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C–H carbonylation

In situ acyl triflates ace it

Nature Chemistry volume 10, pages 116–117 (2018)Cite this article

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A simple palladium catalyst has mediated the facile formation of aroyl triflates — an extremely reactive class of electrophiles. These intermediates, generated in situ, enable the Friedel–Crafts acylation of traditionally unreactive arenes, addressing a significant gap in C–H carbonylation methodology.

Acyl halides, such as acyl chlorides, are versatile electrophiles that can even react with weak nucleophiles. Yet the Friedel–Crafts acylation of several deactivated nucleophiles (such as chlorobenzene) with acid chlorides remains challenging, even with the help of strong Lewis acids as activators (Fig. 1a)2. Interestingly, Effenberger and co-workers noticed nearly 40 years ago that acyl triflates rapidly react with deactivated aromatic compounds in the absence of catalysts3. Unfortunately, acyl triflates cannot be directly obtained from stable precursors, and are usually prepared by treatment of the corresponding acid chloride with AgOTf (ref. 4). Acid chlorides are themselves obtained from the reaction of carboxylic acids with hazardous halogenating reagents, such as thionyl or oxalyl chloride and PCl3. Thus, the traditional preparation of acyl triflates requires two steps from stable carboxylic acid precursors and the handling of moisture-sensitive intermediates, limiting the applicability of these versatile intermediates in organic synthesis (Fig. 1b, top)4.

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Figure 1: Comparison between different strategies to access acyl triflates and synthetic applicability of the reaction developed by Arndtsen and co-workers1.

References

  1. Kinney, R. G. et al. Nat. Chem. 10, 193–199 (2018).

    Article  Google Scholar 

  2. Olah, G. A. Friedel-Crafts Chemistry (Wiley-Interscience, 1973).

  3. Effenberger, F. & Epple, G. Angew. Chem. Int. Ed. 11, 299–300 (1972).

    Article  CAS  Google Scholar 

  4. Effenberger, F., Epple, G., Eberhard, J. K., Bühler, U. & Sohn, E. Chem. Ber. 116, 1183–1194 (1983).

    Article  CAS  Google Scholar 

  5. Wu, X.-F., Neumann, H. & Beller, M. Chem. Soc. Rev. 40, 4986–5009 (2011).

    Article  CAS  Google Scholar 

  6. Petrone, D. A., Ye, J. & Lautens, M. Chem. Rev. 116, 8003–8104 (2016).

    Article  CAS  Google Scholar 

  7. Quesnel, J. S. & Arndtsen, B. A. J. Am. Chem. Soc. 135, 16841–16844 (2013).

    Article  CAS  Google Scholar 

  8. Fang, X., Cacherat, B. & Morandi, B. Nat. Chem. 9, 1105–1109 (2017).

    Article  CAS  Google Scholar 

  9. Roy, A. H. & Hartwig, J. F. J. Am. Chem. Soc. 125, 13944–13945 (2003).

    Article  CAS  Google Scholar 

  10. Shen, X., Hyde, A. M. & Buchwald, S. L. J. Am. Chem. Soc. 132, 14076–14078 (2010).

    Article  CAS  Google Scholar 

Download references

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  1. Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, Mülheim an der Ruhr, 45470, Germany

    Yong Ho Lee & Bill Morandi

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  1. Yong Ho Lee
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  2. Bill Morandi
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Correspondence to Bill Morandi.

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Lee, Y., Morandi, B. In situ acyl triflates ace it. Nature Chem 10, 116–117 (2018). https://doi.org/10.1038/nchem.2934

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