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Interrupted reactions in chemical synthesis

Nature Reviews Chemistry volume 5, pages 604–623 (2021)Cite this article

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Abstract

Interrupted reactions reroute established processes to new and often unanticipated end points. Of particular interest are the cases in which a known reactive intermediate takes on a new reaction pathway, either because this pathway is lower in energy or because the conventional pathway is no longer available. Through analysis of documented cases, we aim to dissect the known interrupted reactions and trace their mechanistic origins. As new chemical processes are being discovered at a seemingly ever-increasing pace, it is likely that new interrupted reactions will continue to emerge. Our hope is that the cases considered in this Review will help identify new classes of these fascinating transformations.

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Fig. 1: Interrupted Nazarov cyclization.
Fig. 2: Interrupted Ugi four-component reaction, Groebke–Blackburn–Bienaymé reaction, Schmidt reaction and hydroaminomethylation of alkenes.
Fig. 3: Interrupted Pummerer reaction.
Fig. 4: Interrupted Fischer indole synthesis, Pictet–Spengler reaction and Bischler–Napieralski reaction.
Fig. 5: Interrupted Povarov reaction and Meyer–Schuster rearrangement.
Fig. 6: Interrupted Baeyer–Villiger oxidation and metathesis reactions.
Fig. 7: Miscellaneous interrupted reactions.
Fig. 8: Miscellaneous interrupted heterocycle syntheses.

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Acknowledgements

The Natural Sciences and Engineering Research Council of Canada (NSERC) is acknowledged for its financial support. C.-H.T. would like to thank the Connaught Fund (University of Toronto) for funding.

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  1. These authors contributed equally: Vincent Trudel, Chieh-Hung Tien.

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  1. Davenport Research Laboratories, Department of Chemistry, University of Toronto, Toronto, Ontario, Canada

    Vincent Trudel, Chieh-Hung Tien, Alina Trofimova & Andrei K. Yudin

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V.T., C.-H.T. and A.T. researched data and designed the figures. All authors contributed to the writing and editing of this Review.

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Dedicated to Professor K. Barry Sharpless on the occasion of his 80th birthday.

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Trudel, V., Tien, CH., Trofimova, A. et al. Interrupted reactions in chemical synthesis. Nat Rev Chem 5, 604–623 (2021). https://doi.org/10.1038/s41570-021-00304-2

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