous and/or toxic waste. Moreover, preliminary mechanistic investigations including stochiometric experiments as well as DFT calculations allow us to shed light on the reaction mechanism.

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

We disclosed herein a straightforward strategy for the synthesis of unprecedented -((trifluoromethyl)thio), -(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.

Metal-Free SF Activation: A New SF -Based Reagent Enables Deoxyfluorination and Pentafluorosulfanylation Reactions.

The activation of SF , a potent greenhouse gas, under metal-free and visible light conditions is reported. Herein, mechanistic investigations including EPR spectroscopy, NMR studies and cyclic voltammetry allowed the rational design of a new fluorinating reagent which was synthesized from the 2-electron activation of SF with commercially available TDAE. This new SF -based reagent was efficiently employed for the deoxyfluorination of CO and the fluorinative desulfurization of CS allowing the formation of useful fluorinated amines.

From Academia to the Market - Air-stable Ni()/Josiphos Catalysts.

The design, synthesis, commercialization and application of air-stable Ni(II)/Josiphos complexes has been realized in a collaboration between Solvias and ICBMS (University Lyon 1). The Ni-complexes are utilized as versatile precatalysts for diverse cross-coupling reactions. Apart from being active in established C-C and C-N couplings at low catalyst loadings, the novel Ni-precatalysts enabled the development of the challenging monoarylation of ammonia, ammonia surrogates and even alkylammonium chlorides with aryl carbamates.

Acridinium Salts and Cyanoarenes as Powerful Photocatalysts: Opportunities in Organic Synthesis.

The use of organic photocatalysts has revolutionized the field of photoredox catalysis, as it allows access to reactivities that were traditionally restricted to transition-metal photocatalysts. This Minireview reports recent developments in the use of acridinium ions and cyanoarene derivatives in organic synthesis. The activation of inert chemical bonds as well as the late-stage functionalization of biorelevant molecules are discussed, with a special focus on their mechanistic aspects.

Metal-Free Visible-Light Synthesis of Arylsulfonyl Fluorides: Scope and Mechanism.

The first metal-free procedure for the synthesis of arylsulfonyl fluorides is reported. Under organo-photoredox conditions, aryl diazonium salts react with a readily available SO source (DABSO) to afford the desired product through simple nucleophilic fluorination. The reaction tolerates the presence of both electron-rich and -poor aryls and demonstrated a broad functional group tolerance.

Forging C-SeCF Bonds with Trifluoromethyl Tolueneselenosulfonate under Visible-Light.

This account highlights some of our recent work on photoinduced trifluoromethylselenolation reactions. This research program relies primarily on the design of a new key shelf-stable selenating reagent that can be involved in various radical processes In particular, we demonstrated that trifluoromethylselenolation of arenes, alkenes, alkynes as well as aliphatic organic building blocks can be readily achieved under visible-light irradiation. Mechanistic investigations based on F NMR studies, EPR spectroscopy, cyclic voltammetry and luminescence studies allowed us to shed the light on the different proposed mechanisms in the designed methodologies.

Nickel-Catalyzed Mono-Selective α-Arylation of Acetone with Aryl Chlorides and Phenol Derivatives.

The challenging nickel-catalyzed mono-α-arylation of acetone with aryl chlorides, pivalates, and carbamates has been achieved for the first time. A nickel/Josiphos-based catalytic system is shown to feature unique catalytic behavior, allowing the highly selective formation of the desired mono-α-arylated acetone. The developed methodology was applied to a variety of (hetero)aryl chlorides including biologically relevant derivatives.

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions.

Copper catalysis and, more generally, copper chemistry are pivotal for modern organofluorine chemistry. Major advances have been made in the field of trifluoromethylselenolations of organic compounds where copper catalysis played a crucial role. Recent developments in this field are highlighted in this minireview.

Chalcogen OCF Isosteres Modulate Drug Properties without Introducing Inherent Liabilities.

The synthesis of SCF as well as SeCF isosteres of two OCF -containing drugs was achieved through visible light and copper-catalyzed processes. Herein, we show that chalcogen replacement modulates physicochemical and ADME properties without introducing intrinsic liabilities. The SCF and SeCF groups are more lipophilic than their oxygen counterpart; however, microsomal stability is unchanged, indicating that these molecular changes may be beneficial for in vivo half-life.

Direct Synthesis of Carbamoyl Fluorides by CO Deoxyfluorination.

Herein, a new concept for the direct synthesis of carbamoyl fluoride derivatives is disclosed. The developed method makes use of CO as an inexpensive and abundant C source; a variety of amines were successfully converted in the presence of a deoxyfluorinating reagent. The corresponding products were often obtained in excellent yields under mild reaction conditions (1 atm and room temperature).

Merging Visible-Light Catalysis for the Direct Late-Stage Group-16-Trifluoromethyl Bond Formation.

