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... 

Nitro sugars are mainly prepared by oxidation, nucleophilic substitution and aldol- or Michael-type condensations. 

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... 

Electrooxidative activation is just one of the tools with which synthetic organic chemists can effect the dearomatization of arenois and their ethers to give cyclohexa-2,4-dienone derivatives. Other methods are based on the utilization of oxidizing reagents that mediate the oxidative nucleophilic substitution of 2-substituted arenois in the presence of appropriate nucleophilic species. These reagents are for the most part all based on metals (Section 15.2.2) or halogens (Section 15.2.3). 

Oxidative nucleophilic substitution is, however, a more versatile technique and a much better choice for target-oriented synthesis (Sections 15.1.1 and 15.1.2.2). In 1950, Wessely and co-workers examined the use of lead tetraacetate (LTA) in acetic acid to determine the structure of phenols and, in doing so, they developed their oxidative acetoxylation reaction, referred to herein as Wessely oxidation (Figure 13) [68-76]. If both an ortho- and a para-position are available to accommodate the entry of the acetoxy nucleophile, ortho products often predominate even when the ortho position is already occupied by a resident alkyl (e.g. 40 —> 41a/b) or allcoxy group (Figure 13) [69, 74]. 

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. 

In contrast, reaction of 2-nitrobenzo[. ]thiophene with -butylamine under the same conditions did not lead to any ring-opened product. Instead, the substrate underwent an oxidative nucleophilic substitution reaction. 

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>. 

After removal of the protecting group (PG) from 134, the system was amenable to the oxidation/nucleophilic substitution process. Since this hnker represents a reversal of the original phenylhydrazide hnker, the traceless part stayed on the sohd support and the desired compound 135 was released. The utility of the linker was demonstrated in the synthesis of mono-ketopiperazines resulting from a cyclative cleavage. 

A range of novel solid catalysts based on chemically modified materials has been prepared and developed for use in important liquid phase reactions including selective oxidations, nucleophilic substitutions and Knoevenagel reactions. 

Chemical surface modification techniques provide effective routes to mesoporous solid catalysts which are active in various liquid phase organic reactions including selective oxidations, nucleophilic substitutions, and oevenagel reactions. 

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. 

This is a synthetically valuable process, as illustrated by the hypervalent iodine-mediated oxidative nucleophilic substitution of 269 with the silyl enol ether 271, leading to the highly functionalized naphthoid cyclohexa-2,4-dienone 272 (Scheme 3.113), which is an important intermediate product in the synthesis of aquayamycin-type angucyclinones [343,344],... 

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],... 

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