Claisen-Type Condensation of Ketones with Carboxylic Acids: Synthesis of α,α-Disubstituted β-Keto Carbonyl Compounds

Abstract A novel and efficient Claisen-type condensation reaction for the synthesis of α,α-disubstituted β-keto carbonyl compounds from ketones and unactivated carboxylic acids in a P2O5/Tf2O system is presented. This approach can be applied to reactions between various open-chain ketones, cyclopentanones, indenones, and tetrahydronaphthones and unactivated alkyl carboxylic acids, aromatic carboxylic acids, and unsaturated carboxylic acids, affording all-carbon spirocyclic 1,3-diketones of various sizes and acyclic 1,3-diketones containing all-carbon quaternary centers in moderate to high yields. Furthermore, we have also confirmed that the reaction proceeds via an enol lactone intermediate.