One Step Synthesis of Optically Active Diazabicyclo[3.3.0]octanones or Diazabicyclo[4.3.0]nonanones by Asymmetric Conjugate Addition of Cyclic Hydrazine

Asymmetric conjugate addition-cyclization of lithium amide of 6-membered hydrazine 4, piperidazine, (or 5-membered hydrazine 6, pyrazolidine) to N-(E)-cinnamoyl-(1S)-2,10-camphorsultam (1S)-3 afforded -amino acid derivative (S)-1 {or (S)-2} for the synthesis of polyamine alkaloids in good yield with good stereoselectivity (up to 86% ee).A number of -amino acids have been isolated in free form and show interesting pharmacological properties. 1 In addition, many classes of natural products contain -amino acid derivatives as fragments.Macrocyclic lactams containing a biogenetic base such as spermine or spermidine alkaloids, which have a framework of -amino acid such as -phenyl--alanine, are particularly interested as synthetic targets in view of their broad biological activity, antibiotics, and antihypertensives. 2,3The conjugate addition of nitrogen anion such as lithium amide reagents (R 2 N -Li + ) to -unsaturated ester derivatives is one of the most versatile synthetic methods for the introduction of a new asymmetric center at the -position of the carbonyl containing motif.Yamamoto et al. have reported nucleophilic reactions of R 2 NM, such as conjugate addition to enoates, and asymmetric synthesis of -lactams was accomplished using amide cuprate reagents as a new class of nitirogen nucleophiles. 4The introduction of chirality using a chiral auxiliary is a useful way of producing a wide variety of optically active