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Development of a palladium-catalyzed decarboxylative arene cross-coupling of pyrrole derivatives in a flow reactor

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Abstract

Palladium-catalyzed decarboxylative cross-coupling was employed to synthesize 2-arylpyrroles via a flow process. This reaction features palladium as the only metal catalyst and uses easily accessible starting materials. The reaction temperature, the residence time, and the quantity of different reactants were investigated to achieve optimal reaction conditions. A variety of N-alkylated and N-arylated 2-arylpyrroles were produced in good to excellent yields. A N-methyl-2-arylpyrrole derivative was produced in 220 min on a 3 g scale in 84% yield. The flow set-up presented in this work is featuring a fixed bed reactor to load the insoluble Cs2CO3 necessary for the decarboxylative cross-coupling to occur, it also comprises a sample loop, and a stainless-steel reactor. This study demonstrated the excellent potential of utilizing a flow process for the synthesis of 2-arylpyrroles derivatives.

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Acknowledgements

We are grateful for the resources provided by the Natural Sciences and Engineering Research Council (NSERC), the CREATE Training Program in Continuous Flow Science at Université de Montréal, and Le Fonds de Recherche du Québec, Nature et Technologies (FQRNT). Additional support was kindly provided by the Québec-funded Centre for Green Chemistry and Catalysis (CGCC). Special thanks to Cynthia Messina for her invaluable suggestions, Vanessa Kairouz and Dr Shawn Collins for fruitful discussions.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrooke O, Montréal, QC, H4B 1R6, Canada

    Cindy Buonomano, Michael Holtz-Mulholland, Sydney Sullivan & Pat Forgione

  2. Centre in Green Chemistry and Catalysis, Montréal, QC, H3C 3J7, Canada

    Cindy Buonomano, Michael Holtz-Mulholland, Sydney Sullivan & Pat Forgione

Authors
  1. Cindy Buonomano
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  2. Michael Holtz-Mulholland
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  3. Sydney Sullivan
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  4. Pat Forgione
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Correspondence to Pat Forgione.

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Highlights

- Pyrrole carboxylic acids and aryl bromides as coupling partners.

- Palladium-catalyzed cross-coupling in a flow reactor using a fixed-bed reactor.

- Large-scale cross-coupling reaction.

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Buonomano, C., Holtz-Mulholland, M., Sullivan, S. et al. Development of a palladium-catalyzed decarboxylative arene cross-coupling of pyrrole derivatives in a flow reactor. J Flow Chem 12, 275–283 (2022). https://doi.org/10.1007/s41981-022-00222-4

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  • DOI: https://doi.org/10.1007/s41981-022-00222-4

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