Palladium-Catalyzed Enantioselective Synthesis of Cyclic Sulfamidates and Application to a Synthesis of Verubecestat

• DOI: 10.1021/acs.orglett.7b03639
• Publication Date: 2018-02-20T18:07:59Z
• Authors: Wenyong Chen; Dongfang Meng; Blaise N’Zemba; William J. Morris
• Keywords: 01 natural sciences; 0104 chemical sciences

An enantioselective arylation reaction catalyzed by palladium complexed with substituted phosphinooxazoline (PHOX) ligands is described. Aza-quaternary stereocenters are readily accessible through the arylation reaction between cyclic iminosulfates and a wide variety of arylboronic acids, including electron-poor and ortho-substituted arylboronic acids. This reaction was applied to the preparation of verubecestat, which is currently undergoing clinical evaluation for the treatment of Alzheimer's disease.