Highlights on the General Preference for Multi-Over Mono-Coupling in the Suzuki-Miyaura Reaction

A systematic synthetic study was performed to explain the usual trend in selectivity towards multi-coupling, over mono-coupling, in Suzuki-Miyaura reactions. This preference was observed under different reaction conditions: for various halobenzenes, using substituents on the boronic acid, and changing the catalyst and temperature. Moreover, this reaction selectivity was found to increase for more reactive systems towards oxidative addition and more diluted media. The results constitute experimental evidence that the formation of the totally substituted coupling product is kinetically favoured by a reaction path location-the proximity between the regenerated catalyst and the newly formed coupling intermediate promotes the subsequent reaction.

Automated summary

A systematic synthetic study was conducted to explain the common trend of selectivity towards multi-coupling over mono-coupling in Suzuki-Miyaura reactions. This preference was observed under various reaction conditions, including different halobenzenes, substituents on the boronic acid, and changes in catalyst and temperature. Additionally, it was found that the reaction selectivity increased for more reactive systems and more diluted media. The results provide experimental evidence that the formation of totally substituted coupling product is kinetically favored by the proximity of the regenerated catalyst and the newly formed coupling intermediate.