Electrophilic and Nucleophilic Aromatic Substitutions are Mechanistically Similar with Opposite Polarity

Abstract

Confrontation of the recently formulated general mechanism of nucleophilic substitution in electron-deficient arenes with the well-known mechanism of electrophilics ubstitution revealed that these fundamental processes are mechanistically identicalb ut proceed according to opposite polarity-anU mpolung relation. In this viewpoint this apparently controversial concept is supported by discussion of a variety of experimental results.

Alkylation of Nitropyridines via Vicarious Nucleophilic Substitution

“… 7 Accordingly, a key difference between electrophilic and nucleophilic aromatic substitution of hydrogen arises from different departure abilities of proton and hydride anion from the initially formed cationic and anionic σ adducts, respectively. 8 When in electrophilic variant the rearomatization step usually runs spontaneously, 4 attack of nucleophile on nitroarene at the position occupied by hydrogen gives Meisenheimer-type adduct. 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).…”

Reactions of Nitroarenes with Corey–Chaykovsky Reagents

“…2 However, almost the same time has gone since first exploration of nucleophilic transformations of electron-deficient arenes, with the milestones of nucleophilic aromatic substitution (SNAr), and Meisenheimer complex isolation. 3 Despite opposite electron demands of the aromatic substrates, 4 both types of the processes run in a parallel fashion, 5 with common two-step mechanisms, and invariable preference toward attack at the positions occupied by hydrogen atoms. 6 Importantly, main difference and challenge of nucleophilic chemistry arises from poor leaving group ability of hydride anion, which (in contrast to labile proton in electrophilic variant) is usually unable to depart, to give C-H functionalization products (Scheme 1).…”

Does Nucleophilic Substitution in Nitroarenes Proceed via Single Electron Transfer (SET)?

“…[10] Investigation of reactions of substitution of hydrogen and competition between substitution of hydrogen and halogens resulted in formulation of a general, corrected mechanism of nucleophilic substitution in nitroarenes [11] and in recognition of similarity between polar electrophilic and nucleophilic substitutions in arenes. [12] Nitroarenes are active electron acceptors and nucleophiles, particularly carbanions are electron donors, thus spontaneous SET between these species can readily take place. Indeed exposure of nitroarenes to carbanions and some other nucleophiles often generates nitroaromatic anion radicals detected by ESR (electron-spin resonance) spectroscopy.…”