Chemical Synthesis of [²H]-Ethyl Tosylate and Exploration of Its Crypto-optically Active Character Combining Complementary Spectroscopic Tools

Abstract

Small chiral molecules are excellent candidates to push the boundaries of enantiodiscrimination analytical techniques. Here is reported the synthesis of two new deuterated chiral probes, (R)-and (S)-[ 2 H]-ethyl tosylate obtained with high ee's. Due to their crypto-optically active properties, the discrimination of each enantiomer is challenging. While their enantiopurity is determined by 2 H-NMR in chiral anisotropic media, their identification was performed by combining quantum chemical calculations and vibrational circular dichroism analysis.

Assignment of the absolute configuration of molecules that are chiral by virtue of deuterium substitution using chiral tag molecular rotational resonance spectroscopy

“…[39][40][41][42][43] A recent study illustrated the success in combining VCD and deuterium NMR spectroscopy in an aligned chiral polymer matrix for full chiral analysis -the measurement of the ee and the assignment of the absolute configuration of the dominant enantiomer -of molecules that are chiral by virtue of deuterium substitution. 44 The recent method of three-wave mixing rotational spectroscopy [45][46][47] has been used to measure an enantiomer-dependent microwave signal for a molecule that is chiral by virtue of deuteration. 48 However, this measurement approach has limitations that preclude its use to support synthetic chemistry.…”

“…Coupled with advances in computational chemistry, the techniques have been used to establish the absolute configuration of enantioisotopomers through the comparison of the experimental VCD spectrum with the spectrum calculated via quantum chemistry 39–43 . A recent study illustrated the success in combining VCD and deuterium NMR spectroscopy in an aligned chiral polymer matrix for full chiral analysis ‐ the measurement of the ee and the assignment of the absolute configuration of the dominant enantiomer ‐ of molecules that are chiral by virtue of deuterium substitution 44 …”

“… 39 – 43 A recent study illustrated the success in combining VCD and deuterium NMR spectroscopy in an aligned chiral polymer matrix for full chiral analysis - the measurement of the ee and the assignment of the absolute configuration of the dominant enantiomer - of molecules that are chiral by virtue of deuterium substitution. 44 …”