Borane adducts of punicine and of its dehydroxy derivatives (pyridinium-1-yl)-2- and 3-phenolates

Article abstract of DOI:10.1016/j.tet.2020.131627

The natural product punicine (Punica granatum) exists in two tautomeric forms, the cross-conjugated mesomeric betaine 1-(pyridinium-1-yl)-2-hydroxy-phenyl-5-olate and the conjugated mesomeric betaine 1-(pyridinium-1-yl)-5-hydroxy-phenyl-2-olate. Punicine

Full text of DOI:10.1016/j.tet.2020.131627

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Borane adducts of punicine and of its dehydroxy derivatives (pyridinium-1-yl)-2- and
3-phenolates
Christian F. Otto, Colin Herzberger, Ming Liu, Jan C. Namyslo, Martin Nieger, Tyll
Freese, Felix Lederle, Eike G. Hübner, Andreas Schmidt
PII:
S0040-4020(20)30834-6
https://doi.org/10.1016/j.tet.2020.131627
TET 131627
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 15 July 2020
Revised Date: 26 August 2020
Accepted Date: 14 September 2020
Please cite this article as: Otto CF, Herzberger C, Liu M, Namyslo JC, Nieger M, Freese T, Lederle F,
Hübner EG, Schmidt A, Borane adducts of punicine and of its dehydroxy derivatives (pyridinium-1-yl)-2-
and 3-phenolates, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131627.
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Graphical Abstract
Borane adducts of punicine and of its
dehydroxy derivatives (pyridinium-1-yl)-2-
and 3-phenolates
Leave this area blank for abstract info.
Christian Friedrich Otto,a Colin Herzberger,a Ming Liu,a Jan C. Namyslo,a Martin Nieger,b Eike G. Hübner,a
Felix Lederle,c Tyll Freesea and Andreas Schmidta*
a Clausthal University of Technology, Institute of Organic Chemistry, Leibnizstrasse 6, D-38678 Clausthal-
Zellerfeld, Germany.
b University of Helsinki, Department of Chemistry, P.O. Box 55, FIN-00014 Helsinki, Finland.
c Clausthal University of Technology, Institute of Technical Chemistry, Arnold-Sommerfeld-Str. 4, D-38678
Clausthal-Zellerfeld, Germany.

1
Tetrahedron
journal homepage: www.elsevier.com
Borane adducts of punicine and of its dehydroxy derivatives (pyridinium-1-yl)-2- and
3-phenolates
Christian F. Otto,a Colin Herzberger,a Ming Liu,a Jan C. Namyslo,a Martin Nieger,b Tyll Freese,a Felix
Lederle,a,c Eike G. Hübner,a and Andreas Schmidta*
a Clausthal University of Technology, Institute of Organic Chemistry, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany.
b University of Helsinki, Department of Chemistry, P.O. Box 55, FIN-00014 Helsinki, Finland.
c Clausthal University of Technology, Institute of Technical Chemistry, Arnold-Sommerfeld-Str. 4, D-38678 Clausthal-Zellerfeld, Germany.
E-mail: schmidt@ioc.tu-clausthal.de
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The natural product punicine (Punica granatum) exists in two tautomeric forms, the cross-
conjugated mesomeric betaine 1-(pyridinium-1-yl)-2-hydroxy-phenyl-5-olate and the conjugated
mesomeric betaine 1-(pyridinium-1-yl)-5-hydroxy-phenyl-2-olate. Punicine as well as its
picoline derivatives reacted with tris(pentafluorophenyl)borane exclusively at the 2´-olate group
to form zwitterionic borates. Correspondingly, the 5´-dehydroxy derivate of punicine, the
conjugated heterocyclic mesomeric betaine 1-(pyridinium-1-yl)-phenyl-2-olate and its picoline
derivatives also gave borates, whereas analogous reactions of the cross-conjugated isomer 2´-
dehydroxypunicine [1-(pyridinium-1-yl)-phenyl-3-olate] did not result in the formation of stable
adducts.
Available online
Keywords:
Mesomeric betaine
Pyridinium-phenolate
Cross-conjugation
Conjugation
2020 Elsevier Ltd. All rights reserved
.
Tris(pentafluorophenyl)borane
development of switchable materials.11-14 Thus punicine proved
to be a suitable model compound to study the different types of
conjugation which are known to govern the chemical behaviour
of mesomeric betaines considerably.15-18 As examples,
conjugated mesomeric betaines such as sydnones19 or
münchnones20 are versatile 1,3-dipoles in cycloadditions.18 By
contrast, cross-conjugated mesomeric betaines, which possess a
π-electronic charge separation, are often 1,4-dipoles18,21 which
can be used in materials chemistry.22 Characteristic dipole
increments can be dissected from the resonance forms,
respectively. Conjugated as well as cross-conjugated mesomeric
betaines are interesting precursors of anionic N-heterocyclic
carbenes.23 Pseudo-cross-conjugation defines the third class of
mesomeric betaines. Examples are imidazolium-2-carboxylates,24
pyrazolium-3-carboxylates25 and indazolium-3-carboxylates26
which decarboxylate readily under mild conditions to form the
corresponding N-heterocyclic carbenes. Thus, pseudo-cross-
conjugated mesomeric betaines are often crypto-NHCs.27 The
fourths and fifth class of mesomeric betaines, which are semi-
conjugated and pseudo-semi-conjugated, respectively, still
remain to be explored in more detail, as only a very limited
number of representatives have been described to date.17 In
continuation of our interest in punicines,9,11-14 conjugation in
hetarenium salts,28 mesomeric betaines29 as well as N-
heterocyclic carbenes30 we report here that the type of
conjugation also influences the borane adduct formation of
mesomeric betaines. We report on the synthesis of the
1. Introduction
Much interest is currently focused on borane adducts of N-
heterocyclic carbenes,1 of phenolate substituted N-heterocyclic
carbenes,2 and on borates of phenols. Interestingly, the latter
mentioned have been formed from p-fluorophenyl-tert.-
butylether and the frustrated Lewis pair consisting of tert.-butyl
phosphane
and
tris(pentafluorophenyl)borane.3
8-
Hydroxyquinoline reacted with the latter mentioned borane to
yield a zwitterionic luminescent adduct,4 whereas 1-naphthols
gave
stabilized
keto
isomers
of
1-naphthol,
i.e.
benzocyclohexadienes.5 Four-coordinated boron compounds of
2-(2-pyridyl)phenol have been developed as hole-blocking
materials for phosphorescent OLEDs,6 and other adducts serve as
building blocks of 2D and 3D crystalline coordination polymer
networks.7 Interest has recently also been directed toward a
thorough investigation of Liebermann betaines and its
derivatives, which possess quinoid partial structures8. In view of
these studies, the alkaloid punicine9 also seemed to be an
interesting target for borate formations. It has been isolated from
the leaves of Punica granatum10 and, as it combines a
hydroquinone and a pyridinium moiety, it is an interesting redox
active compound. Depending on the pH of the solution punicine
can exist as salt 1a, as mixture of mesomeric betaines 2Aa and
2Ba, as anion 3, or as open-chained anionic species 49 (Scheme
1). Redox reactions of punicine derivatives resulted in the
formation of radical anions and radical semiquinones and the

2
Tetrahedron
tris(pentafluorophenyl)borates of punicine and of its
derivatives. We found that the borane adduct formation strongly
depends on the position of the olate group in the mesomeric
betaine, i.e. on the type of conjugation.
OH
O
OH
2´
N
N
N
-H
~H
~H
+H
5´
OH
O
OH
2Aa
2Ba
1a
Punicine
O
-H
+H
O
OH
O
O
N
-H2O
N
H
+H
Fig. 1. Charge distribution as well as calculated frontier orbital profiles of I
and II.
O
4
3
Scheme 1. The alkaloid punicine 2Aa/2Ba.
The 2- und 4-methylpyridinium derivatives 2b,d of punicine
2a have been prepared as described earlier starting from
benzoquinone and the corresponding picolines,11 whereas their 3-
methyl derivative 2c was synthesized according to modified
literature procedures31,32 (Scheme 2).
2. Results and Discussion
The structures I and II represent partial structures of the
punicine tautomers 2Aa and 2Ba, respectively (Fig. 1). They
display the typical characteristics of two distinct classes of
mesomeric betaines. Dehydroxypunicine I is a member of the
class of conjugated mesomeric betaines such as tautomer 2Aa
and possesses sites for positive as well as negative charges in the
resonance forms as shown. By contrast, the charges in cross-
conjugated partial structure II of tautomer 2Ba are restricted to
separated parts of the common π-electron system. In I the cation
is joined to the anion through a starred position of the
isoconjugated equivalent (the benzyl anion), whereas this
position is unstarred in II, and these positions are active and
inactive positions of the highest occupied molecular orbital
(HOMO), respectively.18 The HOMO is essentially located in the
phenolate rings, whereas the lowest unoccupied molecular orbital
(LUMO) is essentially located in the pyridinium rings. The
inactive position in II causes a π-electronic charge separation in
the ground state of the molecule. Thus, punicine as well as its
derivatives are excellent model compounds to study borane
adduct formations under variation of the type of conjugation in
mesomeric betaines.
O
*
N
N
*
*
*
Scheme 2. Syntheses of punicine derivatives and of their borane adducts.
I
conjugated
On titration of a DMSO-d6 solution of 1a with proton sponge
[i.e. 1,8-bis(dimethylamino)naphthalene], the integral of the more
deshielded resonance frequency assigned to the 5´-hydroxy group
diminished twice as fast as the signal of the 2´-hydroxy group
which is indicative for the predominant formation of the cross-
N
*
N
*
*
O
*
cross-conjugated
N
II
conjugated tautomer 2Ba in strongly polar solvents [ET (DMSO)
= 0.444].9 The two tautomers, however, proved to be inseparable.
In addition, no quinhydrone complex formed during the reaction,
although π-stacking complexes have been observed before.11
Single crystals of the 4-methylpyridinium punicine derivative 1d
were obtained by slow evaporation of a concentrated solution in
DMSO-d6. The molecular drawing is shown in Fig. 2. The
sites for negative charges
sites for positive charges
sites for positive and negative
charges in the resonance forms

