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Amides as surrogates of aldehydes for C-C bond formation: amide-based direct Knoevenagel-type condensation reaction and related reactions

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Abstract

Aldehydes are perhaps the most versatile compounds that enable many C-C bond forming reactions, which are not amenable for other subclasses of carbonyl compounds. We report the first use of amides as surrogates of aldehydes for C-C bond formation, namely, the direct Knoevenagel-type condensation based on amides. The one-pot method consists of controlled reduction of an amide with LDBIPA [LiAlH(iBu)2(OiPr)], Lewis acid-mediated release of a reactive iminium ion intermediate, nucleophilic addition, and in situ elimination of amine. The reaction shows good functional group tolerance. We also demonstrated that the Schwartz reagent could be used as an alternative of LDBIPA. The employment of nitromethane and a silyl enol ether as the nucleophiles opens an avenue for the unprecedented amide-based nitro-aldol condensation reaction and aldol condensation reaction, respectively.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21931010, 21672176) and the National Key Research and Development Program of China (2017YFA0207302).

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Authors and Affiliations

  1. Department of Chemistry, Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China

    Wei Ou & Pei-Qiang Huang

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  1. Wei Ou
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  2. Pei-Qiang Huang
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Correspondence to Pei-Qiang Huang.

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11426_2019_9586_MOESM1_ESM.pdf

Amides as Surrogates of Aldehydes for C-C Bond Formation: Amide-Based Direct Knoevenagel-Type Condensation Reaction and Related Reactions

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Ou, W., Huang, PQ. Amides as surrogates of aldehydes for C-C bond formation: amide-based direct Knoevenagel-type condensation reaction and related reactions. Sci. China Chem. 63, 11–15 (2020). https://doi.org/10.1007/s11426-019-9586-3

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  • DOI: https://doi.org/10.1007/s11426-019-9586-3

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