VCD spectroscopy of chiral cinchona modifiers used in heterogeneous enantioselective hydrogenation: conformation and binding of non-chiral acids

Abstract

Vibrational circular dichroism (VCD) spectra of the chiral modifiers cinchonidine, an alkaloid, and (R)-2-(pyrrolidin-1-yl)-1-(1-naphthyl)ethanol (PNE) were measured and simulated. For cinchonidine independent information from NMR investigations on the distribution of conformers was used to simulate VCD spectra from calculated spectra of the individual conformers. Agreement with experiment is reasonably good. For the structurally similar synthetic modifier PNE VCD spectra show that an open conformer predominates in solution. The difference between the most stable conformers of cinchonidine and PNE in solution is the intramolecular hydrogen bond found in the latter, which forms due to the enhanced flexibility of the pyrrolidinyl moiety in PNE as compared to the quinuclidine moiety in cinchonidine. The similar enantiodifferentiating power of cinchonidine and PNE as chiral modifiers in the heterogeneous enantioselective hydrogenation of ethyl pyruvate indicates that the rigidity of this part of the molecule is not a prerequisite for enantioselection. It is furthermore shown that binding of a non-chiral carboxylic acid to the alkaloid induces VCD in vibrations associated with the acid. Observation of this induced VCD allows probing of the chiral binding site.