3
compound crystallized monoclinic. In the elemental cell the 5´-
OH group forms a hydrogen bond to the chloride counter ion
[H…Cl = 221(2) pm; O-H…Cl = 172(2)°], whereas the 2´-OH
group binds one water of crystallization [H…OH2 = 180(1) pm;
O-H…OH2 = 171(2)°]. The pyridinium ring is twisted by -
47.30(15)° from the plane of the hydroquinone ring (C2-N1-C11-
C16; crystallographic numbering).
indicated as cross signals in the HMBC spectra so that the
formation of the alternative regioisomer was eliminated from
consideration. In accordance with the postulated structure no
NOE cross signals between the 5´-OH proton and the protons in
α position of the pyridinium ring were detectable as to be
expected for the regioisomer. Selected peak assignments and
diagnostic NMR results are shown in Fig. 4. DFT-calculations
indeed predict that the obtained structure is by 29.45 kJ/mol
thermodynamically more stable in vacuo than its regioisomer.
Fig. 2. Molecular drawing of punicine derivative 1d (displacement
parameters drawn at 50% probability level).
Fig. 4. Diagnostic NMR results for structure elucidation of borane adduct 5a.
In the elemental cell the phenolate rings stack to the
pyridinium rings of the molecules of the second layer (Fig. 3).
The plane-to-plane distance of 3.7396(2) Å (distance between N1
and C11 of the second layer) suggests attractive π-π-interactions
as it meets the distance criteria described in the literature (3.3-
3.8 Å).33,34 The parallel alignment of the stacked rings is different
in comparison to crystalline benzene, the σ-π-interactions of
which provoke a herringbone structure.33 In the case of the
punicines the stacking presumably is caused by intermolecular
HOMO-LUMO interactions. Therefore, in accordance with the
quadrupole model35 the negative π-cloud of the hydroquinoline
ring interacts with the electron-deficient pyridinium moiety and
hence with an inverted quadrupole in a face-to-face rather than a
According to the calculation, the borane adduct 5a adopts a
conformation in which the pyridinium ring and the phenolate ring
are twisted by 49.9°, and the borate is twisted by 8.9° out of the
plane of the phenolate. The highest occupied molecular orbital
(HOMO) is essentially located in the hydroquinone moiety,
whereas the lowest unoccupied molecular orbital (LUMO) is
located in the pyridinium ring (Fig. 5).
5a
HOMO (5a)
LUMO (5a)
Fig. 5. Results of calculations on borane adduct 5a. Most stable conformation
(above) and frontier orbital profile (below).
face-to-edge interaction.
A single crystal structure was obtained from the 3-
methylpyridinium derivative 5c which is in agreement with the
results of the DFT calculations with respect to the geometrical
properties. Thus, a torsional angle of 54.3(3)° was found between
the pyridinium ring and the phenyl ring [C1-C6-N7-C12;
crystallographic numbering] (Fig. 6). The borate residue is
twisted by -20.5(4)° out of the plane of the phenyl ring [B1-O1-
C1-C2, crystallographic numbering]. The single crystal was
obtained by slow evaporation of a concentrated solution in
DMSO-d6.
Fig. 3. Crystal packing of punicine derivative 1d (only hydrogen atoms
involved in hydrogen bonds shown).
After deprotonation by the ion exchange resin Amberlite IRA-
400 punicine 2a as well as its 2-methyl-, 3-methyl- and 4-methyl
derivatives 2b-c reacted with tris(pentafluorophenyl)borane in
anhydrous dioxane to give regioselectively the zwitterionic
borates 5a-d in good yields (Scheme 2). The NMR spectra of the
adducts displayed only one set of signals. Peak assignments were
3
accomplished by 2D NMR techniques. The JCH couplings
between the 5´-OH proton and the adjacent CH positions were

4
Tetrahedron
ring transformation of pyridinium salt 10 with 3-aminophenol in
DMF,39 followed by an anion exchange of the chloride to the
non-hygroscopic perchlorate in order to precipitate the product
with a yield of 50 %. Conversion of the salt 11 into its cross-
conjugated mesomeric betaine 12, identical to partial structure II
shown in Scheme 2, was accomplished by the anion exchange
resin Amberlite IRA-96 in its hydroxide form in quantitative
yield, however, the sample decomposed rapidly on standing. No
reaction
with
tris(pentafluorophenyl)borane
occurred.
Stabilization of the system by an additional hydroxyl group
adjacent to the 3´-OH group of 2´-dehydroxypunicine was tested
by the synthesis of betaine 15. It was prepared starting from
catechol and pyridine in the presence of bromine which resulted
in the formation of the salt 14 in acceptable yields. Deprotonation
was finally accomplished on treatment of the salt 14 with the
anion exchange resin Amberlite IRA-400 in its hydroxide form.
Indeed, betaine 15 proved to be stable. The resonance frequencies
of the OH groups of the pyridinium salt 14, detected at 9.83 ppm
and 9.97 ppm, respectively, disappeared on betaine formation and
Fig. 6. Molecular drawing of borane adduct 5c (solvent omitted for clarity,
C6F5 moieties represented as wireframe model), displacement parameters
drawn at 50% probability level.
We next focused our interest on the partial structures I and II of
punicine as shown in Fig. 1. Interest has been focused on
pyridinium-2-phenolates (I) as well as on its salts because of
non-linear optical properties36,37 and solvatochromism.38 To the
best of our knowledge pyridinium-3-phenolates (II) are much
less examined. It has been calculated37 and its salt39,40 was
examined mass-spectrometrically.41 In order to prepare a series of
pyridinium-2-phenolates we reacted the pyridine-N-oxides 6a-d
with diphenyliodonium hexafluorophosphate in dichloroethane
under Schlenk conditions for 2 days at 120°C (Scheme 3). A
slight modification of the literature procedure gave considerably
increased yields of 7a (17%42 to 44%) and 7b (8%42 to 62%), and
also opened the access to the isolation and characterization of
7c,d. Potassium carbonate converted the salts 7a-d into their
betaines 8a-d which were obtained as orange solids. They formed
1
all other H NMR signals shifted to higher field. In parallel, a
downfield shift of approximately 4 ppm is found in the 13C NMR
spectra. Reaction with the aforementioned borane, however, in
analogy to the conversion of the 2´-dehydroxypunicines, were
unsuccessful even under prolonged reaction times.
1. 3-aminophenol,
DMF, 4.5 h,
reflux
2. NaClO4
Cl
Amberlite
IRA-96
MeOH
N
N
N
NO2
- 2,4-dinitroaniline
ClO4
OH
O
borane
adducts
9a-d
on
treatment
with
NO2
tris(pentafluorophenyl)borane in anhydrous dioxane at reflux
temperature in low to very good yields. The boron atoms appear
between δ = -3.45 ppm (9a) and -3.43 ppm (9c) in the 11B NMR
spectra. The fluorine atoms were detected at approximately -
134.0 ppm, -161.6 ppm, and -166.5 ppm as doublet, triplet, and
multiplet, respectively, in the 19F NMR spectra.
12
11
10
Amberlite
IRA-400
MeOH
pyridine, Br2,
0°C, MeOH
OH
OH
N
N
Br
HO
HO
OH
14
O
13
15
Scheme 4. Synthesis of 2´-dehydroxypunicine 12 and the punicine isomer 15.
3. Conclusions
Punicine exists as a mixture of a conjugated and a cross-
conjugated heterocyclic mesomeric betaine. On treatment with
tris(pentafluorophenyl)borane the olate group in conjugation
reacted regioselectively to give a zwitterionic borane adduct,
whereas the olate group in cross-conjugated position remained
unchanged. Likewise, the conjugated mesomeric betaines 1-
(pyridinium-1-yl)-2-phenolates gave stable borane adducts,
whereas the cross-conjugated isomer decomposed under
analogous reaction conditions. These results supplement our
knowledge about the chemistry of isomers which belong to
different classes of heterocyclic mesomeric betaines.
Scheme 3. Synthesis and borane adduct formation of 5-dehydroxypunicine.
We finally envisaged the synthesis of the 2´-
dehydroxypunicine 12 to study borane adduct formations
(Scheme 4). Therefore the salt 11 was prepared by a nucleophilic
Acknowledgement

