Development of Bifunctional Thiourea Organocatalysts Derived from a Chloramphenicol Base Scaffold and their Use in the Enantioselective Alcoholysis of meso Cyclic Anhydrides

The synthesis of new chloramphenicol-base-derived thiourea organocatalysts, (1S, 2R)-12a-f and (1R, 2R)-15a-c, and their use in the enantioselective alcoholysis of meso-anhydrides are described. In particular, hemiesters afforded excellent enantioselectivities if low loadings of (1S, 2R)-12a-f were used. Almost no enantioselectivities were achieved with the use of (1R, 2R)-15a-c. This technique was used to synthesize (R)-(-)-baclofen.