Conformational Landscape, Chirality Recognition and Chiral Analyses: Rotational Spectroscopy of Tetrahydro‐2‐Furoic Acid⋅⋅⋅Propylene Oxide Conformers

Abstract

A chiral adduct formed between a chiral carboxylic acid, tetrahydro‐2‐furoic acid (THFA), and a chiral ester, propylene oxide (PO), was investigated using rotational spectroscopy and DFT calculations. Isolated THFA exists dominantly as three different conformers: I, II, and III in a jet, with I and II taking on the trans‐COOH configuration and III having the cis‐COOH configuration. We utilized CREST, a conformational ensemble space exploration tool, to identify the possible conformations of the binary adduct, THFA⋅⋅⋅PO. Subsequent DFT geometry optimizations predicted about two hundred homochiral and heterochiral binary structures with 28 low energy structures within an energy window of 15 kJ mol−1. A rich broadband rotational spectrum was obtained with a mixture of trace amounts of THFA+PO in neon in a supersonic jet expansion. Six THFA⋅⋅⋅PO conformers were identified experimentally. Kinetically favored binary products which contain trans‐COOH I dominate among the observed conformers, while thermodynamically more stable adducts were also detected. Detailed analyses of the structures of the observed conformers show interesting chirality‐controlled structural preferences. Such non‐covalently bound chiral contact pairs are the foundation of chiral‐tag rotational spectroscopy, an exciting new analytical application of rotational spectroscopy for determination of enantiomeric excess. Enantiomeric excess analyses were performed and the results are discussed.

Rapid Enantiomeric Excess Measurements of Enantioisotopomers by Molecular Rotational Resonance Spectroscopy

“…Using the Cahn-Ingold-Prelog labels, the tag-analyte diastereomers can be designated as homochiral when the two chiral centers have (S) or (R) chirality and heterochiral when the labels differ. In chiral tag MRR spectroscopy, the derivatization uses noncovalent interactions such as hydrogen bonds to attach the derivatizing agent. − ,− This is achieved by adding a small amount of the “tag” to the neon carrier gas used to introduce the sample into vacuum. Clusters between the analyte and tag are automatically generated during the pulsed jet expansion.…”

Chiral Control of Gas‐Phase Molecules using Microwave Pulses

“…[7,48,52] By performing two different types of measurements, one with a racemic sample of the chiral tag molecule and one with an enantioenriched sample of known handedness for the tag, the excess enantiomer of the unknown sample as well as its corresponding enantiomeric excess can be determined with impressive statistics. [48,49,51,56,57] While chiral tagging is experimentally more straightforward and thus promising as a routine application in chiral analysis, M3WM can additionally be applied to control and manipulate chiral molecules, which is the central part of this article.…”

Accuracy of quantum chemistry structures of chiral tag complexes and the assignment of absolute configuration

“…This work examines the ability to assign the absolute configuration of a molecule through identification of the structure of a complex formed between an analyte and a small, chiral molecule -called the ''chiral tag.'' [1][2][3][4][5][6][7][8] The geometries of the chiral tag complexes, which are formed in a pulsed jet expansion where the analyte and tag molecule are added to the inert carrier gas, are analyzed using broadband molecular rotational spectroscopy. The goal of this approach is to develop a generally useful analytical chemistry methodology that can assign the absolute configuration of a molecule with high confidence and without the need of a reference sample of the analyte with known configuration.…”

“…In the rotational spectroscopy implementation, this additional chiral center is added using noncovalent interactions via cluster formation in a pulsed molecular beam. [1][2][3][4][5][6][7][8] Noncovalent attachment of the ''chiral tag'' avoids any possible racemization of the analyte during the chiral derivatization process. One advantage of a chiral derivatization approach is that spectrometer signals associated with the two enantiomers now occur at different frequencies (i.e., the rotational transitions of the resulting diastereomers are fully resolved in the spectrometer).…”