| Free radical reaction is an important type of organic reactions,which is mainly mediated by electron transfer and atom transfer.The radical ions generated by electron transfer are a kind of the active radical intermediates,and can be directly converted into free radicals to participate radical reactions,or other active intermediates under different conditions,such as carbocations or carbanions,to undergo ionic reactions.The neutral radicals generated by atom transfer can be involved in radical coupling or addition reactions.These free radical intermediates can be generated by chemical oxidation,photoinduced electron transfer,or anodic oxidation.However,the addition of additional oxidants often leads to some limitations,such as narrow reaction scope and overoxidation.Our research group hopes to use oxygen as the mildest oxidant to achieve a series of free radical reactions.On the other hand,in single electron reduction,a substrate will obtain an electron from the reductant,generating a radical anion intermediate.The most popular reducing agents are usually some low valent alkali metals,however,it is difficult to regulate their reducing reactivity,and only limited substrates can be employed in these reduction reactions.Although the organic reducing agents has been developed to overcome some of these limitations,tedious synthetic steps are generally needed to prepare these organic electron donors.Furthermore,these reducing agents are often suffered from the poor stability,which limits their further applications.Our research group wonders whether commercially available tertiary amine derivatives can be employed as organic electron donors to induce the reduction reactions.The content of this thesis is based on the activation of inert chemical bonds promoted by the reduction and oxidation reactions mediated by free radical intermediates.The main study of this thesis includes:TBN initiated desymmetric oxidation of N-α-sp3 C-H bonds of isoindoles,the C-N bond activation of N-diarylimidazolanes promoted by TBN,the synthesis of furoxans with N-NO skeleton,the single electron reduction enabled C-C bond activation and the decyanation and hydrogenation through single electron reduction.Part Ⅰ:α-hydroxyl lactams are an important derivatives of amide,however,these compounds can not be readily obtained by direct oxidation.Herein,a tert-butyl nitrite initiated desymmetric oxidation of isoindolines via the activation relay of the active sp3 C-H bond is achived,obtaining a series of α-hydroxyl lactams.This reaction is extended to a wide range of substrates with good functional group tolerance,and even N-alkyl isoindolines can be smoothly tolerated.The mechanistic study shows that the oxidation of the C-H bond,the capture of oxygen and the intramolecular 1,5-hydrogen atom transfer are the key steps in this desymmetric oxidation.Part Ⅱ:Amine compounds are widely found in various kinds of functionalized molecules,therefore,the C-N bond activation is crucial to their structural modifications and late stage transformations.The literature procedents on C-N bond activation revealed that through C-N bond cleavage,only one functional group can be introduced into the products,in which the degree of functionality is sustained.In this study,a series of N-nitrosoamines were obtained through the C-N difunctionalization of N,N-diarylimidazolanes,using tertbutyl nitrite as a metal-free catalyst.The mechanistic study shows that the C-N bond cleavage is mediated by an iminium intermediate.In this reaction,the cleavage of the C-N bond is realized under mild reaction conditions and two synthetically important functional groups are introduced in one step,dramatically increasing the molecular complexity through the difunctionalization of the C-N bond.Part Ⅲ:Furoxans are a kind of structural units with various biological activities.The construction of furoxan skeleton is mainly based on the 1,3-dipole cycloaddition reaction ofα-carbonyl nitrile oxide.Using tert-butyl nitrite as the oxidant,the C-N bond cleavage of 1nitromethyl-N-aryl tetrahydroisoquinolines.The two bioactive skeletons,furoxan ring and Nnitroso amine,were grafted into one compound,which greatly improved the complexity of the molecular structure.The mechanistic study reveals that this reaction is mediated by an αcarbonyl nitrile oxide generated in situ,in which the substituent effect exerts obvious effect on the reaction outcome.It can be seen from the results that when the N-aryl ring is substituted by the electron-withdrawing groups,the yields of the desired products are relatively higher.Part Ⅳ:The C-C bond is one of the inert chemical bonds,and the cleavage of C-C bond as well as its construction is an important area in organic chemistry.At current stage,the activation of C-C bond under mild reaction conditions attracts various organic chemists’interests.The reactions of single-electron reduction promoted by organic electron donors have been greatly developed,however,the single-electron reduction enabled activation of C-C bond is still rare.Using Lewis acid and tertiary amine,DIPEA,as the reduction system,the reduction of 1-nitromethyl-N-aryltetrahydroisoquinolines via single electron transfer is achieved,affording the reduction products,N-aryltetrahydroisoquinolines in high yields.This method provides a new way to realize the activation of C-C single bond under mild conditions,which is important in the study of C-C bond activation and organic electron donor promoted reduction reactions.Part Ⅴ:Cyanogroup is a very important functional group in organic compounds.It can be used as the directing group in transition metal catalysis,and also a precursor of amines,aldehydes and ketones.However,due to the high bond dissociation energy of C-CN bond,it is very hard to cleave the C-CN bond.Using the reducing system of Lewis acid and tertiary amine,DIPEA,1-cyano-N-aryl tetrahydroisoquinolines are readily reduced to the corresponding N-aryl tetrahydroisoquinolines via decyanation and further hydrogenation.In this reaction,it is found that when the N-aryl ring is substituted by an electron-donating group,the reaction efficiency is particularly good,and the corresponding reduction products can be obtained in quantitative yields.Furthermore,it is found that in the cleavage of C-C single bond,cyanogroup as a leaving group exhibits higher tendency than nitromethyl group to be cleaved. |
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