Introduction of Carbon Substituents into Nitroarenes via Nucleophilic Substitution of Hydrogen: New Developments

Abstract

Nucleophilic substitution of hydrogen in nitroarenes has become a powerful synthetic tool for functionalization of these important organic substrates, complementary to other modern methods. In this review we present new developments in the area of introduction of alkyl and functionalized alkyl substituents into nitroarene rings via nucleo­philic substitution of hydrogen, followed by application of these processes in the construction of carbo- and heterocyclic rings. Finally, new developments in the investigation of the mechanism of SNArH are summarized.1 Introduction2 Alkylation and Haloalkylation3 Functionalized Carbon Substituents4 Formation of Carbo- and Heterocyclic Rings5 Mechanistic Aspects of SNArH6 Conclusion

Alkylation of Nitropyridines via Vicarious Nucleophilic Substitution

“… 9 Two general routes to transform such adducts into the desired substitution products were developed: oxidative rearomatization 10 and vicarious nucleophilic substitution (VNS), where the nucleophile possesses a leaving group (e.g., halogen; Scheme 1 , top). 11 …”

“…When in electrophilic variant the rearomatization step usually runs spontaneously, attack of nucleophile on nitroarene at the position occupied by hydrogen gives Meisenheimer-type adduct . Two general routes to transform such adducts into the desired substitution products were developed: oxidative rearomatization and vicarious nucleophilic substitution (VNS), where the nucleophile possesses a leaving group (e.g., halogen; Scheme , top) …”

Direct Synthesis of Unprotected Indolines Through Intramolecular sp3 C−H Amination Using Nitroarenes as Aryl Nitrene Precursors

“…Nitroarenes are among the most ubiquitous feedstocks in organic synthesis. [1][2][3] They can be easily accessed by nitration of arenes and heteroarenes, [4][5][6][7] and further functionalized using a plethora of methods such as vicarious nucleophilic substitution, [8][9][10] nucleophilic aromatic substitution, [11,12] crosscoupling reactions, [13][14][15][16][17] among others. Nitroarenes serve as key building blocks and versatile intermediates in synthetic chemistry and are precursors to a range of other academically and industrially relevant molecules, namely anilines, [18][19][20][21] aryl azides, [22][23][24] and aryl diazonium salts (Scheme 1a).…”

Analogy of the Reactions of Aromatic and Aliphatic π-Electrophiles with Nucleophiles

“…These σ adducts tend to recover aromaticity via dissociation or fast further transformations, thus the number of different final reactions appears to be limited. However, recent literature reports indicate that adducts of nucleophiles to aromatic electrophiles can enter a variety of reactions, and thus they display reactivity identical to their aliphatic counterparts [ 1 , 2 , 3 ].…”