Absolute configuration of tert-butyl-1-(2-methylnaphthyl)phosphine oxide

The enantiomers of tert-butyl-1-(2-methylnaphthyl)phosphine oxide 1 have been separated using a homemade HPLC column and an analytical gradient system. Vibrational absorption and circular dichroism spectra for both enantiomers have been measured in CD2Cl2 and CH2Cl2 solutions in the 2000-900 cm(-1) region. The fully relaxed potential energy surface of (S)-tert-butyl-1-(2-methylnaphthyl)phosphine oxide, obtained using the B3LYP functional with a 6-31G basis set, indicated two stable conformers with their populations in a approximately 2:1 ratio. The vibrational absorption and VCD spectra are predicted for these two conformers using the B3LYP functional with a 6-31G basis set. The comparison of predicted and experimental spectra indicated that (+)-tert-butyl-1-(2-methylnaphthyl)phosphine oxide is in the (S)-configuration. This assignment is supported by the ab initio prediction of positive optical rotation for the most stable conformer with an (S)-configuration and the nonequivalence sense of the tert-butyl group chemical shift observed in the 1H NMR spectrum of this enantiomer measured in the presence of (+)-(S)-mandelic acid as a chiral solvating agent.     

Determination of the absolute configuration of chiral alpha-aryloxypropanoic acids using vibrational circular dichroism studies: 2-(2-chlorophenoxy) propanoic acid and 2-(3-chlorophenoxy) propanoic acid

The enantiomers of 2-(2-chlorophenoxy) propanoic acid and 2-(3-chlorophenoxy) propanoic acid were resolved on a chiral HPLC column and investigated using mid-infrared vibrational circular dichroism (VCD). Experimental infrared vibrational absorption and VCD spectra were measured in CDCl3 solution in the 2000-900 cm-1 region and compared with the ab initio predictions of absorption and VCD spectra. The predicted spectra were obtained with density functional theory using B3LYP/6-31G* basis set for the stable and dominant conformers. But the predicted spectra did not provide unambiguous structural information due to intermolecular hydrogen bonding in solution. To eliminate the hydrogen bonding effects, the acids were converted to the corresponding methyl esters and the experimental absorbance and VCD spectra of methyl esters were measured. B3LYP predicted spectra were also obtained for the stable and dominant conformers of the esters. From a comparison of the experimental VCD spectra of methyl esters with corresponding ab initio predictions, the absolute configurations of esters, and therefore of their parent acids, are unambiguously determined to be (+)-(R).     

Chromatographic resolution, solution and crystal phase conformations, and absolute configuration of tert-butyl(dimethylamino)phenylphosphine-borane complex

The enantiomers of tert-butyl(dimethylamino)phenylphosphine-borane complex 2 have been separated by HPLC using cellulose tris-p-methylbenzoate as chiral stationary phase. The borane protection could be removed without racemization and the P-configuration of the free aminophosphine 1 has shown to be stable in solution. Infrared (IR) and vibrational circular dichroism (VCD) spectra have been measured in CD2Cl2 solution for both enantiomers. B3LYP/6-31+G(d) DFT calculations allowed a prediction that complex (S)-2 exists as three conformers in equilibrium and computed population-weighted IR and VCD spectra. Predicted and experimental IR and VCD spectra compared very well and indicate that enantiomer (+)-2 has the S absolute configuration. This assignment has been confirmed by an X-ray diffraction study on a single crystal of (+)-2. The crystal structure of enantiomerically pure 2 appears to be very close to the most stable computed conformer which proved to be predominant in solution.     

Direct determination of absolute configuration of methyl-substituted phenyloxiranes: combined experimental and theoretical approach

Three possible methyl-substituted phenyloxiranes have been synthesized in enantioenriched form (89-99% enantiomeric excess (ee)), and their vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra have been recorded. The experimental spectra are compared to theoretical spectra obtained from quantum mechanical calculations (density functional theory with the B3LYP hybrid exchange correlation functional with 6-31++G*, aug-cc-pVDZ, or aug-cc-pVTZ basis set) and related to the physical structure of the compounds. The absolute configuration could be established directly in each case by comparing experimental and theoretical spectra. In addition, we have been able to document the changes that occur both in structures and in the VA and VCD spectra due to substituent effects on the oxirane ring.     

