Proton-Gated Cobalt Catalysis Redirects Persistent Sulfinyl Radical Coupling toward Enantioselective C–S Bond Formation
Year: 2026
Type: preprint
Abstract: The enantioselective construction of aliphatic C(sp3)–S stereocenters from alkyl radicals remains challenging. Persistent sulfinyl radicals are attractive partners for radical cross-coupling. However, their rapid diffusioncontrolled coupling with transient alkyl radicals provides limited opportunity for stereochemical discrimination. Here, we report a dual photoredox/cobalt catalytic system in which a Brønsted acid acts as a critical mechanistic gate, redirecting persistent sulfinyl radical coupling from a direct PRE-dominated pathway toward cobaltcontrolled enantioselective C–S bond formation. Mechanistic studies support reduction of Co(II) to Co(I) and subsequent formation of a Co(III)–H species in the presence of HX. Hydrogen-atom transfer between Co(III)–H and the sulfinyl radical generates RSOH, which subsequently associates with a chiral cobalt species to organize the sulfur center for stereoselective radical capture. The use of aprotic alkyl radical precursors, including alkyl trifluoroborates and trialkylboranes, decouples radical generation from proton availability and reveals the critical role of the Brønsted acid in stereocontrol. This method accommodates diverse alkyl radical precursors and enables a practical alkene hydroboration–sulfinylation cascade for the synthesis of enantioenriched sulfoxides.
Source: ChemRxiv
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funder: Nanjing Tech University
OpenAlex ID: W7223390113