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

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).

Automated summary

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