秋水仙碱立体异构体电子结构及圆二色谱性质的理论研究

采用量子化学密度泛函理论(DFT)在B3LYP/6-311++G二水平上对秋水仙碱四个立体异构体分子几何构型进行了优化,在优化的基础上进行了振动圆二色谱(VCD),紫外-可见光谱(UV-Vis)和电子圆二色谱(ECD)研究.为模拟真实条件,以水为溶剂,计算其对分子电子结构和光谱性质的影响.研究结果表明:秋水仙碱四个立体...     

Absolute configurations, predominant conformations and tautomeric structures of enantiomeric tert-butylphenylphosphine oxides

Enantiomeric tert-butylphenylphosphine oxides have been isolated via resolution of the racemate with mandelic acid and investigated by using vibrational circular dichroism (VCD). Vibrational absorption and circular dichroism spectra of dextrorotatory, levorotatory, and racemic mixture of tert-butylphenylphosphine oxide have been measured in CDCl(3) and CHCl(3) solutions in the 2000-900 cm(-)(1) region. Experimental spectra are compared with the ab initio predictions of absorption and VCD spectra obtained with density functional theory using B3LYP/6-31G basis set for different tautomeric structures and conformers of (S)-tert-butylphenylphosphine oxide. This comparison indicates that (-)-tert-butylphenylphosphine oxide is of the (S)-configuration and indicates only one tautomeric structure and one conformation predominant for tert-butylphenylphosphine oxide in CDCl(3) and CHCl(3) solutions.     

Vibrational circular dichroism study of optically pure cryptophane-A

Vibrational circular dichroism (VCD) measurements and density functional theory (DFT) calculations were used to obtain the absolute configuration of optically pure cryptophane-A molecule. This large molecule (120 atoms) that possess a globular shape, but no chiral centers, exceeds the molecular size of published structures for which VCD has been used to determine the absolute configuration. VCD spectra recorded in CDCl(3) solution for the two resolved enantiomers are near mirror images, and very good agreement between the observed IR and VCD spectra and intensity calculations performed at the DFT (B3PW91/6-31G) level establish, besides the absolute configuration, the preferential anti conformation of the aliphatic linkers of the chloroform-cryptophane-A complex. Experiments performed in CD(2)Cl(2) and C(2)D(2)Cl(4) solutions show no significant modifications in the IR and VCD spectra, indicating that the conformation of the aliphatic linkers is similar for empty (C(2)D(2)Cl(4) solution) and encaged (CDCl(3) and CD(2)Cl(2) solutions) cryptophane-A molecules.     

Determination of the absolute configuration of a chiral oxadiazol-3-one calcium channel blocker, resolved using chiral chromatography, via concerted density functional theory calculations of its vibrational circular dichroism, electronic circular dichroism, and optical rotation

The chiral oxadiazol-3-one 2 has recently been shown to exhibit myocardial calcium entry channel blocking activity, substantially higher than that of diltiazem. To determine the enantioselectivity of this activity, the enantiomers of 2 have been resolved using chiral chromatography. The absolute configuration (AC) of 2 has been determined by comparison of density functional theory (DFT) calculations of its vibrational circular dichroism (VCD) spectrum, electronic circular dichroism (ECD) spectrum, and optical rotation (OR) to experimental VCD, ECD, and OR data. All three chiroptical properties yield identical ACs; the AC of 2 is unambiguously determined to be S(+)/R(-).     

Vibrational absorption and circular dichroism studies of trans-(3S,4S)-d6-cyclopentene in the gas phase

Vibrational absorption (IR) and circular dichroism (VCD) measurements of trans-(3S,4S)-d6-cyclopentene in the gas phase were performed in the C-H, C-D, and mid-infrared regions. In this study, we report the first VCD spectra recorded at high spectral resolution (up to 0.5 cm(-1)) with a very good signal-to-noise ratio (differential absorbance lower than 5 x 10(-6)). The quality of the experimental spectra allows us the observation of the vibration-rotation structure of the bands in both absorption and VCD spectra. Experimental spectra have been compared with the density functional theory (DFT) absorption and VCD spectra, calculated using B3LYP functional and cc-pVTZ basis set for the axial, equatorial, and planar conformers. Lorentzian and PQR band profiles have been used to convert the calculated dipolar and rotational strengths. In the mid-infrared (<2000 cm(-1)) region, predicted (population-weighted) spectra were in excellent agreement with experiment, allowing the determination of the absolute configuration of this molecule. Above 2000 cm(-1), a reasonable agreement was obtained even if anharmonicity was not considered and if Fermi resonance occurs in the C-D stretching region. Finally, a more precise analysis of the absorption spectrum has been achieved by taking into account anharmonicity of the C-H stretching and its coupling with the ring-puckering motion.     

