Organocatalytic Enantioselective Cascade Aza-Michael/Michael Addition for the Synthesis of Highly Functionalized Tetrahydroquinolines and Tetrahydrochromanoquinolines

An efficient organocatalytic highly asymmetric cascade aza-Michael/Michael addition reaction for the synthesis of tetrahydroquinolines and tetrahydrochromanoquinolines has been developed. This cascade reaction proceeds well at low catalyst loading with a broad substrate scope, furnishing the desired products in excellent yields with excellent diastereoselectivities and enantioselectivities (up to >99:1 dr, 99% ee) under mild conditions. Importantly, it is the first catalytic asymmetric method for tetrahydrochromanoquinolines. This protocol provides a straightforward entry to highly functionalized chiral tetrahydroquinoline and tetrahydrochromanoquinoline derivatives from simple starting materials.