Enantioselective amine ?-functionalization via palladium-catalysed C-H arylation of thioamides.

ABSTRACT: Saturated aza-heterocycles are highly privileged building blocks that are commonly encountered in bioactive compounds and approved therapeutic agents. These N-heterocycles are also incorporated as chiral auxiliaries and ligands in asymmetric synthesis. As such, the development of methods to functionalize the ?-methylene C-H bonds of these systems enantioselectively is of great importance, especially in drug discovery. Currently, enantioselective lithiation with (-)-sparteine followed by Pd(0) catalysed cross-coupling to prepare ?-arylated amines is largely limited to pyrrolidines. Here we report a Pd(II)-catalysed enantioselective ?-C-H coupling of a wide range of amines, which include ethyl amines, azetidines, pyrrolidines, piperidines, azepanes, indolines and tetrahydroisoquinolines. Chiral phosphoric acids are demonstrated as effective anionic ligands for the enantioselective coupling of methylene C-H bonds with aryl boronic acids. This catalytic reaction not only affords high enantioselectivities, but also provides exclusive regioselectivity in the presence of two methylene groups in different steric environments.

SUBMITTER: Jain P 

PROVIDER: S-EPMC5347480 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature