Full Papers
doi.org/10.1002/ejoc.202100044
and 13C), and to the external standard CFCl3 (19F). The 13C NMR
spectra were acquired under proton decoupling conditions with a
The simulated spectra resulting from the Boltzmann averaged sum
of the conformations (relative energies from Table 2) were red-
shifted by 6–12 nm to get the best simulations with the
experimental spectra. All the simulations are reported in Figur-
es S15–S23 of ESI.
1
2
3
4
5
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7
8
9
°
36000 Hz spectral width, 5.5 μs (60 tip angle) pulse width, 1 s
acquisition time and 5 s delay time. A line broadening function of
1–2 Hz was applied before the Fourier transformation. 13C spectra
of compounds 2–5 were also obtained with 19F broadband
decoupling, in order to determine the chemical shifts of the
fluorinated carbons. The assignment of the 13C signals was obtained
by means of DEPT sequences. Assignments of the syn and anti
isomers of compounds 3–5 were achieved by NOE spectra,
recorded at 600 MHz using the DPFGSE sequence[41] and a 50 Hz
selective pulse with an R-SNOB shape[42] (See ESI for full details of
the assignment). Kinetic analysis of the anti/syn diastereomerization
barriers were obtained by keeping the NMR sample at high
tary crystallographic data for this paper. These data are provided
free of charge by the joint Cambridge Crystallographic Data Centre
and Fachinformationszentrum Karlsruhe Access Structures service
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1
temperature, and recording the H spectra at fixed periods of time.
Acknowledgements
A first-order kinetic equation at equilibrium yielded the rate
¼
constants, that were used to derive the ΔG by means of the
The University of Bologna is gratefully acknowledged for financial
support (RFO funds 2018 and 2019).
Eyring equation. Temperature calibrations within the NMR probe
were performed before the experiments, using a digital thermom-
eter and a Cu/Ni thermocouple inserted into a dummy sample filled
with TCE. The conditions were kept as identical as possible with the
subsequent work, in particular the sample was not spun and the
gas flow was the same as that used during the temperature
calibration. The uncertainty in temperature measurements can be
Conflict of Interest
The authors declare no conflict of interest.
°
estimated as �1 C. When an external oil bath was used to heat the
NMR sample, the same thermocouple was used to monitor the
temperature.
Keywords: DFT calculations · Electronic circular dichroism ·
NMR spectroscopy · Noncovalent interactions
°
ECD spectra were recorded at +25 C in far-UV HPLC-grade
acetonitrile solutions. The concentrations of the samples (about
10À 4 M) were tuned by dilution of a mother solution (1·10À 3 M) to
obtain a maximum absorbance of about 0.8�0.9 in the UV
spectrum using a 0.2 cm path length. The spectra were recorded in
the 190–400 nm interval as the sum of 16 spectra. The spectra
shown in Figure 8 were normalized in intensity using the intensities
of the UV spectra, in which the maximum absorbance in the 215–
225 nm range was normalized to A=1.0.
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Ground state optimizations and transition states were obtained by
DFT computations performed by the Gaussian 16 rev. A.03 software
suite[26] using standard parameters. Full optimization and frequency
analysis for ground states and transition states employed the M06-
2X functional[30] and the 6–31+G(d,p) basis set. The IEFPCM
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analysis of the vibrational frequencies showed the absence of
imaginary frequencies for the ground states, and the presence of
one imaginary frequency for each transition state. Visual inspection
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thermal corrections obtained with M06-2X at the lower level were
used to derive the Gibbs free energies reported in Table 2 and in
Table S3 of the ESI. The ECD spectra of the optically active isomers
were calculated using the TD-DFT approach.[47] The electrostatic
surfaces were calculated and shown using Gauss View.[48] For all the
representations, the same range was used for the color code (from
À 3.7eÀ 2 to 3.7eÀ 2; red and blue, respectively). The theoretical ECD
spectra of the GS conformations were obtained with four different
functionals (CAMÀ B3LYP,[49] ωB97XÀ D,[46] BH&HLYP[50] and M06-
2X[30]) with the same 6–311+ +G(2d,p) basis set, in order to have
data redundancy, and to enhance reliability.[51] For each conforma-
tion 70 discrete transitions were calculated, and the ECD spectrum
was obtained by convolution of Gaussian shaped lines (0.5 eV half-
height line width).[48]
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