合成路线1

The intermediate phosphonate (XXI) has been obtained as follows: The reaction of tert-butyl mercaptan (XV) with allyl bromide (XVI) by means of NaOH in ethanol gives the sulfide (XVII), which is oxidized with Oxone in methanol/water to yield the sulfone (XVIII). The bromination of (XVIII) with Br2 in CCl4 followed by dehydrobromination with TEA affords the bromosulfone (XIX), which is finally condensed with tributyl phosphite (XX) by heating at 130 C to provide the target intermediate phosphonate (XXI). The silylation of the known diol (XXII) (obtained by degradation of vitamin D2) with Tes-OTf and lutidine gives the bis silyl ether (XXIII), which is submitted to a Swern oxidation ((COCl)2), yielding the carbaldehyde (XXIV). The Wadsworth-Emmons condensation of aldehyde (XXIV) with the intermediate phosphonate (XXI) by means of tBu-OLi affords the diinsaturated sulfone (XXV), which is desilylated with HF in THF to provide the alcohol (XXVI). The oxidation of (XXVI) with TPAP and NMO furnishes the ketone (XXVII), which is submitted to a Wittig-Horner condensation with the intermediate phosphine oxide (XIV) by means of PhLi, giving the silylated precursor (XXVIII). Finally, this compound is desilylated with HF in ethanol to afford the target vitamin D3 analogue.