Metal-free Cyclization Via C-H Activation To Form Oxindoles

Oxindole represent an important heterocyclic scaffold occurring in many natural products, which shows significant bioactivities and was widely used in materials science, agricultural chemical, and etc. In the past decades, a wide range of synthetic methods have been developed by organic chemists. Among these available methods, metal-free or metal-catalyzed radical C-H cyclization reactions have attracted considerable interests in the past. This dissertation mainly focus on the studies of inexpensive metal-catalyzed and metal-catalyzed radical-mediated tandem annulations toward oxindoles, which include:First of all, this first section reviews recently-reported radical methods for the synthesis of oxindole in the past years. This section were divided into two part based on the couping reactions: a) radical-mediated arylalkylation annulations constructing 3,3-disubstituted oxindoles. b) radical-mediated difunctionalization of alkenes constructing 3,3- disubstituted oxindole;Then the second section describe a kind of high efficient, environmental friendly and metal-free radical-mediated the coupling reaction protocol. In the presence of benzoyl peroxide and acetonitrile, N-arylacrylamides undwent a tandem Meerwein arylation cyclization to construct the 3-benzyl-3-alkyloxindole.This protocol afforded a facile route for the synthesis of oxidole with moderate to good yields; The third section developed a novel copper-catalyzed oxidative radical alkylarylation of activated alkenes.We explored the effects of solvent、catalyst and temperature on the teaction.So the optimal reaction conditions is as follow: copper(I) iodide(20 mol%)、di-tert-butylperoxide(4 equiv.)、diisopropyl azodiformat(3 equiv.)and 100 ℃. The reaction system could tolerate various functional groups and the desired products were obtained in moderate to good yields;Finally, the fourth section developed a novel copper-catalyzed oxidative radical alkylarylation of activated alkenes. A notable feature of the developed process is cascade-type formation of double bonds initiated by the addition of radical-mediated. In addition, the use of safe and readily available aliphatic azo compound and inexpensive copper as the catalyst make this protocol a highly attractive complement for the construction of pharmaceutically interesting cyan-containing oxindoles.