Nickel-catalyzed site- and stereoselective reductive alkylalkynylation of alkynes

Abstract

Summary The development of a catalytic multicomponent reaction by orthogonal activation of readily available substrates for the streamlined di-functionalization of alkynes is a compelling objective in organic chemistry. Alkyne carboalkynylation, in particular, offers a direct entry to valuable 1,3-enynes with different substitution patterns. Here, we show that the synthesis of stereodefined 1,3-enynes featuring a trisubstituted olefin is achieved by merging alkynes, alkynyl bromides, and redox-active N-(acyloxy)phthalimides through nickel-catalyzed reductive alkylalkynylation. Products are generated in up to an 89% yield as single regio- and E isomers. Transformations are tolerant of diverse functional groups and the resulting 1,3-enynes are amenable to further elaboration to synthetically useful building blocks. With olefin-tethered N-(acyloxy)phthalimides, a cascade radical addition/cyclization/alkynylation process can be implemented to obtain 1,5-enynes. This study underscores the crucial role of redox-active esters as superior alkyl group donors compared with haloalkanes in reductive alkyne dicarbofunctionalizations.