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
2000; Elsevier BV; Volume: 11; Issue: 4 Linguagem: Inglês
10.1016/s0957-4166(00)00022-7
ISSN1362-511X
AutoresRamón Badorrey, Carlos Cativiela, María D. Díaz‐de‐Villegas, José A. Gálvez,
Tópico(s)Asymmetric Synthesis and Catalysis
Resumo(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-(tert-butyldimethylsilyloxy)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 β-hydroxy-α-amino acids containing virtually any nucleophile capable of substituting the γ-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.
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