5
Dr. Gerald Dräger, university of Hannover (Germany), is
gratefully acknowledged for measuring a part of the HRESIMS
spectra.
The deprotonated punicine derivatives 2a-d were mixed with
one equivalent of tris(pentafluorophenyl)borane and dried in
vacuo for 30 minutes. Then 6 mL of anhydrous dioxane were
added under inert atmosphere and the resulting suspension was
heated to 150 °C for 18 h in a sealed pressure tube. After cooling
the reaction mixture to room temperature, the solvent was
evaporated and the crude product was subsequently purified by
column chromatography (ethyl acetate on silica gel).
4. Experimental
Calculations. Density-functional theory (DFT)-calculations of
I, II and both regioisomers of 5a were carried out by using the
Jaguar 9.1.013 software43 running on Linux 2.6.18-238.el5 SMP
(x86_64) on five AMD Phenom II X6 1090T processor
workstations (Beowulf-cluster) parallelized with OpenMPI.
MM2 optimized structures were used as starting geometries.
Complete geometry optimizations were carried out on the
implemented LACVP* (Hay-Wadt effective core potential (ECP)
basis on heavy atoms, N31G6* for all other atoms) basis set and
with the B3LYP density functional. All calculated structures
were proven to be true minima by the absence of imaginary
frequencies. Plots were obtained using Maestro 10.5.013, the
graphical interface of Jaguar. Density-functional theory (DFT)-
calculations of 2Aa and 2Ba were carried out by using the
multithreaded Firefly 8.2.0 QC package,44 which is partially
based on the GAMESS (US)45 source code, running on Windows
10 Pro (Version 10.0.17763.475) (x86_64) on a 16 core AMD
2950X processor workstation. MM2 optimized structures were
used as starting geometries. Complete geometry optimizations
were carried out on the implemented N31G6* basis set and with
the B3LYP density functional. All calculated structures were
proven to be true minima by the absence of imaginary
frequencies.
(2-(Pyridinium-1-yl)-4-hydroxy-
phenoxy)tris(pentafluorophenyl)borate 5a. A sample of 73.1
mg (0,39 mmol) of 4-hydroxy-2(N-pyridinium)phenolate and 200
mg (0.39 mmol) of tris(pentafluorophenyl)borane was used to
obtain the product 5a as a bright yellow solid. Yield: 152 mg
(56%), mp: 220 °C (decomp.). 1H NMR (600 MHz, DMSO-d6): δ
= 9.30 (br s. 1H, OH), 8.94 – 8.92 (m, 2H, 2-H, 6-H), 8.65 (tt, J1
=8.0 Hz, J2 = 1.3 Hz, 1H, 4-H), 8.14 – 8.12 (m, 2H, 3-H, 5-H),
6.98 (d, J = 2.9 Hz, 1H, 6’-H), 6.72 (dd, J1 = 9.2 Hz, J2 = 2.9 Hz,
1H, 4’-H), 6.40 (d, J = 9.2 Hz, 1H, 3’-H) ppm. 13C NMR (150
MHz, DMSO-d6): δ = 148.6 (o, 1C, 5’-C), 147.9 (br, o), 146.4
(br, o), 146.3 (+, 2C, 2-C, 6-C), 145.9 (+, 1C, 4-C), 144.6 (o, 1C,
2’-C), 138.9 (br, o), 137.2 (br, o), 136.6 (br, o), 135.0 (br, o),
133.1 (o, 1C, 1’-C), 126.9 (+, 2C, 3-C, 5-C), 122.2 (br, o), 118.5
(+, 1C, 5’-C), 117.7 (+, 1C, 3’-C), 112.1 (+, 1C, 6’-C) ppm. 19F
NMR (376 MHz, DMSO-d6): δ = -133.94 (d, J = 19.6 Hz), -
161.78 (t, J = 19.6 Hz), -166.48 – -166.58 (m) ppm. 11B NMR
(192.6 MHz, DMSO-d6): δ = -3.9 ppm. IR (ATR): ṽ = 3606,
1643, 1510, 1456, 1276, 1083, 975, 955, 897, 772, 764, 692, 680,
668 cm-1. HRESIMS: C29H9BF15NO2Na+: required 722.0385.
Found: 722.0388.
Nuclear magnetic resonance (NMR) spectra were measured
with a Bruker Avance 400 MHz and Bruker Avance III 600
(2-(2-Methylpyridinium-1-yl)-4-hydroxy-
1
MHz. H NMR spectra were recorded at 400 MHz or 600 MHz.
phenoxy)tris(pentafluorophenyl)borate 5b. A sample of 79.0
13C NMR spectra were recorded at 100 MHz or 150 MHz, with
the solvent peak or tetramethylsilane used as the internal
reference. Multiplicities are described by using the following
abbreviations: s = singlet, d = doublet, t = triplet, q = quartet, m =
multiplet, br = broadened. Signal orientations in DEPT
experiments were described as follows, when applied: o = no
signal; + = up (CH, CH3); - = down (CH2). Peak assignments
were defined as follows. Notations such as C-3, C-3´, and C-3´´
correspond to carbon atoms of the pyridinium rings, the
phenolate rings, and the pentafluorophenyl rings, respectively,
and hydrogen (3-H; 3´-H) as well as fluorine atoms (3´´-F) are
described analogously. The mass spectra were measured with a
Varian 320 MS Triple Quad GC/MS/MS with a Varian 450-GC.
The electrospray ionization mass spectra (ESIMS) were
measured with an Agilent LCMSD series HP 1100 with APIES.
Spectra were taken at 30V fragmentor voltage unless otherwise
noted. Melting points are uncorrected and were determined in an
apparatus according to Dr. Tottoli (Büchi). Yields are not
optimized.
mg
(0,39
mmol)
of
4-hydroxy-2(N-2-
methylpyridinium)phenolate and 200 mg (0.39 mmol) of
tris(pentafluorophenyl)borane was used to obtain the product 5b
as a bright yellow solid. Yield: 244 mg (88%), mp: 216 °C. H
1
NMR (600 MHz, DMSO-d6): δ = 9.28 (br s. 1H, OH), 8.84 (br.s.,
1H, 6-H), 8.79 (d, J =6.2 Hz, 1H, 4-H), 8.49 (d, J = 7.9 Hz, 1H,
5-H), 8.04 (dd, J1 = 7.9 Hz, J2 = 6.2 Hz, 1H, 3-H), 6.95 (d, J =
3.0 Hz, 1H, 6’-H), 6.72 (dd, J1 = 9.0 Hz, J2 = 3.0 Hz, 1H, 4’-H),
6.44 (d, J = 9.0 Hz, 1H, 3’-H), 2.46 (s, 3H, 7-H) ppm. 13C NMR
(150 MHz, DMSO-d6): δ = 148.7 (o, 1C, 5’-C), 148.0 (br, o),
146.4 (br, o), 146.1 (+, 1C, 5-C), 146.0 (+, 1C, 6-C), 144.5 (o,
1C, 2’-C), 138.9 (br, o), 137.4 (+, 1C, 2-C), 137.3 (br, o), 136.6
(br, o), 135.0 (br, o), 133.0 (o, 1C, 1’-C), 126.5 (+, 1C, 3-C),
122.1 (br, o), 118.4 (+, 1C, 4’-C), 118.0 (+, 1C, 3’-C), 112.0 (+,
1C, 6’-C), 17.4 (+, 1C, 7-C) ppm. 19F NMR (376 MHz, DMSO-
d6): δ = -133.43 (d, J = 21.8 Hz), -159.54 (t, J = 21.8 Hz), -
166.65 – -166.76 (m) ppm. 11B NMR (192.6 MHz, DMSO-d6):
δ = -3.6 ppm. IR (ATR): ṽ = 3374, 1698, 1511, 1488, 1457,
1290, 1276, 41267, 1083, 1044, 960, 934, 819, 765, 686, 669
cm-1. HRESIMS: C30H11BF15NO2Na+: required 736.0541. Found:
736.0537.
General procedure for deprotonation of punicine
derivatives (2a-d). A column, packed with Amberlite IRA-400 is
treated with 200 mL of 10% NaOH(aq) and rinsed with water until
reaching pH 7, subsequently. The column was than washed with
200 mL of methanol. A sample of the pyridinium salt was
dissolved in a small volume of methanol and added on the ion
exchange resin. The sample was eluted with methanol and the
deep red eluate was collected after passing the column.
Evaporation of the solvent yielded the corresponding betaines in
quantitative yields. The products have been dried in vacuo. The
spectroscopic data correspond to literature values.11,31,32
(2-(3-Methylpyridinium-1-yl)-4-hydroxy-
phenoxy)tris(pentafluorophenyl)borate 5c.
39.3 mg (0,20 mmol) of
methylpyridinium)phenolate and 100 mg (0.20 mmol) of
tris(pentafluorophenyl)borane was used to obtain the product 5c
A
sample of
4-hydroxy-2(N-3-
1
as a bright yellow solid. Yield: 88 mg (63%), mp: 189 °C. H
NMR (600 MHz, DMSO-d6): δ = 9.30 (br s. 1H, OH), 8.85 (br.s.,
1H, 6-H), 8.80 (d, J =6.0 Hz, 1H, 4-H), 8.50 (d, J = 8.0 Hz, 1H,
2-H), 8.04 (dd, J1 = 8.0 Hz, J2 = 6.0 Hz, 1H, 5-H), 6.96 (d, J =
3.0 Hz, 1H, 6’-H), 6.76 (dd, J1 = 9.0 Hz, J2 = 3.0 Hz, 1H, 4’-H),
6.46 (d, J = 3.0 Hz, 1H, 3’-H) 2.47 (s, 3H, 7-H) ppm. 13C NMR
(150 MHz, DMSO-d6): δ = 148.7 (o, 1C, 5’-C), 148.0 (br, o),
General procedure for the synthesis of the borates 5a-d

