合成路线1

The reaction of the chiral cyclohexenone (I) with H2O2 and NaOH in methanol gives the epoxide (II), which is submitted to a Wittig olefination with the phosphonium bromide (III) and KHMDS in toluene to yield the bromomethylene derivative (IV). The opening of the epoxide ring by means of DIBAL in hexane affords the cyclohexanol (V), which is silylated with Tbdms-Cl and imidazole to provide the bis silyl ether (VI). The reaction of (VI), triisopropyl borate and pinacol by means of t-BuLi in ethyl ether gives the boronic ester (VII), which is condensed with alkyl bromide intermediate (VIII) and catalyzed by PdCl2(dppf) and KOH in THF/water to yield the silylated precursor (IX). Finally, this compound is desilylated by means of aq. HF in THF to provide the target 1-alpha,25-dihydroxy-19-nor-vitamin D3. Alternatively, the intermediate (VIII) is reacted with triisiopropyl borate and pinacol, as before, to give the boronic ester (X), which is condensed with the cyclohexylidenemethyl bromide (VI) and catalyzed by PdCl2(dppf) and KOH in THF/water to yield the already reported silylated precursor (IX).