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)dioxirane (Ib) to the oxyfunctionalization of vitamin D-3 and of its 3-acyl derivatives, 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 dioxi...

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Published inJournal of the American Chemical Society Vol. 116; no. 18; pp. 8112 - 8115
Main Authors CURCI, R, DETOMASO, A, PRENCIPE, T, CARPENTER, GB
Format Journal Article
LanguageEnglish
Published WASHINGTON Amer Chemical Soc 07.09.1994
Subjects
Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
METHYL(TRIFLUOROMETHYL)DIOXIRANE
RAY STRUCTURE-ANALYSIS
STEROIDS
CONVERSION
STEREOCHEMISTRY
VITAMIN-D3 EPOXIDES
OXYFUNCTIONALIZATION
DIMETHYLDIOXIRANE
H-1
EPOXIDATION
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Summary:In applying dimethyldioxirane (la) and methyl(trifluoromethyl)dioxirane (Ib) to the oxyfunctionalization of vitamin D-3 and of its 3-acyl derivatives, 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 and 4b, in 85% and 83% isolated yield, respectively; X-ray crystallographic analysis allowed us to determine unambiguously the 5R,6R,7R,8R,10R stereochemistry of 4b. In reacting with 1b under the adopted conditions, vitamin D-3 itself (3c) also gave the corresponding all-R triepoxide 4c (72% isolated yield); here, chemoselectivity is demonstrated by the fact that the unmasked secondary alcohol moiety at C-3 was left unaffected. Steric effects and intermolecular dipolar directing effects, exercised over the incoming oxidant by the epoxide functionalities sequentially introduced, are thought to dictate the high diastereoselectivity observed in the formation of triepoxides 4a-c. By contrast, treatment of 3a with dimethyldioxirane (1a) at -40 OC gave just the corresponding 7,8-epoxide 5 as the major product (yield 60%). High site selectivity was achieved in the subsequent oxyfunctionalization of triepoxide 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.
ISSN:0002-7863
DOI:10.1021/ja00097a018