6
Tetrahedron
146.4 (br, o), 146.1 (+, 1C, 2-C), 146.0 (+, 1C, 6-C), 144.5 (o,
1.2 Hz, 1 H, 6-H), 8.53 (ddd, J₁ = 8.0 Hz, J₂ = 7.7 Hz, J₃ = 1.2
Hz, 1 H, 4-H), 8.04 (dd, J₁ = 8.0 Hz, J₂ = 0.7 Hz, 1 H, 3-H), 7.95
(ddd, J₁ = 7.7 Hz, J₂ = 6.2 Hz, J₃ = 0.7 Hz, 1H, 5-H), 7.56 (ddd,
J₁ = 9.0 Hz, J₂ = 7.9 Hz, J₃ = 1.6 Hz, 1 H, 4’-H), 7.41 (dd, J₁ =
7.8 Hz, J₂ = 1.6 Hz, 1 H, 6’-H), 7.21 (dd, J₁ = 7.9 Hz, J₂ = 1.1
Hz, 1 H, 3’-H), 7.17 (ddd, J₁ = 9.0 Hz, J₂ = 7.8 Hz, J₃ = 1.1 Hz,
1 H, 5’-H), 2.52 (s, 3 H, Me) ppm. ¹³C NMR (150 MHz,
acetonitrile-d₃): δ = 158.5, 151.2, 148.0, 147.3, 134.1, 130.6,
129.4, 127.4, 126.6, 122.2, 118.1, 20.9 ppm. IR (ATR): ṽ = 3527,
3099, 1630, 1463, 1427, 820, 781, 758 cm⁻¹. ESIMS (+): m/z (%)
= 186.0 (100) [M]⁺. HRESIMS: C12H12NO: required 186.0913.
Found: 186.0919.
1C, 2’-C), 138.9 (br, o), 137.4 (o, 1C, 3-C), 137.3 (br, o), 136.6
(br, o), 135.0 (br, o), 133.0 (o, 1C, 1’-C), 126.5 (+, 1C, 5-C),
122.0 (br, o), 118.4 (+, 1C, 4’-C), 118.1 (+, 1C, 3’-C), 112.0 (+,
1C, 6’-C), 17.4 (+, 1C, 7-C) ppm. 19F NMR (376 MHz, DMSO-
d6): δ = -133.46 (d, J = 21.9 Hz), -159.72 (t, J = 21.9 Hz), -
166.77 – -166.89 (m) ppm. 11B NMR (192.6 MHz, DMSO-d6): δ
= -3.7 ppm. IR (ATR): ṽ = 3136, 1644, 1490, 1405, 1274, 1082,
975, 957, 936, 765, 747, 729, 675, 668 cm-1. HRESIMS:
C30H11BF15NO2Na+: required 736.0541. Found: 736.0550.
(2-(4-Methylpyridinium-1-yl)-4-hydroxy-
phenoxy)tris(pentafluorophenyl)borate 5d.
79.0 mg (0,39 mmol) of
A
sample of
4-hydroxy-2(N-4-
1-(2-Hydroxyphenyl)-3-methylpyridinium
methylpyridinium)phenolate and 200 mg (0.39 mmol) of
hexafluorophosphate 7c. A sample of 0.218 g (2.00 mmol) of 3-
methylpyridine-N-oxide 6c and of 0.852 g (2.00 mmol) of
diphenyliodonium hexafluorophosphate(V) was used. The salt 7c
was obtained as orange solid. Yield 0.490 g (74%), mp. 123°C.
¹H NMR (600 MHz, acetonitrile-d₃): δ = 8.66 (s, 1 H, 2-H), 8.64
(d, J = 6.1 Hz, 1 H, 4-H), 8.43 (d, J = 8.0 Hz, 1 H, 6-H), 7.99 (dd,
J₁ = 8.0 Hz, J₂ = 6.1 Hz, 1 H, 5-H), 7.44 (ddd, J₁ = 8.8 Hz, J₂ =
7.8 Hz, J₃ = 1.6 Hz, 1 H, 4‘-H), 7.41 (dd, J₁ = 7.7 Hz, J₂ = 1.6
Hz, 1 H, 6‘-H), 7.37 (dd, J₁ = 7.8 Hz, J₂ = 1.3 Hz, 1 H, 3‘-H),
7.01 (ddd, J₁ = 8.8 Hz, J₂ = 7.7 Hz, J₃ = 1.3 Hz, 1 H, 5‘-H) 2.56
(s, 3 H, Me) ppm. ¹³C NMR (150 MHz, acetonitrile-d₃): δ =
152.8, 147.8, 146.6, 144.4, 140.5, 133.6, 131.4, 128.0, 126.8,
120.2, 118.9, 18.5 ppm. IR (ATR): ṽ = 3043, 2928, 1630, 1460,
838, 756, 713 cm⁻¹. ESIMS (+): m/z (%) = 186.1 (100%) [M]⁺.
HRESIMS: C12H12NO: required 186.0913. Found 186.0925.
tris(pentafluorophenyl)borane was used to obtain the product 5d
1
as a bright yellow solid. Yield: 88 mg (63%), mp: 222 °C. H
NMR (600 MHz, DMSO-d6): δ = 9.26 (br s. 1H, OH), 8.74 (d, J
= 6.5 Hz, 2H, 2-H, 6-H), 7.96 (d, J =6.5 Hz, 2H, 3-H, 5-H), 6.93
(d, J = 3.0 Hz, 1H, 6’-H), 6.69 (dd, J1 = 9.0 Hz, J2 = 3.0 Hz, 1H,
4’-H), 6.36 (d, J = 9.0 Hz, 1H, 3’-H), 2.62 (s, 3H, 7-H) ppm. 13C
NMR (150 MHz, DMSO-d6): δ = 159.4 (o, 1C, 4-C), 148.6 (o,
1C, 5’-C), 148.1 (br, o), 146.5 (br, o), 145.2 (+, 2C, 2-C, 6-C),
144.7 (o, 1C, 2’-C), 138.9 (br, o), 137.3 (br, o), 136.6 (br, o),
135.1 (br, o), 132.8 (o, 1C, 1’-C), 127.2 (+, 2C, 3-C, 5-C), 122.1
(br, o), 118.2 (+, 1C, 4’-C), 117.6 (+, 1C, 3’-C), 112.1 (+, 1C, 6’-
C), 21.3 (+, 1C, 7-C) ppm. 19F NMR (376 MHz, DMSO-d6): δ = -
133.31 (d, J = 21.7 Hz), -159.55 (t, J = 21.7 Hz), -164.76 – -
164.82 (m) ppm. 11B NMR (192.6 MHz, DMSO-d6): δ = -3.6
ppm. IR (ATR): ṽ = 3606, 1642, 1511, 1456, 1275, 1083, 975,
955, 899, 824, 794, 749, 669, 636 cm-1. HRESIMS:
C30H11BF15NO2Na+: required 736.0541. Found: 736.0511.
1-(2-Hydroxyphenyl)-4-methylpyridinium
hexafluorophosphate 7d. A sample of 0.249 g (2.30 mmol) of
4-methylpyridine-N-oxide 6d and of 0.975 g (2.30 mmol) of
diphenyliodonium hexafluorophosphate(V) was used. The salt 7d
was obtained as red solid. Yield 0.529 g (70%), mp. 121°C. ¹H
NMR (400 MHz, acetonitrile-d₃): δ = 8.62 (d, J = 6.6 Hz, 2 H,
2/6-H), 7.94 (d, J = 6.6 Hz, 2 H, 3/5-H), 7.49 (ddd, J₁ = 8.9 Hz,
J₂ = 7.9 Hz, J₃ = 1.6 Hz, 1 H, 4‘-H), 7.45 (dd, J₁ =7.8 Hz, J₂ =
1.6 Hz, 1 H, 6‘-H), 7.17 (dd, J₁ = 7.9 Hz, J₂ = 1.2 Hz, 1 H, 3‘-H),
7.09 (ddd, J₁ = 8.9 Hz, J₂ = 7.8 Hz, J₃ = 1.2 Hz, 1 H, 5'-H), 2.71
(s, 3 H, Me) ppm. ¹³C NMR (100 MHz, acetonitrile-d₃): δ =
162.3, 151.8, 145.9, 133.8, 131.1, 129.3, 127.2, 121.2, 118.6,
22.5 ppm. IR (ATR): ṽ = 3495, 3138, 2960, 2920, 1641, 1454,
1281, 1208 cm⁻¹. ESIMS (+): m/z (%) = 186.0 (100%) [M]⁺.
HRESIMS: C12H12NO required 186.0913. Found 186.0923.
General procedure for the synthesis of the salts 7a-d.33
The pyridine-N-oxides 6a-d and diphenyliodonium
hexafluorophosphate(V) were dried in vacuo in a Schlenk tube
over a period of 1 h. Then, 8 mL of dichloroethane were added
under an inert atmosphere, and the mixture was heated at 120°C
for 48 h. After cooling to rt, 5 mL of methanol were added, the
mixture was poured into a round flask and treated with 1 g of
silica gel. Flash column chromatography was performed with a
mixture of dichloromethane, petroleum ether, and methanol
(10:5:3).
1-(2-Hydroxyphenyl)-pyridinium hexafluorophosphate 7a.
A sample of 0.380 g (4.00 mmol) of pyridine-N-oxide 6a and of
1.704
g
(4.00
mmol)
of
diphenyliodonium
hexafluorophosphate(V) was used. The salt 7a was obtained as
red solid. Yield: 0.554 g (44%), mp. 62 °C. H NMR (600 MHz,
General procedure for the synthesis of the betaines 8a-d.
1
Solutions of the salts 7a-d in 6 mL of methanol were treated
with potassium carbonate (1.5 equivalents) and stirred at reflux
temperature for 2 h. After cooling to rt, the mixture was stirred
for an additional hour. Then, the mixture was treated with 1 g of
silica gel. A flash column chromatography was performed with a
mixture of dichloromethane, petroleum ether, and methanol
(5:3:1). All spectroscopic data correspond to those reported in the
literature.42
acetonitrile-d3): δ = 8.83 (dd, J₁ = 6.8 Hz, J₂ = 1.4 Hz, 2 H, 2/6-
H), 8.52 (tt, J₁ = 7.8 Hz, J₂ = 1.4 Hz, 1 H, 4-H), 8.06 (dd, J₁ =
6.8 Hz, J₂ = 7.8 Hz, 2 H, 3/5-H), 7.33 (dd, J₁ = 7.7 Hz, J₂ = 1.7
Hz, 1 H, 6’-H), 7.30 (ddd, J₁ = 8.8 Hz, J₂ = 7.8 Hz, J₃ = 1.7 Hz,
1 H, 4’-H), 7.03 (dd, J₁ = 7.8 Hz, J₂ = 1.3 Hz, 1 H, 3’-H), 6.75
(ddd, J₁ = 8.8 Hz, J₂ = 7.7 Hz, J₃ = 1.3 Hz, 1 H, 5’-H) ppm. ¹³C
NMR (150 MHz, acetonitrile-d₃): δ = 157.2, 146.9, 146.4, 133.5,
132.2, 128.4, 126.3, 120.4, 116.5 ppm. IR (ATR): ṽ = 3129,
3067, 2926, 1469, 1455, 829, 750, 677 cm⁻¹. ESIMS (100 V, +):
m/z (%) = 172.0 (100) [M]⁺. HRESIMS: C11H10NO: required
172.0762. Found: 172.0764.
General procedure for the synthesis of the borane adducts
9a-d.
The betaines 8a-d and tris(pentafluorophenyl)borane were
dried in vacuo in a Schlenk tube over a short period of time.
Then, 6 mL of anhydrous dioxane were added under an inert
atmosphere, and the mixture was heated at 110°C for 3 h. After
cooling to rt, the mixture was poured into a round flask and
treated with 1 g of silica gel. Flash column chromatography was
performed with ethyl acetate.
1-(2-Hydroxyphenyl)-2-methylpyridinium
hexafluorophosphate 7b. A sample of 0.218 g (2.00 mmol) of
2-methylpyridine-N-oxide 6b and of 0.852 g (2.00 mmol) of
diphenyliodonium hexafluorophosphate(V) was used. The salt 7b
was obtained as grey solid. Yield: 0.408 g (62%), mp. 125°C. ¹H
NMR (600 MHz, acetonitrile-d3): δ = 8.56 (dd, J₁ = 6.2 Hz, J₂ =

