Diastereoselective synthesis of highly functionalized β 2,2,3-substituted amino acids from 4-substituted-1,3-oxazinan-6-ones

Abstract

1,3-Oxazinan-6-ones were used to generate substituted β 2,2,3-substituted amino acid derivatives. The enolates of 1,3-oxazinan-6-ones were trans-selectively intercepted with electrophiles. This alkylation was subsequently optimized for a one-pot dialkylation to form 5,5-disubstituted oxazinanones. The initial 5-monomethylated compounds could be enolized and then diastereoselectively intercepted with different electrophiles to form differentially 5,5-disubstituted products. The 5,5-dialkylated oxazinanones were then transformed to N-methyl β2,2,3- substituted amino acids by reductive cleavage. Hydrolysis or solvolysis of the oxazinanones afforded β2,2,3-substituted amino acids or esters, resp..