Studies On Oxidation Alpha C-H Functionalization Of Alpha Amino Ketones

With the increasing shortage of natural resources and the deteriorating environment,the implementation of sustainable development strategy is imperative.Therefore,the development of efficient synthetic strategies,which aims to eliminate or reduce waste emissions and economizes energy,is a big challenge lying in front of the organic chemists.Cross-dehydrogenation coupling(CDC)reaction is a new type of coupling reaction developed in recent years.This kind of reaction has the advantages of high atom economy and simple operation.Moreover,the reaction substrate does not need pre-functionalization and the byproduct is only hydrogen or water or alcohol.It is green,saves energy and meets the requirements of green chemistry development.Therefore,the study of various cross-dehydrogenation coupling reactions has become a hot topic in organic chemistry.In this field,taking into account the important role of α-amino ketone derivatives,pharmaceutical chemistry and natural product chemistry and so on,the cross-dehydrogenation coupling reaction of α-amino ketones has been extensively studied.However,little is done about the research on the dehydrogenation coupling ring addition reaction of α-amino ketone with various 1,3-dipole and sp~3-hybridated benzyl carbon nucleophiles.In this paper,using the strategy of cross dehydrogenation coupling reaction,with simple and readily available α-amino ketone compounds or their precursors as the starting material,we focused on the coupling reaction between 1,3-dipole,benzyl sp~3 C and aryl sp2 C.The specific studies are as follows:Firstly,the α-amino ketone compounds were used as the starting material,in the presence of DBU conditions,with oxygen as the oxidant,a novel CuBr2-catalyzed [3+2]cycloaddition reaction of α-amino ketone with α-diazo compounds has been developed for the first time via a CDC process,which contained a continuous oxidation/[3+2]cycloaddition/oxidation aromatization process and a series of multi substituted 1,2,3-triazole compounds were prepared.After that,with the ethyl isocyanoacetate as 1,3-dipole,a series of imidazole compounds were synthesized by co-catalysis of CuBr2 and AgOAc with α-amino ketone and it involves a sequential oxidation/[3+2] cycloaddition reaction procedure.The above reaction not only has the advantages of simple substrate availability,mild condition and high atomic economy,but also creates a simple and efficient method for the direct preparation of 1,2,3-triazole and imidazole derivatives by α-amino ketone in one step.Secondly,the cross-dehydrogenation coupling reaction of α-amino ketone with benzyl sp~3 C? H bond was successfully achieved by using tert-butyl benzoate as the oxidant under the condition of metal-free catalyst.This reaction has the advantages of simple and easily obtained raw materials,no transition metal and high atomic economy.After that,the application of synthesis of 3,4-dihydroquinolin-2-one compounds was studied by the introduction and transformation of functional groups.Finally,with the simple 2-alkynyl aniline compounds and the field-generated cyclicα-amino ketone oxidative dehydrogenation coupling reaction as the core step,we have developed a new strategy for the direct and highly efficient synthesis of2,3’-bisindolin-3-ones via an Au(I)/Cu(II)-co-catalyzed tandem reactions by using TBHP as the terminal oxidant and oxygen-atom source for the first time.The single-step process involves a novel tandem intermolecular nucleophilic addition,intramolecular cyclization/oxidative cross-dehydrogenative coupling where up to four new bonds and two indole rings were created simutaneously in a one-pot manner.The reaction has its own special features,such as broad substrate scope,good functional group tolerance,operational simplicity,and high atom-economy.