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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. 

Abstract The use of polar solvents MeCN or dimethylformamide (DMF) was previously shown to induce a selectivity switch in the Pd/P^tBu₃‐catalyzed Suzuki‐Miyaura coupling of chloroaryl triflates. This phenomenon was attributed to the ability of polar solvents to stabilize anionic transition states for oxidative addition. However, we demonstrate that selectivity in this reaction does not trend with solvent dielectic constant. Unlike MeCN and DMF, water, alcohols, and several polar aprotic solvents such as MeNO₂, acetone, and propylene carbonate provide the same selectivity as nonpolar solvents. These results indicate that the role of solvent on the selectivity of Suzuki‐Miyaura couplings may be more complex than previously envisioned. Furthermore, this observation has the potential for synthetic value as it greatly broadens the scope of solvents that can be used for chloride‐selective cross coupling of chloroaryl triflates.