Copper(i)-catalyzed [4+2] cycloaddition of aza-ortho-quinone methides with bicyclic alkenes

A variety of tetrahydroquinoline-fused bicycles bearing multiple stereocenters are prepared in good yields with high diastereoselectivity through Cu2O-catalyzed [4 + 2] cycloaddition of aza-ortho-quinone methides (ao-QMs) with bicyclic alkenes. Mechanistic studies reveal that the Cu(i) catalyst not only promotes the formation of ao-QMs through a radical process by single electron transfer but also accelerates [4 + 2] cycloaddition. The reaction was easily performed on gram scale and the obtained tetrahydroquinoline-fused bicycles can be converted to diverse tetrahydroquinoline scaffolds.

Automated summary

A variety of tetrahydroquinoline-fused bicycles with multiple stereocenters are synthesized in good yields with high diastereoselectivity through Cu2O-catalyzed [4 + 2] cycloaddition. Mechanistic studies show that the Cu(i) catalyst facilitates the formation of ao-QMs through a radical process and accelerates the [4 + 2] cycloaddition. The reaction can be easily scaled up and the products obtained can be converted into diverse tetrahydroquinoline scaffolds.