Regiodivergent Hydroamidation of Alkenes via Cobalt-Hydride Catalysis

Regiodivergent hydroamin(d)ation of alkenes presents a valuable strategy for the synthesis of diverse amines or amides from a common set of starting materials, yet achieving controlled regioselectivity remains a significant challenge. In this work, we present a cobalt-catalyzed regiodivergent hydroamidation of alkenes, enabling enantioselective ipso- and migratory hydroamidation of heterocyclic alkenes. The ability to finely tune various reaction parameters allows for a seamless switch in regioselectivity. Notably, ipso- and migratory selectivity are governed by the choice of cobalt catalyst anions. Mechanistic studies reveal a neutral Co-H species mediating ipso-hydroamidation and a cationic Co-H intermediate promoting migratory hydroamidation. This protocol exhibits a broad substrate scope, high functional group tolerance, and provides an efficient pathway for synthetizing structurally diverse amides.