合成路线1

4) Szantay et al. reported a practical route to epibatidine by using commonly available starting materials under convenient reaction conditions. The alpha,beta-unsaturated ketone (XV) was synthesized by Wittig reaction of 6-chloronicotinaldehyde and the appropriate phosphorane. Ring closure took place by treatment of compound (XV) with KF/Al2O3. Reduction of the keto group followed by mesylation and subsequent reduction of the nitro group afforded amine (XVII). Upon boiling in toluene, (XVII) was immediately transformed into the undesired endo-isomer of epibatidine (XVIII). Taking advantage of Fletcher's endo- to exo-epimerization, (XVIII) was converted into racemic epibatidine in moderate yield. The advantage of this route is that no protection and consequently no deprotection steps are involved. But the combined yield in the last two steps is only 30%.