Absolute configuration and predominant conformations of 1,1-dimethyl-2-phenylethyl phenyl sulfoxide

The absolute configuration of the (+)-1,1-dimethyl-2-phenylethyl phenyl sulfoxide is determined to be (R), using three different chiroptical spectroscopic methods, namely vibrational circular dichroism (VCD), electronic circular dichroism (ECD) and specific rotation. Four solution conformations are identified for 1,1-dimethyl-2-phenylethyl phenyl sulfoxide. In each of the methods used, experimental data for the enantiomers of 1,1-dimethyl-2-phenylethyl phenyl sulfoxide were measured in the solution phase and concomitant quantum mechanical calculations of corresponding properties were carried out using density functional theory with B3LYP functional and 6-31G* and 6-31+G basis sets. Additional VCD and ECD calculations were also undertaken with 6-311G(2d,2p) basis set. A comparison of theoretically predicted data with the corresponding experimental data has allowed us to elucidate the absolute configuration and predominant conformations of (+)-1,1-dimethyl-2-phenylethyl phenyl sulfoxide.     

Vibrational circular dichroism and absolute configuration of chiral sulfoxides: tert-butyl methyl sulfoxide

Mid-infrared vibrational unpolarised absorption and vibrational circular dichroism (VCD) spectra of CCl4 solutions of tert-butyl methyl sulfoxide (1) are reported. The spectra are compared to ab initio density functional theory (DFT) calculations carried out using two functionals, B3PW91 and B3LYP, and two basis sets, 6-31G* and TZ2P. The VCD spectra are calculated using Gauge-invariant atomic orbitals (GIAOs). The analysis of the VCD spectrum confirms the R(-)/S(+) absolute configuration of 1. The advantages and disadvantages of VCD spectroscopy in determining the absolute configurations of chiral sulfoxides are discussed.     

Absolute configurations, predominant conformations, and tautomeric structures of enantiomeric tert-butylphenylphosphinothioic acid.

Vibrational absorption and circular dichroism spectra of dextrorotatory, levorotatory, and racemic mixture of tert-butylphenylphosphinothioic acid have been measured in CCl(4) solutions in the 2000-900 cm(-1) region. The conformations for both tautomeric structures of (S)-tert-butylphenylphosphinothioic acid are investigated using the B3LYP functional with the 6-31G* basis set. For the most stable conformation, the absorption and VCD spectra are predicted ab initio using the B3LYP functional with 6-31G*, 6-311G(2d, 2p), 6-31+G, and 6-311G(3df, 3pd) basis sets. A different functional, B3PW91, was also used with the 6-31G* basis set. The predicted spectra are compared to the experimental spectra. The comparison indicates that (-)-tert-butylphenylphosphinothioic acid is of the (S)-configuration and exists in only one tautomeric structure and one conformation in CCl(4) solution.     

Vibrational circular dichroism,absolute configuration and predominant conformations of volatile anesthetics: 1,2,2,2-tetrafluoroethyl methyl ether

Vibrational absorption and circular dichroism spectra of (−)-1,2,2,2-tetrafluoroethyl methyl ether have been measured in CCl₄ solution in the 2000–900 cm⁻¹ region. These spectra are compared with the ab initio predictions of absorption and VCD spectra obtained with density functional theory using B3LYP/6-31G* and B3PW91/6-311G(2d) basis sets for different conformers of (R)-1,2,2,2-tetrafluoroethyl methyl ether. The results suggest that the trans-conformer of 1,2,2,2-tetrafluoroethyl methyl ether is predominant in the solution phase and that the (−)-enantiomer has the R-configuration.     

