Asymmetric hydrogenation of isoquinolines with chiral cationic ruthenium diamine catalysts

Abstract

A general asymmetric hydrogenation of isoquinolines catalyzed by chiral cationic ruthenium catalysts has been investigated. A wide range of isoquinoline derivatives, including 1-substituted, 3-substituted, 1,3-disubstituted and 3,4-disubstituted isoquinolines, were efficiently hydrogenated to give chiral tetrahydroisoquinolines with up to 92 % ee and >20:1 dr. It was found that the ruthenium catalyst bearing a non-coordinating BArF anion resulted in high enantioselectivity. Preliminary mechanistic studies revealed that the isoquinoline is reduced via a stepwise pathway, including 1,2-hydride addition, isomerization, and 2,3-hydride addition.