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.

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.

C–H amination chemistry promises to streamline access to nitrogen-containing fine chemicals. The typical need for N-activating substituents — such of N-sulfonyl groups, which are challenging to remove and difficult to engage in synthetic elaboration — limits synthetic utility. Here, we demonstrate that N-benzylaminopyridinium species, generated by C–H aminopyridylation, 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, which are important heterocycles in molecular therapeutics, or via aza-Rubottom chemistry with silyl enol ethers to provide alpha-amino ketones. This approach broadens the synthetic utility of N-alkylaminopyridinium intermediates and demonstrates a new approach to C–H amination with synthetically addressable, bifunctional reagents.