“Large-but-flexible” palladium-NHCs complexes catalyzed site-selective Suzuki coupling of 2,5-dichloropyridine

• Published in: Molecular catalysis 2025-02, Vol.572, Article 114758
• Main Authors: Du, Sheng-Nan, Zhang, Meng-Jiao, Wu, Hao, Xu, Chang, Liu, Feng-Shou
• Format: Article
• Language: English
• Subjects: 2,5-dichloropyridine; Palladium NHCS complexes; Site-selective Suzuki coupling
• ISSN: 2468-8231; 2468-8231
• DOI: 10.1016/j.mcat.2024.114758

•Pd-NHCs complexes were synthesized for site-selective Suzuki of 2,5-dichloropyridine.•Structure-activity relationship studies were conducted thoroughly.•Studies revealed that “large‑but-flexible” NHC strategy is crucial for the success.•The method provides the products with excellent C2-selecivity under mild conditions.•The method can be further used for the sequential Suzuki coupling at the C5 position. A highly efficient and site-selective Pd-NHCs complexes-catalyzed Suzuki coupling of 2,5-dichloropyridine with arylboronic acids has been developed. A systematic study on the structure-activity relationship of the catalyst was also conducted, and the results demonstrated that the “large‑but-flexible” NHC ligand strategy is essential for the success of the reaction. This strategy not only boots the yield but also significantly enhances the site-selectivity of the reaction. The developed method provides mild reaction conditions, excellent C2 site-selectivity, and high functional group tolerance for the coupled products. More significantly, the protocol can be further utilized for consecutive Suzuki coupling reaction with another arylboronic acid at the C5 position, thereby constructing more complex and valuable C2, C5-diaryl-substituted pyridine molecules. [Display omitted]