Reactions of Ring Atoms with Electrophiles

Bromine adds across the C=C double bond of the N,N -dioxide 96 to give a mixture of diastereomers of a dibromo derivative 170,119,134 whereas nitrosyl chloride reacts with the 4-bromo analog of 96 forming mixed diastereomers of the nitrochloro derivative 171.134 

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B. Reactions of Ring Atoms with Electrophiles 1. Salt Formation... 

Exactly the same sort of mechanism accounts for the reactions of aryl silanes with electrophiles under Friedel-Crafts conditions. Instead of the usual rules governing ortho, meta, and para substitution using the directing effects of the substituents, there is just one rule the silyl group is replaced by the electrophile at the same atom on the ring—this is known as ipso substitution. Actually, this selectivity comes from the same principles as those used for ordinary aromatic substitution (Chapter 22) the electrophile reacts to produce the most stable cation—in this case (3 to silicon. Cleavage of the weakened C-Si bond by any nucleophile leads directly to the ipso product. 

Reactions at ring atoms consist mainly of electrophilic attack at nitrogen and cycloadditions. Examples of the reaction of 2-substituted 1,3,4-oxadiazoles with bifunctional compounds at both ring nitrogen and at the substituent, leading to cyclic systems, are included in Section 4.06.5.2 irrespective of where the initial point of attack took place. A few examples of nucleophilic attack at unsubstituted carbon are described, the more common nucleophilic attack at substituted carbon being included under reactions of the appropriate substituent (Sections 4.06.7.1-7.5). 

Reactions similar to electrophilic aromatic substitution of 1,4-thiazine carbon atoms with electrophiles are shown below. Compounds 114 and 185 were ring-brominated (Equation 7) <1986LA1648> and 189 and 190 reacted with the electrophilic side chain to give bicyclic products (Equation 8) <1987LA551>. 

In contrast to the ease of reaction of ring nitrogen atoms in 77-deficient six-membered heterocycles with electrophiles, electrophilic heteroaromatic substitution at carbon of the unsubstituted compounds proceeds only under very drastic conditions and yields of products are usually very poor. This is also true with pyridinium, pyrylium and thiopyrylium salts,... 

This chapter covers reactions in which coordination of a transition metal to the ir-system of an arene ring activates the ring toward addition of nucleophiles, to give V-cyclohexadienyl-metal complexes (1 Scheme 1). If an electronegative atom is present in the ipso position, elimination of that atom (X in 1) leads to nucleophilic aromatic substitution (path a). Reaction of the intermediate with an electrophile (E+) can give disubstituted 1,3-cyclohexadiene derivatives (path b). If a hydrogen occupies the ipso posi-... 

In some cases, the function of the metal ion is more to deactivate alternative sites of reaction than to activate a particular atom towards attack by an electrophile. A good example of this is seen in the transamination reaction of ornithine (5.12) with urea. Co-ordination of the ornithine to copper(n) results in the formation of a five-membered chelate ring, leaving the amino group of the 3-aminopropyl substituent as the most nucleophilic site in the complex. Reaction of this complex with urea results in a transamination process and the formation of the copper(n) complex of the substituted urea, which is the amino acid citrulline (5.13) (Fig. 5-20). The complex may be demetallated to yield the free amino acid in respectable yields. 

Azines, reactions of ring N-atoms with electrophiles 88AHC(43)127. Perhydro pyrrolo- and azoloazines with bridgehead N-atoms 90-AHC(49)193. 

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