Probing Through-Space Polar-π Interactions in 2,6-Diarylphenols

Article abstract of DOI:10.1021/acs.joc.8b03147

Although it is well established that the acidity of phenol can be fine-tuned with substituents on its aromatic ring via through-bond effects, the role of through-space effects on the acidity of phenols is presently poorly understood. Here, we present integrated experimental and computational studies on substituted 2,6-diarylphenols that demonstrate the essential contribution from through-space OH -π interactions and O^--π interactions in the observed trends in proton affinities and acidities of 2,6-diarylphenols.

Full text of DOI:10.1021/acs.joc.8b03147

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Probing Through-Space Polar–# Interactions in 2,6-Diarylphenols
Vera Bosmans, Jordi Poater, Roel Hammink, Paul Tinnemans, F. Matthias Bickelhaupt, and Jasmin Mecinovic
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03147 • Publication Date (Web): 22 Feb 2019
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Probing Through-Space Polar–π Interactions in
2,6-Diarylphenols
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†
‡§
†
¶
⊥
⊥
Vera Bosmans, Jordi Poater, Roel Hammink, ⊥ Paul Tinnemans, F.
†
†$
∥
Matthias Bickelhaupt,* and Jasmin Mecinović*
†
Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ
Nijmegen, The Netherlands
‡ ICREA, Passeig Lluís Companys 23, 08010 Barcelona, Spain
§ Departament de Química Inorgànica i Orgànica & IQTCUB, Universitat de Barcelona, Martí i
Franquès 1-11, 08028 Barcelona, Spain
¶
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud
University Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands
∥
Department of Theoretical Chemistry, Amsterdam Center for Multiscale Modeling, Vrije
Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
$ Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55,
5230 Odense, Denmark
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ABSTRACT: Although it is well established that the acidity of phenol can be fine-tuned with
substituents on its aromatic ring via through-bond effects, the role of through-space effects on the
acidity of phenols is presently poorly understood. Here, we present integrated experimental and
computational studies on substituted 2,6-diarylphenols that demonstrate the essential contribution
from through-space OH–π interactions and O-–π interactions in the observed trends in proton
affinities and acidities of 2,6-diarylphenols.
Noncovalent interactions play key roles in many genuinely important (bio)molecular processes.1, 2
Although the nature and strength of many noncovalent interactions have been extensively studied,
the link between molecular structure and properties remains a subject of ongoing molecular
investigations.3 Recent biomolecular studies revealed that the aromatic rings (i.e. π system) are
involved in energetically favorable interactions between proteins and ligands via several types of
polar–π interactions, including π–π interactions, cation–π interactions, anion–π interactions, SH–π
interactions and OH–π interactions.4, 5 Due to direct involvement of aromatic rings of amino acids of
proteins in associations with small molecule inhibitors, an in-depth understanding of polar–π
interactions importantly contributes to current rational drug design and development.6
Phenols represent an important class of aromatic molecules that display interesting
physicochemical properties and biological activities.7, 8 Physical-organic chemistry investigations on
substituted phenols revealed that the acidity of phenol is significantly altered by electron-donating
and electron-withdrawing groups at ortho-, meta-, or para-positions.9-15 Notably, pKa values of para-
substituted phenols exhibit a linear dependence on the Hammett values. Collectively, chemical
studies demonstrated that substituent effects on the acidity of phenols are primarily a result of
through-bond mechanisms. Despite an important insight into the role of through-bond effects on the
acidity of substituted phenols, the mechanistically distinct through-space effect has not been
established to the same level of detail.16-19
Here we report the role of the through-space effect on the acidity of 2,6-diarylphenols (Figure
1). We conceived that the arrangement of two flanking aromatic rings around the central phenolic
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ring in 2,6-diarylphenols enables detailed experimental and computational examinations of proposed
through-space OH–π interactions at the unprecedented level of molecular detail. Physical-organic
studies on the most related 2,6-diarylcarboxylic acids,20 2,6-diarylpyridines,21 and 2,6-diarylanilines22
revealed that the linear trends in acidities of such systems are a result of through-space effects (Figure
1). We hypothesized that the two neighboring flanking aromatic rings of 2,6-diarylphenols do not
stabilize the protonated form of phenol via through-bond interactions, but rather via through-space
OH–π interactions.
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Figure 1. 2,6-Diaryl-substituted aromatic systems for physical-organic examinations of acidity.
