Vibrational circular dichroism (VCD) spectroscopy is one of the most powerful techniques for the determination of absolute configurations (AC), as it does not require any specific UV/vis chromophores, no chemical derivatization, and no growth of suitable crystals. In the past decade, it has become increasingly recognized by chemists from various fields of synthetic chemistry such as total synthesis and drug discovery as well as from developers of asymmetric catalysts. This perspective article gives an overview about the most important experimental aspects of a VCD-based AC determination and explains the theoretical analysis. The comparison of experimental and computational spectra that leads to the final conclusion about the AC of the target molecules is described. In addition, the review summarizes unique VCD studies carried out in the period 2008−2018 that focus on the determination of unknown ACs of new compounds, which were obtained in its enantiopure form either through direct asymmetric synthesis or chiral chromatography.

Spectroscopic characterizations of key reaction intermediates are often considered the final confirmation of a reaction mechanism. This proof‐of‐principle study showcases the application of vibrational circular dichroism (VCD) spectroscopy for the characterization of in situ generated reaction intermediates using the key intermediates of enamine catalysis of Jørgensen–Hayashi‐type prolinol ether catalysts as model system. By comparison of experimental and computed spectra, the enamines are shown to preferentially adopt an anti‐conformation with E‐configured C=C bond. For the parent prolinol catalyst, the structure and stereochemistry of the oxazolidine side product is determined as well. This study thus demonstrates that VCD spectra can provide insights into structural preferences of organocatalysts that utilize a covalent activation mechanism. Thereby it outlines new fields of applications for VCD spectroscopy and finally adds the technique to the toolbox of physical organic chemistry for in‐depth mechanistic studies.

We demonstrate that VCD spectroscopy can reveal insights into the conformational preferences of iminium ion obtained from MacMillan’s imidazolidinone catalyst. For both, the isolated and in-situ generated iminium ion, the...

An enantioselective sulfimidation of 3-thiosubstituted 2-quinolones and 2-pyridones was achieved with astoichiometric nitrene source (PhI=NNs) and as ilver-based catalyst system. Keytothe success of the reaction is the use of achiral phenanthroline ligand with ah ydrogen bonding site.T he enantioselectivity does not depend on the size of the two substituents at the sulfur atom but only on the binding properties of the heterocyclic lactams.Atotal of 21 chiral sulfimides were obtained in high yields (44-99 %) and with significant enantiomeric excess (70-99 %e e). The sulfimidation proceeds with high site-selectivity and can also be employed for the kinetic resolution of chiral sulfoxides. Mechanistic evidence suggests the intermediacy of ah eteroleptic silver complex, in whichthe silver atom is bound to one molecule of the chiral ligand and one molecule of an achiral 1,10-phenanthroline.Support for the suggested reaction course was obtained by ESI mass spectrometry,DFT calculations,and aHammett analysis.

In this study, we characterize the dynamic stereochemistry of a biphenyl‐2,2’‐bis(proline amide) catalyst in chloroform and DMSO as representative weakly and strongly hydrogen bonding solvents. Using vibrational circular dichroism (VCD) spectroscopy and density functional theory (DFT) based spectra calculations, we show that the preferred axial stereochemistry of the catalyst is determined by solute‐solvent interactions. Explicitly considering solvation with DMSO molecules is found to be essential to correctly predict the conformational preferences of the catalyst. Furthermore, we investigate the stereochemistry of the corresponding enamines and imidazolidinones that are formed upon reaction with isovaleraldehyde. The enamines are found to rapidly convert to endo‐imidazolidinones and the thermodynamically favored exo‐imidazolidinones are formed only slowly. The present study demonstrates that the stereochemistry of these imidazolidinones can be deduced directly from the VCD spectra analysis without any further detailed analysis of NMR spectra. Hence, we herein exemplify the use of VCD spectroscopy for an in situ characterization of intermediates relevant in asymmetric catalysts.