Solvent-Induced Conformational Changes of O-Phenyl-cinchonidine:  A Theoretical and VCD Spectroscopy Study

Abstract

The conformational analysis of the synthetic chiral modifier O-phenyl-cinchonidine (PhOCD) used in enantioselective hydrogenations over noble metal catalysts has been performed at a PM3 semiempirical level in vacuum. The minimum energy conformations calculated at the DFT level with a medium-size basis set have been compared to those of the parent alkaloid cinchonidine (CD). PhOCD behaves similarly to CD and shows four main conformers, denoted as Closed(1), Closed(2), Open(3), and Open(4). Open(3) is found to be the most stable in vacuum and in CH2Cl2 and CCl4 solvents. A comprehensive normal-mode analysis has been performed for these conformers, and assignment of the infrared spectrum of PhOCD in CCl4 (epsilon = 2.2) has been performed using the calculated spectrum of Open(3), which appears to be the most populated in this solvent. A combined theoretical-experimental VCD spectroscopy approach was used to increase the spectroscopic sensitivity toward changes in the distribution of conformers upon change of solvent polarity. The VCD spectra confirm that Open(3) is by far the most stable conformation in CCl4 (epsilon = 2.2) and indicate that an excess Closed(2) conformer has to be expected in CD2Cl2 (epsilon = 8.9). The possible influence of this conformational behavior is discussed on the basis of available catalytic data and in relation to the enantioselective potential of PhOCD as a chiral modifier on supported metal catalysts.

Quantum Mechanical Investigations of Organocatalysis: Mechanisms, Reactivities, and Selectivities

“…118 More recently, they also reported a mixed VCD spectroscopy and computational study of O-phenyl cinchonidine. 119 Zaera and co-workers reported a mixed NMR and computational study of the effect of protonation of cinchonidine. 120 Lastly, Szöllösi and co-workers have reported a similar mixed study on the conformational behavior of py -hexahydrocinchonidine.…”

Understanding of matrix embedding: a theoretical spectroscopic study of CO interacting with Ar clusters, surfaces and matrices

“…[10,11] In this study, we use a unified first-principles methodology for all environments (gas phase clusters, molecules adsorbed on a rare-gas surface or embedded into a rare-gas matrix) to derive these interaction potentials and afterwards the vibrational and structural effects caused by clustering and embedding. [10,11] In this study, we use a unified first-principles methodology for all environments (gas phase clusters, molecules adsorbed on a rare-gas surface or embedded into a rare-gas matrix) to derive these interaction potentials and afterwards the vibrational and structural effects caused by clustering and embedding.…”

Theoretical Prediction and the First IR Matrix Observation of Several L‐Cysteine Molecule Conformers

“…[39] Therefore, combination of VCD experiments with theoretical VCD calculations is becoming an increasingly strong scientific instrument in the determination of absolute configuration [40][41][42] or conformation of chiral molecules. [43][44][45] Recently, it has been shown that the VCD method can also be a powerful tool in studying the intermolecular interactions of chiral molecules. [46,47] Continuing our previous study, [35] we undertook a detailed investigation on the conformation behavior of gas-phase cysteine isolated in low-temperature Ar and N 2 matrices.…”