Development of new process for the highly stereoselective synthesis of α-fluoro-β-hydroxy esters

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In this research project directed toward the development of new method (process) for the highly stereoselective synthesis of α-fluoro-β-hydroxy esters, we have explored the radicalic allylation reaction of α-bromo-α-fluoro-β-hydroxy carboxylic acid esters 1 with allylic stannanes.The starting β-hydroxy esters 1 were readily prepared by the Reformatsky reaction between ethyl dibromofluoroacetate and various aldehydes in the presence of zinc dust and diethylaluminum chloride in THF at -20 ℃ for 1 h. When α-bromo-α-fluoro-β-(t-butyldimethylsilyl) oxy esters, prepared by the siylation of 1 with t-butyldimethylsilyl (TBS) chloride or triflate, were allowed to react with allylic stannanes in the presence of a catalytic amount of triethylborane in toluene or dichloromethane at -78 ℃ for 10 h, the corresponding α-allylated α-fluoro-β-TBS-oxy esters were obtained in good yields with fairly good erythro-selectivities. On the other hand, on treatment of the β-hydroxy esters 1 with trimethylaluminum in dichloromethane at -15 ℃ for 0.5 h, followed by the reaction with allylic stannanes and triethylborane catalyst at -15 ℃ for 6-8 h, the corresponding α-allylated α-fluoro-β-hydroxy esters were given in good yields in a highly threo-selective manner. These results provide us with the first stereoselective synthetic method for an α-fluoro-β-hydroxy carbonyl framework, and are expected to serve as a very significant example in organic synthetic chemistry as well as organofluorine chemistry.