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Fluoro Artemisinins: Difluoromethylene Ketones

2001; American Chemical Society; Volume: 66; Issue: 23 Linguagem: Inglês

10.1021/jo0158579

1520-6904

Fatima Chorki, Fabienne Grellepois, Benoı̂t Crousse, Michèle Ourévitch, Danièle Bonnet‐Delpon, Jean‐Pierre Bégué,

Chemical Synthesis and Analysis

The reactions of the ring-contracted aldehydes, derived from anhydrodihydroartemisinin, with gem-difluoroenoxysilanes in the presence of BF3·Et2O afforded the corresponding difluoromethylene ketol adducts in good yields. Similar 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 stereochemistry of these reactions are highly dependent on the nature of the Lewis 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 9α,10β-stereoisomer in high stereoselectivity. When 0.4 equiv of SnCl4 was used for the reaction with the α-(4-methoxyphenylenoxysilane)-β,β-difluoroenoxysilane, however, a rearrangement of the endoperoxide was observed.