Ligand-Enabled Enantioselective Csp3 -H Activation of Tetrahydroquinolines and Saturated Aza-Heterocycles by RhI

Abstract

The first rhodium(I)-catalyzed enantioselective intermolecular Csp3 -H activation of various saturated aza-heterocycles including tetrahydroquinolines, piperidines, piperazines, azetidines, pyrrolidines, and azepanes is presented. The combination of a rhodium(I) precatalyst and a chiral monodentate phosphonite ligand is shown to be a powerful catalytic system to access a variety of important enantio-enriched heterocycles from simple starting materials. Notably, the Csp3 -H activation of tetrahydroquinolines is especially challenging due to the adjacent Csp2 -H bond. This redox-neutral methodology provides a new synthetic route to α-N-arylated heterocycles with high chemoselectivity and enantioselectivity up to 97 % ee.

Keywords: C−H activation; arylation; enantioselectivity; heterocycles; rhodium.