Oxidation of Natural Targets by Dioxiranes. 4. High Stereo- and Regioselective Conversion of Vitamin D₂ to Its (<i>all</i>-<i>R</i>) Tetraepoxide and C-25 Hydroxy Derivative

Upon reaction with methyl(trifluoromethyl)dioxirane (1b) at −40 °C, vitamin D2 (2a) or its 3β-acetyl derivative (2b) give in high yield (78−80%) the corresponding tetraepoxide (3a,b) as a single diastereoisomer having the 5,6(β);7,8(β);10,19(α);22,23(pseudo-α) configuration. Transformation of tetraepoxide 3a into its 3β-(p-bromobenzoyl) derivative 3c allowed X-ray diffraction analysis; this permitted us to ascertain that the stereomeric tetraepoxide product has the R configuration at all of the seven newly generated stereocenters, i.e. 5R,6R;7R,8R;10R(19);22R,23R. The oxidation of 3β-acetyl vitamin D2 (2b) with the less powerful dimethyldioxirane (1a) led to the corresponding 5,6(β);7,8(β);10,19(α)-triepoxide 4 as the major product (62%), accompanied by tetraepoxide 3b (26%). Parallel to vitamin D3 triepoxide, remarkable site selectivity was monitored in oxyfunctionalization of 3β-acetyl vitamin D2 tetraepoxide (3b) at the side-chain tertiary C-25. Reaction of tetraepoxide 3b with the powerful dioxirane 1b at 0 °C left the epoxide groups and remaining C-H functionalities intact, affording the 25-hydroxy derivative 5 in good isolated yield (61%).