In this study, the assignment of E/Z-isomers of N,N-dialkyl trifluoroacetamides (1-8) is investigated by using 1H-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 CF3 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 CF3 group. Thus, an additional one-dimensional 1H-19F 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 C6D6 preferentially shifts trans-methyl/methylene protons to the carbonyl oxygen atom over cis-methyl/methylene protons. Additionally, the ASISs with C6F6 of compounds 4-8 are analyzed to demonstrate the reliability of the ASIS-based method. Considering that 1H-19F 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.
Watanabe et al. (Tue,) studied this question.