7
(2-(Pyridinium-1-
(2-(4-Methylpyridinium-1-
yl)phenoxy)tris(pentafluorophenyl)borate 9a. A sample of
0.041 g (0.24 mmol) of 2-(pyridinium-1-yl)-phenolate 8a and of
0.102 g (0.20 mmol) of tris(pentafluorophenyl)borane was used.
The borane adduct 9a was obtained as colorless solid. Yield
0.127 g (77%), mp. 212°C. ¹H NMR (600 MHz, methanol-d₄): δ
= 8.94 (dd, J₁ = 6.8 Hz, J₂ = 1.4 Hz, 2 H, 2/6-H), 8.64 (tt, J₁ =
7.8 Hz, J₂ = 1.4 Hz, 1 H, 4-H), 8.11 (dd, J₁ = 7.8 Hz, J₂ = 6.8 Hz,
2 H, 3/5-H), 7.48 (dd, J₁ = 7.9 Hz, J₂ = 1.7 Hz, 1 H, 6’-H), 7.26
(ddd, J₁ = 8.4 Hz, J₂ = 7.6 Hz, J₃ = 1.7 Hz, 1 H, 4’-H), 6.89 (ddd,
J₁ = 7.9 Hz, J₂ = 7.6 Hz, J₃ = 1.2 Hz, 1 H, 5’-H), 6.70 (dd, J₁ =
8.4 Hz, J₂ = 1.2 Hz, 1 H, 3’-H) ppm. ¹³C NMR (150 MHz,
methanol-d₄): δ = 152.6, 147.8 (¹JC,F = 244 Hz), 146.4, 145.5,
138.8 (¹JC,F = 270 Hz), 136.5 (¹JC,F = 248 Hz), 133.9, 131.5,
126.8, 124.5, 122.0, 118.1, 117.6 ppm. ¹¹B NMR (193 MHz,
methanol-d₄, BF₃∙Et₂O): δ = -3.45 (s, 1 B) ppm. 19F NMR (376
MHz, methanol-d₄, CFCl₃): δ = -134.01 (d, ¹JC,F = 19.1 Hz, 6 F,
2´´-F, 6´´-F), -161.60 (t, ¹JC,F = 19.6 Hz, 3 F, 4´´-F), -166.39--
166.50 (m, 6 F, 3´´-F, 5´´-F) ppm. IR (ATR): ṽ = 3139, 2964,
2906, 1646, 1452, 1083, 973, 937 cm⁻¹. HRESIMS:
C29H9BF15NONa+ required 706.0435. Found 706.0433.
yl)phenoxy)tris(pentafluorophenyl)borate 9d. A sample of
0.044 g (0.24 mmol) of 2-(4-methylpyridinium-1-yl)-phenolate
8d and of 0.102 g (0.20 mmol) of tris(pentafluorophenyl)borane
was used. The borane adduct 9d was obtained as reddish brown
solid. Yield 50% (0.104 g), mp. 251 °C. ¹H NMR (400 MHz,
methanol-d₄): δ = 8.71 (d, J = 6.6 Hz, 2 H, 2/6-H), 7.92 (d, J =
6.6 Hz, 2 H, 3/5-H), 7.44 (dd, J₁ = 7.8 Hz, J₂ = 1.7 Hz, 1 H, 6’-
H), 7.23 (ddd, J₁ = 8.4 Hz, J₂ = 7.6 Hz, J₃ = 1.7, 1 H, 4’-H), 6.88
(ddd, J₁ = 7.8 Hz, J₂ = 7.6 Hz, J₃ = 1.1 Hz, 1 H, 5’-H), 6.65 (dd,
J₁ = 8.4 Hz, J₂ = 1.1 Hz, 1 H, 3’-H), 2.71 (s, 3 H, Me) ppm. ¹³C
NMR (150 MHz, methanol-d₄): δ = 161.6, 154.1, 149.2 (¹JC,F
=
247 Hz), 146.7, 141.0 (¹JC,F = 256 Hz), 137.9(¹JC,F = 250 Hz),
135.0, 132.6, 128.6, 125.8, 123.2, 119.4, 119.0, 22.0 ppm.¹¹B-
NMR (193 MHz, methanol-d₄, BF₃∙Et₂O): δ = -3.45 (s, 1 B)
ppm. 19F NMR (565 MHz, methanol-d₄, CFCl₃): δ = -135.65 (d,
¹JC,F = 19.1 Hz, 6 F, 2´´-F, 6´´-F), -163.37 (t, ¹JC,F = 19.6 Hz, 3 F,
4´´-F), -168.26--168.35 (m, 6 F, 3´´-F, 5´´-F) ppm. IR (ATR): ṽ =
1643, 1514, 1461, 1452, 1093, 1083, 975, 945, 768, 763 cm⁻¹.
HRESIMS: C30H11BF15NONa+ required 720.0592. Found
720.0579.
(2-(2-Methylpyridinium-1-
N-(3-Hydroxyphenyl)pyridinium perchlorate 11. A sample
of 1.00 g (3.55 mmol) N-(2,4-dinitrophenyl)pyridinium chloride
(10) and 0.775 g (7.10 mmol) of 3-aminophenol were dissolved
in 7 mL of DMF and heated to 90 °C for 24 h. On cooling the
reaction mixture was concentrated in vacuo and then dissolved in
water. The aqueous phase was extracted with ethyl acetate until
the organic phase stayed clear. The aqueous phase was then
concentrated in vacuo and treated with activated carbon after
addition of 0.500 g (3.55 mmol) of sodium perchlorate
monohydrate. This mixture was filtered hot and after the filtrate
was concentrated, some more sodium perchlorate was added. On
cooling, the product 11 precipitated as brown leaves. Yield:
0.482 g (50%). 1H NMR (600 MHz, DMSO-d6): δ = 10.44 (br. s.,
1H, OH), 9.29 – 9.28 (m, 2H, 2-H, 6-H), 8.76 (tt, J1 = 8.3 Hz, J2
= 1.3 Hz, 1H, 4-H), 8.28 – 8.26 (m, 2H, 3-H, 5-H), 7.52(t, J = 8.1
Hz, 1H, 5’-H), 7.26 (ddd, J1 = 8.1 Hz, J2 = 2.3 Hz, J3 = 0.8 Hz,
1H, 4’-H), 7.22 (t, J = 2.3 Hz, 1H, 2’-H), 7.12 (ddd, J1 = 8.1 Hz,
J2 = 2.3 Hz, J3 = 0.8 Hz, 1H, 6’-H) ppm. 13C NMR (150 MHz,
DMSO-d6): δ = 158.6 (o, 1C, 1’-C ), 146.6 (+, 1C, 4-C), 144.8
(+, 2C, 2-C, 6-C), 143.8 (o, 1C, 1’-C), 131.1 (+, 1C, 5’-C), 128.1
(+, 2C, 3-C, 5-C), 118.1 (+, 1C, 6’-C), 115.0 (+, 1C, 4’-C), 111.7
