Asymmetric synthesis of alpha,alpha-disubstituted alpha-amino acids using (S,S)-cyclohexane-1,2-diol as a chiral auxiliary.
Diastereoselective alkylation of ethyl 2-methyl- and/or 2-ethylacetoacetates using the (S,S)-cyclohexane-1,2-diol as an acetal chiral auxiliary afforded enol ethers (2a-f and 5a-f) of 92->95% de in 31-70% yields. Removal of the cyclohexane-1,2-diol with BF(3)-OEt(2) afforded beta-keto esters (3 and 6) bearing a chiral quaternary carbon. The beta-keto esters could be easily converted into optically active alpha-methylated and/or alpha-ethylated alpha,alpha-disubstituted amino acids (12 and 13) in 21-99% yields using Schmidt rearrangement.
Tanaka
M
M
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan. mtanaka@phar.kyushu-u.ac.jp
Oba
M
M
Tamai
K
K
Suemune
H
H
D000596:Amino Acids / Q000138:chemical synthesis*; D003511:Cyclohexanols / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry; D018716:Molecular Mimicry; D013237:Stereoisomerism
D000596:Amino Acids; D003511:Cyclohexanols; D004151:Dipeptides; C064619:1,2-cyclohexanediol