The reaction of vitamin D2 (I) with refluxing liquid SO2 gives a mixture of the 6(R)- and 6(S)-SO2-adducts (II), which by treatment with tert-butyl-dimethylsilyl chloride (TBDMSCI) and imidazole in DMF yields the corresponding mixture of silylated adducts (III). The reaction of the mixture (III) with NaHCO3 in ethanol affords the silylated 5(E)-vitamin D2 (IV), which by oxidation with SeO2 and N-methylmorpholine N-oxide in refluxing methanol-dichloromethane is converted into a mixture of silylated 1(S)- and 1(R)-hydroxy-5(E)-vitamin D2 (V). The silylation of (V) as before, followed by crystallization in ethyl ether-ethanol gives the 1(S)-isomer of the fully silylated compound (VI), which is treated with refluxing SO2 as before to yield the mixture of the 6(R)- and 6(S)-SO2-adducts (VII). The ozonolysis of the mixture (VII) in dichloromethane-methanol at -65 C affords the corresponding mixture of the 6(R)- and 6(S)-SO2-aldehydic adducts (VIII).
The treatment with NaHCO3 of the corresponding mixture of the 6(R)- and 6(S)-SO2-aldehydic adducts (VIII) gives a mixture of the 20(R) and 20(S) epimeric aldehydes (IX). The Wittig condensation of the aldehyde mixture (IX) with cyclopropylcarbonylmethylenetriphenylphosphorane (X) [prepared from acetylcyclopropane (XI) by bromination to bromoacetylcyclopropane (XII), reaction with triphenylphosphine (XIII) to the phosphonium salt (XIV) and treatment with NaOH] in DMSO at 105 C, followed by chromatographic separation yields the epimeric 20(R)-enone (XV). The reduction of (XV) with NaBH4 and CeCl3 in THF-methanol, followed by chromatographic purification affords the epimeric 3'(R)-allylic alcohol (XVI), which is isomerized by irradiation with UV-light from a TQ 718Z2 Hanau lamp in toluene in the presence of anthracene to give the corresponding 5(Z)-derivative (XVII). Finally, this compound is deprotected by a treatment with tetrabutylammonium fluoride in THF at 60 C.