Diosphenol-based approach to the a-ring functionalization of advanced Taxol precursors.

Several different approaches to the A-ring functionalization of an advanced, highly functionalized diosphenol precursor to Taxol are described. The first phase of the undertaking consists of an assessment of those reagents conducive to reaction at the enolic oxygen (silylation, methylation, allylation, and acylation). Transformations involving an alternative attack at the enol carbon center (bromination, selenation) have also been defined. Sodium borohydride reduction operates from the beta-face of C-14 as long as the C-1 hydroxyl is not protected so as to offer steric exclusion. Complications associated with various aspects of these methodological undertakings are addressed. The most advanced oxygenation achievements were realized by way of a noteworthy sequence involving epoxidation of the O-methyl ether, methanolysis under mildly acidic conditions, and regioselective oxidation of diol 38 to give 39.

Oxidative cleavage of p-methoxybenzyl ethers with methyl(trifluoromethyl)dioxirane.

[reaction: see text] The ability of methyl(trifluoromethyl)dioxirane to cleave p-methoxylbenzyl ethers oxidatively in the presence of various additional functional groups has been investigated. These reactions, performed in aqueous acetonitrile, transform a reasonably robust aryl substituent into a dienyl aldehydo ester. The originally generated E,Z-isomer undergoes slow conversion to the more stable E,E-form at 20 degrees C.