Assigning the Absolute Configurations of Chiral Primary Amines Based on Experimental and DFT-Calculated (19)F Nuclear Magnetic Resonance

基于实验和DFT计算的(19)F核磁共振确定手性伯胺的绝对构型

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Abstract

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 (19)F 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 Δδ(α-F (R,S) ) of (R)-FPA-(R)-amide/(S)-FPA-(R)-amide, if the experimental Δδ(α-F (R,S) ) has the same symbol (positive or negative) as one of the theoretical Δδ(α-F (R,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.

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