Nickel-Catalyzed Enantioselective Reductive Vinyl-Alkynylation of Unactivated Alkenes with Bromoalkynes

Abstract

Alkynyl groups are highly valuable functionalities, prompting chemists to continually seek efficient alkynylation reactions. Traditional asymmetric alkynylation strategies using terminal alkynes often rely on complex chiral phosphine ligands, stoichiometric amounts of silver reagents, and elevated temperatures. While using alkynyl halides instead of terminal alkynes presents a promising alternative, their high reactivity, low steric bulk, and propensity to act as radical acceptors have hindered their application in asymmetric reductive coupling reactions. In this work, we develop a novel nickel-catalyzed enantioselective reductive vinyl-alkynylation of 2-bromo-1,6-dienes, the first of its kind for unactivated alkenes using readily generated bromoalkynes. This method facilitates the efficient synthesis of diverse internal alkynes, including pyrrole, cyclopentane, and furan derivatives bearing quaternary stereocenters, achieving up to 96% ee under mild conditions.

Keywords: Nickel, Catalysis, Vinyl-alkynylation, Bromoalkynes, alkene