Solid Phase Synthesis of α,α-Disubstituted Amino Acid Derivatives
M. Guinó, K. K. (M.) Hii
King’s College London and Imperial College London, UK
21 September 2005 (online)
The reaction of Merrifield resin with 4-hydroxybenzaldehyde in the presence of Cs2CO3 was promoted by microwave irradiation at 150 ºC for five minutes to give Wang-aldehyde resin 1. Immobilization and activation of amino acid (gylcine, alanine and phenylalanine) ethyl esters performed on the Wang-aldehyde resin in the presence of trimethyl orthoformate forms iminoresins 2. Alkylation of the polymer-supported amino acids 2 with alkyl halides proceeded with five equivalents of tert-butyliminotri(pyrrolidino)phosphorane in anhydrous NMP at room temperature for 14 h to give the corresponding compounds 3. α,α-Disubstituted amino acid derivatives 4 liberated from the polymerized products 3 were obtained upon acid hydrolysis.