A general copper-catalysed enantioconvergent C(sp³)-S cross-coupling via biomimetic radical homolytic substitution

Although alpha-chiral C(sp(3))-S bonds are of enormous importance in organic synthesis and related areas, the transition-metal-catalysed enantioselective C(sp(3))-S bond construction still represents an underdeveloped domain probably due to the difficult heterolytic metal-sulfur bond cleavage and notorious catalyst-poisoning capability of sulfur nucleophiles. Here we demonstrate the use of chiral tridentate anionic ligands in combination with Cu(I) catalysts to enable a biomimetic enantioconvergent radical C(sp(3))-S cross-coupling reaction of both racemic secondary and tertiary alkyl halides with highly transformable sulfur nucleophiles. This protocol not only exhibits a broad substrate scope with high enantioselectivity but also provides universal access to a range of useful alpha-chiral alkyl organosulfur compounds with different sulfur oxidation states, thus providing a complementary approach to known asymmetric C(sp(3))-S bond formation methods. Mechanistic results support a biomimetic radical homolytic substitution pathway for the critical C(sp(3))-S bond formation step.