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Regiodivergent Hydroamidation of Alkenes via Cobalt-Hydride Catalysis

Bingxue Liu, Qianqian Lü, Xiao Hu, Dandan Li, Zheyuan Xu, Xi Lu, Yao Fu, Qiang Liu

2025Journal of the American Chemical Society15 citationsDOI

Abstract

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.

Topics & Concepts

ChemistryHydrideCobaltCatalysisAlkeneCombinatorial chemistryOrganic chemistryComputational chemistryMetalAsymmetric Hydrogenation and CatalysisCatalytic C–H Functionalization MethodsSynthesis and Catalytic Reactions
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