Synthesis of indoles, benzofurans, and related heterocycles via an acetylene-activated SNAr/intramolecular cyclization cascade sequence in water or DMSO?

Organic & Biomolecular Chemistry Pub Date: 2015-01-22 DOI: 10.1039/C4OB02549K

Abstract

The synthesis of 2-substituted indoles and benzofurans was achieved by nucleophilic aromatic substitution, followed by subsequent 5-endo-dig cyclization between the nucleophile and an ortho acetylene. The acetylene serves the dual role of the electron withdrawing group to activate the substrate for SNAr, and the C1–C2 carbon scaffold for the newly formed 5-membered heteroaromatic ring. This method allows for the bond forming sequence of Ar–X–N/O–C1 to proceed in a single synthetic step, furnishing indoles and benzofurans in moderate to high yields. Since the method is not transition metal mediated, brominated and chlorinated substrates are tolerated, and benzofuran formation can be conducted using water or water–DMSO mixtures as solvent.

Graphical abstract: Synthesis of indoles, benzofurans, and related heterocycles via an acetylene-activated SNAr/intramolecular cyclization cascade sequence in water or DMSO
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