A Ketone Synthesis via Cu(I)-Catalyzed Regioselective Coupling of 2-Pyridylthioesters with Grignard Reagents: In Quest of Straightforward Access to Pharmaceuticals

Abstract

For commercial production of SGLT2 inhibitors, cryogenic conditions (−78 °C) were required at the key C-glycosidation step, which has restricted their supply to the world market. To address the challenge, reported herein is a new synthetic method based on a new ketone synthesis by means of copper(I)-catalyzed coupling of 2-pyridylthioesters with Grignard reagents. The facile transformation from the ketones to the final APIs was realized under mild conditions due to the use of readily cleavable acetyl protecting groups.