Assignment of absolute configuration of chiral carboxylic acids via exciton‐coupled CD treatment: 4‐phenylthioproline as a case study

The exciton (coupled oscillator) model for optical activity is a very useful and powerful method which allows to analyze a circular dichroism (CD) spectrum in a nonempirical way, arriving at a safe assignment of the absolute configuration of organic and inorganic compounds. Usually in this model only the exciton coupling of two electrically allowed transitions (oscillators) is taken into account. This approach has the important advantage of an easy application but, sometimes, it may lead to wrong results. Thus, in this review article a more general treatment, which allows considering the simultaneous coupling of several oscillators, i.e., the DeVoe model, is presented and critically analyzed, discussing in detail the latest applications reported in the literature. In the authors opinion, since the DeVoe model joins generality and reliability requiring an almost negligible computational effort, it represents the method of choice for stereochemical assignments, even by nonspecialists.

Section: Chartmentioning

confidence: 99%

Structural determinations by circular dichroism spectra analysis using coupled oscillator methods: An update of the applications of the DeVoe polarizability model

Superchi¹,

Giorgio²,

Rosini³

2004

“…32 Alternatively, when a compound expresses exciton coupling that is observed in the CD spectrum, the absolute stereochemistry can be assessed in combination with molecular modeling studies of the lowest energy conformers. [33][34][35][36] So-called porphyrin tweezers have also been used in combination with CD to determine absolute stereochemistry. [37][38][39] More recently, the spectroscopic approach of comparing observed and calculated vibrational circular dichroism (VCD) spectra, electronic circular dichroism (ECD), or optical rotation (OR) values has gained popularity due to the ease of data acquisition and the ability to calculate spectra and values with commercially available software and supercomputers or modern, powerful PCs and Linux clusters.…”

Section: Introductionmentioning

confidence: 99%

Application of chiral technology in a pharmaceutical company. Enantiomeric separation and spectroscopic studies of key asymmetric intermediates using a combination of techniques. Phenylglycidols

McConnell¹,

He²,

Nogle³

et al. 2007

Phenylglycidols substituted in the 2-, 3-, and 4- positions with fluorine, chlorine, and trifluoromethyl, and with methoxy in the 3- position, were synthesized from the corresponding E-cinnamic acids and separated into their (R,R)- and (S,S)- enantiomers using subcritical fluid chromatography with mixtures of MeOH in CO(2), on either a Chiralpak AD or AS chiral stationary phase. These compounds and commercially-available (R,R)- and (S,S)-phenylglycidol were analyzed for their vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and optical rotation (OR) properties to exemplify a strategy whereby the absolute stereochemistry of common and key chiral intermediates is established early in the structure-activity and structure-property relationship phase of a drug discovery program in a pharmaceutical company. From this study, substituents in the phenyl group of the synthesized molecules were found not to grossly alter spectroscopic features, and therefore, diagnostic absorption bands in the respective VCD spectra, and the sign and shape of the measured ECD curves could be used to determine and track the absolute stereochemistry of analogs without necessarily requiring time-consuming ab initio calculations of all low energy conformers for all compounds. VCD, OR, and ECD calculations for the determination of absolute configuration carried out at the DFT level with the hybrid B3PW91 functional and the TZVP basis set were found to be especially useful in this study.

“…Our group, 8,9 as well as others, 3,10-12 have combined self-assembling receptors with optical techniques for the rapid screening of ee . Optical instrumentation is an attractive method for ee determination because the analysis is typically fast, inexpensive, and familiar to most organic chemists – all of which lower the barrier to its widespread adoption.…”

Section: Introductionmentioning

confidence: 99%

Chiral Amine Enantiomeric Excess Determination Using Self‐Assembled Octahedral Fe(II)‐Imine Complexes

Dragna¹,

Gade

Tran

et al. 2015

A receptor assembly composed of iron(II) triflate and pyridine-2,6-dicarbaldehyde is used to determine the enantiomeric excess of alpha-chiral primary amines using circular dichroism spectroscopy. The alpha chiral amines condense with the dialdehyde to form a diimine, which forms a 2:1 octahedral complex with iron(II). The enantiomeric excess values of unknown concentrations of alpha-chiral amines were determined by constructing calibration curves for each amine and then measuring the ellipticity at 600nm. This improves our previously reported assay for enantiomeric excess determination of chiral primary amines by further increasing the wavelength at which CD is measured and reducing the absolute error of the assay.