The use of visible light activation/photoredox chemistry for the generation of radical-centered chalcogen-CF has gained widespread interest in the last past three years. Its subsequent reactivity for the synthesis of new chalcogen-CF -containing building blocks gained much attention. To date several methodologies have been developed addressing several challenges in modern organofluorine chemistry and enabled substantial progress in substrates scope and reaction conditions.

Transition-Metal-Free Synthesis of Biarylmethanes from Aryl Iodides and Benzylic Ketones.

An original metal-free procedure for the synthesis of biarylmethanes is disclosed herein. The reactions occur with high selectivity starting from aryl iodides and benzylic ketones in the presence of superbasic media (CsOH/DMSO). This procedure allows a straightforward access to a wide range of biarylmethane derivatives substituted with electron-withdrawing and -donating substituents.

Visible-light promoted fluoroalkylselenolation: toward the reactivity of unsaturated compounds.

The reactivity of fluoroalkylselenotoluenesulfonates with unsaturated substrates is explored herein. The direct activation of these shelf-stable reagents under visible light allows the double functionalisation of alkenes or alkynes efficiently, leading to a wide range of β-fluoroalkylselenolated sulfones. Mechanistic investigations have been undertaken supporting the formation of radical intermediates.

Visible-Light-Mediated Metal-Free Synthesis of Trifluoromethylselenolated Arenes.

The first visible-light-mediated synthesis of trifluoromethylselenolated arenes under metal-free conditions is reported. The use of an organic photocatalyst enables the trifluoromethylselenolation of arene diazonium salts using the shelf-stable reagent trifluoromethyl tolueneselenosulfonate at room temperature. The reaction does not require the presence of any additives and shows high functional-group tolerance, covering a very broad range of starting materials.

Electrophilic trifluoromethylselenolation of terminal alkynes with -(trifluoromethyl) 4-methylbenzenesulfonoselenoate.

Herein the nucleophilic addition of -(trifluoromethyl) 4-methylbenzenesulfonoselenoate, a stable and easy-to-handle reagent, to alkynes is described. This reaction provides trifluoromethylselenylated vinyl sulfones with good results and the method was extended also to higher fluorinated homologs. The obtained compounds are valuable building blocks for further syntheses of fluoroalkylselenolated molecules.

Exploring the Reactivity of Trifluoromethyl Tolueneselenosulfonate with Alkynes under Copper Catalysis.

The direct fluoroalkylselenolation of terminal alkynes is reported herein involving shelf stable electrophilic reagents TsSeR . The use of these reagents allows for the first time performing the reaction under catalytic conditions (copper/ligand). Moreover, the presence of oxygen directing groups allows the selective addition of the reagents to alkynes, therefore yielding a new family of vinyl sulfones.

Synthetic Approaches to Trifluoromethylselenolated Compounds.

The association of trifluoromethyl group to chalcogens gives new fluorinated substituents with specific properties, mainly in term of lipophilicity. The trifluoromethylselenyl group is the last of the series that has been studied and despite pioneering approaches in the late 1960s, CF Se chemistry has been scarcely developed over the last decades. Some modern and efficient methods to obtain trifluoromethylselenolated molecules have recently emerged.

Trifluoromethyl- and Fluoroalkylselenolations of Alkynyl Copper(I) Compounds.

The successful perfluoroalkylselenolation of alkynyl copper(I) compounds is described herein. The reaction occurs under oxidant free conditions at room temperature. This convenient one-pot procedure is based on the in situ generation of trifluoromethylselenyl chlorides.

Electrophilic Trifluoromethylselenolation of Boronic Acids.

Trifluoromethylselenylated compounds are emergent compounds with interesting physicochemical properties that still suffer from a lack of efficient synthetic methods. We recently developed an efficient one-pot strategy to generate in situ CF₃SeCl and use it in various reactions. Herein, we continue our study of the reactivity scope of this preformed reagent.

Synthetic Approaches to Trifluoromethoxy-Substituted Compounds.

Because of the unique properties of the trifluoromethoxy group, molecules bearing this moiety will find applications in various fields, particularly in the life sciences. However, despite the great interest in this functional group, only a small number of trifluoromethoxylated molecules are currently synthetically accessible. Over the last few years, several innovative and promising strategies for the synthesis of trifluoromethoxylated compounds have been described.

Copper-Catalyzed Perfluoroalkylthiolation of Alkynes with Perfluoroalkanesulfenamides.

Copper-catalyzed direct perfluoroalkylthiolation of alkynes by using the corresponding perfluoroalkanesulfenamide reagent is reported. The selective mono- and bis-perfluoroalkylthiolation of alkynes can be conducted under very mild conditions (no base, room temperature) in very good to excellent yields. This approach, which uses a low toxicity, inexpensive copper catalyst that incorporates a commercially available ligand, is applied in the absence of any additional base.