A delicate balance of energetics. Subtleties associated with alpha-ketol-based bridge migration to afford 9-keto-10beta-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 alpha-epoxide at that site. Strikingly, the olefinic construct proved inert to attempted alpha-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.
Paquette
Leo A
LA
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA. paquette.1@osu.edu
Lo
Ho Yin
HY
Hofferberth
John E
JE
Gallucci
Judith C
JC
D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D003500:Cyclization; D006900:Hydroxylation; D007202:Indicators and Reagents; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017239:Paclitaxel / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043823:Taxoids; D013816:Thermodynamics
D001952:Bridged-Ring Compounds; D007202:Indicators and Reagents; D043823:Taxoids; C080625:taxane; D017239:Paclitaxel