(+, 1C, 2’-C) ppm. 35Cl NMR (58.8 MHz, DMSO-d6): δ = 953.47
ppm. IR (ATR): ṽ = 3358, 3125, 3068, 1610, 1569, 1457, 1311,
1296, 1190, 1162, 1073, 1034, 998, 926, 892, 852, 768, 720, 683,
618, 534, 469, 429 cm⁻¹. HRESIMS: C11H9NO+ required
172.0757. Found 172.0757.
yl)phenoxy)tris(pentafluorophenyl)borate 9b. A sample of
0.040 g (0.22 mmol) of 2-(2-methylpyridinium-1-yl)-phenolate
8b and of 0.102 g (0.20 mmol) of tris(pentafluorophenyl)borane
was used. The borane adduct 9b was obtained as brownish solid.
Yield: 0.016 g (10%), mp. 251°C. ¹H NMR (600 MHz, methanol-
d₄): δ = 8.53 (dd, J₁ = 6.0 Hz, J₂ = 1.3 Hz, 1 H, 6-H), 8.49 (ddd,
J₁ = 7.7 Hz, J₂ = 7.6 Hz, J₃ = 1.2 Hz, 1 H, 4-H), 8.08 (dd, J₁ =
7.7 Hz, J₂ = 0.8 Hz, 1 H, 3-H), 7.88 (ddd, J₁ = 7.6 Hz, J₂ = 6.0
Hz, J₃ = 0.8 Hz, 1 H, 5-H), 7.35 (dd, J₁ = 7.8 Hz, J₂ = 1.7 Hz, 1
H, 6’-H), 7.27 (ddd, J₁ = 8.4 Hz, J₂ = 7.5 Hz, J₃ = 1.7 Hz, 1 H,
4’-H), 6.90 (ddd, J₁ = 7.8 Hz, J₂ = 7.5 Hz, J₃ = 1.1 Hz, 1 H, 5’-
H), 6.67 (dd, J₁ = 8.4 Hz, J₂ = 1.1 Hz, 1 H, 3’-H), 2.65 (s, 3 H,
Me) ppm. ¹³C NMR (150 MHz, methanol-d ): δ = 159.6, 154.5,
149.1 (¹JC,F = 240 Hz), 148.2, 147.1, 140.1 (¹JC,F = 243 Hz), 137.8
(¹JC,F = 249 Hz), 133.7, 132.8, 132.4, 129.9, 126.0, 125.7, 119.5,
119.0, 20.6 ppm. 19F NMR (376 MHz, methanol-d , CFCl ): δ
= -134.02 (d, ¹JC,F = 18.9 Hz, 6 F, 2´´-F, 6´´-F), -161.80 (t, ¹JC,F
=
19.4 Hz, 3 F, 4´´-F), -166.61--166.74 (m, 6 F, 3´´-F, 5´´-F) ppm.
IR (ATR): ṽ = 2934, 2854, 1642, 1455, 1080, 976 cm⁻¹.
HRESIMS: C30H11BF15NONa+ required 720.0592. Found
720.0579.
(2-(3-Methylpyridinium-1-
yl)phenoxy)tris(pentafluorophenyl)borate 9c. A sample of
0.040 g (0.22 mmol) of 2-(3-methylpyridinium-1-yl)-phenolate
8c and of 0.102 g (0.20 mmol) of tris(pentafluorophenyl)borane
was used. The borane adduct 9c was obtained as brownish solid.
Yield: 0.145 g (95%), mp. 210 °C. ¹H NMR (600 MHz,
methanol-d₄): δ = 8.82 (s, 1 H, 2-H), 8.73 (d, J = 6.1 Hz, 1 H, 4-
H ), 8.46 (d, J = 8.0 Hz, 1 H, 6-H), 7.99 (dd, J₁ = 8.0 Hz, J₂ = 6.1
Hz, 1 H, 5-H), 7.45 (dd, J₁ = 7.8 Hz, J₂ = 1.7 Hz, 1 H, 6’-H),
7.25 (ddd, J₁ = 9.0 Hz, J₂ = 7.9 Hz, J₃ = 1.7 Hz, 1 H, 4’-H), 6.89
(ddd, J₁ = 9.0 Hz, J₂ = 7.8 Hz, J₃ = 1.0 Hz, 1 H, 5’-H), 6.71 (dd,
J₁ = 7.9 Hz, J₂ = 1.0 Hz, 1 H, 3’-H), 2.55 (s, 3 H, Me) ppm. ¹³C
NMR (150 MHz, methanol-d₄): δ = 153.9, 149.1 (¹JC,F = 240
Hz), 147.8, 147.3, 144.6, 139.7, 140.2 (¹JC,F = 285 Hz), 137.9
(¹JC,F = 247 Hz), 135.3, 132.7, 127.7, 125.9, 123.2, 119.6, 119.1,
18.2 ppm. ¹¹B-NMR (193 MHz, methanol-d₄, BF₃∙Et₂O): δ = -
3.43 (s, 1 B) ppm. 19F NMR (376 MHz, methanol-d₄, CFCl₃): δ =
3-(Pyridinium-1-yl)-phenolate 12. A sample of 100 mg (0.4
mmol) of 1-(3-hydroxyphenyl)pyridinium perchlorate was
dissolved in methanol and slowly run through a column, filled
with Amberlite IRA-96, using methanol as the mobile phase. The
eluate was evaporated in vacuo and the orange residue was dried
in vacuo. Yield: 63 mg (100%), 1H NMR (600 MHz, DMSO-d6):
δ = 6.55 (d, J = 7.1 Hz, 1H, 2’-H), 6.65-6.67 (m, 2H, 4’-H, 6’-H),
7.14 (t, J = 8.2 Hz, 1H, 5’-H), 8.20 (m, 2H, 3-H, 5-H), 8.68 (m,
1H, 4-H), 9.22 (m, 2H, 2-H, 6-H) ppm. 13C NMR (150 MHz,
DMSO-d6): δ = 107.2 (+, 1C, 6’-C), 112.9 (+, 1C, 2’-C), 121.1
(+, 1C, 4’-C), 128.5 (+, 2C, 3-C, 5-C), 130.6 (+, 1C, 5’-C), 144.7
(+, 2C, 2-C, 6-C), 145.2 (o, 1C, 1’-C), 146.3 (+, 1C, 4-C), 168.6
(o, 1C, 3’-C) ppm. On standing, decomposition occurred. Due to
the substance’s instability, no further analytical data have been
recorded.
-134.03 (d, ¹JC,F = 22.6 Hz, 6 F, 2´´-F, 6´´-F), -161.57 (t, ¹JC,F
=
18.8 Hz, 3 F, 4´´-F), -166.39--166.50 (m, 6 F, 3´´-F, 5´´-F) ppm.
IR (ATR): ṽ = 2962, 2930, 1644, 1456, 1084, 975, 953 cm⁻¹.
HRESIMS: C30H11BF15NONa+ required 720.0592. Found
720.0593.
N-(3,4-Dihydroxyphenyl)pyridinium bromide 14. To a
solution of 2.0 mL (24.8 mmol) of freshly distilled pyridine and

