Fluorine-Decoupled Carbon Spectroscopy for the Determination of Configuration at Fully Substituted, Trifluoromethyl- and Perfluoroalkyl-Bearing Carbons: Comparison with ¹⁹F–¹H Heteronuclear Overhauser Effect Spectroscopy

The synthesis of a series of α-trifluoromethylcyclohexanols and analogous trimethylsilyl ethers by addition of the Ruppert–Prakash reagent to substituted cyclohexanones is presented. A method for the assignment of configuration of such compounds, of related α-trifluoromethylcyclohexylamines and of quaternary trifluoromethyl-substituted carbons is described based on the determination of the ³J_CH coupling constant between the fluorine-decoupled ¹³CF₃ resonance and the vicinal hydrogens. This method is dubbed fluorine-decoupled carbon spectroscopy and abbreviated FDCS. The method is also applied to the configurational assignment of substances bearing mono-, di-, and perfluoroalkyl rather than trifluoromethyl groups. The configuration of all substances was verified by either ¹⁹F−¹H heteronuclear Overhauser spectroscopy (HOESY) or X-ray crystallography. The relative merits of FDCS and HOESY are compared and contrasted. ²J_CH, ³J_CH, and ⁴J_CH coupling constants to ¹⁹F decoupled CF₃ groups in alkenes and arenes have also been determined and should prove to be useful in the structural assignment of trifluoromethylated alkenes and arenes.