Solvent-dependent oxidations of 5- and 6-azaindoles to trioxopyrrolopyridines and functionalised azaindoles?

Organic & Biomolecular Chemistry Pub Date: 2008-02-28 DOI: 10.1039/B719776D

Abstract

A regioselective synthesis of 4,7-dimethoxy 5- and 6-azaindoles 2 has been achieved, based on the appropriate choice of ortho-directing or ortho-repulsing groups in the formylation of a pyridine ring. Studies on the regioselectivity of the formylation step and on the preparation of azidoacrylate intermediates 4 are described in this paper. The reactivity of the 5- and 6-azaindole structures towards BBr3-mediated selective monodemethylation and oxidative demethylation reactions were also investigated. The regioselectivity of the deprotection was confirmed using a chemical approach. Oxidation reactions were then carried out on either dimethoxy- or hydroxymethoxyazaindoles, in different solvents, using [bis(trifluoroacetoxy)iodo]benzene. In acetonitrile–water, trioxopyrrolopyridines 12 were obtained, whereas the formation of functionalised azaindoles 17 was observed in acetonitrile–methanol. The tautomeric structure of the trioxopyrrolopyridines was proved by X-ray diffraction analysis.

Graphical abstract: Solvent-dependent oxidations of 5- and 6-azaindoles to trioxopyrrolopyridines and functionalised azaindoles
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