Bi-Catalyzed Trifluoromethylation of C(sp2)-H Bonds under Light.

We disclose a Bi-catalyzed C-H trifluoromethylation of (hetero)arenes using CF3SO2Cl under light irradiation. The catalytic method permits the direct functionalization of various heterocycles bearing distinct functional groups. The structural and computational studies suggest that the process occurs through an open-shell redox manifold at bismuth, comprising three unusual elementary steps for a main group element. The catalytic cycle starts with rapid oxidative addition of CF3SO2Cl to a low-valent Bi(I) catalyst, followed by a light-induced homolysis of Bi(III)-O bond to generate a trifluoromethyl radical upon extrusion of SO2, and is closed with a hydrogen-atom transfer to a Bi(II) radical intermediate.

Bismuth radical catalysis in the activation and coupling of redox-active electrophiles.

Radical cross-coupling reactions represent a revolutionary tool to make C(sp3)-C and C(sp3)-heteroatom bonds by means of transition metals and photoredox or electrochemical approaches. However, the use of main-group elements to harness this type of reactivity has been little explored. Here we show how a low-valency bismuth complex is able to undergo one-electron oxidative addition with redox-active alkyl-radical precursors, mimicking the behaviour of first-row transition metals. This reactivity paradigm for bismuth gives rise to well-defined oxidative addition complexes, which could be fully characterized in solution and in the solid state. The resulting Bi(III)-C(sp3) intermediates display divergent reactivity patterns depending on the α-substituents of the alkyl fragment. Mechanistic investigations of this reactivity led to the development of a bismuth-catalysed C(sp3)-N cross-coupling reaction that operates under mild conditions and accommodates synthetically relevant NH-heterocycles as coupling partners.

Switchable photocatalysis for the chemodivergent benzylation of 4-cyanopyridines.

We report a photocatalytic strategy for the chemodivergent radical benzylation of 4-cyanopyridines. The chemistry uses a single photoredox catalyst to generate benzyl radicals upon N-F bond activation of 2-alkyl N-fluorobenzamides. The judicious choice of different photocatalyst quenchers allowed us to select at will between mechanistically divergent processes. The two reaction manifolds, an ipso-substitution path proceeding via radical coupling and a Minisci-type addition, enabled selective access to regioisomeric C4 or C2 benzylated pyridines, respectively. Mechanistic investigations shed light on the origin of the chemoselectivity switch.

A General Organocatalytic System for Electron Donor-Acceptor Complex Photoactivation and Its Use in Radical Processes.

We report herein a modular class of organic catalysts that, acting as donors, can readily form photoactive electron donor-acceptor (EDA) complexes with a variety of radical precursors. Excitation with visible light generates open-shell intermediates under mild conditions, including nonstabilized carbon radicals and nitrogen-centered radicals. The modular nature of the commercially available xanthogenate and dithiocarbamate anion organocatalysts offers a versatile EDA complex catalytic platform for developing mechanistically distinct radical reactions, encompassing redox-neutral and net-reductive processes. Mechanistic investigations, by means of quantum yield determination, established that a closed catalytic cycle is operational for all of the developed radical processes, highlighting the ability of the organic catalysts to turn over and iteratively drive every catalytic cycle. We also demonstrate how the catalysts' stability and the method's high functional group tolerance could be advantageous for the direct radical functionalization of abundant functional groups, including aliphatic carboxylic acids and amines, and for applications in the late-stage elaboration of biorelevant compounds and enantioselective radical catalysis.

A Photochemical Organocatalytic Strategy for the α-Alkylation of Ketones by using Radicals.

Reported herein is a visible-light-mediated radical approach to the α-alkylation of ketones. This method exploits the ability of a nucleophilic organocatalyst to generate radicals upon SN 2-based activation of alkyl halides and blue light irradiation. The resulting open-shell intermediates are then intercepted by weakly nucleophilic silyl enol ethers, which would be unable to directly attack the alkyl halides through a traditional two-electron path. The mild reaction conditions allowed functionalization of the α position of ketones with functional groups that are not compatible with classical anionic strategies. In addition, the redox-neutral nature of this process makes it compatible with a cinchona-based primary amine catalyst, which was used to develop a rare example of enantioselective organocatalytic radical α-alkylation of ketones.