合成路线1

19) Intramolecular cyclization of substituted proline derivatives. Rapoport et al. developed an asymmetric methodology which had potential for the enantiospecific synthesis of (+)- and (-)-epibatidine. The triflate (LXXIX) was readily synthesized from levulinic acid in 3 straightforward steps. Alkylation of S-thiolactam (LXXX) prepared from L-glutamic acid with triflate (LXXIX), followed by sulfide contraction provided the carbamate (LXXXI). (LXXXI) was then converted into keto acid (LXXXII). (LXXXII) was decarboxylated and the resulting iminium ions were subjected to intramolecular cyclization to give a mixture of trans-2,3-disubstituted-7-azabicyclo[2.2.1]heptanes (LXXXIII) and (LXXXIV). This mixture was selectively converted into (+)- and (-)-N-BOC-7-azabicyclo[2.2.1]heptane-2-ones (VIII), which are versatile intermediates for the enantiospecific synthesis of (+)- and (-)-epibatidine.