Understanding Solvent Effects in Vibrational Circular Dichroism Spectra: [1,1'-Binaphthalene]-2,2'-diol in Dichloromethane, Acetonitrile, and Dimethyl Sulfoxide Solvents

We present a combined experimental and computational investigation of the vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra of [1,1'-binaphthalene]-2,2'-diol. First, the sensitive dependence of the experimental VA and VCD spectra on the solvent is demonstrated by comparing the experimental spectra measured in CH(2)Cl(2), CD(3)CN, and DMSO-d(6) solvents. Then, by comparing calculations performed for the isolated solute molecule to calculations performed for molecular complexes formed between solute and solvent molecules, we identify three main types of perturbations that affect the shape of the VA and VCD spectra when going from one solvent to another. These sources of perturbations are (1) perturbation of the Boltzmann populations, (2) perturbation of the electronic structure, and (3) perturbation of the normal modes.     

Harmonic and anharmonic features of IR and NIR absorption and VCD spectra of chiral 4-X-[2.2]paracyclophanes

The vibrational absorption spectra and vibrational circular dichroism (VCD) spectra of both enantiomers of 4-X-[2.2]paracyclophanes (X = COOCD3, Cl, I) have been recorded for a few regions in the range of 900-12000 cm(-1). The analysis of the VCD spectra for the two IR regions, 900-1600 cm(-1) and 2800-3200 cm(-1), is conducted by comparing with DFT calculations of the corresponding spectra; the latter region reveals common motifs of vibrational modes for the three molecules for aliphatic CH stretching fundamentals, whereas in the mid-IR region, one is able to identify specific signatures arising from the substituent groups X. In the CH stretching region between 2900 and 2800 cm(-1), we identify and interpret a group of three IR VCD bands due to HCH bending overtone transitions in Fermi resonance with CH stretching fundamental transitions. The analysis of the NIR region between approximately 8000 and approximately 9000 cm(-1) for X = COOCD3 reveals important features of the aromatic CH stretching overtones that are of value since the aromatic CH stretching fundamentals are almost silent. The intensifying of such overtones is attributed to electrical anharmonicity terms, which are evaluated here by ab initio methods and compared with literature data.     

Lactic acid in solution: investigations of lactic acid self-aggregation and hydrogen bonding interactions with water and methanol using vibrational absorption and vibrational circular dichroism spectroscopies

The infrared vibrational absorption (VA) and vibrational circular dichroism (VCD) spectral features of L-(+)-lactic acid (LA) in CDCl3 solution are concentration dependent, showing evidence of oligomerization with increasing concentrations. To understand the observed spectra, geometry optimizations, vibrational frequencies, and VA and VCD intensities were evaluated for (LA)n with n=1-4 using density functional theory calculations at the B3LYP6-311++G(d,p), B3LYP/cc-pVTZ, and in some cases, B3LYP/aug-cc-pVTZ levels of theory. Comparisons with the experimental spectra indicate that the lowest energy LA dimer (AA), formed by two C Double Bond O...HO hydrogen bonds, is one of the dominating species in solution at room temperature. Possible contributions from the LA trimer and tetramer are also discussed. To model the VA and VCD spectra of LA in water and in methanol, both implicit polarizable continuum model and explicit hydrogen bonding considerations were used. For explicit hydrogen bonding, geometry optimizations of the AA-(water)n and AA-(methanol)n complexes, with n=2,4,6, were performed, and the corresponding VA and VCD spectra were simulated. Comparisons of the calculated and experimental VA and VCD spectra in the range of 1000-1800 cm(-1) show that AA-(water)n with n=6 best reproduces the experimental spectra in water. On the other hand, AA-(methanol)n with n=2 reproduces well the experimental results taken in methanol solution. In addition, we found evidence of chirality transfer, i.e., some vibrational bands of the achiral water subunits gain VCD strength upon complexation with the chiral LA solute. The study is the first to use VCD spectroscopy to probe the structures of LA aggregates and hydrogen bonding solvation clusters in the solution phase.     

