Greening a Great Experiment: Optimizing the Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling of Phenylboronic Acid and 1-Bromo-4-(trifluoromethyl)benzene

Abstract

Optimized procedures are provided for the Suzuki-Miyaura cross-coupling of 1-bromo-4-(trifluoromethyl)benzene with phenylboronic acid using molecular nickel(II) precatalysts in the green solvent 2-methylbutan-2-ol in the presence of base. Emphasis is placed on evaluating the procedures in the context of the principles of green chemistry. When compared with the existing undergraduate experiment, significant gains are made in reducing the reaction scale, minimizing catalyst loading, reducing or eliminating cooling water use, and improving energy efficiency. The cross-coupling reaction is flexible and can be tailored to a variety of laboratory schedules, equipment availability, and student skill levels. While the greatest efficiency is realized when a commercial microwave synthesizer is employed, viable options are presented for simple reflux and sealed vial reactions. The experiment is suitable for typical 3–4-h lab periods and can easily be incorporated into a variety of laboratory curricula, including mini-projects with or without teamwork.