In search of the perfect conditions for Suzuki–Miyaura cross-couplings

Developments in Suzuki-Miyaura (SM) couplings are discussed from a historical standpoint as they are especially valued C-C bond-forming reactions in the fine chemicals industry today. However, discussion from the increasingly important standpoint of sustainability is also considered when looking for conditions leading to the perfect coupling. Thus, several procedures now exist leading to the desired SM couplings, which reproducibly occur in or on water, rather than in traditional, petroleum-based organic solvents. Moreover, procedures based on low loadings of palladium catalysts are also in hand that ensure that this precious and, at one time, endangered metal will be available indefinitely. In addition, the beginning of a new series of ligands is discussed that, from a life cycle assessment perspective, meet the required criteria (including method of formation, avoidance of intellectual property (IP) issues, number of steps involved, cost, and effectiveness) and should, therefore, feature prominently in the development of SM couplings. This goal may even be more attainable considering the recently reported use of "on dirty water" conditions, which enables close-to-neat reactions to be combined with a highly concentrated "on water" effect.