Received August 8, 2003

Abstract:

N-(-Bromoalkyl)-amino acid derivatives, readily prepared from natural -amino acids, gave cyclic amino acids with a quaternary stereocenter by treatment with potassium hexamethyldisilazaide in DMF. The chirality of parent amino acids was almost completely preserved during an enolate-formation and cyclization process, giving aza-cyclic amino acids in up to 98% ee in retention of configuration. This method is applicable to the asymmetric synthesis of azetidine, pyrrolidine, piperidine, and azepane derivatives. The asymmetric cyclization seems to proceed via an axially chiral enolate intermediate and not through a concerted S_Ei process.

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