合成路线图解说明: Cycloaddition of betaine (I) with phenyl fluorovinyl sulfone (II) in refluxing acetonitrile produced a mixture of 6-b (III), 6-a (IV), and 7-b (V) sulfones, from which the major isomer (III) was separated by column chromatography. Subsequent reduction with NaBH4 in the presence of CeCl3 provided a mixture of epimeric allylic alcohols (VI), which were acetylated with Ac2O in pyridine to yield acetates (VII). Copper (I) cyanide-catalized coupling with n-BuMgBr in Et2O gave butyl compound (VIII). Hydrogenation of the olefinic double bond in the presence of Pd/C yielded the trans isomer (IX), and further desulfonylation with Na-Hg in MeOH afforded the target compound together with a minor amount of the 7-b-fluoro isomer, which was removed by purification by column chromatography.
Alternatively, (VIII) was first desulfonylated to give the major beta-fluoro isomer (X) which, after separation, was hydrogenated to give the target compound. |