A 2-Pyridone Photo-[4 + 4] Approach to the Taxanes

Abstract

Pyridones tethered by a four-carbon chain at the 3- and 6’-positions can undergo [4 + 4] photocycloaddition to simultaneously form three, but not four, tetrasubstituted carbons. In a study directed at the taxanes, photocycloaddition of 28 was found to be fully controlled by a (tert-butyldimethylsilyl)oxy group on the tether, to give a photoproduct with five stereogenic centers and both quaternary carbons found in taxol (paclitaxel). This photoproduct proved to be unstable to silica gel, but saturation of one alkene gave a stable product (30). Epoxidation of the enol ether of 30 proceeds exclusively from one face of the cyclooctene ring, demonstrating the facial bias of the polycyclic system and correctly introducing the C-2 stereogenic center of taxol. As part of this study, 4-methoxy-2-pyridones, known to be inert to [4 + 4] photodimerization, were found to undergo [4 + 4] photocycloaddition with 4-unsubstituted-2-pyridones both inter- and intramolecularly.