Synthesis of 3-aminocyclobutenones via [2 + 2] cycloaddition of ynamides and ketenes

Abstract

Ynamides react with various classes of ketenes in intermolecular [2 + 2] cycloaddition to afford substituted cyclobutenones with complete regioselectivity. The cycloaddition substrates are easily assembled from amine derivatives by copper-catalyzed N-alkynylation with acetylenic bromides. The alkynylation reaction provides access to thermally sensitive compounds such as diynamides. Synthesis of the requisite halo diynes is achieved by Sonogashira coupling followed by base-mediated elimination at low temperature.