Alkylidene β-Ketoesters in Asymmetric Catalysis: Recent Developments

Although alkylidene beta-ketoesters have been known since the beginning of the 20th century, they have only recently attracted the attention of :the synthetic organic community. In these versatile electrophiles, the enone double bond is strongly polarized because of the presence of the ester moiety as a second electron-withdrawing group. The resulting increase in reactivity has recently opened the way to a number of challenging transformations in the field of enantioselective catalysis, but is also responsible for their high sensitivity toward acids, bases, and high temperature, which hampered their application in organic synthesis for a long time. The saturated beta-ketoester moiety generated in these reactions has been used for diverse functionalization reactions, some of which lead to quaternary stereocenters. This perspective highlights the origins of alkylidene beta-ketoester chemistry and focuses on recent developments of the quickly evolving field of asymmetric catalytic reactions of these substrates. After their general properties and preparations, recent developments are discussed, which mainly involve cycloaddition and conjugate addition reactions. A special class of unsaturated beta-ketoesters, ester-substituted divinyl ketones, has been used in Nazarov cyclization reactions.