OXIDATION OF NATURAL TARGETS BY DIOXIRANES .3. STEREOSELECTIVE SYNTHESIS OF (ALL-R)-VITAMIN-D-3 TRIEPOXIDE AND OF ITS 25-HYDROXY DERIVATIVE

In applying dimethyldioxirane (la) and methyl(trifluoromethyl)dioxiran e (Ib) to the oxyfunctionalization of vitamin D-3 and of its 3-acyl de rivatives, remarkable selectivities could be attained. Thus, reaction of 3 beta-acetylvitamin D-3 (3a) and of 3 beta-(p-bromobenzoyl)vitamin D-3 (3b) with dioxirane 1b in CH2Cl2 at -40 degrees C displayed high diastereoselectivity, giving the corresponding all-R triepoxides 48 an d 4b, in 85% and 83% isolated yield, respectively; X-ray crystallograp hic analysis allowed us to determine unambiguously the 5R,6R,7R,8R,10R stereochemistry of 4b. In reacting with 1b under the adopted conditio ns, vitamin D-3 itself (3c) also gave the corresponding all-R triepoxi de 4c (72% isolated yield); here, chemoselectivity is demonstrated by the fact that the unmasked secondary alcohol moiety at C-3 was left un affected. Steric effects and intermolecular dipolar directing effects, exercised over the incoming oxidant by the epoxide functionalities se quentially introduced, are thought to dictate the high diastereoselect ivity observed in the formation of triepoxides 4a-c. By contrast, trea tment of 3a with dimethyldioxirane (1a) at -40 OC gave just the corres ponding 7,8-epoxide 5 as the major product (yield 60%). High site sele ctivity was achieved in the subsequent oxyfunctionalization of triepox ide 3a with excess methyl(trifluoromethyl) dioxirane (1b) in CH2Cl2 at 0 degrees C, which afforded the corresponding C-25 hydroxy derivative (6) in 82% isolated yield.