Sun Jianghui, Cao Mengyu, Ge Xiyang, Ouyang Jin, Na Na
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
Department of Chemistry, College of Arts and Sciences, Beijing Normal University at Zhuhai, Zhuhai City, Guangdong Province, 519087, China.
Rapid Commun Mass Spectrom. 2025 May;39 Suppl 1:e9510. doi: 10.1002/rcm.9510. Epub 2023 Apr 4.
Electronically mismatched Diels-Alder reactions have gained much attention as an alternative pathway for C-C bond formation. To facilitate the development of facile organic transformations, mechanistic investigations are required. Spectroscopic methods (NMR, electron paramagnetic resonance and UV-visible) are normally adopted for mechanistic examinations, but further improvements in directly obtaining structural information of short-lived intermediates are encouraged. Herein, an electronically mismatched Diels-Alder reaction between indole and 1,3-cyclohexadiene was studied using in situ electrospray ionization mass spectrometry (in situ ESI-MS). Based on direct sampling and detection of the in situ ESI-MS without sample pretreatment, the structures and dynamics of important intermediates were examined on-line.
A syringe-based photocatalytic reactor and in situ ambient MS (AMS) evaluation system was constructed for mechanism studies. The role of oxygen was confirmed via control reaction employed in the N-bubbled system. The stepwise cation radical-based pathway and the [2 + 2] cycloaddition process were determined through a series of experiments, including solvent evaluation, MS/MS experiments and dynamic monitoring.
The dependence of the reaction on solvent polarity demonstrated that the reaction occurs via the formation of cation radicals, which were captured, identified and dynamically monitored via in situ ESI-MS. Without pre-separation, the intermediate of [2 + 2] cycloaddition was identified and the cycloaddition process was thereby determined to be the combination of [4 + 2] cycloaddition and [2 + 2] cycloaddition. In addition, oxygen was proved to act as an electron mediator for both catalyst Ru(bpz)(PF) and radical cations.
The mechanism of an electronically mismatched Diels-Alder reaction was successfully deduced by in situ MS associated with a syringe-based photocatalytic reactor. The structures and dynamics of cation radicals, the effect of O for the reaction and the detailed process of [2 + 2] cycloaddition have been well demonstrated. This work could not only promote the understanding and development of facile photocatalytic transformations, but also enlarge the application range of AMS in on-line monitoring.
电子不匹配的狄尔斯-阿尔德反应作为一种形成碳-碳键的替代途径已备受关注。为促进简便有机转化的发展，需要进行机理研究。机理研究通常采用光谱方法（核磁共振、电子顺磁共振和紫外-可见光谱），但鼓励在直接获取短寿命中间体结构信息方面进一步改进。在此，使用原位电喷雾电离质谱（原位电喷雾电离质谱）研究了吲哚与1,3-环己二烯之间的电子不匹配狄尔斯-阿尔德反应。基于无需样品预处理的原位电喷雾电离质谱的直接采样和检测，对重要中间体的结构和动力学进行了在线研究。
构建了基于注射器的光催化反应器和原位常压质谱（常压质谱）评估系统用于机理研究。通过在氮气鼓泡系统中进行的对照反应确认了氧气的作用。通过一系列实验，包括溶剂评估、串联质谱实验和动态监测，确定了基于阳离子自由基的逐步途径和[2+2]环加成过程。
反应对溶剂极性的依赖性表明反应通过阳离子自由基的形成发生，这些阳离子自由基通过原位电喷雾电离质谱被捕获、鉴定和动态监测。无需预先分离，鉴定出了[2+2]环加成的中间体，从而确定环加成过程是[4+2]环加成和[2+2]环加成的组合。此外，证明氧气对催化剂钌（联吡啶）（PF）和自由基阳离子均起电子介质的作用。
通过与基于注射器的光催化反应器相关联的原位质谱成功推导了电子不匹配狄尔斯-阿尔德反应的机理。阳离子自由基的结构和动力学、氧气对反应的影响以及[2+2]环加成的详细过程均得到了很好的证明。这项工作不仅可以促进对简便光催化转化的理解和发展，还可以扩大常压质谱在在线监测中的应用范围。
