Light-driven molecular trap enables bidirectional manipulation of dynamic covalent systems

Abstract

Bond formation between two molecular entities in a closed system strictly obeys the principle of microscopic reversibility and occurs in favour of the thermodynamically more stable product. Here, we demonstrate how light can bypass this fundamental limitation by driving and controlling the reversible bimolecular reaction between an N-nucleophile and a photoswitchable carbonyl electrophile. Light-driven tautomerization cycles reverse the reactivity of the C=O/C=N-electrophiles (‘umpolung’) to activate substrates and remove products, respectively, solely depending on the illumination wavelength. By applying either red or blue light, selective and nearly quantitative intermolecular bond formation/scission can be achieved, even if the underlying condensation/hydrolysis equilibrium is thermodynamically disfavoured. Exploiting light-driven in situ C=N exchange, our approach can be used to externally regulate a closed dynamic covalent system by actively and reversibly removing specific components, resembling a molecular and bidirectional version of a macroscopic Dean–Stark trap.

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Fig. 1: Concept of driving thermally reversible covalent bond formation/scission with light.
Fig. 2: Light-driven bond formation/cleavage cycle.
Fig. 3: UV–vis absorption spectra.
Fig. 4: Light-driven C–N bond formation/scission for an amine nucleophile.
Fig. 5: Light-driven C–N bond formation/scission for a hydrazide nucleophile.
Fig. 6: Light-driven compositional shifting of a coupled thermodynamic equilibrium.

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Acknowledgements

The authors thank S. Ihrig and J. Schwarz for upscaling the synthesis of phenol I. M.K. and F.E. are indebted to the Studienstiftung des deutschen Volkes and the Fonds der chemischen Industrie, respectively, for providing doctoral fellowships. Generous support by the European Research Council via ERC-2012-STG_308117 (Light4Function) is acknowledged.

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M.K., F.E., and C.J. carried out synthesis. M.K. and F.E. conducted optical spectroscopy. M.K. performed condensation/hydrolysis experiments. M.K. and A.D. analysed experiments via NMR spectroscopy. J.G. conducted computations. M.K., F.E., and S.H. conceived the idea, designed the study, and wrote the manuscript. All authors discussed the results and edited the manuscript.

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Correspondence to Stefan Hecht.

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Supplementary information

Synthetic and experimental procedures, computational, spectroscopic and mass spectrometric data, as well as additional experiments

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Kathan, M., Eisenreich, F., Jurissek, C. et al. Light-driven molecular trap enables bidirectional manipulation of dynamic covalent systems. Nature Chem 10, 1031–1036 (2018). https://doi.org/10.1038/s41557-018-0106-8

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