Synthesis of α-(Nitroaryl)benzylphosphonates via Oxidative Nucleophilic Substitution of Hydrogen in Nitroarenes

Abstract

Carbanions of diethyl benzylphosphonate and diethyl 1-phenylethylphosphonate add to nitroarenes to form relatively long-lived sigma(H) adducts that can be oxidized to products of oxidative nucleophilic substitution of hydrogen. By variation of the conditions, o- and p-nitroarylated derivatives of the starting phosphonates can be synthesized regioselectively. It has been proven that addition of carbanions of diethyl benzylphosphonate and diethyl 1-phenylethylphosphonate to nitroarenes is a fast process and the respective sigma(H) adducts are formed almost quantitatively.

Nucleophilic substitution in nitroarenes: a general corrected mechanism

“…The produced σ H adducts can be efficiently oxidized by a variety of oxidants. Even in 2,4-dinitrofluorobenzene, the Sanger reagent in which S N Ar of fluorine is a very fast process, ONSH with carbanions proceeds faster than the replacement of fluorine (Scheme 10) [23].…”

Reactions of Nucleophiles with Nitroarenes: Multifacial and Versatile Electrophiles

“…This occurs when the carbanions are sufficiently nucleophilic and the reaction is carried out at low temperature, when, owing to the entropy factor, dissociation of the σ H adducts is disfavored. Sterically demanding tertiary carbanions add at the para position9 whereas secondary (methylenic) carbanions add at the both para and ortho positions 10. When the para position is occupied, even by a fluorine atom, the addition occurs at a position ortho to the nitro group 10.…”

“…Sterically demanding tertiary carbanions add at the para position9 whereas secondary (methylenic) carbanions add at the both para and ortho positions 10. When the para position is occupied, even by a fluorine atom, the addition occurs at a position ortho to the nitro group 10. The σ H adducts of carbanions can be oxidized either by KMnO 4 in liquid ammonia or by DDQ in THF/DMF to form products of ONSH.…”

Electrochemical Synthesis of Organophosphorus Compounds through Nucleophilic Aromatic Substitution: Mechanistic Investigations and Synthetic Scope

“…However, the nucleophilic aromatic substitution reaction of hydrogen (NASH process) or heteroatom (NASX process) with nucleophiles containing phosphorus, either chemically or electrochemically, is, as far as we are aware, limited to a very small number of mechanistic kinetic [15,18] and synthetic studies. [19][20][21][22] In this regard, in order to obtain esters of substituted phosphonic acids, which are used in many chemical and medical applications (for instance, as an agent in the treatment of osteoporosis), [19] the vicarious nucleophilic aromatic substitution approach is used (Scheme 2). [20][21] In these NASH reactions, a C-C bond is created instead of a C-P one when dialkylbenzyl phosphonates are used as nucleophiles in the presence of external bases and at low temperatures.…”

“…The σ H complex, formed by addition of the carbanion of the benzyl phosphonates to nitroarene, can evolve into the final product with use of a second equivalent of base to promote the β-elimination of HX (vicarious nucleophilic substitution, VNS, Scheme 2A) [21] or by using chemical oxidants, such as potassium permanganate (oxidative nucleophilic substitution of hydrogen, ONSH, Scheme 2B). [22] Scheme 2.…”