Versatile Synthesis of Dissymmetric Diarylideneacetones via a Palladium-Catalyzed­ Coupling–Isomerization Reaction

Abstract

As a twofold Michael system, the diarylideneacetone core is of particular interest in organic synthesis and for therapeutic applications. To overcome the drawbacks of the classical Claisen–Schmidt protocol, a new methodology for the synthesis of dissymmetric (hetero)diarylideneacetones has been developed. Conditions were optimized with a Box–Behnken design of experiment. The milder reaction conditions allow the efficient preparation of fluorinated, or heteroaromatic, dissymmetric diarylideneacetones which cannot be obtained through the classical Claisen–Schmidt protocol.

Key words

heterocycles - catalysis - cross-coupling - isomerization - palladium - solvent effects - substituent effects

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