Palladium-Catalyzed Coupling Reactions of Aryl Chlorides

Collectively, palladium‐catalyzed coupling reactions represent some of the most powerful and versatile tools available to synthetic organic chemists. Their widespread popularity stems in part from the fact that they are generally tolerant to a large number of functional groups, which allows them to be employed in a wide range of applications. However, for many years a major limitation of palladium‐catalyzed coupling processes has been the poor reactivity of aryl chlorides, which from the standpoints of cost and availability are more attractive substrates than the corresponding bromides, iodides, and triflates. Traditional palladium/triarylphosphane catalysts are only effective for the coupling of certain activated aryl chlorides (for example, heteroaryl chlorides and substrates that bear electron‐withdrawing groups), but not for aryl chlorides in general. Since 1998, major advances have been described by a number of research groups addressing this challenge; catalysts based on bulky, electron‐rich phosphanes and carbenes have proved to be particularly mild and versatile. This review summarizes both the seminal early work and the exciting recent developments in the area of palladium‐catalyzed couplings of aryl chlorides. Their relatively low cost and wide availability can make aryl chlorides more attractive substrates for coupling reactions than the corresponding bromides or iodides. Although scattered examples of couplings of aryl chlorides had been reported earlier, for most processes it was not until the last few years that comparatively general and mild methods were described (see scheme for a general reaction). This article furnishes an overview both of the pioneering early developments and the exciting recent discoveries in this area.