Enantioselective Synthesis of Tetrahydropyridines/Piperidines via Stepwise [4 + 2]/[2 + 2] Cyclizations

A phosphine-catalyzed novel enantioselective [4 + 2]-annulation reaction between allene ketones and 1-azadienes has been developed, and tetrahydropyridines were obtained in good yields and with excellent enantioselectivities. Subsequent exposure of tetrahydropyridines to benzyne leads to a [2 + 2]-cyclization, creating optically enriched polycyclic piperidines with a quaternary stereogenic center and a cyclobutene moiety. The reported stepwise [4 + 2]/[2 + 2]-cycloadditions represent a new approach to access enantiomerically enriched nitrogen-containing six-membered ring systems.