Nickel-Catalyzed Site- and Stereoselective Reductive Alkylalkynylation of Alkynes

Development of a catalytic multicomponent reaction by orthogonal activation of readily available substrates for the streamlined difunctionalization 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 <i>N</i>-(acyloxy)phthalimides through nickel-catalyzed reductive alkylalkynylation. Products are generated in up to 89% yield as single regio- and <i>E</i> 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 <i>N</i>-(acyloxy)phthalimides, a cascade radical addition/cyclization/alkynylation process can be implemented to obtain 1,5-enynes. The present study underscores the crucial role of redox-active esters as superior alkyl group donors compared to haloalkanes in reductive alkyne dicarbofunctionalizations.