Michael Additions Of Divinyl Ketones With Indolin-2-one And Benzotriazole

Spiro[cyclohexane-1,3'-indoline]-2',4-diones are useful structures for the pharmaceuticals and pesticides because of the potential biological activities.The reported synthetic methods for spiro[cyclohexane-1,3'-indoline]-2',4-diones include i)the four-step reactions starting from 3-chloromethylene-2-indolones and Danishefsky's diene;ii)the reactions of 3-methyleneindolin-2-one with ?,?-unsaturated ketones catalyzed by secondary amines;iii)the three-step reactions starting from methyl 2-(2-nitrophenyl)acrylate and trans-1-methoxy-3-trimethylsilyloxy-1,3-butadiene;In addition,the asymmetrical synthesis of spiro[cyclohexane-1,3'-indoline]-2',4-diones were also reported.However,these methods have long reaction steps,and use commercial unavailable starting materials,which largely limited the practical applications in the organic synthesis.The aza-Michael addition is a novel atom economic reaction in synthetic organic chemistry,which has broad synthetic applications in pharmaceutical chemistry,biology,and material sciences.The conjugate additions of N-heterocyclic agents,such as benzotriazole,indazole,pyrazole,tetrazole and piperazine,as nucleophiles to Michael acceptors are important reactions for construction of C-N bonds in organic chemistry,and for preparation of fine chemical intermediates bearing N-heterocycles.However,the reported Michael acceptors only limited to one C=C bond substrates,such as ?,?-unsaturated ketones,carboxylic acids,esters,amides and nitriles,and nitroalkenes,etc.Moreover,complex and expensive catalysts,such as transition metal complexes and Br?nsted,Lewis or heteropoly acids,also required.For the Michael acceptors including two C=C bonds,such as divinyl ketones,the corresponding aza-Michael addition poses more problems of regioselective control,there is no report about regioselective aza-Michael additions of divinyl ketones.In this work,we report a simple one-step reaction to prepare 2,6-diarylspiro[cyclohexane-1,3'-indoline]-2',4-diones via chemoselective double Michael additions of indolin-2-one to divinyl ketones.We also report the regioselective mono-aza-Michael additions of divinyl ketones with benzotriazole and other N-heterocycles under mild,transition metal-free and acid-free conditions.This thesis mainly is divided into the following three parts.Chapter I: The synthesis of spiro(indolinones)and aza-Michael additions with N-heterocycles are reviewed.Chapter II: Chemoselective double Michael additions of indolin-2-one to divinyl ketones in the presence of cesium carbonate were developed.A series of spiro(indolinones)were synthesized.This protocol has advantages of mild conditions,commercially available starting materials,atom economy and good functional group tolerance.Chapter III: chemoselective Michael additions of to divinyl ketones under the effect of cesium carbonate.a series of nitrogen heterocyclic products is made.Chemoselective mono aza-Michael additions of benzotriazole to divinyl ketones in the presence of cesium carbonate were developed.A series of enones bearing benzotriazole were synthesized.This protocol has advantages of mild conditions,commercially available starting materials,atom economy and good functional group tolerance.