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

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).