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Electrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications

CHALLENGES IN C−N CROSS-COUPLING REACTIONS

This case study was reported in Electrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications | Journal of the American Chemical Society (acs.org) (M. Neurock, S. D. Minteer, P. S. Baran et al., J. Am. Chem. Soc. 2019, 141, 6392).

C−N cross-coupling is largely dominated by Pd- and Cu-based catalytic systems, but there is still documented and anecdotal evidence that several classes of amines or aryl halides remain particularly challenging substrates for C−N cross-coupling.

LIMITATIONS OF ORIGINAL CATALYTIC CONDITIONS

Critical assessment of the original conditions revealed that aryl halide coupling partners were largely limited to electron-poor derivatives and attempts with historically challenging heteroaryl halides were deemed unsatisfactory. Additionally, the choice of amine was restricted to primary and secondary alkyl substrates; functionalized amines, including amino acids and oligopeptides, did not perform well.

ROLE OF MULTIPLE NI-OXIDATION STATES IN ELECTROCHEMISTRY

It was speculated the success of this transformation relies on the curious coexistence of multiple different Ni-oxidation states in the same reaction vessel, a task perfectly suited to electrochemistry. In this Article, a detailed reaction profile for e-amination is delineated, enabled by the strategic union of nuanced electrochemical analysis, DFT calculations, and empirical optimization. This collaborative endeavor facilitated the development of a robust, well-defined, catalytic system resulting in a greatly expanded substrate scope.