Hydrogen, oxidative nucleophilic substitution

The carbanion of 2,3-dimethylthiazolidine-4-one reacted with nitroarenes to give either a ting opened product (50) via a VNS (vicarious nucleophilic substitution) reaction or a product resulting from oxidative nucleophilic substitution of hydrogen (51). Ring opening VNS reactions with 5-membered 5-heterocycles are limited to those heterocycles which show some conformational flexibility <96TL983>. 

Another approach for oxidative nucleophilic substitution of hydrogen can be carried out with primary amines and CAN in aqueous MeCN (Eq. 9.45).77... 

There has been a short review of the oxidative nucleophilic substitution of hydrogen in nitroarenes in which recent results with carbon, nitrogen, and oxygen nucleophiles are summarized and the preferred oxidants are discussed.11 The oxidative substitution of nitroarenes with carbanions of isopropyl phenylacetate in liquid ammonia-KMn04 initially yields products (4) which may suffer hydroxylation at the o -position, and dimeric and trimeric products may be formed by couplings of nitrobenzylic radicals formed during the reaction.12... 

The oxidative nucleophilic substitution of hydrogen (ONSH) in 2-nitrobenzo[/ ]thiophene involves the initial reversible addition of the nucleophile to the 2,3-double bond. This is discussed in Section 3.10.4.2.1. 

Oxidative nucleophilic substitution of the hydrogen in nitroarenes with the carbanion of isopropyl phenylacetate using lb gives corresponding isopropyl hydroxyaryl(phenyl)acetates, which is not the case with Bu4N Mn04 or 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) oxidants <2005T11952>. 

Reaction of the carbanion derived from 1,3-dithiane 1,1-dioxide with aromatic nitro compounds results in oxidative nucleophilic substitution of hydrogen rather than SnAt displacement of even halogen (94T4913). 

Nitrobenzene and many of its 2-, 3-, and 4-substituted derivatives are converted into nitroaniline derivatives by treatment with sulfenamides in the presence of t-BuOK (eq 90). In this conversion, termed vicarious nucleophilic substitution (VNS), the base presumably promotes both the formation of the nucleophilic sulfenamide anion and the -elimination of the thiocar-bamoyl group from the other examples of t-BuOK-promoted VNS reactions of nitrobenzenes have appeared in recent years. An interesting example of this process involves the synthesis of dithianylated nitrobenzenes which are hydrolyzable to aldehydes (eq 91). The treatment of mixtures of m-nitroaniUne and enoUzable ketones with t-BuOK in DMSO leads to nitroindoles by oxidative nucleophilic substitution of hydrogen (eq 92). The proposed mechanism for this transformation involves attack of the potassium enolate of the ketone on the ring, spontaneous oxidation of the a-adduct, and imine formation and tautomerization. 

Here we intend to present a more detailed discussion of the three major ways of conversion of the adducts into the corresponding products of nucleophilic substitution of hydrogen in nitroarenes, particularly in electron-deficient heterocyclic systems, namely vicarious nucleophilic substitution (VNS), oxidative nucleophilic substitution (ONSET) and conversion into nitrosoarenes according to intramolecular redox stoichiometry. Our main goal is to show that these reactions offer wide possibilities for the synthesis and modifications of heterocycles. 

Since hydride anions are unable to depart spontaneously from the anionic adducts, they should be removed by external oxidants. However, possibilities for conversions of the adducts into products of oxidative nucleophilic substitution of hydrogen (ONSH) appear to be limited, since nucleophiles, and particularly carbanions, are usually sensitive to oxidation. Thus, ONSH can be feasible in two major cases ... 

Oxidative nucleophilic substitution of hydrogen in 2-chloro-3-nitropyridine by action of iV-Uthio-S, S -diphenylsulfilimines has been shown to be accompanied with the SnAt displacement of chloro atom (Scheme 55). Both of these products were oxidized with m-CPBA to form dinitropyridines [164, 165],... 

In this section, we will focus on two main approaches to the synthesis of condensed N-heterocycles based on nitroarenes using the Sn methodology vicarious nucleophilic substitution of hydrogen (VNS) and oxidative nucleophilic substitution of hydrogen (ONS). 

Another important type of the Sn processes is oxidative nucleophilic substitution of hydrogen (ONS). It suggests that aromatization of the intermediate o -adduct (Scheme 26) proceeds by action of an oxidative agent either an external one (e.g., KMnOa, CAN), or air oxygen, or one of components being present in the reaction mixture, for example, the starting nitro compoimd [5]. 

Scheme 26 Oxidative nucleophilic substitution of hydrogen (general scheme)...

Scheme 13 Vicarious and oxidative nucleophilic substitutions of hydrogen in nitroarenes with phosphorous-containing reagents...

Straightforward approach to benzo[ r]selenophenes in which 4-(3-nitroaryl)-1,2,3-selenadiazoles undergo a base-promoted transformation to an intermediate eneselenoate followed by 5-exo-trig cyclization. The regiochemistry of the cyclization is dependent upon the conditions of the reaction. In the presence of an oxidant, the adduct is formed rapidly by the oxidative nucleophilic substitution of hydrogen (ONSH, SnAt ) followed by oxidative aromatization of the rapidly formed adduct. In the absence of an oxidant, the reaction proceeds via intermediate formation of the adduct, followed by nucleophilic aromatic substitution of the halogen (SnAt ). 

SCHEME 8.19 Synthesis of (R)-4-nitroaryIprolines 87 by oxidative nucleophilic substitution of hydrogen... 

Hydride anions cannot depart spontaneously from the a -adducts thus, they should be removed by external agents-oxidants. Oxidation of the a -adducts by external oxidants seems to be the obvious way to products of oxidative nucleophilic substitution of hydrogen (ONSH). However, taking into account the reversibility of the formation of the a -adducts and susceptibility of majority of nucleophiles to oxidation, the ONSH is limited to three variants (i) nncleophiles are insensitive to the oxidants used, (ii) the equilibrium of the addition is shifted toward o -adducts, and (iii) the addition is an irreversible process ... 

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