2,6-Diarylphenols 1–6 were synthesized in three steps from 2,6-dibromophenol (Scheme 1).
The phenolic OH of 2,6-dibromophenol was first protected by the acetyl group to afford 2,6-
dibromophenol acetate, which then underwent the palladium-catalyzed Suzuki cross-coupling with
arylboronic acids.23 The basic hydrolysis of 2,6-diarylphenol acetates provided final 2,6-
diarylphenols 1–6.
Scheme 1. Synthesis of 2,6-Diarylphenols 1–6
pKa values of 2,6-diarylphenols 1–6 were measured by UV-vis spectroscopy in buffered
aqueous solutions containing 20% DMSO (to make phenols 1–6 fully soluble) in the pH range of 8–
13 (Table 1 and Figure S1).24 A strong linear correlation (R2 > 0.99) was observed for measured pKa
values of para-substituted 2,6-diarylphenols 1–5 against the Hammett paravalues (Figure 2). As in
the case of other 2,6-diaryl systems,20-22 2paravalues were used in analysis, because 2,6-
diarylphenols possess two flanking aromatic rings each having one para-substituent (Figure 2). The
observed slope provided the ρ value of +1.1, which is essentially the same as the one found for 2,6-
diarylanilines and 2,6-diarylpyridines.21, 22 These results indicate that para-substituted donating
groups (e.g. OMe, Me) make the neighboring flanking aromatic rings more electron-rich, thus leading
to significant stabilization of 2,6-diarylphenols, as manifested by higher pKa values (i.e. being weaker
acids). In contrast, para-substituted withdrawing groups (e.g. F, CF3) make the flanking aromatic
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rings electron-deficient, thus resulting in lower pKa values when compared to the 2,6-diphenylphenol
reference. Collectively, these results support our hypothesis that the through-space OH–π interactions
essentially contribute to stabilization of 2,6-diarylphenols. Notably, we also measured O-H stretching
frequencies by IR spectroscopy; a linear trend (R2 = 0.94) was observed for a series of para-
substituted 2,6-diarylphenols (Table S1 and Figure S2). The lowest and highest O-H frequencies were
measured for electron-donating OMe (2) and electron-withdrawing CF3 (5), respectively, implying
that favorable through-space OH–π interactions are present in 2,6-diarylphenols.
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A further support for the presence of through-space OH–π interactions was obtained by
comparisons of pKa values of 2,6-diphenylphenols that bear meta-substituted F (6) and para-
substituted F (4) (Table 1). Meta- and para-substituted F have significantly different values of the
Hammett σ constant: 0.06 for meta-substituted F (6) and 0.34 for para-substituted F (4). Despite
having substantially different σ values, 6 and 4 have comparable pKa values of 11.24 and 11.29,
respectively (Table 1). This observation importantly demonstrates that the through-bond resonance
effect does not contribute to trends in pKa values of 2,6-diarylphenols, because a full resonance
stabilization (i.e. from the flanking rings to the central phenol ring) would only be possible for para-
substituted F and not for meta-substituted F, thus leading to different pKa values that we do not
observe. As discussed below, the through-bond resonance effect is also excluded based on the
nonplanar geometry of 2,6-diarylphenols. It is noteworthy that the through-bond inductive effect is
also not contributing to observed pKa trends of 2,6-diarylphenols, due to large distance of para-
substituents (six bonds between the OH of phenol and the Cδ that has an attached substituent).
Table 1. pKa Values for Phenols 1–6
compd
X
H
σ
p
Kaa
1
2
3
4
5
6
0.00
11.38
12.02
11.88
11.29
10.29
11.24
p
p
p
p
-OMe
–0.27
–0.17
0.06
-Me
-F
-CF3
0.54
m
-F
0.34
a Determined in H2O:DMSO = 4:1.
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Figure 2. Correlation between pKa values of phenols 1−5 and the Hammett sigma values (2σ).
