Asymmetric Synthesis of Tetrahydroquinolines with Quaternary Stereocenters through the Povarov Reaction

The asymmetric Povarov reaction with a-alkyl styrenes as dienophiles was catalyzed by an N,N'-dioxide L4Sc(OTf)3 complex. Enantiopure tetrahydroquinoline derivatives with a quaternary stereocenter at the C4 position were synthesized for the first time. A wide variety of a-alkyl styrenes and N-aryl aldimines were tolerated in the reaction, to give excellent diastereo- (up to 99:1 d.r.) and enantioselectivities (92 to >99?% ee). In addition, the reaction could be performed on the gram scale without any loss of yield, diastereoselectivity, or enantioselectivity. An intermolecular hydrogen-shift reaction was found to be a side reaction, which offered a method to synthesize the corresponding quinoline derivatives with chiral quaternary sterocenters.