Madhavi C. Chander

An AC→ABC approach to taxol involving B-ring closure at C-1-C-2

Abstract The treatment of keto aldehyde 13 with low-valent Ti results in a stereoselective intramolecular pinacol coupling that produces taxane synthesis intermediate 14.

TAXANE SYNTHESIS THROUGH INTRAMOLECULAR PINACOL COUPLING AT C-1-C-2. CONSTRUCTION AND OXIDATIVE TRANSFORMATIONS OF A C-AROMATIC TAXANE DIENE

A ten-linear-step construction of C-aromatic taxane diene 14 from ethyl isopropyl ketone, acryloyl chloride, and commercially available 8 is reported. This sequence concludes with an intramolecular pinacol coupling carried out on 13. 14 is oxidized by m-chloroperbenzoic acid and dimethyldioxirane to give 17 through intermediate epoxide 20 and by VO(acac)2−t-BuOOH and Mo(CO)6−t-BuOOH to give 13. 17 is converted efficiently into 22 upon treatment with Mo(CO)6−t-BuOOH, apparently through an unusual equilibration with isomeric 20, which is converted irreversibly to 22. While these oxidative transformations highlight some of the peculiar reactivity patterns characteristic of taxane-related structures, the formation of 14 through an intramolecular pinacol coupling that joins C-1 and C-2 demonstrates the potential of this strategy for stereoselectively delivering advanced taxane synthesis intermediates.

Unusual oxidative transformations of a C-aromatic taxane diene and related structures

The interaction of 1 and related substances with MCPBA, dimethyldioxirane, VO(acac)2—t-BuOOH, and Mo(CO)6—t-BuOOH affords products with oxygenated A-rings and/or cleaved B-rings through novel oxidative processes.