Publication Details (including relevant citation information):
Tetrahedron (2012), 68(24), 4745-4756.
1,3-Oxazinan-6-ones were used to generate substituted β2,2,3-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, respectively. The chemistry thus provides access to a range of symmetrical and stereopure β2,2,3-substituted amino acids and further establishes 1,3-oxazinan-6-ones as useful intermediates.