Effect of 9,10-cyclic acetal stereochemistry on feasible operation of the alpha-ketol rearrangement in highly functionalized paclitaxel (Taxol) precursors.
The convergent, stereocontrolled synthesis of enantiopure stereoisomeric 9,10-cyclic acetals, whose designed role was to serve as potential precursors to Taxol, is reported. These advanced intermediates are multiply functionalized and carry a bridgehead alpha-ketol array which was key to isomerization into the proper framework. In agreement with relative strain energy values obtained by MM3 calculations, a dichotomy was observed between these two families. While the trans-fused acetals failed to undergo bridge migration, their cis counterparts did so efficiently. In fact, isomerization was sufficiently rapid that oxygenation at C2 was now precluded. The operation of several unusual transannular hydride shifts is also detailed.
Paquette
Leo A
LA
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA. paquette.1@osu.edu
Hofferberth
John E
JE
D000080:Acetals / Q000737:chemistry*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D007202:Indicators and Reagents; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D009439:Neuraminidase; D010084:Oxidation-Reduction; D017239:Paclitaxel / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
D000080:Acetals; D007202:Indicators and Reagents; D007659:Ketones; D009439:Neuraminidase; D017239:Paclitaxel