¹H NMR Chiral Analysis of Charged Molecules via Ion Pairing with Aluminum Complexes

Abstract

Chiral analysis, such as determination of identity, concentration, and relative ratio of optically active (chiral) molecules, plays an indispensable role in contemporary synthetic, medicinal, and biological chemistry. Here, we describe the selective control of metal-centered chirality in an octahedral geometry to prepare negatively charged Al(III) complexes, which can be used as versatile (1)H NMR chiral solvating agents for both positively and negatively charged chiral molecules in polar or nonpolar solvents. During the formation of ion pairs between the Al(III) complexes and the chiral analytes such as amines and carboxylic acids, the metal-centered chirality in the Al complexes plays a crucial role in providing anisochronous chemical shifts to the (1)H NMR spectra. As a chiral solvating agent, Al(III) complexes display an unprecedentedly broad substrate scope, good solvent compatibility, and operational simplicity.

Pd‐Catalyzed Allylation of Imines to Access α‐CF3‐Substituted α‐Amino Acid Derivatives

“…Alternatively, the direct use of chiral NMR shift reagents may allow for a simple determination of the enantiomeric composition by just mixing the (crude) reaction product with the shift reagent . Some of us (H. Kim's group) have recently introduced a novel class of chiral aluminum complexes A (Scheme A) that allowed for the straightforward analysis of chiral amines using 1 H NMR spectroscopy . Considering the simplicity of this approach, we reasoned that this would allow us to overcome the difficulties observed for the analysis of compound 7a with HPLC by using standard 19 F NMR to directly quantify the enantiomeric composition of the CF 3 ‐amino acid 7a .…”

A New Chirally Organized Trifluoromethylanthrylmethanol Derivative and Its Application as Chiral Solvating Agent

“…Several CSA's for amines and alcohols enantiodifferentiation had been previously described in the literature . Herein, we have tested the enantiodiscrimination capacity of both diastereoisomers of 4 against four mixtures of enantiomers: 1‐(1‐napthyl)ethylamine, 5 , 1‐ cis ‐amino‐2‐indanol, 6 , N ‐methyl‐3‐phenyl‐3‐[4‐(trifluoromethyl)phenoxy]propan‐1‐amine (fluoxetine), 7 , and 1‐phenylethanediol, 8 (Figure ).…”

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 Several CSA's for amines and alcohols enantiodifferentiation had been previously described in the literature. [41][42][43] Herein, we have tested the enantiodiscrimination capacity of both diastereoisomers of 4 against four mixtures of enantiomers: 1-(1napthyl)ethylamine, 5, 1-cis-amino-2-indanol, 6, N-methyl-3phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine (fluoxetine), [44] 7, and 1-phenylethanediol, 8 (Figure 3). All of them own donor groups and an aromatic moiety that allows pinteraction with the CSA.…”

Enhancement of visual chiral sensing via an anion-binding approach: Novel ionic liquids as the chiral selectors

“…Great progress has been made in the enantioselective analysis of the racemates in recent years. It can be carried out with NMR [2,3], optical sensor [4,5], and spectroscopy [6][7][8][9][10]. Differently, it's worth noting that visual discrimination of racemates has been receiving increasing interest because of its convenience and rapidity, which is divided into two parts: color changes and precipitate formation [11][12][13][14][15][16][17][18][19].…”