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

## TL;DR

This paper presents a method to determine the stereochemistry of N,N-dialkyl trifluoroacetamides using NMR techniques involving spin–spin couplings and solvent-induced shifts.

## Contribution

A novel approach combining through-space couplings and solvent-induced shifts for stereochemical assignment of isomers.

## Key findings

- Through-space spin–spin couplings and aromatic solvent-induced shifts reliably distinguish E/Z isomers.
- C6D6 preferentially shifts trans-methyl/methylene protons over cis ones.
- ASIS-based methods are validated as reliable for stereochemical analysis.

## Abstract

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.