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Diamidocarbenes as versatile and reversible [2 + 1] cycloaddition reagents

Nature Chemistry volume 4, pages 275–280 (2012)Cite this article

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Abstract

We describe the synthesis of a variety of cyclopropanes and epoxides by combining a readily accessible and isolable N,N′-diamidocarbene with a range of structurally and electronically diverse olefins and aldehydes, including electron-rich derivatives. Surprisingly, the cyclopropanation and epoxidation reactions were discovered to be rapid and thermally reversible at relatively low temperatures, two features often desired for applications that utilize dynamic covalent chemistry. In addition, a diamidocyclopropane derivative prepared via this method was hydrolysed successfully to form the corresponding linear carboxylic acid in a metal- and carbon monoxide-free hydrocarboxylation reaction. As such, diamidocarbenes are expected to find utility in the synthesis of cyclopropanes, epoxides and their derivatives, as well as in dynamic covalent chemistry applications.

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Figure 1: Examples of isolable carbenes that may be used as [2 + 1] cycloaddition reagents.
Figure 2: X-ray structures of the [2 + 1] cycloaddition products 2e and 2m.
Figure 3: Stereospecificity of the [2 + 1] cycloaddition with 1 and the formation of a linear carboxylic acid.
Figure 4: Formal [4 + 1] cycloadditions of DAC 1 with α,β-unsaturated ketones and acrolein and [2 + 1] cycloadditions with aldehydes.
Figure 5: Reversible [2 + 1] cycloadditions involving 1.

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Acknowledgements

We are grateful to the National Science Foundation (CHE-0645563), the Robert A. Welch Foundation (F-1621) and the Sloan Foundation for their support.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, 78712, Texas, USA

    Jonathan P. Moerdyk & Christopher W. Bielawski

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  1. Jonathan P. Moerdyk
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Contributions

C.W.B. and J.P.M. conceived and designed the experiments, and co-wrote the paper. J.P.M. performed the experiments and analysed the data. Both authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Christopher W. Bielawski.

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The authors declare no competing financial interests.

Supplementary information

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Supplementary information (PDF 10243 kb)

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Crystallographic data for compound 2e. (CIF 19 kb)

Supplementary information

Crystallographic data for compound 2j. (CIF 20 kb)

Supplementary information

Crystallographic data for compound 2k. (CIF 35 kb)

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Crystallographic data for compound 2m. (CIF 17 kb)

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Crystallographic data for compound 2o. (CIF 32 kb)

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Crystallographic data for compound 3a. (CIF 18 kb)

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Crystallographic data for compound 4b. (CIF 31 kb)

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Moerdyk, J., Bielawski, C. Diamidocarbenes as versatile and reversible [2 + 1] cycloaddition reagents. Nature Chem 4, 275–280 (2012). https://doi.org/10.1038/nchem.1267

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