Project Summary/Abstract The abundance of C(sp3)–H bonds in organic molecules and building blocks, makes the direct functionalization of these structures a very attractive and powerful tool for the synthesis and late-stage functionalization of pharmaceuticals. Unfortunately, current methods to achieve these transformations use metal-catalysts and reagents that do not meet requirements for sustainable development. Similarly, alkyl halides are among the largest groups of commercially available building blocks used in organic chemistry, but bulky tertiary alkyl halides cannot be easily used as alkylating agents because they cannot undergo SN2 processes. Therefore, the development of strategies that are transition-metal-free and orthogonal to current approaches to activate C–H and C–X bonds would be a significant contribution as it addresses an unmet need. Recently, the application of electron-donor-acceptor (EDA) complexes has gained attention as a photo-induced method to perform single electron transfers between otherwise unreactive reagents. Unfortunately, current reactions that proceed via EDA complexes do not take advantage of the formed radicals to perform hydrogen- atom-transfer (HAT) and halogen-atom-transfer (XAT) processes that could enable the use of the abundant chemical feedstock mentioned above. The research objectives of the proposed investigations promise to tackle the above-cited barriers to help establish EDA complexes as a cutting-edge strategy for the photo-induced radical-activation of alkanes and alkyl halides. Our conceptually innovative hypothesis is that sterically and electronically tuned aryl radicals generated from EDA complexes can be used to achieve site-selective HAT and XAT processes. The resulting alkyl radicals generated are then coupled to achieve enantio- and diastereoselective cross-couplings. This work will use computational models to support, guide, and accelerate the design and discovery of EDA complexes of arenes. These explorations will establish new platforms that enable enantio- and regioselective cross-dehydrogenative couplings, and XAT mediated couplings that form challenging C(sp3)–C(sp3) bonds.