Enantioselective synthesis and selective functionalization of 4‐aminotetrahydroquinolines as novel GLP‐1 secretagogues

Abstract

Polysubstituted tetrahydroquinolines were obtained in moderate to high yields (28% to 92%) and enantiomeric ratios (er 89:11 to 99:1) by a three‐component Povarov reaction using a chiral phosphoric acid catalyst. Significantly, post‐Povarov functional group interconversions allowed a rapid access to a library of 36 enantioenriched 4‐aminotetrahydroquinoline derivatives featuring five points of diversity. Selected analogs were assayed for their ability to function as glucagon‐like peptide‐1 (GLP‐1) secretagogues.