A Highly Diastereo- and Enantioselective Synthesis of Tetrahydroquinolines: Quaternary Stereogenic Center Inversion and Functionalization

Abstract

Tetrahydroquinolines containing two quaternary stereogenic centers were synthesized with excellent ee and dr via a four-component cyclization reaction catalyzed by a chiral phosphoric acid. High chemoselectivity was achieved by differentiating anilines with similar reactivities to yield diverse “hybrid” products. The chirality of the quaternary C4 atom of the 4-aminotetrahydroquinoline products was found to undergo highly stereoselective inversion, enabling facile functionalization using a wide range of nucleophiles (C, O, N, and S).