Enantioselective Synthesis of Chiral 3-Substituted Tetrahydroquinolines via a Pd-Catalyzed C–C Cleavage/C–C Coupling Sequence

Abstract

A palladium-catalyzed asymmetric synthesis of 3-substituted tetrahydroquinolines (THQs) through a C–C cleavage/C–C coupling sequence has been developed. By employing Pd(OAc)2/Josiphos L7 as the catalyst, an array of chiral tetrahydroquinolines bearing a C3-ketone pendant was afforded in good to excellent yields and enantioselectivities by using 3-(2-bromoaniline)-tethered cyclobutanols as substrates. Control experiments revealed that only cis-substrates were able to participate in the reaction. In addition, several synthetic transformations derived from the ketone moiety were carried out to demonstrate the practical utility of this protocol.