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 a-trifluoromethylcyclohexanols and analogous trimethylsilyl ethers by addition of the RuppertPrakash reagent to substituted cyclohexanones is presented. A method for the assignment of configuration of such compounds, of related a-trifluoromethylcyclohexylamines and of quaternary trifluoromethyl-substituted carbons is described based on the determination of the (3)J(CH) coupling constant between the fluorine-decoupled (CF3)-C-13 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 F-19-H-1 heteronuclear Overhauser spectroscopy (HOESY) or X-ray crystallography. The relative merits of FDCS and HOESY are compared and contrasted. 2J(CH), (3)J(CH), and (4)J(CH) coupling constants to F-19 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.