Application of asymmetric phase-transfer catalysis in the enantioselective synthesis of cis-5-substituted proline esters

A simple, highly stereoselective three-step sequence for the enantioselective synthesis of cis-5-substituted proline esters is described. This sequence features an asymmetric PTC Michael addition, followed by acid catalysed imine exchange and catalytic hydrogenation. Application of this chemistry in the synthesis of the nonpeptide cholecystokinin antagonist (+)-RP-66803 11 is also described.