The zirconium alkoxide-catalyzed aldol-Tishchenko reaction of ketone aldols.

The aldol-Tishchenko reaction of ketone aldols as enol equivalents has been developed as an efficient strategy to furnish differentiated 1,3-anti-diol monoesters in one step. The thermodynamically unstable ketone aldols undergo a facile retro-aldolization to yield a presumed zirconium enolate in situ, which then undergoes the aldol-Tishchenko reaction in typically high yields and with complete 1,3-anti diastereocontrol. Evaluation of a broad range of metal alkoxides as catalysts and optimization of the reaction protocol led to a modified zirconium alkoxide catalyst with attenuated Lewis acidity and dichloromethane as solvent, which resulted in suppression of the undesired acyl migration to a large extent. Various ketone aldols have been prepared and subjected to the general process, giving rise to a broad range of differently substituted 1,3-anti-diol monoesters, which may be hydrolyzed to the corresponding 1,3-anti-diols.