Conformational study of 9-dehydro-9-trifluoromethyl cinchona alkaloids via 19F NMR spectroscopy: emergence of trifluoromethyl moiety as a conformational stabilizer and a probe

The trifluoromethyl substituent has been incorporated into quinidine as a conformational stabilizer and a probe to provide straightforward insight into the conformational behavior of cinchona alkaloids. By significantly decreasing the rotation rate of the quinoline-carbinol bond, the relatively bulky CF(3) group enables the NMR signals of the syn and anti conformers to be differentiated at room temperature. In addition to the stabilizing effect, the introduction of the fluorinated moiety also facilitates the application of (19)F NMR spectroscopy, thereby allowing conformational studies under various conditions without the use of deuterated solvents.