Stereoselective synthesis of the conformationally constrained glutamate analogue, (-)-(2R,3S)-cis-2-carboxyazetidine-3-acetic acid, from (S)-N-tosyl-2-phenylglycine

The stereoselective synthesis of a novel cis conformationally constrained glutamate analogue containing an azetidine framework was accomplished from (S)-N-tosyl-2-phenylglycine in moderate overall yield. The key steps in the synthesis involved a N-H carbenoid insertion promoted by Cu(acaC)(2), a very efficient Wittig olefination of an azetidin-3-one, followed by a highly stereoselective rhodium-catalyzed hydrogenation. Epimerization of the cis to the trans analogue was performed using DBU as base in toluene at reflux.