Copper-Catalyzed trans-Selective Aryl-Allylation of Ynamide: An Unconventional Route to Skipped Dienes

Skipped dienes are fundamental components of polyunsaturated fatty acids and bioactive molecules like alkaloids, terpenoids, and polyketides. While allylation of alkynes offers straightforward access to such dienes, it poses regio- and stereocontrol challenges in the allyl unit incorporation step. Herein, we present a highly regio- and trans-selective copper-catalyzed three-component aryl-allylation of ynamides using arylboronic acids and allyl halides as coupling partners. The ligand plays a vital role in determining the regio- and stereoselective outcome. Broad substrate scopes demonstrate excellent labile functional group tolerance. Valuable tetrasubstituted α-hydroxy-α'-aryl-α″-allyl ketones and cyclic ether macrocycles were accessed using late-stage transformations. Control experiments and DFT studies elucidate the origin of the trans-selectivity as a consequence of the directing effect provided by the pyrrolidinone moiety of the ynamide.