Synthesis of Paclitaxel. 2. Construction of the ABCD Ring and Formal Synthesis

A formal synthesis of the antitumor
diterpenoid paclitaxel (Taxol) is described. The ABC ring of paclitaxel,
synthesized starting from 1,3-cyclohexanedione and tri-O-acetyl-d-glucal by SmI2-mediated cyclization
as the key transformation, was successfully converted to Takahashi’s
tetracyclic oxetane intermediate. A double Chugaev reaction was employed
for introduction of the strained bridgehead olefin, and stereoselective
formation of the oxetane ring afforded the known synthetic intermediate,
completing the formal synthesis of paclitaxel.