Synthesis of indan-based unusual alpha-amino acid derivatives under phase-transfer catalysis conditions

Abstract

Conformationally constrained cyclic alpha-amino acid derivatives were synthesized under solid-liquid phase-transfer catalysis conditions. This methodology involves the bis-alkylation of ethyl isocyanoacetate with various alpha,alpha'-dibromo-o-xylene derivatives [alpha,alpha'-dibromo-o-xylene 5, 2,3-bis(bromomethyl)-1,4-dimethoxybenzene 6, 1,2-bis(bromomethyl)-4,5-dibromobenzene 7, 2,3-bis(bromomethyl)naphthalene 8, 1,8-bis(bromomethyl)-naphthalene 9, 6,7-bis(bromomethyl)-2,2-dimethyl-1H-phenalene 1,3(2H)-dione 10, 2,3-bis(bromomethyl)-1,4-anthraquinone 11, 6,7-bis(bromomethyl)quinoxaline 12, 3,4-bis(bromomethyl)furan 13, 1,2,4,5-tetrakis(bromomethyl)benzene 28, and hexakis(bromomethyl)benzene 30] using potassium carbonate as a base and tetrabutylammonium hydrogensulfate as a phase-transfer catalyst to give corresponding isonitrile derivatives, which upon hydrolysis with HCl in ethanol gave amino esters. Using this method electron-deficient as well as electron-rich and halogen-substituted indan-based alpha-amino acids were prepared. The preparation of bis-indan as well as tris-indan alpha-amino esters is also described.