Analysis of the mechanism for Rh-mediated C-H amination has led to the development of a remarkably effective dinuclear Rh catalyst derived from 1,3-benzenedipropionic acid. This unique complex, Rh2(esp)2, is capable of promoting both intra- and intermolecular C-H oxidation reactions, and in all cases is superior to Rh2(O2CtBu)4. For the first time, C-H insertion is described with urea and sulfamide substrates to give 1,2- and 1,3-diamine derivatives, respectively. In addition, intermolecular amination of benzylic and secondary C-H bonds is shown to proceed efficiently even under conditions in which the starting alkane is employed as the limiting reagent.

For more than a century, chemists have endeavored to discover and develop reaction processes that enable the selective oxidation of hydrocarbons. In the 1970s, Abramovitch and Yamada described the synthesis and electrophilic reactivity of sulfonyliminoiodinanes (RSO2N=IPh), demonstrating the utility of this new class of reagents to function as nitrene equivalents. Subsequent investigations by Breslow, Mansuy, and Müller would show such oxidants to be competent for alkene and saturated hydrocarbon functionalization when combined with transition metal salts or metal complexes, namely those of Mn, Fe, and Rh. Here, we trace our own studies to develop N-atom transfer technologies for C–H and π-bond oxidation. This Account discusses advances in both intra- and intermolecular amination processes mediated by dirhodium and diruthenium complexes, as well as the mechanistic foundations of catalyst reactivity and arrest. Explicit reference is given to questions that remain unanswered and to problem areas that are rich for discovery. A fundamental advance in amination technology has been the recognition that iminoiodinane oxidants can be generated in situ in the presence of a metal catalyst that elicits subsequent N-atom transfer. Under these conditions, both dirhodium and diruthenium lantern complexes function as competent catalysts for C–H bond oxidation with a range of nitrogen sources (e.g., carbamates, sulfamates, sulfamides, etc.), many of which will not form isolable iminoiodinane equivalents. Practical synthetic methods and applications thereof have evolved in parallel with inquiries into the operative reaction mechanism(s). For the intramolecular dirhodium-catalyzed process, the body of experimental and computational data is consistent with a concerted asynchronous C–H insertion pathway, analogous to the consensus mechanism for Rh-carbene transfer. Other studies reveal that the bridging tetracarboxylate ligand groups, which shroud the dirhodium core, are labile to exchange under standard reaction conditions. This information has led to the generation of chelating dicarboxylate dinuclear rhodium complexes, exemplified by Rh2(esp)2. The performance of this catalyst system is unmatched by other dirhodium complexes in both intra- and intermolecular C–H amination reactions. Tetra-bridged, mixed-valent diruthenium complexes function as effective promoters of sulfamate ester oxidative cyclization. These catalysts can be crafted with ligand sets other than carboxylates and are more resistant to oxidation than their dirhodium counterparts. A range of experimental and computational mechanistic data amassed with the tetra-2-oxypyridinate diruthenium chloride complex, [Ru2(hp)4Cl], has established the insertion event as a stepwise pathway involving a discrete radical intermediate. These data contrast dirhodium-catalyzed C–H amination and offer a cogent model for understanding the divergent chemoselectivity trends observed between the two catalyst types. This work constitutes an important step toward the ultimate goal of achiev...

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Reaction methodology for intermolecular C-H amination of benzylic and 3 degrees C-H bonds is described. This process uses the starting alkane as the limiting reagent, gives optically pure tetrasubstituted amines through stereospecific insertion into enantiomeric 3 degrees centers, displays high chemoselectivity for benzylic oxidation, and enables the facile preparation of isotopically enriched 15N-labeled compounds. Access to substituted amines, amino alcohols, and diamines is thereby made possible in a single transformation. Important information relevant to understanding the initial steps in the catalytic cycle, reaction chemoselectivity, the nature of the active oxidant, and pathways for catalyst inactivation has been gained through mechanistic analysis; these studies are also presented.

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