Mechanochemical synthesis avoids the use of potentially harmful organic solvents, thus providing an attractive and environmentally friendly alternative to solution-based synthesis. Mechanochemical cross-coupling reactions enable cleaner and more sustainable access to a wide range of valuable
synthetic targets in organic materials and modern drug discovery.
In recent years, solvent-less mechanochemical organic transformations using ball milling have come to the forefront of organic synthesis as cleaner and sustainable synthetic alternatives. Apart from the environmental benefits, mechanochemical approaches potentially enable access to novel chemical space that has reactivities and selectivities different from those of conventional solution-based reactions. In this review, we highlight important recent contributions to crosscoupling chemistry using ball milling, with particular emphasis on new synthetic strategies and concepts based on mechanochemical reaction environments that enable the rapid and selective construction of complex molecules.
Unlike conventional solution-based
synthesis, unique reaction parameters such as milling frequency, jar and ball materials, and grinding additives greatly affect the efficiency of cross-coupling reactions. Unprecedented reactivity and selectivity. have been discovered in mechanochemical cross-coupling reactions, suggesting
that mechanochemistry enables access to novel chemical space that is unavailable under solution conditions.