Abstract
A wide range of cyclic and open-chain alpa,alpha-disubstituted alpha-amino acids 1a-p were prepared. The racemic N-acylated alpha,alpha-disubstituted amino acids were resolved by coupling to chiral amines 15-18 derived from (S)- phenylalanine to form diastereoisomers 19/20 or 21/22 that could be separated by crystallization and/or flash chromatography on silica gel (Scheme 3). Selective cleavage via the 1,3-oxazol-5(4H)-ones 10a-p gave the corresponding optically pure alpha,alpha-disubstituted amino-acid derivatives 11 or 12 in high yield (Scheme 3). The absolute configurations of the alpha,alpha-disubstituted amino acids were determined from X-ray structures of the diastereoisomers 20, 21g', 22d.
Obrecht, Daniel