PROJECT SUMMARY/ABSTRACT Synthetic organic chemistry is essential for the preparation of complex small molecules used as drugs and agrochemicals, and advances in this field are driven by the discovery of new types of bond-forming chemical reactions. Research in reaction development allows wider pools of starting materials to be used for the construction of complex molecular architectures, and new fragment-coupling reactions which use widely available, bench stable, and biologically prevalent organic functional groups as reactive handles are highly impactful. Catalytic reactions that use such “native” functional groups, such as alcohols, carboxylic acids, and amines, can be immediately and widely deployed in medicinal chemistry settings for both small-scale drug discovery and in large-scale process development settings because of their greater opportunities for molecular diversification and the lower cost of the associated starting materials. In the proposed research, a new reactivity manifold for amines will be developed that will enable their use as electrophilic alkylating reagents in C-C bond forming reactions with ammonia as the sole byproduct. This contrasts with their traditional reactivity profile, which is limited to their use as nucleophiles in C-N bond forming reactions. A dual-catalysis approach is proposed which will use a strongly reducing photoredox catalyst to transfer a single electron to an alkylammonium cation to form an unstable, neutral ammonium radical. Typically, such hypervalent radicals decompose through loss of hydrogen atoms through N-H bond homolysis to generate hydrogen gas after self- annihilation. However, it is proposed that multiple hydrogen bonding interactions between an alkylammonium cation and a crown ether-type organocatalyst can be exploited to stabilize ammonia as a leaving group and bias the reaction pathway towards C-N bond homolysis, releasing a synthetically useful alkyl radical and ammonia. The alkyl radical thus generated will then be captured by organic and inorganic radicalphiles in C-C bond forming reactions proceeding through conjugate addition, radical aromatic substitution, and transition- metal cocatalyzed cross-coupling pathways. The intermediacy of a free alkyl radical makes this methodology highly modular, and it is anticipated that a wide variety of photoredox C-C coupling methodologies can be developed which will merge reductive C-N activation with oxidative C-CO2-, C-OH, and C-H activation.