Part 1: efficient strategies for the construction of variably substituted bicyclo[5.3.1]undecenones (AB taxane ring systems)

Strategies for the construction of cyclic molecules containing variably substituted bicyclo[5.3.1]undecenones (AB taxane ring systems) are described. These routes employ a multi-component coupling protocol that utilizes sequential magnesium-mediated carbometallation of propargyl alcohols and intramolecular Diels-Alder reactions (IMDA). The cycloaddition generates the key eight-membered taxane ring as a single diastereomer, induced by preferential Lewis acid (diethylaluminum chloride or boron trifluoride etherate) complexation with the cross-ring oxygens. Both the electronic nature of the dienophile and the neighbouring group non-bonded interactions contribute to the success of these cycloadditions. Key words: magnesium chelate, Lewis acid, intramolecular Diels-Alder, cycloaddition.