Scalable Methodology for the Catalytic, Asymmetric α-Bromination of Acid Chlorides

The optimization of a practical, catalytic, asymmetric process for the α-bromination of acid chlorides to produce synthetically versatile, optically active α-bromoesters is reported. A range of products is produced in high enantioselectivity and moderate to good chemical yields with retention of both upon scale-up. The reactions herein are catalyzed by cinchona alkaloid derivatives, with the best performance achieved by the use of a proline cinchona alkaloid conjugate designed in a de novo fashion.