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DOI: 10.1055/s-0043-1775453
Synthesis of 2-Arylpyrroles via an Optimized Palladium Coupling
The authors would like to thank the National Science Foundation (CHE-2247064 and MRI-1919565) for generous support of our research. A.L.O. also thanks the donors of the American Chemical Society Petroleum Research Fund under grant ND3-65702.
Abstract
Using response surface methods, we have re-optimized a palladium-catalyzed method for coupling ClZn(pyrrolide) with aryl bromides to selectively generate 2-arylpyrroles. We optimized based on four variables: temperature, ClZn(pyrrolide)/ArBr ratio, catalyst loading, and time. To find a protocol applicable to most substrates of interest, we optimized three different substrates: a bulky arene (mesityl bromide), an electron-rich arene [4-(NMe2)C6H4Br], and an electron-deficient arene [3,5-(CF3)2C6H3Br]. The re-optimized procedures give as good or better yields than the previously published protocols, always in a fraction of the time. In addition, the reactions are generally cleaner with the new conditions, especially with electron-rich substrates, making the products easier to isolate. We applied the conditions to a variety of different substrates in each category, which provided good to excellent isolated yields.
Key words
palladium catalysis - design of experiments - pyrroles - optimization - cross-coupling - zinc - response surface methodsSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0043-1775453.
- Supporting Information
Publication History
Received: 16 December 2024
Accepted after revision: 06 February 2025
Article published online:
19 March 2025
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