Solvent-induced conformational changes of O-phenyl-cinchonidine: a theoretical and VCD spectroscopy study.
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.
Vargas
Angelo
A
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Hönggerberg, CH-8093 Zurich, Switzerland.
Bonalumi
Norberto
N
Ferri
Davide
D
Baiker
Alfons
A
D002930:Cinchona Alkaloids / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D012997:Solvents / Q000737:chemistry*; D013055:Spectrophotometry, Infrared / Q000379:methods*; D013237:Stereoisomerism
D002930:Cinchona Alkaloids; D012997:Solvents; C041622:cinchonidine