Asymmetric synthesis of (2R,3S)-4-halo-3-benzyloxy-2-(N-methoxycarbonyl-N-benzylamino)butyronitriles as precursors for the synthesis of β-hydroxy-α-amino acids

(2R,3S)-4-Halo-3-benzyloxy-2-(N-methoxycarbonyl-N-benzylamino)butyronitriles have been prepared through an efficient three-step sequence from (2R,3S)-2-benzylamino-3-benzyloxy-4-(ter silyloxy)butyronitrile, which is readily available in diastereomerically pure form by a Strecker-type reaction of the N-benzylimine, derived from selectively protected (R)-glyceraldehyde, and trimethylsilyl cyanide. These compounds enable the facile synthesis of chiral B-hydroxy-cx-amino acids containing virtually any nucleophile capable of substituting the gamma-halogen atom. As an illustration of their synthetic potential, the 4-bromo derivative has been successfully converted into (1R,2R)-2-benzyloxy-1-(N-methoxycarbonyl-N-benzylamino)cyclopropanecarboxamide, which is a new conformationally restricted serine analogue, in two steps: base-induced cyclisation and subsequent hydrolysis of the nitrile group. (C) 2000 Elsevier Science Ltd. All rights reserved.