Asymmetric synthesis of α,α-disubstituted α-amino acids using (S,S)-cyclohexane-1,2-diol as a chiral auxiliary

Article abstract of DOI:10.1021/jo001423m

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 BF₃-OEt₂ afforded β-keto esters (3 and 6) bearing a chiral quaternary carbon. The β-keto esters could be easily converted into optically active α-methylated and/or α-ethylated α,α-disubstituted amino acids (12 and 13) in 21-99% yields using Schmidt rearrangement.