The Study On The Lewis Acid-promoted Transition Metal Catalyzed Organic Synthesis Reactions

Catalytic oxidation is one of the most representative reactions in many fields such as petrochemicals,pharmaceuticals,and fine chemicals,many pharmaceutical intermediates and fine chemicals need to be synthesized through efficient catalytic oxidation processes.Therefore,the development of new catalytic oxidation technologies applied in the organic synthesis field has drawn considerable attentions from chemists.In catalytic oxidation reactions,transition metals are an extremely important class of catalysts,thus,precisely regulating the catalytic ability of transition metals in catalytic oxidation has great academic value and application value.In enzyme-catalyzed,heterogeneous catalytic and homogeneous catalytic reactions,regulating the catalytic ability of transition metal ions by adding Lewis acids is very common.Therefore,there is tremendous value in expanding our understanding of how Lewis acids can enhance the oxidation ability of transition metal catalysts and broaden their application to organic synthesis reactions.In this thesis,we have carried out further application development and mechanism research on the Pd（II）/LA catalytic system based on the reported synthetic reactions in our group,which provides a more realistic and theoretical basis for the potential application of this Pd（II）/LA catalyst.In chapter 2,a new synthetic method for the efficient Wacker-type oxidation of alkynes into 1,2-diketones has been developed by using a Pd（II）/Al（III）catalyst.Notebly,Al Cl₃alone was insoluble in DMSO,interestingly,adding one equivalent of Pd（OAc）₂ can make the Al Cl₃ salt completely soluble in DMSO solution.Under the optimal reaction conditions,this approach tolerated a variety of functional groups and afforded 1,2-diketone derivatives in 62-99%yields,whilst reactions with Pd（OAc）₂ alone were sluggish and afforded a low yield of the corresponding diketone only limited to 39%.It can be seen that Al（III）played a quite important role in promoting the catalyst’s effectiveness.Subsequently,based on our previous works and NMR/UV-vis characterizations,we supposed that a new heterobimetallic Pd（II）/Al（III）active species linked by diacetate bridges was formed in the reaction system.The linkage of the positively charged Al³⁺cation to the Pd（II）species made the Pd（II）moiety more electron deficient,thus improving its catalytic efficiency for alkyne oxidation.In chapter 3,the oxidative olefination/annulation of N-methoxybenzamides catalyzed by Pd（II）/LA with oxygen as the oxidant is studied.It was found that adding Sc（OTf）₃ to Pd（TFA）₂ can significantly promote its catalytic efficiency and surprisingly obtain products with yields up to 68%,while when Pd（II）alone catalyzed the reaction,the yields were only limited to 28%.Kinetic isotopic effect（KIE）experiments disclosed that C-H activation is the rate determining step.UV-vis kinetics and NMR experiments indicated that Sc（III）interacting with the Pd（II）to form a heterobimetallic active species,rather than coordinating to the carbonyl group of the substrate,accelerated this Pd（II）/Sc（III）catalyzed olefination/annulation reaction.Although Pd（II）-catalyzed C-H activation of arenes have been extensively investigated in organic synthesis,the direct observation of theπ-complex was not reported yet possibly due to its instability.In this chapter,two reaction intermediates,including an unsymmetricalη⁶-complex and a palladacycle species without the proton releasing to the environment were successfully identified through NMR characterizations.According to our previous studies,we believe that the in-situ generated heterobimetallic Pd（II）/Sc（III）species having the trifluoroacetate bridge may have enhanced the electrophilic properties of the Pd（II）cation,thus improving its catalytic efficiency and the stability of theπ-complex which can be identified by NMR.The observed insensitive electronic effect preferred the concerted metalation-deprotonation（CMD）mechanism for this Pd（II）/Sc（III）-catalyzed C-H activation in arenes.And the¹H-¹³C HSQC spectrum of the second intermediate also supports the CMD mechanism.This reaction further shows the merits of the Pd（II）/Sc（III）bimetallic catalyst in catalytic oxidation reactions,and the identified intermediates serve as important evidence to the theory of Pd（II）-catalyzed arene C-H activation.In order to verify whether the Pd（II）/LA catalytic system can extend to other non-noble metals,a new Ni（II）/Y（III）catalyst is discussed in chapter 4,which was successfully applied in the oxidative coupling reaction between thiol and phosphate,and further extended to the synthesis of biological activity and medicinal value compounds.It was found that the catalytic activity of Ni（II）alone for this reaction is very poor,and the highest yield of the desired products were only limited to 38%.Adding Y（III）,a non-redox metal ion,to Ni（OAc）₂ can dramatically improve its catalytic efficiency with the corresponding products and were obtained at up to 88%yield.The promotional effect is highly dependent on the added Lewis acid,and generally,a stronger Lewis acid provided a better promotional effect.The stopped-flow kinetics confirmed that adding Y（OTf）₃ can obviously accelerate the activation of thiols by Ni（II）and next accelerate its reaction with phosphonate to generate the phosphorothioate product.More importantly,we have detected the heterobimetallic Ni（II）/Y（III）species by ESI-MS characterization for the first time,which provides important evidence for the Pd（II）/LA catalyst and improves our understanding on the mechanism of Lewis acids promoted transition metal catalyzed reactions.