Fluoro artemisinins: Difluoromethylene ketones

The reactions of the ring-contracted aldehydes, derived from anhydrodihydro artemisinin, with gem-difluoroenoxysilanes in the presence of BF3. Et2O aff orded the corresponding difluoromethylene ketol adducts in good yields. Sim ilar Lewis acid catalyzed reactions of dihydroartemisinin acetate with the difluoroenoxysilanes provided the 10-substituted difluoromethylene ketones in good to moderate yields. Interestingly enough, the course and the stereo chemistry of these reactions are highly dependent on the nature of the Lewi s acids used; the addition reaction was accompanied by epimerization at C-9 , and the stereochemistry at C-10 depends on the difluoroenoxysilane used. The best results were obtained using SnCl4 to give the 9 alpha ,10 beta -st ereoisomer in high stereoselectivity. When 0.4 equiv of SnCl4 was used for the reaction with the alpha-(4-methoxyphenylenoxysilane)-beta,beta -difluor oenoxysilane, however, a rearrangement of the endoperoxide was observed.