Diastereoselective synthesis of β2-amino acids

As part of an ongoing project concerning the synthesis of nonnatural amino acids, we have now developed a general strategy for the preparation of beta(2)-amino acids (or 2-aminocarboxylic acid derivatives). Our procedure involves the synthesis of the sultam beta-alaninate precursor 5 whose alkylation led with high yields and excellent diastereoselectivity to the precursor of beta(2)-homophenylalanine, beta(2)-homoalanine, and beta(2)-homoleucine. Subsequent deprotection and Boc-protection yielded the expected beta(2)-amino acids. X-ray analysis of the alkylation product established that (-)-sultam yielded (R)-beta(2)-amino acids, conversely (+)-sultam yielded the enantiomer. The topicity of this alkylation is in agreement with the alkylation of Oppolzer's precursor for the synthesis of a-amino acids and opposite to that observed for gem-dialkylation.