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

• DOI: 10.1021/acs.joc.0c01758
• Publication Date: 2020-11-27T17:27:46Z
• Authors: Santiago Barroso; Markus Joksch; Pim Puylaert; Sergey Tin; Stephen J. Bell; Luke Donnellan; Stewart Duguid; Colin Muir; Peichao Zhao; Vittorio Farina; Duc N. Tran; Johannes G. de Vries
• Keywords: Borylation; Carboxylate; Catalytic cycle

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 current reaction conditions. By using lipophilic bases such as potassium 2-ethyl hexanoate, could be achieved at 35 °C less than 2 h with very low palladium loading (0.5 mol %). A preliminary mechanistic study shows a hitherto unrecognized inhibitory effect by carboxylate anion on catalytic cycle, whereas hexanoate minimizes this effect. improved methodology enables wide range substrates under mild