An efficient route to chiral N-heterocycles bearing a C–F stereogenic center via asymmetric hydrogenation of fluorinated isoquinolines

Abstract

An efficient iridium-catalyzed asymmetric hydrogenation of the fluorinated isoquinoline derivatives has been successfully developed for the synthesis of chiral fluorinated tetrahydroisoquinoline derivatives with up to 93% ee. This methodology features the use of a hydrochloride salt as well as a catalytic amount of halogenated hydantoin which were vital for the reactivity, enantioselectivity, and inhibition of the hydrodefluorination pathway.