We then attempted to solve a crystal structure of a representative 2,6-diarylphenol. Crystals of
the phenol that bears the para-substituted F (4) were obtained from methanol at room temperature.25
X-ray crystallographic data revealed that the structure has two independent diarylphenol molecules
in the asymmetric unit and that the three aromatic rings in 4 are not coplanar. Dihedral angles between
the middle phenol ring and both flanking aromatic rings were observed to be in the range of 31–69°
(Figures 3 and S3 and Table S2). Aromatic rings appear to be both in ‘‘parallel’’ or ‘‘eclipsed’’
conformation (i.e. both flanking aromatic rings are pointed in the same direction relative to the central
phenol ring) and ‘‘antiparallel’’ or ‘‘staggered’’ conformation (i.e. both flanking aromatic rings are
pointed in the opposite direction relative to the central phenol ring) (Figure 3). Both arrangements,
however, enable a formation of strong hydrogen bond between the phenolic OH and the electron-rich
aromatic system of the adjacent aromatic rings. The shortest distances between the hydrogen atom of
OH and the carbon atom of the flanking rings were measured to be: OH-Cα 2.4 Å, OH-Cβ 2.2 Å, OH-
Cγ 3.4 Å, and OH-Cδ 4.2 Å. In dimer, the shortest distance between hydrogen atoms in OH–HO is
2.6 Å.
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Figure 3. View on the crystal structure of 4.
Having shown that quantum chemical analyses on related 2,6-diarylanilines and 2,6-
diarylpyridines provided an important insight into energetics and geometry,21, 22 we used the same
computational approach to examine through-space polar–π interactions in 2,6-diarylphenols (Figure
4). In particular, we were interested in: 1) dependence of energy (enthalpy) change for ArOH  ArO-
+ H+ on the substituent X; and 2) for X = H, rotational barrier for internal rotation around C-C bond
of XPh—ArOH (rotation of one single XPh- substituent, i.e. the lowest energy of X = H is computed
and then we calculate the rotational barrier around C-C for one ring while keeping the other at the
lowest energy conformation). The computational analyses were done using the ADF program at the
BLYP-D3BJ/TZ2P level of DFT in aqueous solvation simulated using COSMO (Tables S3–S11).26
Figure 4. a) Eclipsed and staggered conformations for 2,6-diarylphenol. Dihedral φ1 corresponds to
HOC-C2-Cα-Cβ and φ2 to HOC-C6-Cα-Cβ angles. b) Dependence of the relative energy ∆E (in kcal
mol-1) of 2,6-diphenylphenol (1) with the rotation of the HOC-C2-Cα-Cβ dihedral angle (φ, in degrees)
in water and in gas phase.
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The panel of 2,6-diarylphenols 1–6 was optimized, and two conformations appear to be nearly
isoenergetic (Table 2 and Figure 4a) with respect to the dihedral angles with the two aryl rings:
parallel or eclipsed vs. antiparallel or staggered. Similar energetics of eclipsed and staggered
orientations are in line with observed conformations in the crystal state (see above). Both in water
and in the gas phase, the eclipsed conformation is slightly more stable by a maximum of 0.27 kcal
mol-1. The calculated HOC-C2-Cα-Cβ and HOC-C6-Cα-Cβ dihedral angles for the eclipsed and the
staggered conformation (Table S12) are in line with those obtained from structural characterization
of 4 (see above).
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The almost isoenergetic eclipsed and staggered conformations for this set of systems has been
also confirmed by the calculation of the rotational barrier for 2,6-diarylphenol (1, X = H) in the range
0–180º (Figure 4b). Note that only one HOC-C2-Cα-Cβ dihedral angle was varied, whereas the other
dihedral angle was kept at 50.2º (water) or 47.8º (gas phase). The most unstable conformers are those
close to either 0 or 180º, whereas those in the range 40–140º differ by less than 1 kcal mol-1.
Table 2. Energies of Eclipsed and Staggered Conformations and Proton Affinities for both
Conformations in Water and in the Gas Phase in the Series of 2,6-Diarylphenols 1–6 (in kcal
mol-1)
water
vacuo
compd
X
∆∆Eecli-stag ∆EPA
∆EPA
∆∆Estag-ecli
–0.10
∆EPA
∆EPA
ecli
stag
ecli
stag
1
2
3
4
5
6
H
–0.18
–0.27
–0.21
–0.18
–0.18
–0.15
174.9
176.5
176.0
174.3
172.2
173.1
174.7
176.1
175.7
174.1
172.1
172.9
342.0
344.3
343.6
337.1
328.0
335.8
342.0
344.5
343.6
337.1
328.0
335.9
p-OMe
p-Me
p-F
–0.16
–0.13
–0.11
p-CF3
m-F
–0.08
–0.09
Next, we have calculated the proton affinities of all the substituted 2,6-diarylphenols (∆EPA,
Table 2). It can be observed that both conformations present almost the same ∆EPA values. The ∆EPA
for the eclipsed conformation has been plotted against twice the Hammett constant (2), both in water
and in the gas phase (Figure 5 and S4). Good correlations were observed, both in water (Figure 5)
and in vacuo (Figure S4); in water the slope is –2.67 (R2 = 0.99), whereas in the gas phase the slope
is –10.6 (R2 = 0.95). The observed larger slope in the gas phase than in water indicates that the proton
affinities in the gas phase are significantly larger than those in water, which we attribute to much
stronger solvation of the proton than of the protonated phenol (and the phenol). In addition, an
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observation that meta- and para-substituted F have similar proton affinities provided additional
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support for the presence of through-space interactions in 2,6-diarylphenols (Table 2).
