Copper-Catalyzed Transfer Hydrodeuteration of Aryl Alkenes with Quantitative Isotopomer Purity Analysis by Molecular Rotational Resonance Spectroscopy
Copper-Catalyzed Transfer Hydrodeuteration of Aryl Alkenes with Quantitative Isotopomer Purity Analysis by Molecular Rotational Resonance Spectroscopy
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DOI：
10.1021/jacs.1c00884
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发表时间：
2021-05-17
影响因子：
15
通讯作者：
Clark, Joseph R.
中科院分区：
文献类型：
--
作者：
Vang, Zoua Pa;Reyes, Albert;Clark, Joseph R.
描述了一种铜催化的烯烃转移氢化氘代反应，其选择性地将一个氢原子和一个氘原子引入芳基烯烃。的转移加氢氘代协议是选择性的各种内部和终端烯烃，也证明了对含烯烃的复杂的天然产物类似物。除了使用H-1、H-2和C-13 NMR分析来测量反应选择性之外，还通过分子旋转共振（MRR）光谱分析了六种转移氢化氘代产物。通过与高通量样品分析兼容的测量方法，进一步探讨了MRR光谱在氘代化学同位素杂质分析中的应用。在第一步中，使用宽带啁啾脉冲傅里叶变换微波光谱仪分析反应化学中可获得的所有同位素变体的MRR光谱特征。有了这些特征，就可以创建测量脚本，使用商用腔增强MRR光谱仪定量分析样品成分。样品消耗量低于10毫克，分析时间为10分钟的顺序，使用这种仪器-都代表数量级减少相比，宽带MRR光谱。迄今为止，这些测量代表了转移加氢氘代反应中选择性的最精确的光谱测定，并证实在这种温和的方案下可实现>140：1的产物区域选择性比。
A copper-catalyzed alkene transfer hydrodeuteration reaction that selectively incorporates one hydrogen and one deuterium atom across an aryl alkene is described. The transfer hydrodeuteration protocol is selective across a variety of internal and terminal alkenes and is also demonstrated on an alkene-containing complex natural product analog. Beyond using H-1, H-2, and C-13 NMR analysis to measure reaction selectivity, six transfer hydrodeuteration products were analyzed by molecular rotational resonance (MRR) spectroscopy. The application of MRR spectroscopy to the analysis of isotopic impurities in deuteration chemistry is further explored through a measurement methodology that is compatible with high-throughput sample analysis. In the first step, the MRR spectroscopy signatures of all isotopic variants accessible in the reaction chemistry are analyzed using a broadband chirped-pulse Fourier transform microwave spectrometer. With the signatures in hand, measurement scripts are created to quantitatively analyze the sample composition using a commercial cavity enhanced MRR spectrometer. The sample consumption is below 10 mg with analysis times on the order of 10 min using this instrument-both representing order-of-magnitude reduction compared to broadband MRR spectroscopy. To date, these measurements represent the most precise spectroscopic determination of selectivity in a transfer hydrodeuteration reaction and confirm that product regioselectivity ratios of >140:1 are achievable under this mild protocol.