A Convenient Transformation of 2-Alkylidenecycloalkanones into Alkyl-Substituted Bicyclo[n.1.0]alkan-1-ols: Application to the Synthesis of Capsaicin

Abstract

Treatment of 2-alkylidenecycloalkanones with hydrogen iodide in benzene and subsequent reaction of the obtained b-iodo ketones with zinc dust in THF in the presence of chlorotrimethylsilane or titanium(IV) chlorotriisopropoxide led to exo-and endo-(n+3)-alkylbicyclo[n.1.0]alkan-1-ols in high yields. Cyclization of the intermediate b-iodo ketones under these conditions proceeded in a moderate to good diastereoselectivity, and the resulted bicyclic cyclopropanols were easily separated by column chromatography over silica gel. exo-7- Isopropylbicyclo[4.1.0]heptan-1-ol obtained in this manner was efficiently employed as a key intermediate in the synthesis of capsaicin.

Capsaicin derivatives: Synthesis and biological activity

“…In recent years, Dzmitry et al synthesized capsaicin by employed exo-diastereomers of bicyclic alcohols 17 as synthetic intermediates (Kananovich et al, 2010), which can be stereoselectively prepared into pure alkanoic acid 7 F I G U R E 1 Molecular structure of capsaicin.…”

“…In recent years, Dzmitry et al. synthesized capsaicin by employed exo‐ diastereomers of bicyclic alcohols 17 as synthetic intermediates (Kananovich et al., 2010), which can be stereoselectively prepared into pure alkanoic acid 7 by oxidative ring cleavage. After transformation of acid 7 into the corresponding acid chloride, capsaicin 1 was obtained by coupling vanillylamine 4 and the acid chloride (Figure 4).…”