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Figure 5. Correlation between proton affinities ∆E in water and the Hammett sigma values (2) of
phenols 1–5 in an eclipsed conformation.
We then investigated the foundation of the para-substituent effect on the proton affinities of
2,6-diarylphenols 2 and 5 with the largest PA (OMe, 176.5 kcal mol-1) and the lowest PA (CF3, 172.2
kcal mol-1). We have analyzed the interaction between one substituted benzene ring (Aryl) and either
H2O or OH- (Table 3 and Figure S5). We previously performed a similar procedure to study the origin
of through-space cation–π interactions in para-substituted 2,6-diarylanilines.22 The interaction ∆Eint
in the case of pCF3 (–1.1 kcal mol–1) is less stabilizing than that of pOMe (–1.3 kcal mol–1; Table 3),
in line with measured (vide supra) and computed (vide infra) O–H stretch frequencies. Note however
that these OH–π interactions are relatively weak and, thus, contribute little to the difference in PA
values. Thus, the difference in the PA must be found in the deprotonated systems, i.e. with the
-
hydroxyl fragment. And indeed, ∆Eint in the case of the pCF3 (–20.9 kcal mol-1) is clearly more
stabilizing than in the case of pOMe- (–11.4 kcal mol-1). The EDA decomposition of these latter ∆Eint
into electrostatic, Pauli, and orbital interaction terms provided evidence that such difference is due to
-
∆Velstat, which is reduced from –8.7 to –0.7 kcal mol-1 as we go from pCF3 to pOMe-. On the other
hand, both substituents present similar ∆EPauli and ∆Eoi magnitudes (Table 3). Note that the interaction
with OH- is significantly more attractive than with water, despite Pauli repulsion is quite similar to
-
the previous case. To investigate the much smaller contribution of ∆Velstat in pOMe- than in pCF3 , the
Voronoi Deformation Density (VDD) charges were calculated (Figure 6 and Table S13) for both
-
separate fragments for either pCF3 and pOMe- systems. More negatively charged carbon atoms were
found in the latter case, reflecting the electron-pushing character of OMe as compared to the electron-
pulling character of CF3. This statement is also supported by the isosurface of the molecular
electrostatic potential of both pOMe to pCF3 depicted in Figure 6, in which the π system of pOMe
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appears more negative (more red). Thus, the more positively charged pCF3-substituted aryl rings
interact more favorably with the hydroxyl anion, as revealed by our EDA analysis (Table 3). This
also leads to a somewhat shorter HO––Aryl distance in pCF3 (2.896 Å) than in pOMe (2.903 Å, see
Table S13).
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Table 3. Through-space interaction analyses (in kcal mol-1) in simplified models of para-substituted
2,6-diarylphenols and their conjugate bases.a
System Interaction
pCF3 H2O···Aryl(CF3)
∆Eint ∆EPauli ∆Velstat ∆Eoi ∆Edisp
R
–1.1
8.8
9.5
7.6
7.8
–4.8 –2.9
–5.3 –3.2
–8.7 –18.4
–0.7 –17.2
–2.2
–2.3
–1.4
–1.4
pOMe H2O···Aryl(OMe) –1.3
H2O
OH-
Aryl
Aryl
-
R
pCF3
OH-···Aryl(CF3)
–20.9
pOMe- OH-···Aryl(OMe) –11.4
a
See Figure S5. Calculated at ZORA-BLYP-D3BJ/TZ2P level of theory. As the values of eclipsed and staggered
conformations are almost the same, only the former ones are enclosed.
Figure 6. a) VDD charges (in milli-electrons) for fragments in model systems used in through-space
-
interaction analysis for pCF3 and pOMe- (see Table 3), and b) molecular electrostatic potential
isosurfaces for pCF3 and pOMe, calculated at ZORA-BLYP-D3BJ/TZ2P level.
