Elucidating Mechanism and Selectivity in Pyridine Functionalization Through Silylium Catalysis

• Published in: Chemistry : a European journal 2024-09, Vol.30 (51), p.e202402078-n/a
• Main Authors: Shen, Yanling, Zhang, Yan, Zhang, Cefei, Li, Haoze, Hu, Changwei, Yu, Zhipeng, Zheng, Ke, Su, Zhishan
• Format: Article
• Language: English
• Subjects: Acidity; Anions; Catalysis; Density functional theory; DFT calculations; Electronegativity; Functionalization of pyridine; Lewis acid; Mechanism; Pyridines; Regioselectivity; Steric effect; Substrates; Sulfonamides
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202402078

The functionalization of aromatic N‐heterocycles through silylium activation demonstrates exceptional selectivity and efficiency. Density functional theory (DFT) calculations unveil the detailed silylium catalysis mechanism and elucidate the origins of selectivity in this reaction. The phosphoramidimidate sulfonamide (PADI) precatalyst orchestrates of the catalytic cycle via three elementary steps. The Brønsted acidity of precatalyst significantly influences both the formation of silylium‐based Lewis acid active species and the silylium activation of pyridine. Unlike disulfonimide (DSI)‐type precatalysts, both Tf2NH and PADI precatalysts with strong acidities can easily promote the generation of activated silylium pyridine species. A semi‐enclosed ′rigid’ electronegative cavity in PADI‐type anions constructs a well‐defined recognition site, facilitating engagement with the positively charged silylium pyridine species. Due to the high electrophilicity and less steric demand at the C4‐position of the pyridine substrate, the product with C4‐regioselectivity was predominantly generated. Density functional theory (DFT) calculations reveal that a semi‐enclosed ′rigid’ electronegative cavity in PADI‐type anions creates a well‐defined recognition site, facilitating interaction with positively charged silylium pyridine species. Due to the high electrophilicity and minimal steric demand at the C4‐position of the pyridine substrate, the reaction predominantly produces a C4‐regioselective product.