Bidirectional Electron Transfer Strategies for Anti-Markovnikov Olefin Aminofunctionalization via Arylamine Radicals.

Arylamines are common structural motifs in pharmaceuticals, natural products, and materials precursors. While olefin aminofunctionalization chemistry can provide entry to arylamines, classical polar reactions typically afford Markovnikov products. Nitrogen-centered radical intermediates provide the opportunity to access anti-Markovnikov selectivity; however, anti-Markovnikov arylamination is unknown in large part due to the lack of arylamine radical precursors.

Synthesis of Secondary Amines via Self-Limiting Alkylation.

-centered nucleophilicity increases upon alkylation, and thus selective partial alkylation of ammonia and primary amines can be challenging: Poor selectivity and overalkylation are often observed. Here we introduce -aminopyridinium salts as ammonia surrogates for the synthesis of secondary amines via self-limiting alkylation chemistry. Readily available -aryl--aminopyridinium salts engage in -alkylation and depyridylation to afford secondary aryl-alkyl amines without any overalkylation products.

-Amino Pyridinium Salts in Organic Synthesis.

C-N bond forming reactions hold immense significance to synthetic organic chemistry. In pursuit of efficient methods for the introduction of nitrogen in organic small molecules, myriad synthetic methods have been developed, and methods based on both nucleophilic and electrophilic aminating reagents have received sustained research effort. In response to continued challenges - the need for substrate prefunctionalization, the requirement for vestigial -activating groups, and the need to incorporate nitrogen in ever more complex molecular settings - the development of novel aminating reagents remains a central challenge in method development.

N-Aminopyridinium reagents as traceless activating groups in the synthesis of N-Aryl aziridines.

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.

Traceless Benzylic C-H Amination via Bifunctional N-Aminopyridinium Intermediates.

C-H amination reactions provide the opportunity to streamline the synthesis of nitrogen-containing organic small molecules. The impact of intermolecular C-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 C-H amination-which enables application of selective C-H amination chemistry to the preparation of diverse N-functionalized products-via sequential benzylic C-H N-aminopyridylation followed by Ni-catalyzed C-N cross-coupling with aryl boronic acids.

Diversification of Amidyl Radical Intermediates Derived from C-H Aminopyridylation.

The -activating substituents typically encountered in C-H amination chemistry are challenging to remove and have limited scope for synthetic elaboration. Here, we demonstrate that -benzylaminopyridinium species provide a platform for synthetic elaboration via reductive N-N bond activation to unveil electrophilic -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.