Improvement in the Palladium-Catalyzed Miyaura Borylation Reaction by Optimization of the Base: Scope and Mechanistic Study

Aryl boronic acids and esters are important building blocks in API synthesis. The palladium-catalyzed Suzuki-Miyaura borylation is the most common method for their preparation. This paper describes an improvement of the current reaction conditions. By using lipophilic bases such as potassium 2-ethyl hexanoate, the borylation reaction could be achieved at 35 degrees C in less than 2 h with very low palladium loading (0.5 mol %). A preliminary mechanistic study shows a hitherto unrecognized inhibitory effect by the carboxylate anion on the catalytic cycle, whereas 2-ethyl hexanoate minimizes this inhibitory effect. This improved methodology enables borylation of a wide range of substrates under mild conditions.

Automated summary

This study presents an improvement in the preparation of aryl boronic acids and esters, with the use of specific bases allowing for fast reactions at lower temperatures and low palladium loading. Mechanistic studies reveal that the inhibitory effect of carboxylate anions on the catalytic cycle can be minimized by 2-ethyl hexanoate, enabling borylation of a wide range of substrates under mild conditions.