8
Tetrahedron
1.36 g (12.4 mmol) of catechol in 4 mL of methanol, 0.64 mL
= 0.055 (for 5237 I > 2σ(I)), wR2 = 0.153 (all data), S = 1.03,
(12.4 mmol) of bromine were added dropwise at 0 – 10 °C. The
resulting solid was recrystallized from a 1:1 mixture of
concentrated hydrobromic acid and water and precipitated as a
largest diff. peak / hole = 0.96 / -0.47 e Å-3.
CCDC 2005556 (1d), and 2005556 (5c) contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge
Crystallographic
www.ccdc.cam.ac.uk/data_request/cif.
1
colorless powder. Yield: 2.14 g (64 %), H NMR (600 MHz,
DMSO-d6): δ = 7.02 (d, J = 8.5 Hz, 1H, H-5‘), 7.14 (dd, J1 = 8.5
Hz, J2 = 2.8 Hz, 1H, H-6‘), 7.22 (d, J = 2.8 Hz, 1H, H-2‘), 8.22-
8.24 (m, 2H, H-3), 8.70 (tt, J1 = 7.8 Hz, J2 = 1.3 Hz, 1H, H-4),
9.22-9.23 (m, 2H, H-2), 9.83 (br.s., 1H, H-7‘/H-8‘), 9.97 (br.s.,
1H, H-7‘/H-8‘) ppm. 13C NMR (150 MHz, DMSO-d6): δ = 111.8
(+, 1C, C-2‘), 115.5 (+, 1C, C-6‘), 115.8 (+, 1C, C-5‘), 128.1 (+,
2C, C-3), 134.6 (o, 1C, C-1‘), 144.5 (+, 2C, C-2), 145.7 (+, 1C,
C-4), 146.3 (o, 1C, C-3‘), 148.1 (o, 1C, C-4‘) ppm. HRESIMS:
C11H10NO2+ required 188.0706. Found 118.0707
Data
Centre
via
References
1. Review: D. P. Curran, A. Solovyev, M. M. Brahmi, L.
Fensterbank, M. Malacria, E. Lacôte, Angew. Chem. Int. Ed.
Engl., 2011, 50, 10294 – 10317.
2-Hydroxy-4-(pyridinium-1-yl)phenolate 15. 1.14 g (4.25
mmol) of 14 was dissolved in 10 mL distilled water and heated to
60 °C. To that solution, 0.60 mL (8.0 mmol) of ammonia (25 %)
were added. The product precipitated immediately as a yellow
solid. After cooling to 4 °C, the mixture was filtered cold to
collect 15 as a bright yellow powder after washing the residue
2. Recent example: M. Liu, M. Nieger, E. G. Hübner, A. Schmidt,
Chem Eur. J., 2016, 22, 5416 – 5424.
3. M. H. Holthausen, T. Mahdi, C. Schlepphorst, L. J. Hounjet, J. J.
Weigand, D. W. Stephan, Chem. Commun., 2014, 50, 10038 –
10040.
4. J. Ugolotti, S. Hellstrom, G. J. P. Britovsek, T. S. Jones, P. Hunt,
A. J. P. White, Dalton Trans., 2007, 1425 – 1432.
5. D. Vagedes, R. Fröhlich, G. Erker, Angew. Chem. Int. Ed., 1999,
38, 3362 – 3365.
6. N. G. Kim, C. H. Shin, M. H. Lee, Y. Do, J. Organomet. Chem.,
2009, 694, 1922 – 1928.
7. M. Karsch, H. Lund, A. Schulz, A. Villinger, K. Voss, Eur. J.
Inorg. Chem., 2012, 5542 – 5553.
8. L. Hintermann, P. J. Altmann, P. Naumov, K. Suzuki, Helv. Chim.
Acta, 2017, 100, e1600392.
9. A. Schmidt, T. Mordhorst, M. Nieger, Nat. Prod. Res., 2005, 19,
541 – 546.
10. M. A. M. Nawwar, S. A. M. Hussein, I. Merfort, Phytochemistry,
1994, 37, 1175 – 1177.
1
with water and acetone. Yield: 0.674 g (85 %), H NMR (600
MHz, DMSO-d6): δ = 6.77 (d, J = 8.5 Hz, 1H, H-5‘), 6.91 (dd, J1
= 8.5 Hz, J2 = 2.6 Hz, 1H, H-6‘), 7.04 (d, J = 2.6 Hz, 1H, H-2‘),
8.15-8.18 (m, 2H, H-3), 8.61 (tt, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H,
H-4), 9.17 (d, J = 5.7 Hz, 2H, H-2) ppm. 13C NMR (150 MHz,
DMSO-d6): δ = 109.5 (+, 1C, C-2‘), 113.2 (+, 1C, C-6‘), 114.2
(+, 1C, C-5‘), 127.9 (+, 2C, C-3), 132.4 (o, 1C, C-1‘), 143.9 (+,
2C, C-2), 144.6 (+, 1C, C-4), 150.0 (o, 1C, C-3‘), 152.8 (o, 1C,
C-4‘) ppm. IR (ATR): ṽ = 3446, 3404, 3115, 3040, 3004, 1624,
1468, 1450, 1282, 1269, 1201, 1192, 1112, 1097, 1047, 1020,
919, 867, 817, 791, 766, 738, 716, 680, 616, 594, 536, 472, 455,
11. M. Albrecht, M. Gjikaj, A. Schmidt, Tetrahedron, 2010, 66, 7149
– 7154.
12. M. Albrecht, O. Schneider, A. Schmidt, Org. Biomol. Chem.,
2009, 7, 1445 – 1453.
+
438 cm⁻¹. HRESIMS: C11H10NO2 required 188.0706. Found
118.0706
13. A. Schmidt, M. Topp, T. Mordhorst, O. Schneider, Tetrahedron,
2007, 63, 1842 – 1848.
Crystal Structure Determinations of 1d and 5c
14. A. Schmidt, M. Albrecht, T. Mordhorst, M. Topp, G. Jeschke, J.
Mater. Chem., 2007, 17, 2793 – 2800.
15. W. P. Oziminski, C. A. Ramsden, Tetrahedron, 2015, 71, 7191 –
7198.
16. C. A. Ramsden, W. P. Oziminski, Tetrahedron, 2014, 70, 7158 –
7165.
17. C. A. Ramsden, Tetrahedron, 2013, 69, 4146 – 4159.
18. W. D. Ollis, S. P. Stanforth, C. A. Ramsden, Tetrahedron, 1985,
41, 2239 – 2329.
19. D. L. Browne, J. P. A. Harrity, Tetrahedron 2010, 66, 553–568.
20. (a) R. Huisgen, H. Gotthardt, H. O. Bayer, Angew. Chem. Int. Ed.
Engl. 1964, 3, 135 – 136. (b) H.-U. Reißig, R. Zimmer, Angew.
Chem. Int. Ed. 2014, 53, 9708 – 9710.
21. W. Friedrichsen, R. Schmidt , G. J. van Hummel, D. M. W. van
den Ham, Liebigs Ann. Chem. 1981, 521 – 531.
The single-crystal X-ray diffraction studies were carried out on a
Bruker D8 Venture diffractometer with Photon100 detector at
123(2) K using Mo-Ka radiation (1d, l = 0.71073 Å) or Cu-Ka
radiation (5c, l = 1.54178 Å). Direct Methods (SHELXS-97)46
were used for structure solution and refinement was carried out
using SHELXL-2014 (full-matrix least-squares on F2).47
Hydrogen atoms were localized by difference electron density
determination and refined using a riding model (H(O) free).
Semi-empirical absorption corrections were applied. For 1d an
extinction correction was applied. In 5c there is a positional
disorder of the solvent DMSO and water in the ratio 3:1 (see cif-
file for details).
22. (a) A. Theis, H. Ritter, F. Böhme, C. Klinger, S. Mittler, B.
Menges, Chem. Mater. 2002, 14, 2109 – 2112. (b) A. Theis, B.
Menges, S. Mittler, M. Mierzwa, T. Pakula, H. Ritter,
Macromolecules 2003, 36, 7520 – 7526.
23. A. Schmidt, S. Wiechmann, T. Freese, ARKIVOC 2013, i, 424 -
469.
1d: yellow crystals, C12H12NO2.Cl·H2O, Mr = 255.69, crystal size
0.40 × 0.30 × 0.20 mm, monoclinic, space group P21/n (no. 14),
a = 11.9694 (7) Å, b = 7.3995 (4) Å, c = 13.9474 (7) Å, β =
103.151 (2)°, V = 1202.89(11) Å3, Z = 4, ρ = 1.412 Mg/m-3,
µ(Mo-Kα) = 0.31 mm-1, F(000) = 536, 2θmax = 55.2°, 23509
reflections, of which 2777 were independent (Rint = 0.027), 168
parameters, 5 restraints, R1 = 0.029 (for 2511 I > 2σ(I)), wR2 =
0.084 (all data), S = 1.08, largest diff. peak / hole = 0.34 / -0.28 e
Å-3.
24. (a) M. Fèvre, J. Pinaud, A. Leteneur, Y. Gnanou, J. Vignolle, D.
Taton, K. Miqueu, J.-M. Sotiropoulos, J. Am. Chem. Soc. 2012,
134, 6776 – 6784. (b) X. Sauvage, A. Demonceau, L. Delaude,
Adv. Synth. Catal. 2009, 351, 2031 – 2038. (c) E. L. Kolychev, T.
Bannenberg, M. Freytag, C. G. Daniliuc, P. G. Jones, M. Tamm,
Chem. Eur. J. 2012, 18, 16938 – 16946. (d) X. Sauvage, G.
Zaragoza, A. Demonceau, L. Delaude, Adv. Synth. Catal. 2010,
352, 1934 – 1948. (e) J. Li, J. Peng, G. Zhang, Y. Bai, G. Lai, X.
Li, New J. Chem. 2010, 34, 1330 – 1334.
25. (a) A. Schmidt, N. Münster, A. Dreger, Angew. Chem. 2010, 122,
2851 – 2854; Angew. Chem. Int. Ed. 2010, 49, 2790 – 2793. (b) A.
Schmidt, T. Habeck, Lett. Org. Chem. 2005, 2, 37 - 39.
26. (a) Z. Guan, S. Wiechmann, M. Drafz, E. Hübner, A. Schmidt,
Org. Biomol. Chem. 2013, 11, 3558 – 3567. (b) A. Schmidt, L.
Merkel, W. Eisfeld, Eur. J. Org. Chem. 2005, 2124 – 2130.
5c: yellow crystals, C30H11BF15NO2·0.75(C2H6OS)·0.25(CH4O),
Mr = 779.81, crystal size 0.20 × 0.15 × 0.03 mm, triclinic, space
group P-1 (No. 2), a = 10.4962 (3) Å, b = 10.7207 (3) Å, c =
15.2469 (5)Å, α = 89.500 (2)°, β = 71.634 (2)°, γ = 74.483 (2)°, V
= 1563.58 (8) Å3, Z = 2, ρ = 1.656 Mg/m-3, µ(Cu-Kα) = 1.94 mm-
1, F(000) = 780, 2θmax = 144.2°, 27439 reflections, of which 6117
were independent (Rint = 0.035), 490 parameters, 86 restraints, R1