Finally, we also calculated O-H stretching frequency shifts of the series of 2,6-diarylphenols
1–6 in water and in the gas phase (Table S14 and Figures S6–S7). In line with the experimentally
observed trend, we found that electron-donating groups lead to frequency lowering, whereas electron-
withdrawing groups show frequency increasing, for both eclipsed and staggered conformations (R2 =
0.88–0.96) (Figures S6–S7). These results demonstrate that electron-rich flanking aromatic rings
form stronger OH–π interactions with the OH group of the central phenol.
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In conclusion, we have demonstrated that 2,6-diarylphenols are stabilized by a combination of
intramolecular OH–π interactions and, interestingly, O-–π interactions, as manifested by linear
correlations in pKa values and proton affinities for 2,6-diarylphenols that bear para-substituents at the
two neighboring aromatic rings. Unlike many substituted phenols whose acidity is strongly affected
by the through-bond effect, the acidity of 2,6-diarylphenols is influenced by the mechanistically
distinct through-space effect. Along with physical-organic chemistry examinations of related
molecular systems,20-22, 27, 28 the work further highlights that the 2,6-diaryl substituted aromatic
scaffolds are good models for studying the role of the through-space effect between polar functional
groups and aromatic rings.
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EXPERIMENTAL SECTION
Synthesis of 2,6-diarylphenols.
To a mixture of 2,6-dibromophenol acetate23 (0.5 mmol) and Pd(PPh3)4 (0.1 mmol) in toluene (4 mL)
were added a solution of the arylboronic acid (1 mmol) in THF (5 mL) and an aqueous solution of
Na2CO3 (2 M, 2 mL). After refluxing at 80 C for 18 hours, the reaction mixture was poured into 20
mL of water and extracted with 20 mL of diethyl ether. The combined organic layers were dried with
MgSO4, filtered and evaporated in vacuo to obtain acetylated 2,6-diarylphenols that were
deacetylated using an aqueous solution of NaOH (2M, 5 ml) and then acidified with HCl (2M, 6 ml)
and extracted with ethyl acetate (2 × 20 ml). The products were purified by column chromatography
using heptane with an increasing gradient (0–50%) of ethyl acetate to afford 2,6-diarylphenols 1–6.
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2,6-Diphenylphenol (1): White solid (67 mg, 55% yield); mp 102–103 C; H NMR (400 MHz,
CDCl3) δ 5.40 (1H, s), 7.06 (1H, t, J = 7.0 Hz), 7.25–7.30 (2H, m), 7.38–7.40 (2H, m), 7.45–7.50
(4H, m), 7.54–7.58 (4H, m); 13C{1H} NMR (101 MHz, CDCl3) δ 120.7, 127.7, 128.8, 128.9, 129.4,
130.0, 137.6, 149.3; HRMS (EI-TOF) [M+] m/z: calcd for C18H14O 246.1045; found; 246.1045.
2,6-Di(4-methoxy)phenylphenol (2): Red solid (20 mg, 13% yield); mp 102–103 C; 1H NMR (400
MHz, CDCl3) δ 3.84 (6H, s), 5.36 (1H, s) 6.95 (2H, d, J = 9.0 Hz), 7.00–7.02 (2H, m), 7.22 (1H, d, J
= 8.0 Hz), 7.34 (2H, s), 7.38–7.40 (2H, d), 7.49 (2H, d, J = 9.0 Hz); 13C{1H} NMR (101 MHz, CDCl3)
δ 55.3, 113.7, 114.3, 126.4, 129.4, 129.5, 129.7, 130.1, 130.5, 130.7; HRMS (EI-TOF) [M+] m/z:
calcd for C20H18O3 306.1256; found; 306.1271.
