Silver-catalyzed regioselective synthesis of acridines, quinolines, and naphthalenes from 3-(2-alkynyl)aryl-β-ketoesters

A facile, efficient, and general synthetic method for a wide range of medicinally useful 2-carboxylate derivatives of acridinols, quinolinols, and naphthalenols has been developed via silver-catalyzed electrophilic cyclization of 3-(2-alkynyl)aryl-beta-ketoesters. The designed reaction involved selective C C bond formation on more electrophilic alkynyl carbon, which resulted in the regioselective 6-endo-dig cyclized product, as confirmed by X-ray crystallographic studies. The deuterium labeling experiments were performed to support the proposed mechanism. The synthetic methodology accommodates wide functional group variations on alkyne, which proves to be highly advantageous for structural and biological activity assessments. (C) 2012 Elsevier Ltd. All rights reserved.