Direct Asymmetric Aldol‐Tishchenko Reaction

The asymmetric direct aldol reaction of nonpreactivated substrates constitutes one of the most powerful tools in current synthetic chemistry. In the last few years, chiral metal complexes have been found to catalyze the direct aldol addition of unmodified ketones to aldehydes with both high efficiency and selectivity. However, many problems have to be overcome in this still young field of chemistry. The most challenging aspect of this chemistry is the substrate limitation of known catalysts. In this field, the asymmetric aldol‐Tishchenko reaction can be regarded as a parallel methodology that expands the scope of possible applications. In the 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 through a [3,3]‐bond reorganization. With the use of aldehydes and ketones in the aldol‐Tishchenko reaction, diols with three adjacent stereogenic centers can be created in one single operation. Thus, the reaction can be regarded as an extremely atom efficient method for the construction of enantiomerically enriched products that can serve as fundamental building blocks in synthesis. Moreover, the aldol‐Tishchenko condensation is nowadays the most efficient methodology available for the direct catalytic asymmetric aldol reaction of methylene ketones. This article provides a synopsis of this field and highlights some of the challenges that still remain.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)