Nickel Metallaphotoredox Catalysis Enabling Desulfurative Cross Coupling Reactions

Abstract

Metallaphotoredox processes have emerged as powerful methods for CÀ C bond formations. The Ni-photoredox catalyzed desulfurative cross-coupling of thiol derivatives with aryl bromides has now been established. This procedure provides access to simple and complex unsymmetrical diarylmethane molecules under mild reaction conditions with a broad functional group tolerance. The key steps of the reaction involve a silane-mediated halogen-atom transfer (XAT) and a subsequent intramolecular homolytic substitution (S H ), forming C-centered radicals from various thiol derivatives as shown by mechanistic studies. This study paves the way for new transformations of abundant, naturally occurring thiols.

Photo‐induced Desulfurative Processes for Carbon Radical Generation

“…In this context, several photomediated approaches have been developed based on the use of thioether derivatives. [28][29][30] Two families of thioethers have been established depending on the mechanistic steps involved in the carbon radical generation through desulfurization (Scheme 8). After an activation step, substrates belonging to family A, can be involved in an intramolecular homolytic substitution (S H ) that triggers the desulfurization and the generation of the expected carbon radicals.…”

“…[31] In all the photomediated reactions, the S H step consists in the intramolecular cyclization of aryl radicals B onto the sulfur center, releasing the expected carbon radicals along with sulfur-containing heterocycles C (Scheme 8A). [28][29][30][31] On the other hand, the desulfurization of the second class of thioethers (D or G) can be achieved by initial SET reduction of thioethers containing either tetra-fluoropyridine or thiazolium cores (Scheme 8B). [32][33][34][35][36][37][38][39][40] The splitting of the CÀ S bond in the radicals E or H then leads to the carbon radicals and either a stabilized thiolate F or the 3methylthiazolidine-2-thione J byproduct.…”

“…In 2022, Prieto and co‐workers reported a desulfurative process enabling the C−C bond formation through a nickel‐catalyzed cross‐coupling (Scheme 11). [30,41] This strategy allows the formation of a wide range of unsymmetrical diarylmethanes 30 using aryl bromides 29 and benzyl thiols 28 as coupling partners. While the reaction was effective for delivering C−C bond products with benzyl thiols affording 30 in modest to good yields, the reaction was unsuccessful when alkyl thiols were used leading mainly to the formation of defunctionalized compounds.…”

“…The occurrence of side‐reactions, especially defunctionalizations, during the desulfurization of native thiols, has fostered the exploration of strategies involving pre‐functionalized thiols to overcome certain limitations. In this context, several photo‐mediated approaches have been developed based on the use of thioether derivatives [28–30] . Two families of thioethers have been established depending on the mechanistic steps involved in the carbon radical generation through desulfurization (Scheme 8).…”

“…After an activation step, substrates belonging to family A , can be involved in an intramolecular homolytic substitution ( S H ) that triggers the desulfurization and the generation of the expected carbon radicals [31] . In all the photo‐mediated reactions, the S H step consists in the intramolecular cyclization of aryl radicals B onto the sulfur center, releasing the expected carbon radicals along with sulfur‐containing heterocycles C (Scheme 8A) [28–31] . On the other hand, the desulfurization of the second class of thioethers ( D or G ) can be achieved by initial SET reduction of thioethers containing either tetrafluoropyridine or thiazolium cores (Scheme 8B) [32–40] .…”