Oxidation of natural targets by dioxiranes .4. High stereo- and regioselective conversion of vitamin D-2 to its (all-R) tetraepoxide and C-25 hydroxy derivative

Upon reaction with methyl(trifluoromethyl)dioxirane (Ib) at -40 degrees C, vitamin D-2 (2a) or its 3 beta-acetyl derivative (2b) give in high yield (78-80%) the corresponding tetraepoxide (3a,b) as a single diastereoisomer having the 5,6(beta);7,8(beta);10,19(alpha);22,23(pseudo-alpha) configuration. Transformation of tetraepoxide 3a into its 3 beta-(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 3 beta-acetyl vitamin D-2 (2b) with the less powerful dimethyldioxirane (la) led to the corresponding 5,6(beta);7,8(beta);10,19(alpha)-triepoxide 4 as the major product (62%), accompanied by tetraepoxide 3b (26%). Parallel to vitamin D-3 triepoxide, remarkable site selectivity was monitored in oxyfunctionalization of 3 beta-acetyl vitamin D-2 tetraepoxide (3b) at the side-chain tertiary C-25. Reaction of tetraepoxide 3b with the powerful dioxirane 1b at 0 degrees C left the epoxide groups and remaining C-H functionalities intact, affording the 25-hydroxy derivative 5 in good isolated yield (61%).