Vinylpyridines indole

Indoles can also be alkylated by conjugate addition under alkaline conditions. Under acidic conditions, alkylation normally occurs at C3 (see Section 11.1). Table 9.1 includes examples of alkylation by ethyl acrylate, acrylonitrile, acrylamide and 4-vinylpyridine. 

Recently, the quaternized poly-4-vinylpyridine, 50-54 (QPVP) was found to be an electron acceptor in the charge-transfer interactions 104 Ishiwatari et al.105) studied alkaline hydrolyses of p-nitrophenyl-3-indoleacetate 58 (p-NPIA) and N-(indole-3-acryloyl) imidazole 59 (IAI) (electron donor) in the presence of QPVP. The fcobs vs. polyelectrolyte concentration plots are shown in Fig. 12. As is seen in... 

Combining the nucleophilicity of the indole 3-position just illustrated and the well-known tendency of C-2 and C-4 vinyl pyridines to add nucleophiles, a convenient synthesis of the tranquilizer benzindopyrine (19) was devised.6 Reaction of N-benzylindole (17) with 4-vinylpyridine (18) in acetic acid produced 19 directly. 

Tetrabromocyclopropene underwent addition to vinylpyridines, giving eventually indoles 1, in a reaction which apparently proceeded by initial [4 + 2] cycloaddition, followed by dehy-drohalogenation. 1 ... 

An olefin attached to an electron-deficient heterocycle such as pyridine may be viewed as a Michael acceptor as well. When indole was heated in acetic acid with vinyl pyridine or vinyl pyrimidine, C3 electrophilic substitutions readily take place, giving rise to the adducts. Interestingly, when indole and 4-vinylpyridine were treated with sodium metal in the presence of CUSO4, Michael addition at the indole nitrogen took place. 

Such a principle was effectively employed in the synthesis of both achiral and chiral heterocyclic compounds. For instance, O Shea et al. [8] have demonstrated the benefit of intermolecular carbolithiations of o-substituted styrenes 9a in a one-pot synthesis of substituted indoles 11a and have extended this principle to the carbolithiation of 3-vinylpyridin-2-ylamines 9b eventually resulting in 7-azaindoles 11b (Scheme 10.5). 

Scheme 10.5 Intermolecular carbolithiation of functionalized styrenes and vinylpyridines in the preparation of indoles and 7-azaindoles [8].

Additions of aryl residues to vinylpyridines have not been observed, except in the case of indole mentioned above. 

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