Assigning the absolute configurations of chiral primary amines based on experimental and DFT-calculated 19F nuclear magnetic resonance

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 19F NMR chemical shift differences of its derived two fluorinated amides by reacting with two enantiomers of a chiral derivatizing agent FPP (a-fluorinated phenylacetic phenylselenoester) separately. Comparing the experimental chemical shift difference ΔσR,S/ α-F of (R)-FPA-amide/(S)-FPA-amide with the calculated Δσ R,S of (R)-FPA-(R)-amide/(S)-FPA-(R)-amide, if the experimental Δσ R,S has the same symbol (positive or negative) as one of the theoretical Δσ 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.