Synthesis of trans-fused tetrahydrooxepins: stereoselective allylation of sulfur or fluoro-substituted tetrahydrooxepins.

An efficient route to the trans-fused tetrahydrooxepin corresponding to the E ring of ciguatoxin was developed. Wide screening of allylation reactions of sulfur or fluoro-substituted tetrahydrooxepin revealed that the optimum method for obtaining the beta-allylation product selectively was the use of a combination of allyltrimethylsilane and TiCl(4) with 6-fluoro-7-hydroxytetrahydrooxepin.