Data_Sheet_2_Assigning the Absolute Configurations of Chiral Primary Amines Based on Experimental and DFT-Calculated 19F Nuclear Magnetic Resonance.CDX

In this work, a novel method for assigning the absolute configuration of a chiral primary amine has been developed based on the experimental and DFT-calculated 19F NMR chemical shift differences of its derived two fluorinated amides by reacting with two enantiomers of a chiral derivatizing agent FPP (α-fluorinated phenylacetic phenylselenoester) separately. Comparing the experimental chemical shift difference Δδα-FR,S of (R)-FPA-amide/(S)-FPA-amide with the calculated Δδα-FR,S of (R)-FPA-(R)-amide/(S)-FPA-(R)-amide, if the experimental Δδα-FR,S has the same symbol (positive or negative) as one of the theoretical Δδα-FR,S, the assigned configuration of the amine is considered to be consistent with the theoretical one. Our method could be applied to a broad substrate scope avoiding wrong conclusion due to empirical judgment.

本研究开发了一种全新的手性伯胺绝对构型指认方法：该方法通过将底物与手性衍生化试剂FPP（α-fluorinated phenylacetic phenylselenoester）的两种对映体分别反应，得到两个氟化酰胺，进而基于二者的实验与密度泛函理论（DFT）计算得到的19F核磁共振（NMR）化学位移差值开展分析。将(R)-FPA-酰胺/(S)-FPA-酰胺的实验化学位移差值Δδα-FR,S，与(R)-FPA-(R)-酰胺/(S)-FPA-(R)-酰胺的计算化学位移差值Δδα-FR,S进行对比：若实验所得Δδα-FR,S与某一组理论计算所得Δδα-FR,S具有相同的符号（正或负），则可认为该伯胺的指认构型与理论构型一致。本方法可适配宽泛的底物范围，有效规避了经验性判断导致错误结论的风险。