title: A delicate balance of energetics. Subtleties associated with alpha-ketol-based bridge migration to afford 9-keto-10beta-p-methoxybenzyloxytaxanes.
abstract: 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.
authors.affiliation: Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA. paquette.1@osu.edu
authors.forename: Leo A
authors.initials: LA
authors.lastname: Paquette
authors.forename: Ho Yin
authors.initials: HY
authors.lastname: Lo
authors.forename: John E
authors.initials: JE
authors.lastname: Hofferberth
authors.forename: Judith C
authors.initials: JC
authors.lastname: Gallucci
mesh_terms: 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
chemical_list: D001952:Bridged-Ring Compounds; D007202:Indicators and Reagents; D043823:Taxoids; C080625:taxane; D017239:Paclitaxel