AN ABBREVIATED, HIGHLY STEREOCONTROLLED ROUTE TO PRECURSORS OF TAXOL - ELABORATION OF A FULLY FUNCTIONALIZED C-RING BY MEANS OF INTRAMOLECULAR ALDOL CYCLIZATION

The asymmetric synthesis of an advanced taxol precursor is reported. T he scheme involves the conversion of (R)-glyceraldehyde acetonide into the Q-vinyl iodide 2, transmetalation of this intermediate, and 1,2-a ddition to the D-camphor derivative 11 from the endo direction. This c onvergent coupling gives rise to exo alcohol 12, which undergoes anion ic oxy-Cope rearrangement at low temperatures. In situ methylation of the resulting enolate anion delivers 13, which is chemoselectively tra nsformed into aldehyde 18. In a key step, the aldol cyclization of 18 proceeds without beta-elimination to deliver a tricyclic product in wh ich proper absolute configuration is adopted at the two stereogenic ce nters being newly introduced. Following protection of the hydroxyl sub stituent as in 19b,the alpha-hydroxy ketone 21 is heated with aluminum tri-tert-butoxide in benzene in order to effect near-quantitative rea rrangement to the taxol-like isomer 22.