Solvent Effects in the Enantioselective Catalytic‐Phase‐Transfer Alkylation of Polymer‐Supported Glycine–Imine tert‐Butyl Ester: Asymmetric Solid‐Phase Synthesis of (R)‐α‐Amino Acid Derivatives

Abstract

AbstractPolymer‐supported glycine–imine tert‐butyl esters (3, 8) were prepared from Merrifield‐ or Wang‐resin and used in the enantioselective synthesis of (R)‐α‐amino acid derivatives by using (S,S)‐3,4,5‐trifluorophenyl‐NAS bromide (5) as the chiral phase‐transfer catalyst. The chemical yields and enantioselectivities were found to be dramatically dependent upon the ratio of water to organic solvent. The optimal solvent was a mixture of toluene/chloroform/water (9:1:0.5). The catalytic enantioselective solid‐phase phase‐transfer alkylation of polymer‐supported glycine–imine substrate 3 with various alkyl halides with the use of 50 % aqueous CsOH in the optimal solvent system at 0 °C followed by hydrolysis and benzoylation afforded the corresponding (R)‐N‐benzoyl‐α‐amino acid tert‐butyl esters 11 in 60–80 % yield and with enantiomeric ratios (er) of 96.5:3.5 to 99.5:0.5.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)