Schöllkopf Bis-Lactim Amino Acid Synthesis

U. Schöllkopf et al., Angew. Chem. Int. Ed. 18, 863 (1979); 20, 798 (1981).

Asymmetric amino acid synthesis via diastereoselective alkylation of the lithiated bis-lactim ether (derived from L-Val and Gly or Ala) by an electrophile. Subsequent acid hydrolysis liberates L-Val-OCH3 and the (R)-α-substituted amino acid ester. When the bis-lactim is generated from D-Val, the (S)-enantiomer forms:

Synthetic applications: S. Kotha, A. Kuki, Chem. Commun. 1992, 404; M. S. Allen et al., Synth. Commun. 22, 2077 (1992). Isotopic labeling: N. R. Thomas, D. Gani, Tetrahedron 47, 497 (1991). Reviews: U. Schöllkopf, Top. Curr. Chem. 109, 65-84 (1983); idem, Pure Appl. Chem. 55, 1799-1806 (1983); R. M. Williams, Synthesis of Optically Active α-Amino Acids (Pergamon, New York, 1989) pp 1-33.