Applications to Synthesis of Heterocyclic Compounds

Because the nucleophiles can be introduced at the ortho-position of the nitro group, various heterocycles can be prepared via VNS and related reactions. Indoles and related compounds are prepared via the VNS reaction and subsequent cyclization. The VNS reaction of nitroarenes followed by cyclization with Et3N-Me3SiCl gives 1-hydroxyindoles (Eq. 9.53).86 Cyclization is also catalyzed on treatment with bases, in which nitroso intermediates are postulated. 

The novel cyclization takes places by the silane-mediated condensation of nitroarenes with allylic carbanions, in which a six-membered nitrogen-containing ring is constructed (Eq. 9.54).87 

Base-promoted condensation of ketones with 3-nitroaniline results in the formation of indoles. The reaction proceeds in one pot via a NASH-type reaction and subsequent cyclization (Eq. 9.55).88 

The foregoing examples show that the nucleophilic attack to nitroarenes at the o T/ o-position followed by cyclization is a general method for the synthesis of various heterocycles. When nucleophiles have an electrophilic center, heterocyclic compounds are obtained in one step. Ono and coworkers have used the anion derived from ethyl isocyanoacetate as the reactive anion for the preparation of heterocyclic compounds. The carbanion reacts with various nitroarenes to give isoindoles or pyrimidines depending on the structure of nitroarenes (Eqs. 9.56 and 9.57).89 The synthesis of pyrroles is discussed in detail in Chapter 10. 

There are many variants of such syntheses of heterocycles. Recent examples are presented in Eqs. 9.58 and 9.59.90 Because these transformations do not require aromatic halides or transition metals, they may provide a clean technology for production of biologically important materials. 

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