Suzuki-Miyaura Cross-Coupling Using Ketones

The Suzuki-Miyaura cross-coupling is among the most frequently used methods to forge new C–C bonds. Organohalides are recognized as the classical electrophilic coupling partner in these reactions. However, given the abundance of oxygen in common feedstock molecules, researchers have sought new and improved methods to harness C–O bonds as alternatives to halides. Today, methods exist to directly cross-couple functional groups such as alcohols, carboxylic acids, and phenols. However, methods to directly engage ketones in cross-coupling reactions are lacking. Herein, we present how ketones can be utilized in the Suzuki-Miyaura cross-coupling reaction to form valuable alkenyl arenes. The reaction makes use of a Ni/bipyridine catalyst in the presence of pivalic anhydride and KOtBu. Mechanistic studies suggest that the reaction proceeds by a rapid in situ activation of the ketone to form an alkenyl pivalate intermediate, which acts as a pseudohalide in a Ni-catalyzed Suzuki-Miyaura coupling. The compatibility of the base, activating agent, and low-valent metal catalyst is shown to be central to the reaction’s success.