Non-Innocent Electrophiles Unlock Exogenous Base-Free Coupling Reactions

Transition metal catalysis has revolutionized our ability to precisely manipulate matter and has placed itself at the forefront of the combat against societal challenges through key discoveries in drug design, agriculture, material synthesis and environmental sciences. Numerous important transition metal catalyzed reactions rely on stoichiometric quantities of an exogenous base to enable catalytic turnover. Despite playing a fundamental role, paradoxically, the base poses major challenges on several fronts, such as restricting the accessible chemical space due to functional group incompatibilities, or causing heterogeneous reaction mixtures that affect reproducibility, scale-up campaigns, and the implementation of emerging technologies, e.g. flow chemistry or high-throughput experimentation. Ultimately, this impedes innovation across multiple areas. Here we introduce a unifying strategy that eliminates the need for an exogenous base through the use of non-innocent electrophiles (NIE). Key to its success was the encryption of the base into the electrophile rendering it non-innocent, thus preserving the synthetic utility of the original reaction while overcoming the challenges associated with the exogenous base. The use of nickel as an earth-abundant metal catalyst as well as the employment of ubiquitous phenol derivatives as non-innocent electrophiles are further salient features of this sustainable protocol. The universal applicability of this concept was demonstrated by turning multiple traditionally base-dependent catalytic reactions, e.g. the Buchwald-Hartwig amination, the Mizoroki-Heck reaction and the Suzuki-Miyaura coupling, into exogenous base-free homogeneous processes. In a broader context, the results presented in this work provide a conceptual blueprint for the utilization of non-innocent electrophiles to overcome core limitations and unlock novel features in catalysis.