Ligand-Enabled Enantioselective C-sp3-H Activation of Tetrahydroquinolines and Saturated Aza-Heterocycles by Rh-I

The first rhodium(I)-catalyzed enantioselective intermolecular C-sp3-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 C-sp3-H activation of tetrahydroquinolines is especially challenging due to the adjacent C-sp2-H bond. This redox-neutral methodology provides a new synthetic route to -N-arylated heterocycles with high chemoselectivity and enantioselectivity up to 97%ee.