Chirality transfer through hydrogen-bonding: experimental and ab initio analyses of vibrational circular dichroism spectra of methyl lactate in water

The infrared vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra of methyl lactate were measured in the 1000-1800 cm(-1) region in the CCl(4) and H(2)O solvents, respectively. In particular, the chirality transfer effect, i.e. the H-O-H bending bands of the achiral water subunits that are hydrogen-bonded to the methyl lactate molecule exhibit substantial VCD strength, was detected experimentally. A series of density functional theory calculations using B3PW91 and B3LYP functionals with 6-311++G(d,p) and aug-cc-pVTZ basis sets were carried out to simulate the VA and VCD spectra of the methyl lactate monomer and the methyl lactate-(H(2)O)(n) complexes with n = 1, 2, 3. The population weighted VA and VCD spectra of the methyl lactate monomer are in good agreement with the experimental spectra in CCl(4). Implicit polarizable continuum model was found to be inadequate to account for the hydrogen-bonding effect in the observed VA and VCD spectra in H(2)O. The methyl lactate-(H(2)O)(n) complexes with n = 1, 2, 3 were used to model the explicit hydrogen-bonding. The population weighted VA and VCD spectra of the methyl lactate-H(2)O binary complex are shown to capture the main spectral features in the observed spectra in aqueous solution. The theoretical modeling shows that the extent of chirality transfer depends sensitively on the specific binding sites taken by the achiral water molecules. The observation of chirality transfer effect opens a new spectral window to detect and to model the hydrogen-bonding solvent effect on VCD spectra of chiral molecules.     

DFT study of vibrational circular dichroism spectra of D-lactic acid-water complexes

This paper presents a discussion of the interaction energies, conformations, vibrational absorption (VA, harmonic and anharmonic) and vibrational circular dichroism (VCD) spectra for conformers of monomeric chiral d(-)-lactic acid and their complexes with water at the DFT(B3LYP)/aug-cc-pVDZ and DFT(B3LYP)/aug-cc-pVTZ levels. A detailed analysis has been performed principally for the two most stable complexes with water, differing by lactic acid conformation. The VCD spectra were found to be sensitive to conformational changes of both free and complexed molecules, and to be especially useful for discriminating between different chiral forms of intermolecular hydrogen bonding complexes. In particular, we show that the VCD modes of an achiral water molecule after complex formation acquire significant rotational strengths whose signs change in line with the geometry of the complex. Using the theoretical prediction, we demonstrate that the VCD technique can be used as a powerful tool for structural investigation of intermolecular interactions of chiral molecules and can yield information complementary to data obtained through other molecular spectroscopy methods.     

Absolute configuration, predominant conformations, and vibrational circular dichroism spectra of enantiomers of n-butyl tert-butyl sulfoxide

Alkylation of the alpha-carbanion of (R)-(-)-tert-butyl methyl sulfoxide (4) with n-propyl bromide afforded (+)-n-butyl tert-butyl sulfoxide (1) to which the absolute configuration (R) was ascribed. This assignment was confirmed by X-ray analysis of the complex 6 obtained from the enantiomerically pure sulfoxide (-)-1 and mercury chloride. Vibrational absorption and circular dichroism spectra of (+)-1 were measured in CDCl3 solution in the 2000-900 cm(-1) region and compared with the ab initio predictions of absorption and VCD spectra obtained with density functional theory using the B3LYP/6-31G basis set for different conformers of (R)-1. This comparison indicated also that (+)-1 is of the (R)-configuration.     

Absolute configuration and conformational stability of (+)-2,5-dimethylthiolane and (-)-2,5-dimethylsulfolane

Enantiopure (+)-2,5-dimethylthiolane and (-)-2,5-dimethylsulfolane were prepared using literature procedures and investigated using vibrational circular dichroism (VCD). Experimental absorption and VCD spectra of (+)-2,5-dimethylthiolane and (-)-2,5-dimethylsulfolane in CCl(4) solution in the 2000-900 cm(-)(1) region were compared with the ab initio predictions of absorption and VCD spectra obtained with density functional theory using the B3LYP/6-311G(2d, 2p) basis set for different conformers of (2R,5R)-2,5-dimethylthiolane and (2R,5R)-2,5-dimethylsulfolane. This comparison indicates that (+)-2,5-dimethylthiolane is of the (2R,5R)-configuration and has two predominant conformations in CCl(4) solution. In addition, (-)-2,5-dimethylsulfolane is of (2R,5R)-configuration and has only one predominant conformation. The stereochemical assignment is in agreement with literature.