【作者】 周虎；

【导师】 宋恒； 徐晨；

【作者基本信息】 江苏科技大学 ， 化学， 2023， 硕士

【摘要】 烯烃是一类极易获取的重要化工原料,对其官能团化反应可以获得多种类型的高附加值产物。随着过渡金属催化策略的不断成熟,目前已发展出烯烃的远程官能团化方法,可有效构建远程C-X(X=C,Si,B,O,N)键。然而,对于远程C(sp3)-D键的构筑方法,还未见报道。烯烃的氢芳基化反应,大多采用Friedel-Crafts烷基化方法,还存在反应条件苛刻、反应步骤复杂等问题。(1):发展镍催化未活化烯烃的远程氢氘化反应方法。经过一系列优化实验,确定Ni-4作为催化剂前体,D2O作为D+源,HBpin(频哪醇硼烷)作为H-源时反应效果最好。通过将“链行走”策略和转移氢氘化反应相结合,以高产率和高选择性的合成46种酰胺α-单氘化产物。实验结果表明,导向基团在烯烃异构化过程中起到关键作用。DFT(密度泛函理论)计算也表明,在烯烃插入和异构化过程中,[NiII]-H物种而非[NiI]-H为反应的活性中间体。(2):发展一种非过渡金属催化,HFIP(六氟异丙醇)促进的烯烃氢芳基化反应。利用HFIP作为质子化试剂和溶剂,以高区域选择性和高化学选择性在吲哚C3位引入季碳中心。经过一系列优化实验,确定最优反应条件:烯烃作为底物,吲哚作为芳基源,n Bu4NOAc作为催化剂,在HFIP中90℃反应24 h,以较高产率合成33种烯烃氢芳基化产物。该反应无过渡金属参与,并利用绿色溶剂(HFIP)为质子源,具有绿色环保的特点。进一步将其应用于药物分子((±)MCRA)的合成,与先前技术相比,能显著提高目标产物收率。催化动力学和同位素标记实验均证明烯烃质子化形成碳正离子的过程是可逆的且是反应的决速步。更多还原

【Abstract】 Olefin is a class of important chemical raw material that can be easily available.Many types of high value-added products can be obtained by functionalization of olefins.With the development of transition metal catalysis,remote functionalization of olefins has been developed,which can effectively construct remote C-X(X = C,Si,B,O,N)bonds.However,protocols for construction remote C(sp3)-D bonds of olefins have not been reported until recently.The Friedel-Crafts alkylation is mostly used in the hydroarylation of olefins,but there are still some problems to be resolved,such as harsh reaction conditions and complex reaction steps.(1).The remote transfer hydrodeuteration of unactivated olefins catalyzed by nickel has been developed.After some optimization experiments,the best result was achieved by adopting nickel complex Ni-4 as a precatalyst together with D2 O and pinacolborane(HBpin)as the deuterium and hydride sources,respectively.Through the synergistic combination of chain-walking strategy and transfer hydrodeuteration,46 amide α-monodeuterated products have been synthesized with high yield and high selectivity.Experimental results demonstrated the directing group plays the critical role in the olefin isomerization process.Density functional theory(DFT)calculations suggest that the [NiII]-H species rather than the [NiI]-H species are the active intermediates of the reaction during olefin insertion and isomerization.(2).The transition metal-free catalyzed,HFIP promoted olefin hydroarylation has been developed.The regio-and chemoselective construction of indole bearing an all-carbon center at the C3-position has been achieved through utilization of hexafluoroisopropanol(HFIP)as the protonation reagent and solvent.After some optimization experiments,the optimal reaction conditions were determined: Olefin as substrate,indole as aryl source,n Bu4 NOAc as catalyst,reacted at 90℃ in HFIP for 24 hours.33 olefin hydroarylation products have been synthesized with high yields.The reaction involves transition metal-free and utilizes a green solvent(HFIP)as the protonation reagent,making it environmentally friendly.In contrast to previous report,application of this protocol to the synthesis of drug((±)MCRA)was pursued with an improved yield.Catalytic kinetics and deuterium-labeling experiments suggest that the protonation of olefin to generate carbocation is reversible and the rate-determining step.更多还原