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

Abstract

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.

Keywords

• oxidative addition
• organocatalysis
• Pd catalyst
• multi-coupling
• reaction selectivity