Fluorine Labeling in Biosynthetic Studies (I) : Synthesis of Fluorfarnesols

The Synthesis of E, E, E-12-fluorofarnesol and E, Z-6-fluorofarnesol which are key intermediates for the study of biosynthesis of some sesquiterpenes, is described. E, E-Farnesyl acetate is treated with selenium dioxide to give E, E, E-12-hydroxy farnesyl acetate, whih is transformed by DAST into E, E, E-12-hydroxy farnesyl acetate, which is transformed by DAST into E, E, E,-12-fluorofarnesylacetate. The latter compound is hydrolyzed to E, E, E,-12-fluorofarnesol. The reformatsky reaction of 6-methyl-5-hepten-2-one with ethyl bromofluoroacetate affords ethyl 2-fluoro-3-hydroxy-3, 7 dimethyl-6-octanoate. This ester is acetylated and eliminated to give ethyl (Z)-2-fluoro-3, 7-dimethylocta-2, 6-dienoate, which is transformed to allyl bromide via allylic alcohol. The allyl bromide is treated with dianion of methyl acetate to give-keto ester. The $\beta$-keto ester is converted to diethyl phosphoryloxy compound. The conjugate addition of lithium dimethylcuprate to the latter compound gives fluoro ester, which is treated with DIBAL to afford E, Z-6-fluorofarnesol.