Studies On The Hydrocyanation Of 3-Aryliminoindolin-2-Ones With Benzoyl Cyanide And The Mono-Aza-Michael Additions Of 3-Aryliminoindolin-2-Ones With 1,4-Dien-3-Ones

Hydrocyanation is an important reaction in the synthesis of organic compounds containing cyano group.And these cyano compounds have important applications in organic synthesis because cyano group can be further converted into various functional groups,such as amines,carbonyls,amides and carboxylic acids.However,at present,the cyanating agent used in hydrocyanation is mainly highly toxic hydrocyanic acid,sodium cyanide,potassium cyanide,etc.,so it is of great significance to develop low toxic or non-toxic cyanating agent for hydrocyanation.Benzoyl cyanide is less toxic cyanating agent,which can be easily prepared by reaction of commercial available benzoyl chloride and nontoxic potassium hexacyanoferrate?II?.Therefore,it has potential application value in the hydrocyanation as a cyanating agent.Aza-Michael addition reaction is an important reaction for the construction of C-N bonds,which is widely used in pharmaceutical chemistry,life science,material chemistry and other aspects.Therefore,it is the basic reaction for the construction of complex natural products and pharmaceutical active molecules.However,at present,the aza-Michael addition reaction using various nitrogen-heterocycles as electron donors is still very limited,and there is still necessity for further study.In particular,the aza-Michael reactions of nitrogen-hetrocycles with some multifunctional Michael receptors?e.g.1,4-dien-3-ones?are of great significance for the construction of multifunctional products of nitrogen-heterocycles.The 3,3-disubstituted indolin-2-one moiety is a special heterocyclic subunit in a large number of bioactive compounds,natural products,and drugs.As a typical example of 3,3-disubstituted indolin-2-one,3-aryliminoindolin-2-one has many applications.For example,the C=N bond in its structure can react with nucleophiles such as cyanating agents to produce 3-cyano-3-arylaminoindolin-2-ones,and the nitrogen-heterocycles in its structure may participate in aza-Michael addition reaction to produce N1-functionalized 3-aryliminoindolin-2-ones.The above two kinds of compounds may have many potential applications.On the basis of the above background,this thesis mainly studies the hydrocyanation of 3-aryliminoindolin-2-ones using less toxic and easy-to-handle benzoyl cyanide as a hydrocyanating agent,and the regioselective mono-aza-Michael additions of 3-aryliminoindolin-2-ones with 1,4-dien-3-ones as Michael receptor,which can effectively synthesize 3-cyano-3-arylaminoindolin-2-ones and N1-functionalized 3-aryliminoindolin-2-ones.This thesis is divided into three chapters.Chapter 1:The applications of cyanating agents,the progress of aza-Michael addition reactions in organic synthesis,and the synthesis and applications of3,3-disubstituted indoline-2-ones were reviewed.Chapter 2:The effective hydrocyanation of 3-aryliminoindolin-2-ones with benzoyl cyanide as cyanide source and methanol as solvent under catalyst-free and room temperature conditions was investigated.Twenty examples of2-oxo-3-arylaminoindolin-3-cabonitriles were synthesized.The structures were confirmed by ¹H NMR,¹³C NMR and HRMS.Among them seventeen compounds were not reported so far by literature.This protocol benefits from the use of safe,inexpensive,low-toxic and easy-to-handle cyanide source,no catalysts,no additives,mild conditions,good substrate tolerance,and simple work-up procedures.Chapter 3:The regioselective mono-aza-Michael additions of 3-aryliminoindolin-2-ones with 1,4-dien-3-ones using cesium carbonate as a base and dichloromethane as solvent under transition-metal-free,acid-free and room temperature conditions were investigated.Twenty-one new N1-enone-functionalized3-aryliminoindolin-2-ones were efficiently synthesized.The structures were confirmed by ¹H NMR,¹³C NMR and HRMS.The salient features of this protocol are high regioselectivity,high yield,and mild conditions.