Construction of axially chiral 2-arylpyrroles using catalytic asymmetric Suzuki-Miyaura cross-coupling: an efficient approach to esaxerenone.

A general and efficient method has been developed to access axially chiral 2-arylpyrroles using catalytic asymmetric Suzuki-Miyaura cross-coupling. A wide range of axially chiral arylpyrroles were obtained in high yields with good to excellent enantioselectivities. The key to success is the use of a combined catalytic system involving a palladium catalyst and chiral ferrocene diphosphine ligand for achieving effective enantiocontrol. More importantly, this axially chiral CF-substituted 2-arylpyrrole serves as a key intermediate in the preparation of the anti-hypertensive and diabetic nephropathy drug esaxerenone. It was directly asymmetrically synthesized with high enantioselectivity (92% ee). Thus, a new strategy is provided for the catalytic asymmetric synthesis of esaxerenone.