A Delicate Balance of Energetics. Subtleties Associated with α-Ketol-Based Bridge Migration to Afford 9-Keto-10β-p-methoxybenzyloxytaxanes
The feasibility of the title reaction has been pursued for the purpose of advancing a concise total synthesis of Taxol. Of the two closely related series examined, the first featured an exo-methylene group at C4. The second consisted of an α-epoxide at that site. Strikingly, the olefinic construct proved inert to attempted α-ketol rearrangement. In contrast, the oxiranyl derivative isomerized smoothly. The reaction sequence associated with arrival at taxane 18 is short (15 steps from a d-camphor derivative) and notably efficient. The thermodynamic issues that are raised by this investigation have been clarified by an assessment of molecular mechanics-derived (MM3) steric energy calculations.
Journal of Organic Chemistry