Atroposelective synthesis of N-N axially chiral pyrrolylamides by combined-acid catalytic Paal-Knorr reaction

Abstract

A general and efficient method for construction of enantiomerically pure N-N axially chiral pyrrolylamides by utilizing the catalytic asymmetric Paal-Knorr reaction has been developed. A wide range of N-N pyrrolylamides atropisomers were obtained in high yields with good to excellent enantioselectivities. The key to success is the use of the binary-acid catalytic system involving the dramatic synergistic effect of a Lewis acid and a chiral phosphoric acid for achieving effective stereocontrol. The synthetic N-N axially chiral compounds could be modified by their conversion to various valuable products, indicating the potential synthetic application of this method.