合成路线1

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.