合成路线1

The intermediate triphenylphosphonium salt (XXI) has been obtained as follows: The Reformatsky condensation of 4-methoxybenzaldehyde (I) with methyl 2-bromopropionate (II) gives a mixture of the syn and anti hydroxyesters (III) and (IV). The syn isomer (III) was dehydrated by means of MsOH yielding the unsaturated ester (V), which is reduced with LiAlH4 to the unsaturated alcohol (VI). The hydroboration of (VI) affords the diol (rac)-anti-(VII), which is also obtained by direct reduction of the anti-hydroxyester (IV) with LiAlH4. The optical resolution of (rac)-(VII) with lipase Amano P and vinyl acetate affords the chiral monoacetate (2R,3R)-(VIII), which is fully acetylated with Ac2O giving the diacetate (IX). Selective catalytic hydrogenolysis of (IX) with H2 over Pd/C in methanol yields the primary monoacetate (X), which is hydrolyzed with K2CO3 in methanol to affords the primary alcohol (XI). The reaction of (XI) with CBr4 and PPh3 in THF provides the bromide (XII), which by treatment with sodium phenylsulfinate (A) affords the phenylsulfone (XIII). Ozonolysis of (XIII) with O3, followed by oxidation with H2O2 gives the carboxylic acid (XIV), which is methylated with diazomethane to the ester (XV). The reduction of (XV) with LiBH4 in THF yields the alcohol (XVI), which is protected with DHP and PPTS yielding the tetrahydropyranyl ether (XVII). The condensation of sulfone (XVII) with the iodoalkane (XVIII) by means of LDA, followed by treatment with HCl in ethanol affords the intermediate addition compound (XIX), which by elimination of the THP group provides the alcohol (XX). Finally, the reaction of (XX) with CBr4 and PPh3 affords the target intermediate phosphonium salt (XXI).