We previously reported the development of an electron-deficient olefin (EDO) ligand, Fro-DO, that promotes the generation of quaternary carbon centers via Ni-catalyzed Csp³-Csp³ cross-coupling with aziridines. By contrast, electronically and structurally similar EDO ligands such as dimethyl fumarate and electron-deficient styrenes afford primarily β-hydride elimination side reactivity. Only a few catalyst systems have been identified that promote the formation of quaternary carbons via Ni-catalyzed Csp³-Csp³ cross-coupling. Although Fro-DO represents a promising ligand in this regard, the basis for its superior performance is not well understood. Here we describe a detailed mechanistic study of the aziridine cross-coupling reaction and the role of EDO ligands in facilitating Csp³-Csp³ bond formation. This analysis reveals that cross-coupling proceeds by a Ni^0/II cycle with a Ni^II azametallacyclobutane catalyst resting state. Turnover-limiting C-C reductive elimination occurs from a spectroscopically observable Ni^II-dialkyl intermediate bound to the EDO. Computational analysis shows that Fro-DO accelerates turnover limiting reductive elimination via LUMO lowering. However, it is no more effective than dimethyl fumarate at reducing the barrier to Csp³-Csp³ reductive elimination. Instead, Fro-DO's unique reactivity arises from its ability to associate favorably to Ni^II intermediates. Natural bond order second-order perturbation theory analysis of the catalytically relevant Ni^II intermediate indicates that Fro-DO binds to Ni^II through an additional stabilizing donor-acceptor interaction between its sulfonyl group and Ni^II. Design of new ligands to evaluate this proposal supports this model and has led to the development of a new and tunable ligand framework.

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