A Concise Stereoselective Synthesis of 2-Substituted 1-Aminocyclopropanecarboxylic Acids

A simple and stereoselective method for the preparation of (Z)-2-substituted 1-aminocyclopropanecarboxylic acids is described. The common key step for these reaction sequences involves the stereoselective Ti-mediated coupling of benzyloxy nitrile and homoallylic alcohol. The resulting 2-hydroxyethyl-substituted cyclopropylamine can be transformed shortly into various cyclopropane amino acid analogues on the gram scale, in good overall yields. Several syntheses of 2,3-methanoamino acids, that is, ACCs derived from proteinogenic alpha-amino acids or analogues, such as glutamic acid, arginine, homoarginine, and lysine derivatives are presented to exemplify the usefulness of the method. Additionally, starting from cyanoesters, spirocyclopropane gamma-amino acid analogues are available in this way. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)