Recent Advances in the Retro-Claisen Reaction and Its Synthetic Applications

Marko      Jukic; Damjan      Sterk; Zdenko      Casar

Abstract

In 1881, Rainer Ludwig Claisen discovered a carbon-carbon bond-forming reaction between two esters or an ester and a carbonyl compound in the presence of a base. The reaction leads to β-keto esters or β-diketones respectively, and it was later named Claisen condensation, or classic Claisen condensation in the former case, and mixed ('crossed') Claisen condensation in the latter. The reaction now sits firmly in the repertoire of organic synthesis as one of the earliest name reactions. In continuing research, it became evident that the products of this aldol type reaction can be cleaved to produce starting materials. Namely, β-diketone moieties were reported to undergo the retro-Claisen reaction, which is β-dicarbonyl carbon-carbon bond cleavage. Although it was first described as a side, or even parasitic reaction, it was later incorporated into the body of carbon-carbon base-promoted cleavage reactions. Moreover, numerous recent reports have demonstrated the wide selection of methodologies that can be used in these transformations. The scope ranges from various base-mediated or acid-mediated reactions and biocatalyzed transformations, and it extends to recently discovered homogeneous catalyzed reactions. Interestingly, further synthetic applications of retro-Claisen reaction are now being realized, and this is reflected in syntheses of natural products and other fine chemicals. This reaction is nowadays a useful synthetic tool and this review surveys and consolidates the recent literature on the retro-Claisen reaction.

Keywords: Asymmetric synthesis, carbon-carbon bond cleavage, Claisen reaction, coordination chemistry, homogeneous catalysis, ketones, natural-product synthesis, retro reactions, retro-Claisen reaction, synthetic methodology.