Copper-catalyzed propargylic substitution for the highly selective construction of multi-substituted 1,4-enynes

Abstract

An efficient copper-catalyzed propargyl substitution reaction of propargylic esters containing multi-substituted alkenes with salicylaldehydes or arylamines to directly synthesize multi-substituted 1,4-enyne derivatives is disclosed. This reaction demonstrates excellent substrate scope, affording moderate to excellent yields (47–91%). Furthermore, we explored the asymmetric catalytic variants of this transformation. This method could serve as a new attractive strategy for the practical syntheses of 1,4-enyne derivatives under mild reaction conditions with operational simplicity. Gram-scale synthesis and derivatization studies were also successfully performed. This work provides a novel synthetic methodology for the efficient construction of functionalized 1,4-enyne compounds.