Studies On Single And Double Functionalization Of Aryl Tertamine C(sp~3)-H Bonds Mediated By N-halogenated Amides

Oxidation of tertiary amines is one of the most basic reactions in nature and plays an important role in the life process.The chemical oxidation of tertiary amines can not only provide a new method and pathway for the synthesis of nitrogen-containing compounds,but also help us to understand the reaction process and mechanism of tertiary amine oxidation in life.At present,with the development of economy,people pay more and more attention to green chemistry.Therefore,the development of metal-free or even no catalyst to promote the functionalization of tertiary amines is not only an economical and efficient synthesis route,but also in line with the development concept of green chemistry.Here,the C-H bonds of tertiary amines were activated under green and mild reaction conditions to achieve several oxidative cross-coupling reactions.The specific studies are as follows:(1)Single C-N oxidative cross-coupling reaction of aromatic tertiary amines: at room temperature without catalyst and oxidant,ethyl acetate as solvent,aromatic tertiary amines and N-iodine(bromine)substituted amides / imides react.The corresponding C-N cross-coupling products were formed(including halogenation with aromatic rings).when a small amount of2,2,6,6-tetramethylpiperidine oxide(TEMPO)was added to the reaction system,the aromatic tertiary amines of strong electron-absorbing groups(cyano,nitro,sulfonyl,etc.)could also be activated to obtain a single C-N target compound with high yield.The mechanism of the above reaction is discussed by a series of control reactions and kinetic isotopic effects.It is found that the reaction is mainly ionic reaction.(2)Oxidative double cross-coupling reaction of aromatic tertiary amines: in the absence of catalysts and oxidants,TEMPO is used as the reaction promoter to activate the C-H bonds on the two methyl groups of N,N-dimethylaniline.Symmetric C-N/C-N bifunctionalization and asymmetric bifunctionalization C-C(P)/ C-N bifunctionalization are realized.The symmetric double coupling reaction is mainly realized by the one-step reaction of N,N-dimethylaniline and excess N-iodine(bromine)substituted amides / imides.The asymmetric dual coupling reaction consists of two steps: first,a C-C or C-P single coupling reaction occurs N,N-dimethylaniline with the corresponding nucleophilic reagent under the synergistic action of the NIS/TEMPO,and then,under the same conditions(NIS/TEMPO),a C-N coupling reaction occurs on another methyl group of N,N-dimethylaniline.(3)C-C oxidative cross-coupling reaction of aromatic tertiary amines: first,the C-C cross-dehydrogenation coupling(CDC)reaction between N,N-dimethylaniline and nitroalkanes with different substituents was attempted under the NIS/TEMPO reaction system.The target compound with high yield was obtained when the reaction system was further extended to N-phenyl tetrahydroisoquinoline compounds.On the other hand,the C-C cross-coupling nitrile reaction between N,N-dimethylaniline derivatives and trimethyl cyanosilane(TMSCN)was successfully realized under the similar reaction system.