N-nitrosuccinimide: a powerful reagent for the installation of nitro group Subrata Patra and Dmitry Katayev University of Bern, Switzerland Nitro-containing compounds are privileged building blocks and key intermediates in the preparation of various pharmaceuticals, drugs, and materials. Nitro group is also a valuable functionality in organic synthesis and serves as a precursor to amines, aldehydes, carboxylic acids, and many other functionalities. However, methods for direct nitration of organic molecules mostly rely on the formation of nitronium (NO 2 + ) ion in highly caustic nitric acid mixtures, which causes many limitations on the practical use. 1 Unsaturated hydrocarbons are readily available chemical feedstock and their consumption via efficient nitration would represent a valuable entry in synthetic chemistry. However, electrophilic approaches were found to be inefficient, leading to the formation of various by-products via polynitration and oxidation processes. Therefore, olefin nitration in chemo- and diastereoselective fashion, while tolerating acid-sensitive groups, remains a main challenge for synthetic chemists. We herein report a visible light-mediated slow liberation of nitryl radicals (•NO 2 ) from a bench stable, inexpensive N -nitrosuccinimide reagent allowing highly selective nitrative difunctionalization of unsaturated compounds via photochemical-mediated net-neutral radical/polar crossover (RPC) process. This reagent provides access to β-nitro cyclopentanones via semipinacol rearrangement, an eco-friendly route to construct all-carbon quaternary stereocenters. Alkenes in the presence of nucleophiles such as water, alcohols, amines, and acids, yield the corresponding 1,2-disubstituted products. In addition, radical nitration makes it possible to synthesize nitro- derived lactams/lactones in good to excellent yields by an intramolecular reaction. Of note, the presence of halogen source in the reaction mixture leads to vicinal 1,2-halonitro compounds, which can be further converted into vital small building blocks. Furthermore, hydrogen atom transfer (HAT) prior to oxidative RPC generates nitroalkanes, and transition metal-mediated radical ligand transfer produces structurally important carbonitration products. Due to the mildness and robustness of this methodology, a large variety of functional groups are well tolerated using standard reaction conditions. Detailed mechanistic studies strongly suggested that a mesolytic N−N bond fragmentation originates liberation of a nitryl radical in a controllable fashion. 2, 3, 4 The practicability of this strategy is demonstrated in late-stage functionalization of complex structures and biorelevant molecules.
References 1. S. Patra, I. Mosiagin, R. Giri, D. Katayev, Synthesis 2022 , DOI: 10.1055/s-0040-1719905. 2. K. Zhang, B. Jelier, A. Passera, G. Jeschke, D. Katayev, Chem. Eur. J. 2019 , 25 , 12929‒12939. 3. R. Giri, S. Patra, D. Katayev, ChemCatChem , 2023 , e202201427. 4. S. Patra, R. Giri, D. Katayev, in preparation , 2023 .
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