CÀ H amination reactions provide the opportunity to streamline the synthesis of nitrogen-containing organic small molecules. The impact of intermolecular CÀ H amination methods, however, is currently limited the frequent requirement for the amine precursors to bear activating groups, such as N-sulfonyl substituents, that are both challenging to remove and not useful synthetic handles for subsequent derivatization. Here, we introduce traceless nitrogen activation for CÀ H amination-which enables application of selective CÀ H amination chemistry to the preparation of diverse Nfunctionalized products-via sequential benzylic CÀ H N-aminopyridylation followed by Ni-catalyzed CÀ N cross-coupling with aryl boronic acids. Unlike many CÀ H amination reactions that provide access to protected amines, the current method installs an easily diversifiable synthetic handle that serves as a lynchpin for CÀ H amination, deaminative NÀ N functionalization sequences.

N-functionalized aziridines, which are both useful intermediates and important synthetic targets, can be envisioned as arising from the addition of nitrenes (i.e., NR fragments) to olefinic substrates. The exceptional reactivity of most nitrenes, in particular with respect to unimolecular decomposition, prevents general application of nitrene-transfer to the synthesis of N-functionalized aziridines. Here we demonstrate N-aryl aziridine synthesis via 1) olefin aziridination with N-aminopyridinium reagents to afford N-pyridinium aziridines followed by 2) Ni-catalyzed C–N cross-coupling of the N-pyridinium aziridines with aryl boronic acids. The N-pyridinium aziridine intermediates also participate in ring-opening chemistry with a variety of nucleophiles to afford 1,2-aminofunctionalization products. Mechanistic investigations indicate aziridine cross-coupling proceeds via a noncanonical mechanism involving initial aziridine opening promoted by the bromide counterion of the Ni catalyst, C–N cross-coupling, and finally aziridine reclosure. Together, these results provide new opportunities to achieve selective incorporation of generic aryl nitrene equivalents in organic molecules.

The N-activating substituents typically encountered in C−H amination chemistry are challenging to remove and have limited scope for synthetic elaboration. Here, we demonstrate that N-benzylaminopyridinium species provide a platform for synthetic elaboration via reductive N−N bond activation to unveil electrophilic N-centered radicals. These reactive intermediates can be trapped either via anti-Markovnikov olefin carboamination to provide access to tetrahydroisoquinolines or via aza-Rubottom chemistry with silyl enol ethers to provide α-amino ketones.Letter pubs.acs.org/OrgLett

CÀ H amination reactions provide the opportunity to streamline the synthesis of nitrogen-containing organic small molecules. The impact of intermolecular CÀ H amination methods, however, is currently limited the frequent requirement for the amine precursors to bear activating groups, such as N-sulfonyl substituents, that are both challenging to remove and not useful synthetic handles for subsequent derivatization. Here, we introduce traceless nitrogen activation for CÀ H amination-which enables application of selective CÀ H amination chemistry to the preparation of diverse Nfunctionalized products-via sequential benzylic CÀ H N-aminopyridylation followed by Ni-catalyzed CÀ N cross-coupling with aryl boronic acids. Unlike many CÀ H amination reactions that provide access to protected amines, the current method installs an easily diversifiable synthetic handle that serves as a lynchpin for CÀ H amination, deaminative NÀ N functionalization sequences.

This review summarizes the synthesis and reactivity of N-aminopyridinium salts, discusses applications in organic synthesis, and highlights the potential for these reagents to enable novel synthetic disconnections and innovations.