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In Scheme I, step a, the aldehyde defined by structure (2) is treated with the anion of the phosphonate defined by structure (1) to provide the alcohol defined by structure (3). For example, an equivalent of the appropriately substituted phosphonate (1), such as dimethyl difluoromethylphosphonate dissolved in a suitable organic solvent, such as tetrahydrofuran, is added dropwise to a stirring solution of lithium diisopropylamide at approximately -78° C. The mixture is stirred for 2 minutes to 2 hours. An appropriately substituted aldehyde (2), such as farnesal [prepared by a Swern Oxidation of trans, transfarnesol following the procedure of Biller, S. A. and Forster, C., Tetrahedron 1990, 46(19), 6645] dissolved in a suitable organic solvent, such as tetrahydrofuran, is slowly added to the anion of (1) maintaining the reaction temperature below -72° C. After approximately 2 hours the reaction is poured into a suitable aqueous acid, such as 0.1N hydrochloric acid, and extracted with a suitable organic solvent, such as diethyl ether. The organic phase is dried over a suitable drying agent, such as anhydrous magnesium sulfate, filtered and concentrated under vacuum. The residue is then purified by techniques well known in the art. For example, the residue can be purified by flash chromatography using a suitable organic eluent, such as 40% ethyl acetate/hexane to provide dimethyl 1,1-difluoro-2-hydroxy-4,8,12-trimethyl-3,7,11-tridecatrienylphosphonate.

1. temperaturemaintaining the reaction temperature below -72° C
2. extractionextracted with a suitable organic solvent, such as diethyl ether
3. dry with materialThe organic phase is dried over a suitable drying agent, such as anhydrous magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated under vacuum
6. customThe residue is then purified by techniques