NiH-Catalyzed Enantioconvergent α-Alkenylation of Carbonyl Compounds via Markovnikov Alkyne Hydronickellation

Abstract

β-Methylene carbonyl motifs constitute privileged structural frameworks that play vital roles as a pharmacophore and serve as key intermediates in the assembly of architecturally complex molecules. Despite their synthetic importance, asymmetric approaches for their preparation remain scarce and are largely confined to substrate-controlled or stoichiometric chiral auxiliary methods. Herein, we report a nickel hydride-catalyzed enantioconvergent α-alkenylation of carbonyl compounds with alkynes, providing a direct and general route to α-chiral β-methylene carbonyl derivatives. The transformation proceeds via Markovnikov-selective alkyne hydronickellation followed by nickel-radical recombination to forge the α-stereogenic center, delivering the desired products with high levels of regio- and enantioselectivity. The protocol accommodates a wide range of alkynes and α-halocarbonyl partners, displays excellent functional group tolerance, and can be applied to the modification of biologically relevant molecules. Mechanistic investigations indicate that a partially protic Ni(II)H species governs the observed regioselectivity, while enantio-discrimination occurs during the radical capture step. This work establishes NiH catalysis as a versatile platform for expanding the synthetic repertoire for enantioenriched β-methylene carbonyl architectures. © 2026 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.