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

Xiao-Yan Zhang; Yang An; Zhou-Zhou Liu; Ling-Tao Fan

doi:10.1055/s-0043-1775472

Synthesis, Table of Contents

Synthesis 2025; 57(15): 2337-2344
DOI: 10.1055/s-0043-1775472

paper

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

Xiao-Yan Zhang ‡

,

Yang An ‡

,

Zhou-Zhou Liu

,

Ling-Tao Fan

Abstract

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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.

Key words

Claisen-type condensation - α,α-disubstituted β-keto carbonyl compounds - ketones - carboxylic acids - P₂O₅/Tf₂O

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References

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