Nickel-catalyzed Highly-Efficient Construction Of C_sp3-S And C_sp3-C_sp2 Bonds And Their Applications

Transition metal-catalyzed C-H bond activation reactions that can be used to directly construct various types of chemical bonds are the hot areas of current research.However,the activation of the C-H bond often required precious metals such as rhodium,ruthenium and palladium.Therefore,the development of an efficient and cheap catalyst system for the C-H bond activation has great theoretical and practical value.The direct activation of C(sp~3)-H bondsavoided the cumbersome pre-functionalization procedures for the substrates,also improved the reaction efficiency with great atomic economy.In addition,it has a wide range of sources fo r the reaction substrates,greatly increasing the practicability of the reaction,in line with the purpose of the development of green chemistry today.However,aliphatic C(sp~3)-H bonds are more relatively inert than aromatic C(sp~2)-H bonds because of the thermodynamic stability,and it also had the weaker coordination than aromatic C-H bond.In addition,the aliphatic carbon-transition metal intermediates are more easily generated side reactions such as the?-hydrogen elimination.Therefore,the strategy of using bidentate directing group to assist the C-H bond activation has been applied to the inert methyl C(sp~3)-H bond functionalization reaction.As a powerful directing group,8-aminoquinoline can effectively promote the C-H bond activation reaction.However,most of these reactions were catalyzed by the precious metals.Therefore,it has great value to establish a methodthatcan use an inexpensive transition-metal to catalyze the inert C(sp~3)-H activation reaction with a directing group.In order to further solve the problem of construct C-C bonds or C-X bonds.A nickel/photoredox dual catalysis system has been developed to realize some reactions which are difficult to complete in the single catalytic system.There are recent many efforts targeting the nickel/photoredox dual catalysis system in organic synthesis area.In this paper,we will tese the C(sp~3)-H activation catalyzed by nickel,and also investigate the reactivity of the 8-aminoquinoline-guided aliphatic amide compounds and diaryl-disulfide or thiophene bromide to form the important C-C bonds or C-S bonds.Further applications of the C-H activation reactionswere explored.The trifluoroborate-boronaphthalene heterocyclic compound was used as the reaction substrates in the cross-coupling reaction under nickel/photoredox dual catalysis system.The main research work is as follows:(1)The Ni-catalyzed synthesis of inert methyl C(sp~3)-S bond by"one-pot"reaction was carried out.The reaction of N-(8-quinolyl)trimethylacetamide and diphenyl disulfide was used as the model reaction.We had investigated different nickel catalysts,ligand,base,solvent and temperature.When we got theoptimized conditions,we had tested the substrates scope such as different aliphatic amide,different diaryldisulfides,dialiphatic disulfides and diaryldiselenides.28examples of thiolated aliphatic amide compounds were synthesized in yields of up to 91%.All products were confirmed by NMR,MS and HRMS.With theresults of control experimentsand the KIE values obtained from deuterated experiments,the possible reaction mechanismwas proposed.The The aliphatic carboxylic acid thioether compound with the removed directing groupwas used as the starting material,and got the final functionalized product.(2)The Ni-catalyzed C(sp~3)-C(sp~2)bond forming reaction was developed by"one-pot"reaction that using the aliphatic amide compound to react with the thiophene bromide.TBAI was added as phase transfer catalyst.The substrate scopes of different aliphatic amides,different thiophe ne bromides and the brominated nitrogen heterocycles were investigated.26 examples of heteroarylated aliphatic amides with a yield up to 92%were investigated.All products were confirmed by NMR,MS and HRMS.(3)The cross-dehydrogenation coupling reaction(CDC reaction)between aliphatic amide and simple hydrocarbon thiophene was investigated by Nickel catalyzed.Silver salt was used as oxidant in the reaction to help the double C(sp~3)-H/C(sp~2)-H cleavage process.The model reaction was carried out of N-(8-quinolyl)-trimethylacetamide and thiophene.Different nickel catalysts,phase transfer catalysts,ligand,oxidant,solvent and other conditions were examined.With the optimized conditions,the substrate scopes were also tested.33 examples of heteroarylated aliphatic amides were obtained with high yield.The structures of all products were characterized by NMR,MS and HRMS.The KIE values obtained withcontrol experiments and deuterated experiments,it suggest a possible mechanisms for the reaction.The final iodo-thiophene product has been used as a starting material for the next application.The excellent classical coupling reaction results proved that the CDC reaction have an excellent tolerance for the active functional groups during the reaction pro cess.(4)Azo-substituted Azaborine compounds were synthesized by the reaction of azaborine functionalization.In this reaction,we used trifluoroboraminated azaborines to react with(hetero)aryl bromide in nickel/photoredox dual catalysis system.A series of trifluoroborated compounds were prepared from different azaborine compounds.The reaction of trifluoroborated N-2-phenyl-2,1-azabarinane and bromoacetonitrile was used as the model reaction.With the optimized conditions,the effects of different groups on boron atoms were investigated,and these reactions gave28(hetero)arylated products with higher yields.The structures of all products were confirmed by NMR and MS.