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same conditions and using the same sample. However, in the
19F-{1H} NMR spectra, the signals are more separated than in 1H
leading to a better fitting of the exponential decays and thus,
diffusion coefficients measured more accurately.18
Conflicts of interest
There are no conflicts to declare.
DOI: 10.1039/C9CC04268G
The importance of fluorine analysis is easily seen in compound
19. The pulse sequence employed to acquire the DOSY
experiments has no fluorine decoupling, so the methyl signal
has a coupling constant with the benzylic hydrogen and another
constant with the fluorine, which precludes the 1H analysis, but
19F-{1H}-DOSY allows the diffusion analysis of compounds 19-21
(Fig. S45).
The separation of signals in 19F-{1H} spectra for the three
compounds were observed only using CSA 5, CSAs 1 and 2
differentiated only the enantiomers of compounds 20 and 21.
For the diffusion experiments, the ΔD when observing the 19F
nuclei was greater than the measurement observing the 1H
nuclei, since there is no signal overlap and signal decay is due to
diffusional process.
Curiously, for compounds 20 and 21, a better enantiomer
differentiation in diffusion dimension was observed using a
cheaper CSA, BINOL (1 or 2), as in comparison to an expensive
CSA (5). This is unusual because as the molecular weight of the
CSA grows, the observed diffusion coefficient of the
diastereoisomeric complex should get smaller, but in this case,
the ΔD is smaller when using 5. So, the observed ΔD depends
not only on the hydrogen bond strength of each
diastereoisomeric complex and the molecular weight of the
CSA, but it also depends on the enantioselectivity of the CSAs
interactions with the analyte. In the worst-case scenario,
without enantioselectivity, the CSA will interact equally with
both enantiomers and no separation will be observed. On the
other hand, in the best-case scenario, with an enantiospecific
interaction, the CSA will interact with only one enantiomer and
its diffusion coefficient will be significantly reduced.
Notes and references
1
2
3
4
5
6
J. Szyszkowiak and P. Majewska, Tetrahedron: Asymmetry,
2014, 25, 103.
J. M. Seco, E. Quiñoá, and R. Riguera, Chemical Reviews,
2012, 112, 4603.
P. Lesot, C. Aroulanda, H. Zimmermannb, and Z. Luz.
Chemical Society Reviews, 2015, 44, 2330.
L. Fang, C. Lv, G. Wang, L. Feng, P. Stavropoulos, G. Gao, L.
Ai, and J. Zhang, Organic Chemistry Frontiers, 2016, 3, 1716.
L. Bai, P. Chen, J. Xiang, J. Suna, and X. Lei, Organic &
Biomolecular Chemistry, 2019, 17, 1466.
(a) N. Jain, A. N. Khanvilkar, S. Sahoo, and A. V. Bedekar,
Tetrahedron, 2018, 74, 68; (b) E. Tayama and T. Sugawara,
European Journal of Organic Chemistry, 2019, 803; (c) S. Ito,
M. Okunoa, and M. Asami, Organic & Biomolecular
Chemistry, 2018, 26, 213; (d) S. R. Chaudhari and S. N.
Suryaprakash, Journal of Molecular Structure, 2013, 1033,
75.
7
8
M. Seo, S. Jang, and H. Kim, Chemical Communications, 2018,
54, 6804.
(a) Ref. 5; (b) Y. Zhu, X. Wu, S. Gu, and L. Pu, Journal of the
American Chemical Society, 2019, 141, 175; (c) T. Ema, D.
Tanida, and T. Sakai, Journal of the American Chemical
Society, 2007, 129, 10591.
(a) Z. Chen, H. Fan, S. Yang, G. Bian, and L. Song, Organic &
Biomolecular Chemistry, 2018, 16, 8311; (b) L. Feng, G. Gao,
H. Zhao, L. Zheng, Y. Wang, P. Stavropoulos, L. Ai, and J.
Zhang, The Journal of Organic Chemistry, 2018, 83, 13874; (c)
G. Li, J. Cao, W. Zong, X. Lei, and R. Tan. Organic Chemistry
Frontiers, 2016, 3, 96.
9
10 (a) I. Pal, S. R. Chaudhari, and N. Suryaprakash, New Journal
of Chemistry, 2014, 38, 4908; (b) G. Bian, S. Yang, H. Huang,
H. Zong, L. Song, H. Fan, and X. Sun, Chemical Science, 2016,
7, 932.
11 S. R. Chaudhari, Srinivasa, and N. Suryaprakash, RSC
Advances, 2012, 2, 8689.
The MAD methodology has proven to be very effective to
discriminate enantiomers and investigate which enantiomer
interacts more strongly with a given CSA. An inexpensive CSA
was used, and even with severe overlaps, it was possible to
measure diffusion coefficients for different diastereoisomeric
complexes, which eliminates the requirement of baseline
separation if the goal is to detect the enantiomeric pair in a
mixture of compounds. From the experiments with aromatic
compounds, it was concluded that the substituent has some
influence on the ΔD value, possibly due to a competition of the
hydroxyl groups and the substituents for the binding site of the
CSA. For the diffusion experiments, even though it is possible to
measure ΔD with overlapping signals, if the Δδ is greater than
the signal broadening in singlets or the J-coupling in multiplets,
the diffusion coefficients can be measured with increased
accuracy. Finally, using different CSAs we were able to
understand that the molecular weight of the CSA is not directly
related to discrimination on diffusion dimension, but the
strength of the non-covalent bond has to be taken into account.
The authors gratefully acknowledge the financial support from
FAPESP (#2015/08541-6) and CAPES for the scholarship to KSS
and CNPq for the fellowship to CFT.
12 T. M. Barbosa, G. A. Morris, M. Nilsson, R. Rittner, and C. F.
Tormena, RSC Advances, 2017, 7, 34000.
13 L. Castañar, P. Moutzouri, T. M. Barbosa, C. F. Tormena, R.
Rittner, A. Phillips, S. Coombes, M. Nilsson, and G. A. Morris,
Analytical Chemistry, 2018, 90, 5445-5450.
14 R. Evans and I. J. Day, RSC Advances, 2016, 6, 47010.
15 G. Uccello-Barretta, F. Balzano, J. Martinelli, M. Berni, C.
Villani, and F. Gasparrini, Tetrahedron: Asymmetry, 2005, 16,
3746.
16 B. A. Jones, T. Balan, J. D. Jolliffe, C. D. Campbell, and M. D.
Smith, Angewandte Chemie International Edition, 2019, 58,
4596.
17 T. M. Barbosa, R. Rittner, C. F. Tormena, G. A. Morris and M.
Nilsson, RSC Advances, 2016, 6, 95173.
18 The use of fluorine-19 instead of proton to measure diffusion
coefficients by NMR has already been discussed: (a) G. Dal
Poggetto, V. Antunes, M. Nilsson, G. A. Morris, and C. F.
Tormena, Magnetic Resonance in Chemistry, 2017, 55, 323;
(b) G. Dal Poggetto, D. C. Favaro, M. Nilsson, G. A. Morris,
and C. F. Tormena, Magnetic Resonance in Chemistry, 2014,
52, 172; (c) C. Dalvit and A. Vulpetti, Magnetic Resonance in
Chemistry, 2012, 50, 592.
4 | J. Name., 2012, 00, 1-3
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