【作者】 张伟；

【导师】 余达刚；

【作者基本信息】 四川大学 ， 有机化学， 2022， 博士

【摘要】 在资源紧缺的当今社会,实现对有限资源的有效开发和高值化利用显得尤为重要。二氧化碳（CO₂）作为一种温室效应气体,对当前全球的气候变化有着重要影响,但从资源利用的角度考虑,CO₂因廉价易得、无毒、可再生的优点,是一种理想的碳一（C₁）资源。利用CO₂作为C₁资源参与有机合成转化,不仅能促进碳循环的进行,还能合成一系列高附加值的化学品,例如基础化学原料、燃料、生物医药和高分子材料等。然而,CO₂作为一种惰性分子,由于自身的热力学稳定性和动力学惰性,导致其化学转化面临多种问题。围绕解决CO₂的活化这一关键问题,科学家们提出了CO₂的双电子活化和单电子活化策略。双电子活化主要是利用亲核性物种对CO₂进攻,通过双电子转移实现CO₂的活化,这类模式被广泛研究。CO₂的单电子活化是利用单电子还原CO₂形成CO₂自由基负离子,虽然研究较少,但由于CO₂自由基负离子活性高,可以促进惰性化合物的羧基化反应,有望实现通过双电子活化模式难以完成的新型化学转化,实现独特的化学选择性和区域选择性,因此具有重要研究价值。另一方面,电合成作为一种高效的有机合成技术,因其绿色、可控、高效等优点,备受化学家的青睐。通过对电解参数的调控,能够轻松达到理想的氧化还原电位,从而实现一系列惰性分子的活化,产生传统化学方法难以形成的高活性中间体。虽然电化学促进CO₂参与的羧基化反应已经取得了一定的进展,但该领域仍然存在许多的问题,如底物类型受限（通常仅有活化底物才能实现羧化反应）;反应模式单一（电化学净还原过程）等问题。针对这些问题,本论文基于电化学促进CO₂单电子活化策略,系统研究了CO₂参与非活化烯烃的羧基化反应,在温和条件下高效的构建了一系列结构多样的二酸单体与高烯丙酸类化合物。本论文主要包含以下两个部分:第一部分:电化学促进CO₂参与的非活化烯烃还原双羧基化反应研究。我们通过电化学强还原体系实现CO₂单电子活化,利用高活性的CO₂自由基负离子对非活化烯烃加成,然后利用强还原体系将烷基自由基还原为烷基碳负离子中间体,进而捕获第二分子CO₂形成重要的二元羧酸化合物。本研究突破了CO₂转化通常需要依赖活泼底物的局限,首次成功地实现电促进CO₂参与的非活化烯烃高效双羧基化反应。该反应体系条件温和,适用于非共轭二烯和简单烷基烯烃等多种类型底物。通过该方法可以高效合成磷酸二酯酶4型酶（PDE4）抑制剂同系物,有助于减少药物中间体冗长繁琐的合成步骤。在构建了多种新型二酸单体之后,我们进一步探究了产物在高分子聚合材料中的应用。例如,它们不仅可以作为微交联剂实现对聚己二酸丁二醇酯（PBA）的改性,还能合成具有优良热稳定性的新型生物可降解聚材料。第二部分:电化学促进CO₂参与的非活化烯烃氧化还原中性的羧基化反应。我们使用电化学强还原体系产生高活性的CO₂自由基负离子,对非活化烯烃加成形成羧基化的烷基自由基,再经化学转化得到形式上碳氢键羧基化的高烯丙酸类产物。该方法首次成功地实现电促进CO₂参与的非活化烯烃氧化还原中性羧基化反应,突破了传统电羧化反应的还原羧化机制。本体系条件温和多种类型的非活化烯烃都可以较好反应,非牺牲阳极体系也能完成该转化。这种新颖的电化学模式有望为更多氧化还原中性的电化学转化提供重要参考。综上,我们借助高效的电化学手段实现CO₂的单电子活化,探究了CO₂自由基负离子中间体参与的新反应与新选择性,成功实现了电促进CO₂参与非活化烯烃的新型羧基化反应。本论文通过对CO₂自由基负离子性质的研究,为揭示CO₂自由基负离子新型转化的化学本质,设计更高效的羧化反应体系、加强对CO₂这种C₁资源的利用,合成出更多高附加值羧酸提供了重要参考。更多还原

