Enantioselective Aldol-Tishchenko Reaction

Significance

The first enantio-and diastereoselective synthesis of 1,3,5-triol monoesters using an aldol-Tishchenko reaction is reported. The reaction was performed on a range of aryl aldehydes and β-hydroxyketones in the presence of Ti(Ot-Bu)₄ and cinchona alkaloids. Almost exclusively one diastereomer was formed although statistically 31 other stereoisomers are possible. Both enantiomers can be readily accessed by either using cinchona or cinchonidine. In order to explain the ‘non-classical Tishchenko’ configuration in the product, a tricyclic transition state illustrated above was proposed to rationalize the excellent stereoselectivities observed.