Synthesis of conformationally restricted glutamate and glutamine derivatives from carbonylation of orthopalladated phenylglycine derivatives

Abstract

A new method for the regioselective synthesis of 2-alkoxycarbonyl- and 2-(aminocarbonyl)phenylglycinate methyl esters has been developed. The reaction of the orthopalladated complex [Pd(μ-Cl)(C 6H 4(CH(CO 2Me)NMe 2)-2)] 2 (1) with nucleophiles HNu under a CO atmosphere results in the selective incorporation of the C(O)Nu moiety to the phenyl ring and formation of the carbonyl species ortho-C 6H 4(C(O)Nu)(CH(CO 2Me)NMe 2) (2a-j) (Nu = OR, NHR, NR 2). Compounds 2a-j are conformationally restricted analogues of glutamic acid and glutamine and are interesting due to their biological and pharmacological properties. The reaction of [Pd(μ-Cl)(C 6H 4(CH(CO 2Me)NHTf)-2)] 2 (3) with nucleophiles in a CO atmosphere results, however, in the formation of the cyclic isoindolinone or the open 2-carboxyphenylglycine methyl esters, with the reaction outcome being driven by the choice of the solvent. © 2012 Urriolabeitia et al; licensee Beilstein-Institut.