CPA-catalyzed asymmetric domino thia-Michael/aldol reactions for simultaneous chiral center and axial chirality formation

Abstract

A highly enantio- and diastereoselective domino thia-Michael/aldol reaction applying 5H-dibenzo[a,c][7]annulen-5-one as a Michael acceptor, catalyzed by a chiral phosphoric acid (CPA), has been developed. The bridged biaryl adduct contains multiple stereogenic centers in the bridging linkage as well as a thermodynamically controlled stereogenic axis. The energy difference between the two atropodiastereomers is about 9.1 kcal mol⁻¹, which accounts for the observed excellent diastereoselectivity (>20 : 1).