Project Summary Enantioenriched amines are prevalent functional groups found in various bioactive compounds and pharmaceuticals. Current methods for accessing them come with limitations, such as poor atom-economy, poor selectivity, poor reactivity, or requirement for high-pressure gases. Transition metal catalyzed cross-coupling reactions represent a powerful approach towards accessing enantioenriched amine compounds, which could overcome some of the inherent issues with current state-of-the-art. However, the discovery of new asymmetric transition metal catalyzed processes often requires exhaustive ligand screening and search for an optimal set of conditions that enable satisfactory activity, chemoselectivity, and stereoselectivity. In some processes, the best metal catalysts employed are those without any added ligands or with ligands to which no chiral equivalents exist, presenting challenging scenarios for enantioinduction. This proposal outlines an alternative approach towards the development of new transition metal catalyzed methodology, utilizing hydrogen-bond donor (HBD) catalysis to activate C(sp3)–O bonds towards a Ni-catalyzed cross-coupling reaction. This dual catalytic platform is a conceptually unexplored approach towards cross-coupling chemistry, wherein the role of the HBD is to accelerate the oxidative addition while simultaneously imparting stereoselectivity to the step through ion pairing. These roles have traditionally been assigned to ligand properties as the driver of reaction development, however this proposed research will demonstrate the feasibility of leveraging both catalytic modes to cooperatively engage mild electrophiles in an enantioconvergent C(sp3)–C(sp2) cross-coupling to generate amine compounds. Suzuki- Miyaura and Mizoroki-Heck type couplings of readily-accessible hemiaminal substrates will be explored by leveraging HBD-mediated substrate ionization for the generation of iminium ions. HBDs have been demonstrated to be effective catalysts for the generation of iminium ions, and their subsequent engagement in enantioselective trapping by standard nucleophiles. Unlike these traditional reaction profiles, the trapping of iminium ions by a metal is proposed here. Interestingly, various stereoselective Ni-catalyzed couplings of C(sp3)–O bonds have been reported to perform the best under “ligandless” conditions or with olefinic ligands that are not easily converted to chiral equivalents, thus highlighting the strategy of this approach. Successful execution of this proposal will reveal a new method for accessing enantioenriched amines and establish a proof-of-concept for the synergistic cooperation of HBD-catalysis with transition metal catalysis.