Conjugate Addition of Indoles to Electron-Deficient Olefins Catalyzed by CuFe2O4@SO3H under Mild Conditions

Abstract

Over the past few years a variety of methods has been reported for the preparation of 3- substituted indoles. Addition reactions of indoles to electron deficient olefins have received much interest because a number of their derivatives occur in nature and possess a variety of biological activities. Since the 3-position of indole is the preferred site for electrophilic substitution reactions, 3-alkyl indoles are versatile intermediates for the synthesis of a wide range of indole derivatives. A simple and direct method for the synthesis of 3-alkylated indoles involves the conjugate addition of indoles to α,β-unsaturated compounds in the presence of either protic or Lewis acids. However, the acid-catalyzed conjugate addition of indoles requires careful control of acidity to prevent side reactions such as dimerization or polymerization [1- 3]. In continuation of our work on the development of useful synthetic methodologies we recently observed that CuFe2O4@SO3H catalyzes the conjugate addition of indoles to electrondeficient olefins to form the corresponding Michael adducts under mild conditions. Initial research was focused on the reaction of indole with chalcone, and different solvents and different amounts of the catalyst were tested to find the optimized conditions.