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2,6-Di(4-methyl)phenylphenol (3): White solid (30 mg, 22% yield); mp 94–95 C; H NMR (400
MHz, CDCl3) δ 2.38 (6 H, s), 7.21 (4H, d, J = 6.5 Hz), 7.20–7.24 (1H, m), 7.34 (4H, d, J = 7.0 Hz),
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7.35 (2 H, s), 7.43–7.45 (1 H, m); C{1H} NMR (101 MHz, CDCl3) δ 21.2, 128.8, 129.0, 129.9,
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129.6, 129.9, 135.0, 135.7, 137.2; HRMS (EI-TOF) [M+] m/z: calcd for C20H18O 274.1358; found;
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2,6-Di(4-fluoro)phenylphenol (4): White solid (128 mg, 91% yield); mp 66–67 C; 1H NMR (400
MHz, CDCl3) δ 5.23 (1H, s), 7.05 (1H, t, J = 7.0 Hz), 7.11–7.19 (4H, m), 7.23–7.26 (2H, m), 7.48–
7.55 (4H, m); 13C{1H} NMR (101 MHz, CDCl3) δ 115.7, 120.8, 122.9, 130.1, 131.0, 133.3, 149.3,
161.2, 163.6; HRMS (EI-TOF) [M+] m/z: calcd for C18H12F2O 282.0856; found; 282.0851.
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2,6-Di(4-trifluoromethyl)phenylphenol (5): Orange solid (120 mg, 63% yield); mp 97–98 C; H
NMR (400 MHz, CDCl3) δ 5.23 (1H, s), 7.12 (1H, dd, J = 7.5 Hz, 8.0 Hz), 7.31 (1 H, d, J = 7.5 Hz),
7.42–7.45 (1H, m), 7.57 (2H, d, J = 7.5 Hz), 7.67–7.70 (3H, m), 7.73–7.77 (2H, m); 13C{1H} NMR
(101 MHz, CDCl3) δ 121.3, 125.3, 125.9, 126.9, 127.6, 129.4, 129.8, 130.7, 134.9; HRMS (EI-TOF)
[M+] m/z: calcd for C20H12F6O 382.0792; found; 382.0792.
1
2,6-Di(3-fluoro)phenylphenol (6): White solid (80 mg, 57% yield); mp 86–87 C; H NMR (400
MHz, CDCl3) δ 5.36 (1H, s), 7.03–7.09 (2H, m), 7.15–7.20 (2H, m), 7.21–7.24 (2H, m), 7.35–7.45
(5H, m); 13C{1H} NMR (101 MHz, CDCl3) δ 113.41, 113.62, 114.87, 115.09, 123.71, 123.72, 125.67,
128.78, 128.86, 129.34; HRMS (EI-TOF) [M+] m/z: calcd for C18H12F2O 282.0856; found; 282.0864.
Quantum chemical analyses.
All calculations were carried out with the Amsterdam Density Functional (ADF) program using
dispersion-corrected density functional theory at the BLYP-D3BJ/TZ2P level of theory.26, 29 The
effect of solvation in water was simulated by means of the Conductor like Screening Model
(COSMO) of solvation as implemented in ADF. The approach has been benchmarked against highly
correlated post-Hartree-Fock methods and experimental data and was found to work reliably.21, 30, 31
The bonding mechanism of water (taken from phenol) or hydroxyl (taken from unprotonated phenol)
with the two substituted benzene rings (taken from aryl rings) was analyzed within the framework of
quantitative Kohn-Sham molecular orbital theory32 in combination with a quantitative energy
decomposition analysis (EDA)32 in the gas phase. The electronic bond energy ∆E can be decomposed
into the strain energy ∆Estrain associated with deforming the fragments from their equilibrium structure
to the geometry they adopt in modified aniline, plus the interaction energy ∆Eint between these
deformed fragments. The latter is further decomposed into the classical electrostatic attraction ∆Velstat
,
Pauli repulsion ∆EPauli between occupied orbitals, stabilizing orbital interactions ∆Eoi, and dispersion
∆Edisp. Atomic charges were computed with the Voronoi deformation density (VDD) method.33
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ASSOCIATED CONTENT
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Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website.
NMR spectra, pKa measurements, IR data, X-ray crystallography data, computational studies.
Crystallographic data for 4.
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AUTHOR INFORMATION
Corresponding Authors
*E-mail: mecinovic@sdu.dk
*E-mail: f.m.bickelhaupt@vu.nl
ORCID
Jordi Poater: 0000-0002-0814-5074
Roel Hammink: 0000-0001-8721-5271
F. Matthias Bickelhaupt: 0000-0003-4655-7747
Jasmin Mecinović: 0000-0002-5559-3822
Author Contributions
⊥ These authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKOWLEDGMENTS
We thank the Netherlands Organization for Scientific Research (NWO) for financial support. J.P.
thanks the Spanish MINECO (CTQ2016-77558-R and MDM-2017-0767) and the Generalitat de
Catalunya (2017SGR348).
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