A Protocol for NMR Analysis of the Enantiomeric Excess of Chiral Diols Using an Achiral Diboronic Acid Template

Abstract

A practically simple derivatization protocol for determining the enantiopurity of chiral diols by (1)H NMR spectroscopic analysis is described. Diols were treated with 0.5 equiv of 1,3-phenyldiboronic acid to afford mixtures of diastereomeric boronate esters whose homochiral/heterochiral ratios are an accurate reflection of the diol's enantiopurity.

A Three-Component Derivatization Protocol for Determining the Enantiopurity of Sulfinamides by 1H and 19F NMR Spectroscopy

“…These protocols involve treatment of a scalemic chiral analyte with 2-formylbenzeneboronic acid 2 (2-FPBA) and an enantiopure chiral selector (amine or diol) to afford pairs of diastereomeric iminoboronate esters. The diastereomeric ratio ( dr ) of these iminoboronate esters can then be measured by comparing the relative intensities of the integrals of their well-resolved imine proton singlets in their 1 H NMR spectra (see Scheme for how this method is used to determine the ee of α-methylbenzylamine) . Given its proven utility, we decided to investigate whether this type of three-component 1 H NMR chiral derivatization protocol, often referred to as the Bull–James assembly, could be applied to determine the ee of scalemic samples of S -chiral sulfinamides.…”

NMR analysis of the enantiomeric purity of chiral diols by a new chiral boron agent

“…Chiral diols are very important chiral inducers and organic synthons. 13 So far, only a few NMR methods, 14 including chiral solvating agents (CSAs) [15][16][17][18] and chiral derivatizing agents (CDAs), 19,20 have been reported for the chiral recognition of diols, but the obtained chemical shi nonequivalent (DDd) values are small in general. Among, chiral boric acids are potential excellent chiral recognition agents for diols, because diols are very easy to be derivatized by boric acids to generate stable cyclic ester compounds, resulting in a relatively large DDd values.…”

High-throughput assay for determining enantiomeric excess of chiral diols, amino alcohols, and amines and for direct asymmetric reaction screening

“…[15][16][17] 3 Kubo et al were among the pioneers in the development of enantioselective optical sensors for ee; in their initial work, they described screening of amines using derivatized calixarenes in ethanol. 18,19 Later a number of research groups, such as Anslyn et al, [20][21][22][23] Wolf et al, [24][25][26][27] James et al, [28][29][30] among other groups have developed high-throughput screening (HTS) methods for realtime analysis of enantiomers, contributing to the development and optimization efforts in the discovery of efficient catalysts and conditions for asymmetric reactions. 14 Our research team has developed a versatile fluorescence-based assay for determination of ee in mixtures of enantiomers of 1,2-and 1,3-diols, amines, amino acid esters, and amino alcohols (Figure 1).…”