Catalytic Asymmetric Addition and Substitution Reactions with Grignard Reagents: Do We Know It All?

Catalysis has been a cornerstone in organic synthesis, enabling a variety of highly efficient and selective C−C bond formation reactions, in particular enantioselective addition and substitution of Grignard reagents. Throughout time, we have gained significant understanding into how various factors, such as the influence of the metal source, the nature of the ligands, the substrates or temperature, affect these processes. Recent advances in computational chemistry have further enriched our understanding of this chemistry by elucidating the potential reaction mechanism and providing insight into the rate and enantio‐determining steps in these catalytic transformations. However, challenges persist, and aspects such as ligand optimisation, full mechanistic understanding and scalability remain underexplored. Computational methods, however, present a remarkable potential to surmount these enduring challenges.