Nucleophilic additions bases, isoquinoline

In this section, useful cascade reactions, including the reaction between C=X and alkynes, which are not presented in the sections above, are introduced briefly. As mentioned in Section 19.2.1, isoquinoline formation proceeds through cationic iso-quinolinium intermediates 160 (Scheme 19.39). Many cascade reactions based on the electrophilic reactivity of 160 were reported in the literature, including intermolec-ular nucleophilic addition to produce 161 (path A), a second cyclization through... 

Only one example of an attachment of heteroarenes by addition/elimination strategy has been devised [77, 111]. Although arenes are more or less resistant toward addition, heteroaromatic systems such as isoquinolines 118 are prone to addition of nucleophiles. Subsequent reaction with addition of electrophiles furnishes the so-called Reissert compounds 120. These are stable compounds which can, for example, be alkylated. In solid-phase synthesis the electrophile chosen was a polymer-based acid chloride. Detachment can be achieved by simple addition of hydroxide ions (Scheme 6.1.30). 

Nucleophilic Reactions of Aromatic Heterocyclic Bases Heterocyclic aromatic compounds containing a formal imine group (pyridine, quinoline, isoquinoline, and acridine) also react readily with nucleophilic reagents. A dihydro-derivative results, which is readily dehydrogenated to a new heteroaromatic system. Since the nucleophile always attacks the a-carbon atom, the reaction formally constitutes an addition to the C=N double bond. An actual localization of the C=N double bond in aromatic heterocyclic compounds is incompatible with molecular orbital theory. The attack of the nucleophilic reagent occurs at a site of low 77-electron density, which is not... 

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