Correlations between Substituent Effects and Catalytic Activities: A Quantitative Approach for the Development of Halogen-Bonding-Driven Anion-Binding Catalysts.

A quantitative approach for the development of halogenbonding- driven anion-binding catalysts was studied using 4- substituted perfluorinated iodobenzene. 19F NMR titrations were used to determine the binding constants K for chloride, and their catalytic activities were evaluated in the allylation reaction of a N-activated pyridine. We discovered that the log K and product yields were linearly correlated, and that they were dependent on the Hammett substituent parameter, σmeta (r²= 0.99). This linear correlation provided a quantitative predictive model for both the binding constant and the reaction yield. Concomitantly, this efficiently permitted the development of a highly active anion-binding catalyst, namely 4-CNC6F4I (K= 489±5 M-1. Additionally, the catalytic activity of 4-CNC6F4I was established in the allylation and crotylation of N-activated isoquinolines (7 examples). Overall, this approach highlights the value of quantitative analysis by exploring experimentally informed correlations in the development of halogen bond donor catalysts. [ABSTRACT FROM AUTHOR]