The Aldol-Tishchenko Reaction: A Tool in Stereoselective Synthesis

R.      Mahrwald

doi:10.2174/1385272033486224

Abstract

The classic Tishchenko reaction embodies dimerization of aldehydes to their corresponding esters via a formal oxidation-reduction sequence, whereas the classic aldol-Tishchenko reaction involves the trimerization of enolizable aldehydes. In an aldol-Tishchenko reaction, two aldehyde molecules undergo addition to form an aldol adduct which is subsequently reduced by a third aldehyde to yield 1,3-diol monoesters, with the occurrence of an intramolecular hydride shift. This step - the intramolecular reduction - has been utilized for highly diastereoselective reduction of ß-hydroxyketones. Many literature examples of this transformation are found in natural product syntheses. The utility of this transformation becomes clear upon reaction of aldehydes with ketones. By the use of these substrates in the aldol-Tishchenko reaction, a facile approach to stereotriades is provided. Three adjacent stereogenic carbon centers, with defined configuration, can be synthesized in a single step. In this review, examples of diastereoselective and enantioselective reactions utilizing the aldol-Tishchenko reaction, as well as several related reactions, are presented and the proposed mechanisms of reaction are discussed.

Keywords: aldol-tishchenko reaction, stereoselective synthesis, oxidation-reduction sequence, classic aldol-tishchenko reaction, hydroxyketones