An efficient approach toward taxane analogs: Atrop- and diastereoselective eight-membered B ring cyclizations for synthesis of aromatic C-ring taxinine derivatives

Article abstract of DOI:10.1021/jo00090a039

We have developed efficient methods for construction of the C-2 oxygenated aromatic C-ring taxane skeleton based on an eight-membered ring cyclization involving a Lewis acid-mediated intramolecular coupling reaction of the dienol silyl ether at C-10 and the acetal at C-9. The C-2 stereogenic center strongly influences the conformation of the forming eight-membered ring during the cyclization reaction. 1β,2α-Siloxy derivative 13b gives exo isomer 15 as the major product, and 1β,2β-siloxy derivative 13a exclusively yields endo isomer 14. Both of these cyclization products, which had undesired stereochemistry, were converted to stereochemically refined aromatic C-ring taxinine analogs by multistep transformations. The chelation-controlled, eight-membered ring cyclization of 1β,2α-hydroxy derivative 31 was found to give exclusively the desired 1β,2α,9α,10β-endo isomer 16 in good yield. This remarkably stereoselective cyclization, when combined with stereocontrolled AC ring coupling reactions, should provide an efficient, convergent route toward various taxane derivatives. The aromatic C-ring taxinine analogs could be converted to natural taxinine by further transformation of the aromatic C-ring.