NiH-Catalyzed Regio- and Enantioselective Hydrosulfinamidation of Aryl Alkenes

Despite the significant potential of chiral sulfinamides in drug discovery, the stereocontrolled synthesis of such molecules remains a formidable challenge. Herein, we report a nickel-catalyzed regio- and enantioselective hydrosulfinamidation of readily available aryl alkenes that provides efficient access to diverse chiral sulfinamides bearing two contiguous stereocenters. This method exhibits broad functional group tolerance, complete regioselectivity, and excellent enantioselectivity (up to 98% ee). The reaction is readily scalable to gram quantities, and the resulting products can be further transformed into a variety of sulfur-containing compounds with full retention of enantiopurity. Mechanistic studies elucidate the radical reaction pathway and rationalize the origins of regio- and enantioselectivity. The process commences with the regio- and enantioselective syn-hydronickelation of the alkene by an in situ-generated Ni(II)-H species, yielding an alkylnickel intermediate. Subsequently, a turnover-limiting step occurs through 2,3-addition of the alkylnickel species across the S═N bond of the sulfinylamines.