Conformational Panorama and Chirality Controlled Structure–Energy Relationship in a Chiral Carboxylic Acid Dimer

Abstract

Chirality recognition in dimers of tetrahydro‐2‐furoic acid (THFA) was studied in a conformer‐specific manner using rotational spectroscopy and theoretical approaches. THFA shows a strong preference for the trans‐ over the cis‐COOH configuration. Two drastically different scenarios are possible for the detectable (THFA)2: a kinetically preferred dimer bound by feeble interactions between two trans THFAs or a thermodynamically favored dimer with a double hydrogen‐bonded ring structure between two cis subunits. To identify the conformers responsible for the extremely dense rotational spectra observed, it was essential not only to locate several hundred homo/heterochiral (THFA)2 minima in ab initio calculations but also to evaluate the energetic connectivities among the minima. The study further reveals an interesting chirality dependent structure–energy ordering relationship. A method for enantiomeric excess (ee) determination of THFA is presented using a recently proposed chiral self‐tag approach.

Matrix Isolation‐Vibrational Circular Dichroism Spectroscopic Study of Conformations and Non‐Covalent Interactions of Tetrahydro‐2‐Furoic Acid

“…If there were significant dimer formation in the gas phase already, one would expect mainly Type 1 species, following the thermodynamic mechanism. The current study supports the conclusion reported for THFA in a previous rotational spectroscopic study [8b] …”

“…Three representative geometries of Type 1 (THFA) 2 , namely D33, D34, and D56, are shown in Figure 4, while all of their optimized geometries are provided in Figure S3, SI. These dimers identified are similar to those reported previously although calculated at different levels of theory and under different conditions (in the gas phase or in solution) compared to the current case [8b,10] . Their relative free energies and Boltzmann population factors at 24 K, 30 K and 298 K of all ten Type 1 binary conformers at the B3LYP‐D3BJ/def2‐TZVP without and with PCM of Ar are listed in Table 2.…”

“…The binary structures are separated into Type 1 , 2 , 3 groups with energy gaps of ∼15 to 22 kJ mol −1 between the most stable structures in Type 1 and 2 and in Type 1 and 3 , respectively. Interestingly, neither the Type 1 structures, which feature the double H‐bonded cyclic ring and are the dominant species in chloroform solution, [10] nor the Type 2 geometries, which are the main species in a jet expansion, [8b] make much contribution under the current experimental condition. Rather, a new type of dimeric structures, Type 3 conformers, which are the least thermodynamically stable among the three types, account for the majority of dimeric species in the observed IR and VCD spectra.…”

Chiral analysis of pantolactone with molecular rotational resonance spectroscopy

“…[16][17][18] Chiral tagging, meanwhile, uses in situ chiral derivatization through the formation of gas-phase diastereomeric complexes between a small, chiral molecule of known enantiopurity (the tag), and the analyte. [19][20][21] The complexes form through non-covalent interactions between the tag and analyte and are generated in the pulsed jet expansion used to inject samples into MRR spectrometers. In this paper, we employ the chiral tagging method for enantiomeric analysis of pantolactone.…”

“…In three‐wave mixing rotational spectroscopy, a sequence of excitation pulses is applied to the sample to generate a single‐frequency signal where the phase determines the dominant enantiomer of the sample and the amplitude is proportional to the enantiomeric excess 16–18 . Chiral tagging, meanwhile, uses in situ chiral derivatization through the formation of gas‐phase diastereomeric complexes between a small, chiral molecule of known enantiopurity (the tag), and the analyte 19–21 . The complexes form through non‐covalent interactions between the tag and analyte and are generated in the pulsed jet expansion used to inject samples into MRR spectrometers.…”