A combined NMR, DFT, and X-ray investigation of some cinchona alkaloid O-ethers

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Busygin I, Nieminen V, Taskinen A, Sinkkonen J, Toukoniitty E, Sillanpaa R, Murzin DY, Leino R
Publisher: AMER CHEMICAL SOC
Publication year: 2008
Journal: Journal of Organic Chemistry
Journal acronym: J ORG CHEM
Volume number: 73
Issue number: 17
Start page: 6559
End page: 6569
Number of pages: 11
ISSN: 0022-3263


Abstract

Structures and conformational behavior of several cinchona alkaloid O-ethers in the solid state (X-ray), in solution (NMR and DFT), and in the gas phase (DFT) were investigated. In the crystal, O-phenylcinchonidine adopts the Open(3) conformation similar to cinchonidine, whereas the O-methyl ether derivatives of both cinchonidine and cinchonine are packed in the Closed(l) conformation. Dynamic equilibria in Solutions of the alkaloids were revealed by combined experimental-theoretical spin simulation/iteration techniques for the first time. In the H-1 NMR spectra in CDCl3 and toluene-d(8) at room temperature, Closed(l) conformation was observed for the O-silyl ethers as a separate set of signals. For O-methyl ether derivatives Closed(l) could be separated only at -30 degrees C in CDCl3 or toluene-d(8) and for O-phenylcinchonidine at -70 degrees C in CDCl3/CD2Cl2. The ratio between the Closed(2) and Open(3) conformers was estimated by analyzing the vicinal coupling constant (3)J(H9,H8) at ambient and low temperatures. The observed conformational equilibria of O-(tert-butyldimethylsily)cinchonidine in CDCl3 and toluene-d(8) are in good agreement with the theoretically estimated equilibrium Populations of the conformations according to Boltzmann statistics. The confirmational equilibria of four cinchona alkaloid O-ether solutes in CDCl3 and toluene-d(8) are discussed in the light of their relevance to the mechanism of 1-phenyl-1,2-propanedione (PPD) hydrogenation over cinchona alkaloid modified heterogeneous platinum catalysts. It was demonstrated that the conformation found to be abundant in the liquid phase has no direct Correlation with the enantioselectivity of the PPD hydrogenation reaction.

Last updated on 2019-17-10 at 04:13