RESUMO
The reactions of the ring-contracted aldehydes, derived from anhydrodihydroartemisinin, with gem-difluoroenoxysilanes in the presence of BF(3).Et(2)O 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 SnCl(4) to give the 9alpha,10beta-stereoisomer in high stereoselectivity. When 0.4 equiv of SnCl(4) was used for the reaction with the alpha-(4-methoxyphenylenoxysilane)-beta,beta-difluoroenoxysilane, however, a rearrangement of the endoperoxide was observed.
Assuntos
Artemisininas , Medicamentos de Ervas Chinesas/química , Fluorenos/química , Cetonas/química , Metano/análogos & derivados , Metano/química , Sesquiterpenos/química , Animais , Antimaláricos/síntese química , Antimaláricos/química , Medicamentos de Ervas Chinesas/síntese química , Hidrocarbonetos , Plasmodium falciparum/efeitos dos fármacos , Sesquiterpenos/síntese químicaRESUMO
[reaction: see text] alpha-Benzyloxy alpha-CF(3)-beta-lactams are shown to offer the first examples of the enolate [1,2]- and enolate ortho-[2,3]-Wittig rearrangements which provide a unique entry to the alpha-benzyl-alpha-hydroxy lactams and the alpha-aryl-alpha-hydroxy lactams, respectively. Both products are potential precursors of new trifluoromethyl isoserines, and the latter is not accessible via the usual alkylation methodology.
