Enantioselective C(sp3)–H Sulfilimination via Dual Photoredox/Copper Catalysis

Abstract

Enantioenriched sulfilimines are important sulfur(IV) stereogenic entities in medicinal chemistry, agrochemicals and serve as versatile intermediates in organic synthesis. However, while significant efforts have centered on prefunctionalized substrates to construct these motifs, the direct enantioselective sulfilimination of C(sp³)–H bonds remains a formidable challenge. Herein, we report a dual photoredox and copper-catalyzed asymmetric sulfilimination of abundant C(sp³)–H feedstocks with sulfenamides. Notably, by employment of a rationally designed N,N,N-tridentate ligand, the corresponding chiral sulfilimine products can be accessed with high efficiency and enantiocontrol. Under mild conditions, a broad substrate scope of this method is demonstrated, enabling the facile synthesis of enantioenriched sulfilimines in good yields (up to 99% yield) and high enantioselectivities (up to 99% ee). Mechanistic investigations reveal that the sulfilimination reaction proceeds via an aryl radical-mediated intermolecular HAT (hydrogen atom transfer) pathway to generate the alkyl radical for the subsequent enantioselective S-alkylation.