Emerging ground-state and photoexcited-state reactivity of the nitro group

In 1979, Dieter Seebach coined the phrase "nitroalkanes as ideal intermediates in organic synthesis"; subsequently, he commented on their "chameleon-like" switchable chemical properties. Similarly, depending on their distinct electronic nature and coordination ability, nitroarenes exhibit diverse ground-state reactivity. This ranges from decarboxylative cross-couplings and denitrative couplings to meta- vs. ortho-C-H functionalizations, reductive C-N couplings, traditional activated aromatic nucleophilic substitution (S_NAr) reactions, acyl anion equivalent chemistry, and Smiles rearrangements. The selective reduction of nitroarenes to the corresponding reactive nitrosoarenes in situ, followed by radical couplings, has emerged as a promising research field. More recently, the photoexcitation of nitroarenes is being reinvestigated to explore diverse reactivities under mild conditions, such as metal-free, reductive C-N coupling with boronic acids via a 1,2-boronate shift triggering the n → π* transition. Alternatively, the π → π* transition of relatively electron-rich nitroarenes evokes photosensitizer properties for photochemical transformation. Using these two distinct electronic transition modules, a diverse array of transformations is being rapidly explored, ranging from directed ortho-functionalization via intramolecular oxygen transfer and oxidative cleavage of unsaturated bonds via intermolecular oxygen transfer to molecular editing via dearomative nitrene insertion. Remarkably, novel chemical space, such as azepine, azepane, pyrroline, pyridine and other heterocycles, can be achieved for medicinal chemistry and drug discovery. Furthermore, the multimodal reactivity of nitroarenes is being explored for protein profiling, bioconjugation and chemical biology applications. In this review, we present the strategic use, conceptual development, critical analysis and synthetic applications of aromatic and aliphatic nitro groups in diverse fields.