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

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.