Copper-Catalyzed Cycloisomerization of Unactivated Allene-Tethered O-Propargyl Oximes: A Domino Reaction Sequence toward the Synthesis of Hexahydropyrrolo[3,4-b]azepin-5(4H)-ones.

Abstract

A novel copper-catalyzed cycloisomerization of unactivated allene-tethered O-propargyl oximes has been developed for the synthesis of hexahydropyrrolo[3,4-b]azepin-5(4H)-ones. This one-pot domino reaction proceeds via a [2,3]-sigmatropic rearrangement, a [3 + 2] cycloaddition, and another [3,3]-sigmatropic rearrangement. The methodology offers a practical and straightforward route for the rapid assembly of both ring components of the fused bicyclic motifs from acyclic precursors by simultaneously forming four new bonds (a C═O, a C═N, and two C-C bonds) in a single step.