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Enhanced reactivity of twisted amides inside a molecular cage

Nature Chemistry volume 12, pages 574–578 (2020)Cite this article

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Abstract

When an amide group is distorted from its planar conformation, the conjugation between the nitrogen lone pair and the π* orbital of the carbonyl is disrupted and the reactivity towards nucleophiles is enhanced. Although there are several reports on the synthesis of activated twisted amides, amide activation through mechanical twisting is much less common. Here, we report twisted amides that are stabilized through their inclusion in a self-assembled coordination cage. When secondary aromatic amides are included in a Td-symmetric cage, the cis-twisted conformation is favoured over the trans-planar one—as evidenced by single-crystal X-ray diffraction analysis—revealing that the amide can twist by up to 34°. As a consequence of this distortion, the hydrolysis of amides is significantly accelerated upon inclusion.

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Fig. 1: Trapping of twisted amides by inclusion in a molecular cage.
Fig. 2: Amide inclusion in a coordination cage.
Fig. 3: Conformation control of an amide by co-inclusion.
Fig. 4: Hydrolysis of twisted amides in a cavity.

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Data availability

The data supporting the findings of this study are available within this article and its Supplementary Information. Crystallographic data for inclusion complexes 1b•(2a)2, 1a•(2b)2, 1a•(2b•3a), 1a•(2b•4), 1a•(2c)2, 1a•2d and 1a•(2e)2 are free of charge from the Cambridge Crystallographic Data Centre (www.ccdc.cam.ac.uk) under reference nos. 1949143, 1949144, 1949145, 1949146, 1949149, 1949150 and 1949151, respectively.

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Acknowledgements

This research was supported by Grants-in-Aid for Specially Promoted Research (19H05461 to M.F.), for Young Scientists (19K15581 to H.T.) and the Noguchi Institute (to H.T.).

Author information

Authors and Affiliations

  1. Department of Applied Chemistry, School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    Hiroki Takezawa, Kosuke Shitozawa & Makoto Fujita

  2. Division of Advanced Molecular Science, Institute for Molecular Science (IMS), Okazaki, Aichi, Japan

    Makoto Fujita

Authors
  1. Hiroki Takezawa
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  2. Kosuke Shitozawa
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  3. Makoto Fujita
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Contributions

H.T. and K.S. performed the described experiments and analysed the data. H.T. and M.F. conceived and designed the experiments and co-wrote the manuscript.

Corresponding authors

Correspondence to Hiroki Takezawa or Makoto Fujita.

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Competing interests

The authors declare no competing interests.

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Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary experimental details and compound characterization data.

Crystallographic data

CIF for 1b·(2a)2; CCDC reference: 1949143.

Crystallographic data

CIF for 1a·(2b)2; CCDC reference: 1949144.

Crystallographic data

CIF for 1a·(2b·3a); CCDC reference: 1949145.

Crystallographic data

CIF for 1a·(2b·4); CCDC reference: 1949146.

Crystallographic data

CIF for 1a·(2c)2; CCDC reference: 1949149.

Crystallographic data

CIF for 1a·2d; CCDC reference: 1949150.

Crystallographic data

CIF for 1a·(2e)2·S1; CCDC reference: 1949151.

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Takezawa, H., Shitozawa, K. & Fujita, M. Enhanced reactivity of twisted amides inside a molecular cage. Nat. Chem. 12, 574–578 (2020). https://doi.org/10.1038/s41557-020-0455-y

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