Stereochemical Analysis of Tertiary Trifluoroacetamides Leveraging Both Through-Space 1 H··· 19 F Spin–Spin Couplings and Anisotropic Solvent-Induced Shifts

High Resolution Image Download MS PowerPoint Slide In this study, the assignment of E / Z -isomers of N, N -dialkyl trifluoroacetamides ( 1–8 ) is investigated by using 1 H-nuclear magnetic resonance spectroscopy, and data pertaining to both through- space spin–spin couplings (TSCs) and aromatic solvent-induced shifts (ASISs) are utilized to develop a reliable and convenient approach for determining the stereochemistry of these isomers. Although TSCs─observed when the F from the CF 3 group is spatially close to protons─alone may be useful for determining E / Z isomers, through- bond couplings (TBCs) are also observed when the proton is five bonds apart from the F in the CF 3 group. Thus, an additional one-dimensional 1 H– 19 F heteronuclear Overhauser enhancement spectroscopy (HOESY) experiment is required to distinguish between the TSCs and TBCs. By contrast, the ASIS results for all compounds are consistent with the general observation that C 6 D 6 preferentially shifts trans -methyl/methylene protons to the carbonyl oxygen atom over cis -methyl/methylene protons. Additionally, the ASISs with C 6 F 6 of compounds 4–8 are analyzed to demonstrate the reliability of the ASIS-based method. Considering that 1 H– 19 F HOESY experiments are somewhat specialized and uncommon, factoring both the TSCs and ASISs during the deduction process proves highly effective for determining the stereochemical assignment of E / Z -isomers of N, N -dialkyl trifluoroacetamides.