Stereoselective addition of formaldehyde to the ethylidene indanol (I) in the presence of dimethylaluminium chloride gave rise to the homoallylic alcohol (II). After tosylation of the primary alcohol of (II) to give tosylate (III) , the secondary hydroxyl group of (III) was silylated with triethylsilyl triflate and lutidine to afford (IV). Displacement of the tosylate group of (IV) with KCN yielded nitrile (V), which was further reduced to aldehyde (VI) by means of DIBAL in cold toluene. A Reformatskii reaction using (VI), ethyl bromodifluoroacetate and activated zinc gave the gem-difluoro ester (VII). Reduction of the free hydroxyl group of (VII) to afford (IX) was achieved via formation of the thianocarbonate (VIII) and then treatment with tributyltin hydride and azobis(isobutyronitrile). Addition of ethyllithium to the ester group of (IX) produced carbinol (X). After desilylation of (X) by treatment with tetrabutylammonium fluoride, the resulting secondary alcohol (XI) was oxidized to ketone (XII) using pyridinium chlorochromate in CH2Cl2.

Protection of (XII) as the silyl ether (XIII), followed by Wittig reaction with the ylide resulting from the racemic phosphine oxide (XIV) furnished diene (XV) as a diastereomeric mixture. After desilylation with tetrabutylammonium fluoride, separation of the diastereoisomers by semipreparative RP-HPLC provided the title compound.

1-Ethylideneperhydroindan-4-ol (I) reacts with Me2AlCl and paraformaldehyde via an ene process to give the homoallylic diol (II), the primary hydroxyl group of which is tosylated by means of TsCl and DMAP and the secondary hydroxyl group silylated by means of TESOTf and lutidine to yield (III). Conversion of (III) into the corresponding nitrile by means of KCN in DMSO, followed by reduction with DIBALH in toluene, affords the aldehyde (IV) (1), which is further reduced in THF by treatment with DIBALH in hexanes to yield (V). The hydroxy silyl ether (V) is then converted into the iodo derivative (VI) by treatment with PPh3, imidazole and I2 in dichloromethane. The iodo silyl ether (VI) reacts with t-BuSH in the presence of DBU in benzene to afford sulfide (VII), which is then oxidized and deprotected with oxone to provide the hydroxy sulfone (VIII). Oxidation of (VIII) with pyridinium dichromate (PDC) in CH2Cl2 gives the keto sulfone (IX), which reacts with the phosphine oxide derivative (X) in THF in the presence of PhLi. Finally, the protecting silyl ether moiety is removed by means of Bu4NF in THF.

Stereoselective addition of formaldehyde to the ethylidene indanol (I) in the presence of dimethylaluminium chloride gave rise to the homoallylic alcohol (II). After tosylation of the primary alcohol of (II) to give tosylate (III) , the secondary hydroxyl group of (III) was silylated with triethylsilyl triflate and lutidine to afford (IV). Displacement of the tosylate group of (IV) with KCN yielded nitrile (V), which was further reduced to aldehyde (VI) by means of DIBAL in cold toluene. A Reformatskii reaction using (VI), ethyl bromodifluoroacetate and activated zinc gave the gem-difluoro ester (VII). Reduction of the free hydroxyl group of (VII) to afford (IX) was achieved via formation of the thianocarbonate (VIII) and then treatment with tributyltin hydride and azobis(isobutyronitrile). Addition of ethyllithium to the ester group of (IX) produced carbinol (X). After desilylation of (X) by treatment with tetrabutylammonium fluoride, the resulting secondary alcohol (XI) was oxidized to ketone (XII) using pyridinium chlorochromate in CH2Cl2.

Protection of (XII) as the silyl ether (XIII), followed by Wittig reaction with the ylide resulting from the racemic phosphine oxide (XIV) furnished diene (XV) as a diastereomeric mixture. After desilylation with tetrabutylammonium fluoride, separation of the diastereoisomers by semipreparative RP-HPLC provided the title compound.