Controlled Fluoroalkylation Reactions by Visible-Light Photoredox Catalysis

SAr) to organic substances. In these studies, electron-deficient carbon-centered fluoroalkyl radicals were successfully generated by the appropriate choice of fluoroalkyl source, photocatalyst, additives, and solvent. The redox potentials of the photocatalysts and the fluoroalkyl sources and the choice of sacrificial electron donor or acceptor as the additive affected the photocatalytic pathway, determining whether an oxidative or reductive quenching pathway was operative for the generation of key fluoroalkyl radicals. Notably, we have observed that additives significantly affect the efficiencies and selectivities of these reactions and can even change the outcome of the reaction by playing additional roles during its course. For instance, a tertiary amine as an additive in the reaction medium can act not only as a sacrificial electron donor in photoredox catalysis but also as a hydrogen atom source, an elimination base for dehydrohalogenation of the intermediate, and also a Brønsted base for deprotonation. In the same context, the selection of solvent is also critical since it affects the rate and selectivity of reactions depending upon its polarity and reagent solubilizing ability and plays additional roles in the process, for example, as a hydrogen atom source. By clearly understanding the roles of additives and solvent, we designed several controlled fluoroalkylation reactions where different products were formed selectively from the same starting substrates. In addition, we could exploit one of the most important advantages of radical reactions, that is, the use of unactivated π-systems such as alkenes, alkynes, arenes, and heteroarenes as radical acceptors without prefunctionalization. Furthermore, fluoroalkylation processes under mild room-temperature reaction conditions tolerate various functional groups and are therefore easily applicable to late-stage modifications of highly functionalized advanced intermediates.