化学键能相关的热力学参数是物理有机化学的基础，可为有机合成中的化合物构效关系和反应活性分析、反应机理甄别和新反应设计提供理论指导。目前氮氧自由基及其衍生物在有机合成中得到了广泛应用，但是对这类化合物反应性质的认识仍存在许多局限。针对这一问题，本论文通过对氮氧自由基及其衍生物热力学参数的研究，揭示了该类化合物的性质：氮氧自由基为中等强度的氢原子受体、氧合铵盐是强的负氢受体、羟胺是中等强度的氢原子和电子给体、羟胺负离子为强碱和强还原剂；并将相关热力学参数用于指导机理研究和新反应设计。主要取得如下研究成果：第一部分研究工作，系统研究了羟胺化合物TEMPOH在乙腈溶液中的电化学氧化性质，发现TEMPOH的电化学氧化机理为协同的质子耦合电子转移（CPET），该氧化电位Eox(TEMPOH)为0 V vs Fc+/0，远低于文献报道值（?Ep = 0.7 V）。通过酸碱实验和单电子转移实验确定了该实验值的准确性。基于TEMPOH的电化学氧化性质，对氮氧自由基催化循环中催化剂的再生途径提出了新的理解：羟胺可直接经1e/1H+氧化再生氮氧自由基。此外，TEMPOH类羟胺具在碱性条件下有可调节的还原性质，可作为单电子还原剂。第二部分研究工作，基于负氢转移和氢原子转移过程建立热力学循环，结合氮氧自由基和羟胺的氧化还原电位，系统测定了20个代表性羟胺化合物O-H键不同断裂模式的键能参数，建立了相应的键能标度，包括均裂能、负氢异裂能、质子异裂能和羟胺阳离子自由基的质子异裂能和均裂能。并考察了取代基效应和环结构等因素对这些键能参数的影响。基于热力学参数，分析了不同种类氮氧自由基催化醇氧化反应的热力学驱动力的差异和可能的反应机理。第三部分研究工作，基于TEMPOH类羟胺的CPET氧化性质，通过碱调节TEMPOH的还原能力。基于此，成功实现了烯烃的三氟甲基和烷氧胺基双加成反应。该反应具有中等产率，较好的区域选择性和立体选择性。同时，通过改变羟胺化合物结构，实现了三氟甲基单加成的Z-式烯烃的合成。
Chemical bond energy and related thermodynamic parameters are crucial physical properties of covalent bonds, which provide essential insights for organic syntheses, such as diagnosing reaction mechanisms, analyzing chemical reactivity and selectivity, and designing new reactions and catalysts. Aminoxyl radicals and their derivatives exhibit distinct property, reactivity, and involvement in various chemical and electrochemical oxidations, polymerization, and biological antioxidant processes. Despite extensive research on the applications, there remain limitations in comprehending the reaction properties of aminoxyl radicals and their derivatives. This study primarily focuses on investigating thermodynamic parameters, including O-H bond heterolytic and homolytic bond dissociation energies of hydroxylamines and related redox potentials. Based on the energetic data, we have summarized the reaction properties of aminoxyl radicals and their derivatives. It can be concluded that:In the first part, we remeasured the electrochemical oxidation properties of TEMPOH and its derivatives in acetonitrile. The newly-determined Eox(TEMPOH) value (0 V) is found to be 0.7 V smaller than preciously-reported one, implying an unexpectedly good electron-donating ability of TEMPOH. Such an energy discrepancy gave several implications. 1) Oxidation of TEMPOH occurs prior to that of TEMPO (0.2 V), avoiding the unsubstantiated hypothesis proposed in electrochemical syntheses that regeneration of TEMPO+ from TEMPOH at electrodes was initiated by compropor-tionation of TEMPOH to easily oxidizable TEMPO. 2) Beyond serving as a conventional hydrogen-atom donor, TEMPOH can also work well as a good electron donorIn the second part, we studied the enthalpy changes of 20 important hydroxylamines to release a hydride, a proton, a neutral hydrogen atom in acetonitrile by using the experimental method. And the redox potentials of nitroxides were examined by using CV and DPV methods, respectively. The following conclusions can be made: 1) The oxoammonium salts are the strong organic hydride acceptors which can be used as oxidation agents in organic syntheses. Based on this, we achieved the oxidation of triphenylsilane to the triphenylsilanol; 2) The nitroxides belong to moderate hydrogen-atom acceptors and their corresponding hydroxylamines can also be used as hydrogen-atom donors due to the thermochemical bias toward concerted H? transfer reactions; 3) The proton-donating abilities of the hydroxylamines are weak, which imply the corresponding anions are strong bases. And considering the oxidation potentials of hydroxylamine anions, these salts should be good reducing agent.In the third part, we have found the CPET oxidation mechanism of TEMPOH. Then the combined utilization of TEMPOH and base offers versatile tunable reducing capabilities. Herein, we have devised an efficient and practical approach for achieving highly site-selective trifluoromethylaminoxylation of unactivated olefins using TEMPOH as reducing agents and persistent radical precursor.