【Abstract】 Due to the shortage of natural resource,it is particularly important to realize the effective exploitation and high-value utilization of limited resources.As a greenhouse gas,CO₂ exerts a profound impact on the current global climate change.However,from the perspective of resource utilization,CO₂ is an ideal C₁synthon with abundant,nontoxic and renewable features.Realizing direct CO₂incorporation into organic skeleton does not only benefit the carbon circulation,but also furnishes a series of high value-added chemicals.For example,CO₂ could be valorized to basic chemical raw materials,fuel energy molecules,biomedical products and polymer materials.However,the chemical conversion of CO₂is challenging due to its thermodynamic stability and kinetic inertness.In order to achieve the efficient activation of CO₂,scientists have developed two types activation modes,such as two-electron activation and one-electron activation.The former type uses nucleophilic species to react with CO₂,which have been widely studied.Differently,the single-electron activation involves the reduction of CO₂ to generate CO₂ radical anion which is so reactive that it can lead to the carboxylation reaction of inert compounds,thus achieving the challenging reactions which are difficult to complete through the two-electron activation mode.Moreover,the new reactivity of CO₂ radical anion may also result in unique chemoselectivity and regioselectivity.On the other hand,as an efficient organic synthesis technology,electrosynthesis has attracted chemists’much attention due to its sustainable,controllable and efficient advantages.Electrochemistry provides chemists a powerful synthetic tool whose potential can be dialed in at will,by manipulating the electric current or potential at the electrode,enabling access to achieving inert molecular activation and generating highly reactive intermediates which are difficult to form by traditional chemical methods.Although significant progress of electrochemical promoted reductive carboxylation has been achieved,there are still many problems in this field.For example,the type of substrates is limited（usually only applicable to the activated substrates）;the reaction type is restricted（limited to the reductive carboxylation mechanism）and the catalytic mode is restricted（electrochemical net reduction process）.In order to solve these problems,based on the electrochemical single electron activation strategy of CO₂,this dissertation systematically studied the carboxylation reaction of unactivated alkenes with CO₂,obtaining a series of structurally diverse diacid monolayers and alkenoic acid compounds under mild reaction conditions.This dissertation mainly includes following two parts:For the first part,we have achieved the electrochemistry-promoted dicarboxylation of unactivated alkenes with CO₂.The electroreductive system which owns potent reduction potentials,achieves the single electron activation of CO₂ to generate highly active CO₂radical anion,which complete the addition with unactivated alkene.The potent reduction potentials guarantee the challenging transformation of alkyl radical to alkyl carbanion,and the highly active alkyl carbanion were trapped by another molecule CO_2,furnishing the important diacid compounds.This study breaks the limitation that CO₂ conversion usually relies on activated substrates,serving as the first successful example to realize the efficient dicarboxylation of unactivated alkenes with CO₂.In addition,due to the mild conditions,many substrates,such as non-conjugated dienes and simple alkenes,are compatible in the system.The dicarboxylation strategy can be applied to simplify the tedious synthesis steps of drug intermediates.For instance,the phosphodiesterase type 4 enzyme（PDE4）inhibitor homologs can be efficiently synthesized by using our method.After constructing of a series of structurally diverse diacid monolayers,we further explored the application of the products in polymer materials.For example,the polycarboxylic acid monomer can be used as micro-crosslinking agent to modify polybutylene adipate（PBA）,and a new biodegradable polymer material which expresses excellent thermal stability can also be synthesized by leveraging the synthesized diacid product.For the second part,we have achieved the electrochemistry-promoted redox-neutral carboxylation of unactivated alkenes with CO₂.The electroreductive system,owning potent reduction potentials,generates CO₂radical anion which can subsequently trigger the addition of unactivated alkenes due to its high activity,consequently furnishing alkenyl carboxylic acid compounds in the corporation of further chemical event.This work breaks the limitation of the restricted catalytic mode of electrochemical carboxylation of CO₂,and successfully realizes the electrochemically promoted redox-neutral carboxylation of unactivated alkenes for the first time.Furthermore,due to the mild conditions,diverse unactivated alkenes are compatible in the system,and this reaction can also be carried out with a non-sacrificial anode system.This novel electrochemical mode will provide an important reference for more redox-neutral electrochemical transformations.In conclusion,we have achieved the electrochemically single-electron reduction of CO₂,exploring the new reactivity and selectivity of CO₂ radical anion and successfully realizing the new chemical conversion of CO₂ radical anion and unactivated alkenes.By studying the properties of CO₂ radical anion and revealing the chemical essence of the new transformation about CO₂ radical anion,this dissertation will provide an important reference for designing more efficient carboxylation reaction system,strengthening the utilization as CO₂ C₁ resource and synthesizing more high value-added carboxylic acids.更多还原