Halogen and Chalcogen Activation by Nucleophilic Catalysis

The high utility of halogenated organic compounds has prompted the development of numerous transformations that install the carbon-halogen motif. Halogen functionalities, deemed as "functional and functionalizable" molecules due to their capacity to modulate diverse internal properties, constitute a pivotal strategy in drug discovery and development. Traditional routes to these building blocks have commonly involved multiple steps, harsh reaction conditions, and the use of stoichiometric and/or toxic reagents. With the emergence of solid halogen carriers such as N-halosuccinimides, and halohydantoins as popular sources of halonium ions, the past decade has witnessed enormous growth in the development of new catalytic strategies for halofunctionalization. This review aims to provide a nuanced perspective on nucleophilic activators and their roles in halogen activation. It will highlight critical discoveries in effecting racemic and asymmetric variants of these reactions, driven by the development of new catalysts, activation modes, and improved understanding of chemical reactivity and reaction kinetics.