8-Quinox Cobalt Catalyst Enables the Reductive Alkylative Addition of Sulfinylamines with Unactivated Alkyl Halides
Ning Liu, Hanyu Xia, Yue Shi, Kailin Xu, Zhiming Yu, Xianqing Wu, Genping Huang, Jingping Qü, Yifeng Chen
Abstract
Sulfur-based chiral centers play a critical role in drug discovery yet pose significant challenges in achieving precise stereochemical control. Sulfinamides, serving as versatile intermediates and chiral auxiliaries, have traditionally required multistep synthesis or auxiliary-dependent strategies. Recent advances using N -sulfinyltritylamine (TrNSO) enabled catalytic arylative additions; however, stereoselective alkylative approaches remain underdeveloped, likely due to the highly reactive alkyl radical intermediate. Herein, we report a cobalt-catalyzed reductive addition strategy for direct enantioselective C(sp 3 )–S bond formation between TrNSO and unactivated alkyl halides. Leveraging an unprecedented 8-Quinox cobalt catalyst, this method delivers alkyl-substituted sulfinamides with broad substrate scope, excellent functional group tolerance, and high enantioselectivity. The protocol is further extended to a cascade addition/cyclization sequence, facilitating the efficient synthesis of enantioenriched sultims. DFT calculations reveal stereochemical control arises from selective alkyl radical addition orchestrated by the chiral cobalt catalyst.