Evaluation of D-ribose as an enantiopure building block for construction of the C-ring of taxol and its congeners

Article abstract of DOI:10.1021/jo00129a026

The enantiomerically pure Z vinyl iodide 20 is shown to be readily available from D-ribose via a sequence involving zinc-promoted reductive unmasking of an aldehyde and homologation with (iodomethylene)triphenylphosphorane. The vinyl anion produced by halogen-metal exchange adds from the endo direction to an enantiopure ketone prepared from D-camphor. The resulting carbinol undergoes anionic oxy-Cope rearrangement and C-methylation with complete stereocontrol to set the appropriate C-3 stereochemistry of taxol. Dihydroxylation of this intermediate brings about facile transannular hemiketalization. DIBAL-H reduction of this intermediate does not affect the hemiketal, but does reduce the acetonide regiospecifically. An unusual transannular hydride shift occurs during subsequent heating with dibutyltin oxide, as confirmed by X-ray crystallography. When transannular hemiketalization is skirted, hydroboration-oxidation of the side chain leads to an acetaldehyde which is notably prone to β-elimination. Treatment with potassium carbonate in methanol does eventuate in ring closure via an aldol addition reaction, but only after methanol has been added in Michael fashion to the α,β-unsaturated aldehyde.