9
27. A. Schmidt, S. Wiechmann, C. F. Otto, Adv. Heterocycl. Chem.
2016, 119, 143 – 172.
28. (a) S. Batsyts, J. C. Namyslo, E. Hübner, A. Schmidt, Eur. J. Org.
Chem. 2019, 6168 – 6176. (b) A. Schmidt, M. Nieger,
Heterocycles 1999, 51, 2119 – 2126. (c) A. Schmidt, M. K.
Kindermann, J. Org. Chem. 1997, 62, 3910 – 3918.
29. A. Schmidt, S. Batsyts, A. Smeyanov, T. Freese, E . G. Hübner,
M. Nieger, J. Org. Chem. 2016, 81, 4202 – 4209.
30. (a) S. Deev, S. Batsyts, E. Sheina, T. S. Shestakova, I.
Khalimbadzha, M. A. Kiskin, V. Charushin, O. Chupakhin, A. S.
Paramonov, Z. O. Shenkarev, J. С. Namyslo, A. Schmidt, Eur. J.
Org. Chem. 2020, 450 – 465. (b) A. T. Freese, J. C. Namyslo, M.
Nieger, A. Schmidt, RSC Advances 2019, 9, 4781 – 4788. (c) A.
Dreger, R. Cisneros Camuña, N. Münster, T. A. Rokob, I. Pápai,
A. Schmidt, Eur. J. Org. Chem. 2010, 4296 – 4305.
31. M. L. Jain, J. P. Saxena, Acta Cienc. Indica Chem., 1982, 8, 228.
32. M. L. Jain, R. P. Soni, Indian J. Chem., 1980, 19B, 718.
33. C. Janiak, J. Chem. Soc., Dalton Trans., 2000, 3885 – 3896.
34. S. Alvarez, Dalton Trans., 2013, 42, 8617 – 8636.
35. C. A. Hunter, J. K. M. Sanders, J. Am. Chem. Soc., 1990, 112,
5525 – 5534.
36. (a) Review: Md. M. Alam, M. Chattopadhyaya, S. Chakrabarti, K.
Ruud, Acc. Chem. Res., 2014, 47, 1604
–
1612.
(b) Recent examples: Md. M. Alam, M. Chattopadhyaya, S.
Chakrabarti, J. Phys. Chem. A, 2012, 116, 8067 – 8073.
37. (a) W. Niewodniczanski, W. Bartkowiak, J. Mol. Model., 2007,
13, 793 – 800. (b) E. M. Torres, H. C. Georg, T. L. Fonseca, M. A.
Castro, Chem. Phys. Lett. 2018, 699, 261.
38. (a) L. B. A. Oliveira, T. L. Fonseca, K. Coutinho, S. Canuto,
Chem. Phys. Lett., 2011, 514, 251 – 256; (b) M. Dominguez, M.
C. Rezende, J. Phys. Org. Chem., 2010, 23, 156 – 170; (c) C.
Mascayano, M. C. Rezende, C. Mendez, G. Nunez, V. Chiang, J.
Sol. Chem., 2009, 38, 363 – 371; (d) N. A. Murugan, H. Aagren, J.
Phys. Chem. A, 2009, 113, 2572 – 2577; (e) T. L. Fonseca, K.
Coutinho, S. Canuto, Chem. Phys., 2008, 349, 109 – 114; (f) D.
Gonzalez, O. Neilands, M. C. Rezende, J. Chem. Soc., Perkin
Trans. 2, 1999, 713 – 718.
39. N. Zeghbib, R. Thelliere, M. Rivard, T. Martens, J. Org. Chem.,
2016, 81, 3256 – 3262.
40. G. Asskar, M. Rivard, T. Martens, J. Org. Chem., 2020, 85, 1232.
41. H. M. R. El-Mouafi, Zagazig J. Pharm. Sci., 1993, 2, 10 – 18.
42. J. Peng, C. Chen, Y. Wang, Z. Lou, M. Li, C. Xi, H. Chen, Angew.
Chem. Int. Ed., 2013, 52, 7574 – 7578.
43. Jaguar, version 9.1, Schrodinger, Inc., New York, NY, 2016.
44. Alex A. Granovsky, Firefly version 8,
http://classic.chem.msu.su/gran/firefly/index.html.
45. M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert, M. S.
Gordon, J. H. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S.
Su, T. L. Windus, M. Dupuis, J. A. Montgomery. J. Comput.
Chem., 1993, 14, 1347 – 1363.
46. G. M. Sheldrick, Acta Crystallogr. 2008, A64, 112-122.
47. G. M. Sheldrick, Acta Crystallogr. 2015, C71, 3-8.

Punicine, consisting of a pyridinium attached to a 4-hydroxyphenyl-olate moiety, exists as two
tautomers, a conjugated mesomeric betaine and a cross-conjugated mesomeric betaine.
Reaction with tris(pentafluorophenyl)borane occurs exclusively at the conjugated 2´-olate group to
form zwitterionic borane adducts.
Conjugated as well as cross-conjugated dehydroxypunicines as model compounds behave similarly.

Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
☐The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests: