Prediction of 19F NMR Chemical Shifts for Fluorinated Aromatic

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Prediction of 19F NMR Chemical Shifts for Fluorinated Aromatic Compounds Carla Saunders, Mohammed B. Khaled, Jimmie D. Weaver, and Dean J Tantillo J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00104 • Publication Date (Web): 22 Feb 2018 Downloaded from http://pubs.acs.org on February 23, 2018

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The Journal of Organic Chemistry

Prediction of 19F NMR Chemical Shifts for Fluorinated Aromatic Compounds Carla Saunders,‡ Mohammad B. Khaled, § Jimmie D. Weaver III,§ Dean J. Tantillo*‡ ‡

Department of Chemistry, University of California‒Davis, Davis, CA 95616

§

Department of Chemistry, Oklahoma State University, Stillwater, OK 74078

Table of Contents Graphic

benzenes naphthalenes heterocycles

Fn

Abstract Scaling factors are reported for use in predicting

19

F NMR chemical shifts for

fluorinated (hetero)aromatic compounds with relatively low levels of theory. Our recommended scaling factors were developed using a curated data set of 52 compounds, with 100 individual 19F shifts spanning a range of 153 ppm. With a maximum deviation of 6.5 ppm between experimental and computed shifts, or 4% of the range tested, these scaling factors allow for the assignment of chemical shifts to specific fluorines in multifluorinated aromatics. The utility of this approach is highlighted by several structural reassignments.

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Introduction The incorporation of fluorine atoms in organic molecules (e.g., materials,1 agrochemicals,2-3 pharmaceuticals4) is becoming increasingly common, as a result of the unique electronic and steric properties of fluorine atoms.5-12 Consequently, 19F NMR is applied ever more frequently in structural assignments. Fortunately for chemists working with fluorine, there are many appeals of using

19

F NMR, e.g., the NMR active isotope is 100%

naturally abundant, has a gyromagnetic ratio of about 0.94 times 1H , and is spin ½.13 Nonetheless, 19F spectra can be difficult to interpret, especially when multiple fluorine atoms are present in a molecule. Some of us have been involved in developing methods for regioselective defluorination of polyfluorinated aromatics, methods that produce exactly the sort of compounds subject to assignment difficulties.5-9, 14 Useful resources are available to assist organic chemists in the interpretation of 19F NMR, but it remains challenging to reliably assign all 19F shifts within a multifluorinated molecule.13 Here we endeavor to provide a readily accessible method for reliably predicting 19F shifts of fluorinated aromatic compounds. Predicting

1

H and

13

C NMR chemical shifts with quantum chemical methods

(especially density functional theory [DFT]) is now commonplace.15-18 Often, linear scaling methods are used with such approaches to remove systematic errors in computations.19-20 In doing so, absolute isotropic shieldings are computed for a “training set” of molecules and compared to experimental chemical shifts. When tight linear correlations between computed and experimental data are found, simple scaling factors (slope and y-intercept for the correlation line, particular to the specific theoretical method used) fall out, and can then be used for predicting chemical shifts for molecules not included in the training set. This approach has been explored previously for 19F chemical shifts, including fluorinated aromatic compounds,21-28 but we provide scaling factors here that work with relatively low level theoretical methods accessible to non-experts. We also demonstrate the applicability of these scaling factors for heterocycles (common in bioactive compounds) and highlight their use in assigning structures of multifluorinated compounds.


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Our training set consisted of 52 compounds, with 100 individual 19F shifts spanning a range of 153 ppm (Chart 1). This set contains fluorinated aromatics, many with multiple fluorine atoms in the same molecule, and mono- and bicyclic heteroaromatics. A variety of issues made compiling this data set difficult, including variations in reported shifts across the literature and the use of different reference compounds.27 The compounds in Chart 1 were chosen not just for the variety of environments in which their fluorine atoms reside, but because their 19F shifts were supported by multiple published reports or a single report with sufficient experimental details to make us confident in their validity.27, 29-42

-140 F

A -70 F

N

-87 F

F

F

-153 N

F

-91 F

F

N

F

-141

F

-88

F

F N

F

O -130 F

F

-182 F

F

F

F

Cl

F F

-195

F

F

F

N

O -123 F

-196

F

F

F

F

-121.8 F

N H

-161 F

F

-164 F

F

F

-164 F -169 F

F

F -145

CH3

-110 F

N

-96 F

tBu

-109 F

TMS

F -121

CH3 -110 F

CH3

Cl

tBu F -122 CH3

Cl

F

-43

F

-111

Cl

O

F

F -141 OH

-70

CH3 Cl

CH3

F O

-109.7 F

F

-114

Cl

-106.8 F

Br

-120.7

CH3 O2N

-109.7

CH3 F

-134 F

F CN

F -124

F -156

O

F

F -137

F N

F

-112.3 N H

-172 F

S -165 F

F

F

N

F

F

F -156

F

-113 F

F -46

S

F -141 NH2 O

F -161

F

N

F

-124.9

-156

F -48 F

S -148 F

-133

N

F

-137

-139

-166 F

N

-72

F F

CH3

-146 F

F

-150

F

F -138

Br

-137 F

F -141

F

S F

O -137 F

F

N

F

F

F

F

-89 N

N

-158

-142 F

F

-139

F

-73

-83 N

Br

-134

F

-188

O -122 F

-171

C

-88

F

N

F

F

F

O

F

F

F

-93

F

-133 F

-86

N

F

-69

F F

-141

F

-134

-162

F -116

F -162

-147

F F

Cl

F

N

-83

-84

-65

N

F

-170

F

-125

F

-165

F -154

B

F

N

N

F -95

F

-123

F

N

-129

F

F

-148 F -146

-63

-73

N

F -130

F -109

-136

F

-134

O

F

-113.3

O

N

Chart 1. Experimental shifts of compounds used as training set to develop scaling factors: A: substituted monocyclic heterocycles, B: substituted non-heterocyclic aromatics, C: substituted bicyclic heterocycles.



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Methods Geometry optimizations were run using B3LYP/6-31+G(d,p) in the gas phase using

Gaussian09, and resulting structures were confirmed as minima using frequency calculations.43-47,26 These structures were subjected to NMR (GIAO)48-54 calculations at B3LYP/6-31+G(d,p), B3LYP/6-311+G(2d,p) and B3LYP/6-31G levels in the gas phase. B3LYP/6-31+G(d,p)//B3LYP/6-31+G(d,p) calculations were repeated using the SMD implicit solvent model for experimental solvents in NMR calculations.55 Experimental shifts were plotted against calculated isotropic shielding values, and scaling factors were derived according to equation (1): 𝜎"#$%&'(%)*+, = 𝑠𝑙𝑜𝑝𝑒 ∗ 𝜃567*&7$'8 + 𝑖𝑛𝑡𝑒𝑟𝑐𝑒𝑝𝑡

(1)

These scaling factors were applied to each test compound using equation (2): ?@ABCDBEFG H')*%&8%$* 6,7

%$= 𝜎I8+,%J

(2)

While the compounds in Chart 1 were chosen, in part, for their lack of conformational flexibility, some compounds to which the developed scaling factors were applied were conformationally flexible. For such compounds, conformational searches were run with

Spartan10, and then optimized in Gaussian09 with B3LYP/6-31+G(d,p) in the gas phase. 26,5657

Conformers within 3 kcal/mol of the lowest energy conformer were included in the NMR

calculations, with their contributions weighted with a Boltzmann distribution based on their relative free energies.

Results and Discussion Initially, gas phase calculations of isolated molecules were used to establish scaling factors. Using B3LYP/6-31+G(d,p)//B3LYP/6-31+G(d,p), the maximum error on any one 19F shift was 6.5 ppm, with a mean absolute deviation (MAD) of 2.1 ppm over a range of 153 ppm


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(Figure 1, middle). Performance was similar when NMR calculations were repeated with a larger basis set (B3LYP//6-311+G(2d,p))//B3LYP/6-31+G(d,p)): maximum error of 6.6 ppm and MAD of 1.7 ppm (Figure 1, right). Use of a smaller basis set (B3LYP/6-31G//B3LYP/631+G(d,p)) resulted in a much higher maximum deviation (28 ppm) and a much higher MAD of 4.0 ppm (Figure 1, left). On the basis of these results, we recommend the B3LYP/6-

400 350 300 250 200 150

-200

-100

Experimental Shift

0

y = -0.9968x + 184.92 R² = 0.99375

400 350 300 250 200

-200

-100

0

Computed Isotropic Shekding

y = -1.0394x + 154.36 R² = 0.96713

Computed Isotropic Shielding

31+G(d,p)//B3LYP/6-31+G(d,p) for rapid predictions of 19F chemical shifts.

Computed Isotropic Shielding

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Experimental Shift

y = -1.0647x + 161.91 400 R² = 0.99601 350 300 250 200 150

-200

-100

0

Experimental Shift

Figure 1. Correlation data for two NMR computational methods (all using B3LYP/6-31+G(d,p) gas phase geometries): Left: B3LYP/6-31G Middle: B3LYP/6-31+G(d,p); Right: B3LYP/6-311+G(2d,p). Mono-cyclic heteroaromatic compounds (group A, Chart 1) are shown in green, non-heterocyclic compounds (group B) are shown in grey, and bicyclic-heterocyclic compounds (group C) are shown in yellow.

Although the 19F spectra for compounds used in the training set were taken in a variety of solvents, the majority were taken in either CDCl3 or CCl4 (a full list of the solvents is available in the Supporting Information). Although it has been shown that solvent has little effect on 19F shifts, we wanted to confirm this with our data. To test the effect of solvent on our predictions, the gas phase optimized structures were subjected to NMR calculations in continuum solvent (SMD) and new scaling factors were determined (Figure 2). For the 45 19F shifts from our test set that were measured in chloroform, gas phase NMR calculations had a maximum error of 8.2 ppm, while continuum chloroform calculations had a maximum error of 7.2 ppm. The MAD also decreased slightly, from 2.9 to 2.6 ppm. For the 27 shifts determined in carbon tetrachloride, the maximum error decreased from 5.1 to 4.6 ppm, while the MAD



remained the same at 1.5 ppm. Although including solvent in the calculations did provide small improvements in prediction accuracy, gas phase calculations appear to be sufficient, and were used in all test cases.

Experimental Solvent = CDCl3

Gas Phase NMR Calculation

Experimental Solvent = CCl4

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Solvent Phase NMR Calculation

y = -0.9652x + 194.71 R² = 0.98765

-200

-150

-100

400 350

-150

-100

-50

350 300

250

250

200

200 -200

-150

400

-100

-50

y = -1.0048x + 183.71 R² = 0.99653

350

400 350

300

300

250

250

200 -200

400

300

-50

y = -0.9735x + 191.05 R² = 0.99634

y = -0.9976x + 185.55 R² = 0.98985

200 -200

-150

-100

-50

Figure 2. Experimental and computed shifts for the training set used for optimization and NMR calculation at B3LYP/6-31+G(d,p) ‒ structures taken in chloroform (top) and calculated in gas (left) and chloroform (right), structures taken in carbon tetrachloride (bottom). Mono-cyclic aromatic compounds (group A) are shown in green, non-heterocyclic compounds (group B) are shown in grey, and bicyclic-heterocyclic compounds (group C) are shown in yellow.

To put our scaling factors to the test, we applied them to several multifluorinated compounds synthesized in one of our labs (Chart 2). The original assignment of one structure ̶ compound 7̶ was found to be in error on the basis of our predicted 19F shifts. The shifts for the corrected structure (7 revised, Chart 2) are completely consistent with the


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experimental spectrum. In addition, independent synthesis and X-ray crystallographic characterization of 7 revised validate the computation-derived revision (see Supporting Information for details). O

O

HN

O

HN

-82 (-8) F

HN

-82 (-8) F

-171 (-8) F

N

F -100 (-7)

-171 (-8) F

N

1

F -100 (-7)

-171 (-5) F

N

2 O

HN

N H

-86 (-11) F F -144 (-11)

-158 (3) F

CF3

4

O tBuO -97 (-7) F -147 (7) F

OtBu F -199 (-65)

N

O

Ph NH

O -151 (-6) F

O

-142 (-8) F

F -99 (-8)

5

O N

N

F -99 (-7)

3

O

-124 (-4) F

Ph

-82 (-7) F

O tBuO

F -125 (-9)

6

O N

OtBu

N

F -82 (-7)

-96 (-6) F -157 (-3) F

7 revised

7

Chart 2. Initial compounds explored, including a structure that was corrected by computations (highlighted in red). Computed shifts and error from experiment are shown for each aromatic fluorine.

After discovering this misassignment, a group of 13 substituted benzene and pyridine compounds with various substitution patterns (Chart 3) were examined to confirm, or correct, the published structures.7, 9, 12 Although many of the spectra match experiment, two of the structures had large errors (Chart 3, red). Based on the correction described above, revised structures were tested and these match the experimental values within the error expected for our scaling factors. These straightforward applications of computational

19

F shift

prediction highlight its utility in avoiding mistakes in assignments for highly fluorinated compounds.



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NH

EtO2C

-112 (7) NHAc F

OH Et

NHAc

-117 (1)

F -139 (1)

F

F

F -135 (2)

F

CF3

A (9a)

F

F

F

-67 (2)

CO2Me MeO2C

HN

O

-79 (-8)

F (34c)

OMe

F

K (13a)

-117 (1)

OMe

F

N CF3

I (33a) NH O

F

-121 (-5)

-136 (-4)

F

J (36c) NH

EtO2C

MeO

CO2Et O

-110 (-5)

F

-76 (-4)

EtO2C

MeO

-149 (-1) F

NH2

CO2Me

O

F

H (35a) NH

-90 (1) F

HN

CO2Me MeO2C

CF3

EtO2C

N

E revised [G (32c)]

CO2Me

-113 (-2) NHAc

OMe

O

MeO

OMe

F

-137 (-3)

OMe

-143 (-6)

-79 (-8) F

O

N

O

F

-162 (-5)

O

E (31c)

G (32c)

F

CO2Et

F

MeO2C

-136 (0) F

F

HN

O

F N

F -92 (0)

F

F

MeO CN

MeO2C

-136 (-1)

-126 (-56) F

CO2Et O

-123 (-5)

-137 (-3)

N

D revised

CO2Me

CO2Me

O

-136 (0)

F

MeO2C

-109 (0)

CO2Et

F -151 (-5)

D (27a)

F

C (26a) NH

EtO2C

-90 (1)

N

F -142 (-4) CO2Me

O

-148 (-1)

-131 (-62)

-137 (1)

B (25a) HN

O

F -142 (2)

-116 (-1) F

CF3

NH

EtO2C

O

-139 (1)

N

F

OMe

-72 (1)

L (14a)

N

F

OMe

-72 (-1)

M (27a) product 1

-72 (-1) F

N

F

OMe

-68 (1)

M (27a) product 2

Chart 3. Fluorinated aromatic compounds for which assignments were not certain. Numbers in parenthases are numbering from the original paper. The calculated shifts and error from experimental shift are shown for each aromatic fluorine.

Conclusion We have developed scaling factors aimed at fast and accurate prediction of 19F shifts for fluoroaromatics. In particular, the methods described here allow for the assignment of challenging structures bearing multiple fluorine atoms. The application of these scaling factors does not require advanced computations and, as a result, we hope that it will be applied broadly.


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ASSOCIATED CONTENT

Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Energies for all computed structures, table with shifts and experimental solvents for all compounds used, details on synthesis and characterization of 7 revised (PDF)

Coordinates for all computed structures (mol2)

AUTHOR INFORMATION Corresponding Author * [email protected]

ACKNOWLEDGMENT We gratefully acknowledge support from the National Science Foundation (CHE-1565933, CHE-0957416 and CHE-030089 [via XSEDE]).

References 1. Berger, R.; Resnati, G.; Metrangolo, P.; Weber, E.; Hulliger, J., Organic fluorine compounds: a great opportunity for enhanced materials properties. Chemical Society Reviews 2011, 40 (7), 3496-3508. 2. Fujiwara, T.; OʼHagan, D., Successful fluorine-containing herbicide agrochemicals. Journal of Fluorine Chemistry 2014, 167 (Supplement C), 16-29. 3. Theodoridis, G., Chapter 4 Fluorine-Containing Agrochemicals: An Overview of Recent Developments. In Advances in Fluorine Science, Tressaud, A., Ed. Elsevier: 2006; Vol. 2, pp 121-175. 4. Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V., Fluorine in medicinal chemistry. Chemical Society Reviews 2008, 37 (2), 320-330. 5. Senaweera, S. M.; Singh, A.; Weaver, J. D., Photocatalytic Hydrodefluorination: Facile Access to Partially Fluorinated Aromatics. Journal of the American Chemical Society 2014, 136 (8), 3002-3005.



6. Senaweera, S. M.; Weaver, J. D., Selective Perfluoro- and Polyfluoroarylation of Meldrumʼs Acid. The Journal of Organic Chemistry 2014, 79 (21), 10466-10476. 7. Singh, A.; Kubik, J. J.; Weaver, J. D., Photocatalytic C-F alkylation; facile access to multifluorinated arenes. Chemical Science 2015, 6 (12), 7206-7212. 8. Arora, A.; Weaver, J. D., Visible Light Photocatalysis for the Generation and Use of Reactive Azolyl and Polyfluoroaryl Intermediates. Accounts of Chemical Research 2016, 49 (10), 2273-2283. 9. Senaweera, S.; Weaver, J. D., Dual C‒F, C‒H Functionalization via Photocatalysis: Access to Multifluorinated Biaryls. Journal of the American Chemical Society 2016, 138 (8), 2520-2523. 10. Cybulski, M. K.; Nicholls, J. E.; Lowe, J. P.; Mahon, M. F.; Whittlesey, M. K., Catalytic Hydrodefluorination of Fluoroarenes Using Ru(IMe4)2L2H2 (IMe4 = 1,3,4,5Tetramethylimidazol-2-ylidene; L2 = (PPh3)2, dppe, dppp, dppm) Complexes. Organometallics 2017, 36 (12), 2308-2316. 11. Liu, Y.; Zhou, Y.; Zhao, Y.; Qu, J., Synthesis of gem-Difluoroallylboronates via FeCl2Catalyzed Boration/β-Fluorine Elimination of Trifluoromethyl Alkenes. Organic Letters 2017, 19 (4), 946-949. 12. Singh, A.; Fennell, C. J.; Weaver, J. D., Photocatalyst size controls electron and energy transfer: selectable E/Z isomer synthesis via C-F alkenylation. Chemical Science 2016, 7 (11), 6796-6802. 13. Dolbier, W. R., Guide to Fluorine NMR for Organic Chemists. Wiley: 2009. 14. Muir, M.; Baker, J., A simple calculational model for predicting the site for nucleophilic substitution in aromatic perfluorocarbons. Journal of Fluorine Chemistry 2005, 126 (5), 727-738. 15. Lodewyk, M. W.; Siebert, M. R.; Tantillo, D. J., Computational Prediction of 1H and 13C Chemical Shifts: A Useful Tool for Natural Product, Mechanistic, and Synthetic Organic Chemistry. Chemical Reviews 2012, 112 (3), 1839-1862. 16. Grimblat, N.; Sarotti, A. M., Computational Chemistry to the Rescue: Modern Toolboxes for the Assignment of Complex Molecules by GIAO NMR Calculations. Chemistry ‒ A European Journal 2016, 22 (35), 12246-12261. 17. Di Micco, S.; Chini, M. G.; Riccio, R.; Bifulco, G., Quantum Mechanical Calculation of NMR Parameters in the Stereostructural Determination of Natural Products. European Journal of Organic Chemistry 2010, 2010 (8), 1411-1434. 18. Willoughby, P. H.; Jansma, M. J.; Hoye, T. R., A guide to small-molecule structure assignment through computation of (1H and 13C) NMR chemical shifts. Nature Protocols 2014, 9, 643. 19. Jain, R.; Bally, T.; Rablen, P. R., Calculating Accurate Proton Chemical Shifts of Organic Molecules with Density Functional Methods and Modest Basis Sets. The Journal of Organic Chemistry 2009, 74 (11), 4017-4023.


Page 10 of 13

Page 11 of 13 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


20. Bally, T.; Rablen, P. R., Quantum-Chemical Simulation of 1H NMR Spectra. 2. Comparison of DFT-Based Procedures for Computing Proton‒Proton Coupling Constants in Organic Molecules. The Journal of Organic Chemistry 2011, 76 (12), 4818-4830. 21. Fadeev, D. S.; Chuikov, I. P.; Mamatyuk, V. I., Non-empirical and DFT calculations of 19F and 13C chemical shifts in the NMR spectra of substituted pentafluorobenzenes. Journal of Structural Chemistry 2013, 54 (1), 180-185. 22. Ghiviriga, I.; Zhang, L.; Martinez, H.; Contreras, R. H.; Tormena, C. F.; Nodin, L.; Dolbier, W. R., 19F chemical shifts, coupling constants and conformational preferences in monosubstituted perfluoroparacyclophanes. Magnetic Resonance in Chemistry 2011, 49 (3), 93-105. 23. Kasireddy, C.; Bann, J. G.; Mitchell-Koch, K. R., Demystifying fluorine chemical shifts: electronic structure calculations address origins of seemingly anomalous 19F-NMR spectra of fluorohistidine isomers and analogues. Physical Chemistry Chemical Physics 2015, 17 (45), 30606-30612. 24. Sanders, L. K.; Oldfield, E., Theoretical Investigation of 19F NMR Chemical Shielding Tensors in Fluorobenzenes. The Journal of Physical Chemistry A 2001, 105 (34), 8098-8104. 25. Shaghaghi, H.; Ebrahimi, H.; Tafazzoli, M.; Jalali-Heravi, M., A survey of wave function effects on theoretical calculation of gas phase 19F NMR chemical shifts using factorial design. Journal of Fluorine Chemistry 2010, 131 (1), 47-52. 26. Sternberg, U.; Klipfel, M.; Grage, S. L.; Witter, R.; Ulrich, A. S., Calculation of fluorine chemical shift tensors for the interpretation of oriented 19F-NMR spectra of gramicidin A in membranes. Physical Chemistry Chemical Physics 2009, 11 (32), 7048-7060. 27. Hogben, M. G.; Graham, W. A. G., Chemical shifts and coupling constants in pentafluorophenyl derivatives. I. Correlations of chemical shifts, coupling constants, and .pi.-electronic interactions. Journal of the American Chemical Society 1969, 91 (2), 283-291. 28. Saielli, G.; Bini, R.; Bagno, A., Computational 19F NMR. 2. Organic compounds. RSC Advances 2014, 4 (78), 41605-41611. 29. He, K.-H.; Tan, F.-F.; Zhou, C.-Z.; Zhou, G.-J.; Yang, X.-L.; Li, Y., Acceptorless Dehydrogenation of N-Heterocycles by Merging Visible-Light Photoredox Catalysis and Cobalt Catalysis. Angewandte Chemie International Edition 2017, 56 (11), 3080-3084. 30. Yuan, X.; Yao, J.-F.; Tang, Z.-Y., Decarboxylative Fluorination of Electron-Rich Heteroaromatic Carboxylic Acids with Selectfluor. Organic Letters 2017, 19 (6), 1410-1413. 31. Boden, N.; Emsley, J. W.; Feeney, J.; Sutcliffe, L. H., The effects of π-electron distribution and intramolecular electric fields on the 19F N.M.R. shielding in substituted perfluorobenzenes. Molecular Physics 1964, 8 (2), 133-149. 32. Plevey, R. G.; Rendell, R. W.; Tatlow, J. C., Fluorinations with complex metal fluorides. Part 6 [1] fluorination of yridine and related compounds with caesium tetrafluorocobaltate(III) [2]. Journal of Fluorine Chemistry 1982, 21 (2), 159-169. 33. Coe, P. L.; Holton, A. G.; Tatlow, J. C., Fluorinations with potassium tetrafluorocobaltate(III) Part VII. Further investigations on the fluorination of pyridine. Journal of Fluorine Chemistry 1982, 21 (2), 171-189.



34. Gribble, G. W.; Keavy, D. J.; Olson, E. R.; Rae, I. D.; Staffa, A.; Herr, T. E.; Ferraro, M. B.; Contreras, R. H., Fluorine deshielding in the proximity of a methyl group. An experimental and theoretical study. Magnetic Resonance in Chemistry 1991, 29 (5), 422-432. 35. Burdon, J.; Chivers, G. E.; Tatlow, J. C., Highly fluorinated heterocycles. Part III. The preparation and reactions of some polyfluorofurans. Journal of the Chemical Society C: Organic 1970, (16), 2146-2151. 36. Burdon, J.; Campbell, J. G.; Parsons, I. W.; Tatlow, J. C., Highly fluorinated heterocycles. Part V. The preparation and some reactions of tetrafluorothiophen and some polyfluorothiophens. Journal of the Chemical Society C: Organic 1971, (0), 352-355. 37. Baasner, B.; Klauke, E., A new route to the synthesis of 5-fluorouracil. Journal of Fluorine Chemistry 1989, 45 (3), 417-430. 38. D. Chambers, R.; W. Hall, C.; Hutchinson, J.; W. Millar, R., Polyhalogenated heterocyclic compounds. Part 42.1 Fluorinated nitrogen heterocycles with unusual substitution patterns. Journal of the Chemical Society, Perkin Transactions 1 1998, (10), 1705-1714. 39. Schlosser, M.; Bobbio, C.; Rausis, T., Regiochemically Flexible Substitutions of Di-, Tri-, and Tetrahalopyridines: The Trialkylsilyl Trick. The Journal of Organic Chemistry 2005, 70 (7), 2494-2502. 40. Bobbio, C.; Rausis, T.; Schlosser, M., Removal of Fluorine from and Introduction of Fluorine into Polyhalopyridines: An Exercise in Nucleophilic Hetarenic Substitution. Chemistry ‒ A European Journal 2005, 11 (6), 1903-1910. 41. Božilović, J.; Bats, J. W.; Engels, J. W., Synthesis and structure of fluoroindole nucleosides. Canadian Journal of Chemistry 2007, 85 (4), 283-292. 42. Lemal, D. M.; Akashi, M.; Lou, Y.; Kumar, V., Tetrafluorothiophene S,S-Dioxide: A Perfluorinated Building Block. The Journal of Organic Chemistry 2013, 78 (24), 1233012337. 43. Becke, A. D., A new mixing of Hartree‒Fock and local density‐functional theories. The Journal of Chemical Physics 1993, 98 (2), 1372-1377. 44. Becke, A. D., Density‐functional thermochemistry. III. The role of exact exchange. The Journal of Chemical Physics 1993, 98 (7), 5648-5652. 45. Lee, C.; Yang, W.; Parr, R. G., Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Physical Review B 1988, 37 (2), 785-789. 46. Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J., Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields. The Journal of Physical Chemistry 1994, 98 (45), 11623-11627. 47. Tirado-Rives, J.; Jorgensen, W. L., Performance of B3LYP Density Functional Methods for a Large Set of Organic Molecules. J Chem Theory Comput 2008, 4 (2), 297-306. 48. London, F., Théorie quantique des courants interatomiques dans les combinaisons aromatiques. J. Phys. Radium 1937, 8 (10), 397-409. 49. McWeeny, R., Perturbation Theory for the Fock-Dirac Density Matrix. Physical Review 1962, 126 (3), 1028-1034.


Page 12 of 13

Page 13 of 13 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


50. Ditchfield, R., Self-consistent perturbation theory of diamagnetism. Molecular Physics 1974, 27 (4), 789-807. 51. Wolinski, K.; Hinton, J. F.; Pulay, P., Efficient implementation of the gaugeindependent atomic orbital method for NMR chemical shift calculations. Journal of the American Chemical Society 1990, 112 (23), 8251-8260. 52. Cheeseman, J. R.; Trucks, G. W.; Keith, T. A.; Frisch, M. J., A comparison of models for calculating nuclear magnetic resonance shielding tensors. The Journal of Chemical Physics 1996, 104 (14), 5497-5509. 53. Bagno, A.; Saielli, G., Addressing the stereochemistry of complex organic molecules by density functional theory-NMR. Wiley Interdisciplinary Reviews: Computational Molecular Science 2015, 5 (2), 228-240. 54. de Albuquerque, A. C.; Ribeiro, D. J.; de Amorim, M. B., Structural determination of complex natural products by quantum mechanical calculations of (13)C NMR chemical shifts: development of a parameterized protocol for terpenes. J Mol Model 2016, 22 (8), 183. 55. Marenich, A. V.; Cramer, C. J.; Truhlar, D. G., Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions. The Journal of Physical Chemistry B 2009, 113 (18), 6378-6396. 56. Spartanʼ10 (Wavefunction, Ind.: Irvine, CA, USA (2010). 57. Gaussian 09, Revision D. 01 (Gaussian, Inc.: Wallingford, CT, USA, 2013).


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