Enantioselective Synthesis of Conformationally Restricted Analogs of NMDA: cis- and trans-Piperidine-2,3-dicarboxylic Acids and Methylated Derivatives

Various enantiopure stereoisomeric cyclic amino diacids belonging to the 2,3-piperidinedicarboxylic acid series were obtained via an aza-annulation reaction between enamino esters and acryloyl, methacryloyl, or crotonyl chloride. Enantioselective syntheses of these conformationnally restricted analogs of N -methyl- d -aspartic acid were realized owing to a chiral induction originated from (2 S )-2-phenylglycinol. New information about the mechanism of the aza-annulation process is inferred from AM1 calculations which were performed in order to explain the steroselectivity displayed during the formation of the C-4 stereocenter in compound 4 .