Base-Catalyzed Domino Double Michael Reactions of 1-Hydroxy-1,4-dien-3-ones and 2-Alkylidenemalononitriles: A Diastereoselective Route to Polysubstituted 3-Alkanoyl-4-hydroxycyclohex-3-enes

Abstract

The diastereoselective synthesis of 2,6-disubstituted 3-alkanoyl-4-hydroxycyclohex-3-ene-1,1-dicarbonitriles has been developed through domino double Michael addition of 1,5-disubstituted 1-hydroxy-1,4-dien-3-ones to 2-alkylidenemalononitriles catalyzed by triethylamine. This simple domino process affords a variety of highly functionalized 3-alkanoyl-4-hydroxycyclohex-3-enes, some of which are not easily accessible using other methodologies, in moderate to good yields and excellent diastereoselectivity (dr > 95:5). Thus, the generality of this process and feasibility of introducing bioactive moieties make this reaction highly valuable in synthetic and medicinal chemistry.

Key words

domino reaction - Michael addition - diastereoselectivity - cyclohexanone - curcumin

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• 12 The structure of 3aaa was determined by X-ray crystal structure analysis (CCDC number: 940043), and further information is provided in the Supporting Information.

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