Construction of Axially Chiral 4-Aminoquinolines by Cycloaddition and Central-to-Axial Chirality Conversion

Org Lett. 2024 Nov 22;26(46):9984-9989. doi: 10.1021/acs.orglett.4c03827. Epub 2024 Nov 14.

Abstract

A two-step strategy has been established for the enantioselective synthesis of 4-aminoquinolines possessing axial chirality. This approach involves a chiral phosphoric acid-catalyzed cycloaddition, followed by a DDQ oxidation step. The method offers efficient access to a variety of 1,1'-biaryl-2,2'-amino alcohol derivatives in excellent yields and enantioselectivities (up to 98% yield and 93% ee). Furthermore, the synthetic transformation of the products was also investigated.