Oxidation of Natural Targets by Dioxiranes. 4.1 High Stereo- and Regioselective Conversion of Vitamin D2 to Its (all-R) Tetraepoxide and C-25 Hydroxy Derivative

Upon reaction with methyl(trifluoromethyl)dioxirane ( 1b ) at −40 °C, vitamin D 2 ( 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. 5 R,6 R;7 R,8 R;10 R (19);22 R,23 R . The oxidation of 3β-acetyl vitamin D 2 ( 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 D 3 triepoxide, remarkable site selectivity was monitored in oxyfunctionalization of 3β-acetyl vitamin D 2 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%).