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

• Main Authors: Esteban P. Urriolabeitia, Eduardo Laga, Carlos Cativiela
• Format: Article
• Language: English
• Published: Beilstein-Institut 2012-09-01
• Series: Beilstein Journal of Organic Chemistry
• Subjects: C–H functionalization; carbonylation; glutamic acid; glutamide; palladium; phenylglycine
• Online Access: https://doi.org/10.3762/bjoc.8.179

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)(C6H4(CH(CO2Me)NMe2)-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-C6H4(C(O)Nu)(CH(CO2Me)NMe2) (2a–j) (Nu = OR, NHR, NR2). 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)(C6H4(CH(CO2Me)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.