Organocatalytic enantioselective conjugate addition-cyclization domino reactions of o-N-protected aminophenyl α,β-unsaturated aldehydes

A highly enantioselective synthesis of biologically useful tetrahydroquinolines has been developed through the asymmetric organocatalytic conjugate addition-cyclization reaction of malonates with o-N-protected aminophenyl α,β-unsaturated aldehydes using a diphenylprolinol TMS ether as an organocatalyst followed by reductive deoxygenation. This novel protocol allows for the formation of 4-substituted chiral tetrahydroquinolines, which are not easily accessible using other methodologies, in good yields with high enantioselectivities (up to >99% ee).