Iridium-catalyzed asymmetric hydrogenation of tetrahydro-γ-carboline: a versatile approach to chiral cis-hexahydro-γ-carboline derivatives compatible with C6-substituted carbolines†

Abstract

An efficient iridium-catalyzed asymmetric hydrogenation (AH) of tetrahydro-γ-carboline has been developed for the synthesis of chiral cis-hexahydro-γ-carboline derivatives. This method overcomes the challenge posed by C6 substituents on the carboline ring, proceeding smoothly under mild conditions to deliver the desired products in high yields with exceptional enantioselectivities. The success of this transformation is attributed to the use of a ZhaoPhos ligand bearing an electron-withdrawing F-substituted phenyl group on phosphorus. Notably, the strategy's versatility is further demonstrated by its concise and efficient application in the synthesis of lumateperone intermediates.