Intramolecular C–H Cyclization of Benzimidazoles with Alkenes

Intramolecular C–H Cyclization of Benzimidazoles with Alkenes

Author: ChemistryViews

Polycyclic imidazoles are often found, e.g., in biologically active molecules. They can be prepared, for example, using transition-metal-catalyzed C–H cyclizations of imidazoles with alkenes. This approach provides a one-step route with good atom economy. However, it is often limited to exo-selective cyclizations. Corresponding endo-selective cyclizations have been more difficult to achieve.

Xue-Tao Xu, Wuyi University, Jiangmen, China, Mengchun Ye, Wuyi University and Nankai University, Tianjin, China, and colleagues have developed a nickel-catalyzed intramolecular endo-selective C–H cyclization of benzimidazoles with alkenes (example product pictured). The team used Ni(cod)2 (cod = 1,5-cyclooctadiene) as a catalyst together with an N-heterocyclic carbene (NHC) ligand precursor and KOtBu as a base, as well as AlMe3. The reactions were performed in toluene at 70 °C.

Under these conditions, different benzimidazole derivatives functionalized with internal and terminal alkenes were converted to the desired cyclization products with high yields and high endo-selectivity. (Z)-alkenes gave a lower yield and lower endo-selectivity than (E)-alkenes. Substrates with electron-withdrawing substituents on the phenyl ring were not well suited to the reaction. According to the researchers, the endo-selectivity can be attributed to steric repulsion in a reaction intermediate that involves both Ni and Al. Thus, the Ni–Al bimetallic catalyst plays an important role in the selectivity of the transformation.


 

Update (January 8, 2023)
The article originally had AlCl3 in place of AlMe3; this has been corrected.

 

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