An abbreviated, highly stereocontrolled route to precursors of taxol. Elaboration of a fully functionalized C ring by means of intramolecular aldol cyclization

Article abstract of DOI:10.1021/jo00129a027

The asymmetric synthesis of an advanced taxol precursor is reported. The scheme involves the conversion of (R)-glyceraldehyde acetonide into the (Z)-vinyl iodide 2, transmetalation of this intermediate, and 1,2-addition to the D-camphor derivative 11 from the endo direction. This convergent coupling gives rise to exo alcohol 12, which undergoes anionic oxy-Cope rearrangement at low temperatures. In situ methylation of the resulting enolate anion delivers 13, which is chemoselectively transformed into aldehyde 18. In a key step, the aldol cyclization of 18 proceeds without β-elimination to deliver a tricyclic product in which proper absolute configuration is adopted at the two stereogenic centers being newly introduced. Following protection of the hydroxyl substituent as in 19b, the α-hydroxy ketone 21 is heated with aluminum tri-tert-butoxide in benzene in order to effect near-quantitative rearrangement to the taxol-like isomer 22.