A detailed understanding of the reaction mechanism(s) leading to stereoselective product formation is crucial to understanding and predicting product formation and driving the development of new synthetic methodology. One way to improve our understanding of reaction mechanisms is to characterize the reaction intermediates involved in product formation. Because these intermediates are reactive, they are often unstable and therefore difficult to characterize using experimental techniques. For example, glycosylation reactions are critical steps in the chemical synthesis of oligosaccharides and need to be stereoselective to provide the desired α- or β-diastereomer. It remains challenging to predict and control the stereochemical outcome of glycosylation reactions, and their reaction mechanisms remain a hotly debated topic. In most cases, glycosylation reactions take place via reaction mechanisms in the continuum between S_N1- and S_N2-like pathways. S_N2-like pathways proceeding via the displacement of a contact ion pair are relatively well understood because the reaction intermediates involved can be characterized by low-temperature NMR spectroscopy. In contrast, the S_N1-like pathways proceeding via the solvent-separated ion pair, also known as the glycosyl cation, are poorly understood. S_N1-like pathways are more challenging to investigate because the glycosyl cation intermediates involved are highly reactive. The highly reactive nature of glycosyl cations complicates their characterization because they have a short lifetime and rapidly equilibrate with the corresponding contact ion pair. To overcome this hurdle and enable the study of glycosyl cation stability and structure, they can be generated in a mass spectrometer in the absence of a solvent and counterion in the gas phase. The ease of formation, stability, and fragmentation of glycosyl cations have been studied using mass spectrometry (MS). However, MS alone provides little information about the structure of glycosyl cations. By combining mass spectrometry (MS) with infrared ion spectroscopy (IRIS), the determination of the gas-phase structures of glycosyl cations has been achieved. IRIS enables the recording of gas-phase infrared spectra of glycosyl cations, which can be assigned by matching to reference spectra predicted from quantum chemically calculated vibrational spectra. Here, we review the experimental setups that enable IRIS of glycosyl cations and discuss the various glycosyl cations that have been characterized to date. The structure of glycosyl cations depends on the relative configuration and structure of the monosaccharide substituents, which can influence the structure through both steric and electronic effects. The scope and relevance of gas-phase glycosyl cation structures in relation to their corresponding condensed-phase structures are also discussed. We expect that the workflow reviewed here to study glycosyl cation structure and reactivity can be extended to many other reaction types involving difficult-to-characterize ionic intermediates.

中文翻译：

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使用红外离子光谱表征难以捉摸的反应中间体：在糖基阳离子的实验表征中的应用

详细了解导致立体选择性产物形成的反应机制对于理解和预测产物形成以及推动新合成方法的发展至关重要。提高我们对反应机制理解的一种方法是表征参与产物形成的反应中间体。由于这些中间体具有反应性，因此它们通常不稳定，因此难以使用实验技术进行表征。例如，糖基化反应是寡糖化学合成中的关键步骤，需要立体选择性才能提供所需的 α-或 β-非对映异构体。预测和控制糖基化反应的立体化学结果仍然具有挑战性，其反应机制仍然是一个备受争议的话题。在大多数情况下，_N 1 和 S _N 2 样途径。通过接触离子对的置换进行的S _N 2 样途径相对容易理解，因为所涉及的反应中间体可以通过低温 NMR 光谱来表征。相比之下，通过溶剂分离的离子对（也称为糖基阳离子）进行的 S _N 1 样途径知之甚少。信噪比_{_}1 样途径的研究更具挑战性，因为所涉及的糖基阳离子中间体具有高反应性。糖基阳离子的高反应性使它们的表征复杂化，因为它们的寿命短并且与相应的接触离子对快速平衡。为了克服这一障碍并能够研究糖基阳离子的稳定性和结构，它们可以在没有溶剂和反离子的气相中在质谱仪中生成。已经使用质谱 (MS) 研究了糖基阳离子的易形成性、稳定性和碎裂性。然而，单独的 MS 提供的关于糖基阳离子结构的信息很少。通过将质谱 (MS) 与红外离子光谱 (IRIS) 相结合，已经实现了糖基阳离子气相结构的测定。IRIS 能够记录糖基阳离子的气相红外光谱，可以通过匹配从量子化学计算的振动光谱预测的参考光谱来分配。在这里，我们回顾了能够实现糖基阳离子 IRIS 的实验装置，并讨论了迄今为止已表征的各种糖基阳离子。糖基阳离子的结构取决于单糖取代基的相对构型和结构，可以通过空间和电子效应影响结构。还讨论了气相糖基阳离子结构与其相应凝聚相结构的范围和相关性。