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Geometry-controlled reactivity and dynamics in organic molecules

Nature Synthesis (2024)Cite this article

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Abstract

It is well established that strain in organic molecules is linked to having nonideal bond lengths, bond angles and unfavourable non-covalent interactions. The constrained geometries of ring systems are particularly predisposed to creating strain. Recently, there has been increased interest in leveraging this property of rings as a synthetic tool by building strain into substrates to activate a desired bond-cleavage step. However, one could also envisage alternative uses of strain. Here we outline how geometry control can be exploited to ‘switch on’ dynamic processes or stabilize reactive transition states. By designing constrained molecular structures that direct strain on particular bonds or functional groups, transformations that are otherwise energetically uphill can become favoured. This phenomenon can subvert our expectations about the reactivity and properties of organic molecules, giving rise to unusual bonding modes.

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Fig. 1: The design principles of geometry-controlled transformations or molecular conformations.
Fig. 2: The effect of geometry control on pericyclic reactions.
Fig. 3: Dynamic sp3 stereochemistry.
Fig. 4: Type III geometry control examples.
Fig. 5: Accessing transition-state analogues through type IV geometry control.
Fig. 6: Neutral homoaromaticity through type IV geometry control.
Fig. 7: Emergent phenomena associated with geometry control.

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Acknowledgements

P.K.S. gratefully acknowledges the Engineering and Physical Sciences Research Council (EPSRC) for a Doctoral Training Grant (EP/R513039/1). P.R.M. acknowledges a Leverhulme Trust Research Project Grant (RPG-2023-191) and an EPSRC Fellowship (EP/V040049/2).

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Authors and Affiliations

  1. Department of Chemistry, University of York, York, UK

    Promeet K. Saha & Paul R. McGonigal

  2. Department of Chemistry, Durham University, Durham, UK

    Promeet K. Saha

  3. Technische Universität Chemnitz, Institut für Chemie, Fakultät für Naturwissenschaften, Chemnitz, Germany

    Trung Tran Ngoc & Johannes F. Teichert

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  1. Promeet K. Saha
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  2. Trung Tran Ngoc
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  3. Paul R. McGonigal
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All authors conceived the main outline and idea of the Review and contributed to the writing. P.K.S. and T.T.N. prepared the figures.

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Correspondence to Paul R. McGonigal or Johannes F. Teichert.

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Saha, P.K., Tran Ngoc, T., McGonigal, P.R. et al. Geometry-controlled reactivity and dynamics in organic molecules. Nat. Synth (2024). https://doi.org/10.1038/s44160-024-00526-4

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