And nucleophilic aromatic substitution

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

Cycloamidation has been used extensively to prepare 17-membered cycloisodityrosines. The acyclic biaryl ether precursors were prepared by methods including the Ullmann reaction 2-5 and nucleophilic aromatic substitution (SNAr)J6 7 Since these methods have all been used intramolecularly in cyclization reactions, they will be discussed in Sections 9.5.3 and 9.5.4. Evans and co-workers employed the pentafluorophenyl ester method of macrolactamization 8] to prepare 11, an intermediate in their total synthesis of OF4949-III (7) (Scheme 2)J3 In this case, the acidic removal of a Boc group was employed to release the cyclization substrate, although hydrogenolysis of a Z group is also effective 3 ... 

However, the formation of molecular complexes between nucleophile and electrophile (with a possible participation of solvents) in both electrophilic aromatic substitutions and nucleophilic aromatic substitutions is clearly expected, as shown by the conventional use of the terms electrophile and nucleophile these reactions belong to apparently different fields of organic chemistry, but the unification of the two kinds of reaction is mainly a matter of terminology and of details. 

One solution for this problem, the most optimistic, suggested the existence of three independent sets of o--constants. The first set, the Hammett constants, would be applicable to side-chain reactions in which resonance interactions between the substituent and the side-chain were either small or insignificant. The second set, the w-constants, would apply to side-chain reactions of phenols and anilines and nucleophilic aromatic substitution reactions in which a negative charge was introduced in the aromatic nucleus (Miller, 1956). A third set, the c7+-constants, would apply to electrophilic substitution and electrophilic side-chain reactions for which resonance interactions between the reaction site and the substituent were important. 

Substituted 1,2,3-triazole 1-oxides 448 have been reported to undergo electrophilic and nucleophilic aromatic substitution and are subject to debromination, proton-metal exchange, and halogen-metal exchange followed by electrophilic addition. Transmetallation and cross-coupling have not been described. 3-Substituted 1,2,3-triazole 1-oxides 448 can be proton-ated or alkylated at the O-atom and they can be deoxygenated and deal-kylated. The individual reactions are described in Section 4.2.7.1-4.2.7.14. 

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