Access to Hexahydrocarbazoles: The Thorpe–Ingold Effects of the Ligand on Enantioselectivity

A novel cyclization reaction of methylenemalonate with indoles is reported, and it provides efficient access to a variety of hexahydrocarbazoles. The enantioselective version was realized by a finely tuned ligand/Cu^II catalyst. The optically active hexahydrocarbazoles contain three quaternary carbon centers and are obtained in up to 99 % yield with greater than 99:1 d.r. and up to greater than 99 % ee. This reaction can be carried out on gram scale and stereoselective transformation of the product led to the core structure of a series of alkaloids from Kopsia plants.