Title

Effect of 9,10-Cyclic Acetal Stereochemistry on Feasible Operation of α-Ketol Rearrangement in Highly Functionalized Paclitaxel (Taxol) Precursors

Document Type

Article

Publication Date

2003

Abstract

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 α-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.

Journal

Journal of Organic Chemistry

Volume

68

Issue

6

First Page

2266

Last Page

2275