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 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 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.

Application of the 2-deoxyglucose scaffold as a new chiral probe for elucidation of the absolute configuration of secondary alcohols

“…7,8 Some time ago, our group proposed a novel method of assigning the stereochemistry of secondary alcohols, which already echoed in the world literature. [9][10][11][12][13] It has originated from the model studies on amphotericin B; its complete historical background has been presented in our previous work. 14 Long story short, this approach is based on an observation that a glycosidic bond, formed between a pyranose and virtually any chiral aglycone, displays almost nonconformational freedom.…”

The Assignment of the Absolute Configuration of β-Chiral Primary Alcohols with Axially Chiral Trifluoromethylbenzimidazolylbenzoic Acid

“…This NMR-based method, in general, works for various types of compounds, such as α-chiral primary alcohols and amines, ,,− thiols, cyanohydrins, , tertiary alcohols, , and even conformationally complex cyclic secondary amines and polyfunctional compounds. ,, Further developments include the use of barium to improve the observed Δδ RS , the application of 13 C NMR, and the use of resin-bound regents , or direct in-tube derivatization …”

Chiral Discrimination by a Binuclear Pd Complex Sensor Using 31P{1H} NMR

“…In addition, the narrow spectral range of 1 H NMR is not conducive to producing large and easily distinguishable split signals. To address these limitations, one of the most convenient approaches is to use signals of heteronuclear NMR sensors. − 19 F and 31 P NMR signals , are the most used heteronuclear signals in NMR chiral recognition due to observable spectral split signal and wide spectral range.…”

“…The developed heteronuclear NMR chiral sensors are mainly divided into two kinds: one is based on covalent derivatization with two enantiomers of an analyte to generate a pair of diastereoisomers, − and the other is a metal complex which distinguishes chiral analytes by coordinating two enantiomers of an analyte with the metal center of the metal complex. Because the metal center has a rigid cavity like a capsule, analytes with subtle chiral differences can be solved.…”