Effective N-Heterocyclic Carbenes with Indole Moiety Applied in the Pd-Catalyzed Synthesis of Sterically Hindered Biaryls

Indolyl-based benzimidazolium salts have been designed and prepared using three easy steps, namely indole alkylation, iodine-catalyzed C-N bond coupling, and substitution. These salts have high catalytic performance in Pd-catalyzed sterically hindered biaryl synthesis. The variability of the salt scaffold can be modified by the substitution of indole and alkyl halides. The Suzuki-Miyaura cross-coupling (SMC) of aryl chlorides was performed with satisfactory functional group tolerance and biaryls were obtained in 42-87% yield at 90 degrees C by using 0.5 mol% of Pd(OAc)(2)/1 i as the catalyst. Our results highlight the importance of maintaining a balance between the length of the carbon chain of substituents on the indole moiety and the steric congestion of substituents on the indole moiety for catalytic activity; this can be beneficial in difficult coupling processes. In addition, an asymmetric SMC reaction of aryl chloride under optimal reaction conditions was achieved with an 8% ee preliminarily.

Automated summary

Indolyl-based benzimidazolium salts were synthesized in three steps, including indole alkylation, iodine-catalyzed C-N bond coupling, and substitution. These salts exhibited high catalytic activity in Pd-catalyzed sterically hindered biaryl synthesis, with the scaffold variability adjusted by substituting indole and alkyl halides. The Suzuki-Miyaura cross-coupling of aryl chlorides was performed with good functional group tolerance, yielding biaryls in 42-87% yield at 90 degrees C using 0.5 mol% of Pd(OAc)(2)/1 i as the catalyst. The balance between the carbon chain length of substituents on the indole moiety and the steric congestion of substituents was found to be crucial for catalytic activity.