The Trifluoromethyl Group as a Conformational Stabilizer and Probe: Conformational Analysis of Cinchona Alkaloid Scaffolds.

Journal article, 2014

The introduction of the CF3 group on the C9 atom in quinidine can significantly increase the conformational interconversion barrier of the cinchona alkaloid scaffold. With this modification the conformational behavior of cinchona alkaloids in various solvents can be conveniently studied via 19F NMR spectroscopy. Based on the reliable conformational distribution information obtained, the accuracy of both theor. (PCM) and empirical (Kamlet-Taft) solvation models was assessed using linear free energy relation methods. The empirical solvation model provides accurate prediction of solvent effects, while PCM demonstrated a relatively low reliability. Using similar empirical solvation models along with Karplus-type equations, the conformational behavior of quinidine and 9-epi-quinidine also was studied. A model SN2 reaction was presented to reveal the important role of solvent-induced conformational behavior of cinchona alkaloids in their reactivity. [on SciFinder(R)]