Proton-Gated Cobalt Catalysis Redirects Persistent Sulfinyl Radical Coupling toward Enantioselective C–S Bond Formation
- 1State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, South Puzhu Road 30, Nanjing, China, 211816
- 2School of Pharmaceutical Sciences
- 3Sun Yat-sen University
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.
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BibTeX
@misc{he2026protongated,
title = {{Proton-Gated Cobalt Catalysis Redirects Persistent Sulfinyl Radical Coupling toward Enantioselective C–S Bond Formation}},
author = {Yuxuan He and Xuezhi Wang and Zibing Zheng and Chunlei Liu and Minghao Zhao and Yang Yang and Yong Luo and Danqing Zheng},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010938/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010938/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Proton-Gated Cobalt Catalysis Redirects Persistent Sulfinyl Radical Coupling toward Enantioselective C–S Bond Formation
AU - Yuxuan He
AU - Xuezhi Wang
AU - Zibing Zheng
AU - Chunlei Liu
AU - Minghao Zhao
AU - Yang Yang
AU - Yong Luo
AU - Danqing Zheng
PY - 2026
DA - 2026/10/23
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010938/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010938/v1
AB - 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.
ER -