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

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(6)H(4)(CH(CO(2)Me)NMe(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(6)H(4)(C(O)Nu)(CH(CO(2)Me)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(6)H(4)(CH(CO(2)Me)NHTf)-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.