Double Porphyrin Cage Compounds

Article abstract of DOI:10.1002/ejoc.202001211

The synthesis and characterization of double porphyrin cage compounds are described. They consist of two porphyrins that are each attached to a diphenylglycoluril-based clip molecule via four ethyleneoxy spacers, and are linked together by a single alkyl chain using “click”-chemistry. Following a newly developed multistep synthesis procedure we report three of these double porphyrin cages, linked by spacers of different lengths, i.e. 3, 5, and 11 carbon atoms. The structures of the double porphyrin cages were fully characterized by NMR, which revealed that they consist of mixtures of two diastereoisomers. Their zinc derivatives are capable of forming sandwich-like complexes with the ditopic ligand 1,4-diazabicyclo[2,2,2]octane (dabco).

Full text of DOI:10.1002/ejoc.202001211

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Porphyrin-Based Receptors
Double Porphyrin Cage Compounds
Kathleen Stout,[a] Theo P. J. Peters,[a] Mathijs F. J. Mabesoone,[a] Fabian L. L. Visschers,[a]
Eline M. Meijer,[a] Joëlle-Rose Klop,[a] Jeroen van den Berg,[a] Paul B. White,[a]
Alan E. Rowan,[b] Roeland J. M. Nolte,*[a] and Johannes A. A. W. Elemans*[a]
Abstract: The synthesis and characterization of double por- different lengths, i.e. 3, 5, and 11 carbon atoms. The structures
phyrin cage compounds are described. They consist of two por- of the double porphyrin cages were fully characterized by NMR,
phyrins that are each attached to a diphenylglycoluril-based which revealed that they consist of mixtures of two diastereo-
clip molecule via four ethyleneoxy spacers, and are linked to- isomers. Their zinc derivatives are capable of forming sandwich-
gether by a single alkyl chain using “click”-chemistry. Following like complexes with the ditopic ligand 1,4-diazabicyclo[2,2,2]-
a newly developed multistep synthesis procedure we report octane (dabco).
three of these double porphyrin cages, linked by spacers of
Introduction
stored again by making use of the four nucleobases present in
the DNA chain.
In the past decades, nature has served as a source of inspiration
for scientists working on the design of new molecular systems
that are capable of mimicking the action of enzymes, e.g. with
respect to rate and substrate selectivity. A class of enzymes
that stands at the basis of life are the DNA-polymerases, which,
together with exonucleases, replicate and break down the DNA
present in organisms.[1] During DNA replication, the information
stored in the pattern of nucleotides on the encoding (mother)
strand is transferred to the new daughter strand. One of the
factors contributing to the high replication fidelity of DNA-
polymerases is the fact that they make use of sequential proces-
sive catalysis, meaning that the enzyme stays bound to the sub-
strate while it performs multiple rounds of consecutive reac-
tions.[2] During these reactions the movement of the polymer-
ase along the biopolymer chain is discrete and unidirectional,
as it repeatedly moves one nucleotide further to carry out the
next reaction. In this way, information is reliably copied and
Taking the natural processive enzymes as a blueprint, our
group has developed synthetic processive catalysts that are
based on a glycoluril-based manganese porphyrin cage, MnSC
(Figure 1A).[3] This compound is capable of threading an alkene-
containing polymer chain and catalytically converting it to its
polyepoxide in an efficient, processive fashion (Figure 1B).[4] Our
current research focuses on achieving more control over the
processive epoxidation catalysis, i.e., in terms of the directional-
ity of performing the catalytic reactions along the polymer
chain, and the ability to stereoselectively epoxidize trans-
double bonds in the polymers into (R,R)- or (S,S)-epoxides.
When such control can be realized, we envisage the use of the
epoxidized polymers as a new type of data storage material,[5]
with the two mirror image epoxides acting as the digits 0
and 1 in a binary code.
In order to be able to manipulate the reactivity and/or selec-
tivity of the manganese porphyrin cage catalyst, we have de-
signed double porphyrin cage molecules, in which one of the
cages is meant to serve as the “writing cage” and the other as
the “instructing cage” (Figure 1C-D). Here, the “writing cage”
threads a polymer chain and catalytically converts its double
bonds into epoxides. It receives its instructions via an external
stimulus, e.g., a light-induced binding event, coming from the
“instructing cage”. This stimulus is transferred via a ditopic li-
gand, e.g. dabco (1,4-diazabicyclo[2,2,2]octane) that binds be-
tween the two cages via their porphyrin metal centers. An ex-
ample of such an external stimulus could be the binding of a
cofactor guest,[6] such as Me2V (N,N′-dimethyl-4,4-bipyridinium
dihexafluorophosphate). Me2V is known to have a high affinity
for the receptor cavity of the porphyrin cages.[7] In this paper
we report our synthetic efforts to covalently link two porphyrin
cage compounds in a geometry that ensures close proximity of
the metal centers in the two porphyrin planes (Figure 1D). We
[a] Dr. K. Stout, T. P. J. Peters, Dr. M. F. J. Mabesoone, F. L. L. Visschers,
E. M. Meijer, J.-R. Klop, J. van den Berg, Dr. P. B. White, Prof. R. J. M. Nolte,
and Dr. J. A. A. W. Elemans
Institute for Molecules and Materials, Radboud University,
Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands
E-mail: J.Elemans@science.ru.nl
R.Nolte@science.ru.nl
URL: https://www.ru.nl/science/molecularnanotechnology/
[b] Prof. A. E. Rowan
Australian Institute for Bioengineering and Nanotechnology (AIBN), Corner
College and Cooper Rds (Bldg 75), The University of Queensland,
Brisbane Qld 4072, Australia
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.202001211.
© 2020 The Authors. European Journal of Organic Chemistry published by
Wiley-VCH GmbH · This is an open access article under the terms of the
Creative Commons Attribution License, which permits use, distribution and
reproduction in any medium, provided the original work is properly cited.
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Figure 1. (A) Molecular structure of catalytic porphyrin cage compound MnSC and the axial ligand bupy. (B) Schematic representation of the processive
catalytic conversion of cis-polybutadiene (yellow) into its polyepoxide, carried out by MnSC (blue), to which a bupy ligand (green) is axially coordinated. (C)
Schematic representation of a double porphyrin cage compound (yellow) in which the “writing” cage serves as a processive catalyst for the epoxidation of a
polymer chain (red) and the “instructing” cage binds a Me2V cofactor (blue), which transfers information via the ditopic ligand dabco (orange) to the “writing
cage”. (D) Molecular structures of the double porphyrin cage compounds described in this paper.
previously showed that the coordination of axial ligands such as third meso-aryl substituent was accomplished by nucleophilic
dabco to the metal center in the porphyrin cage is allosterically addition of o-methoxyphenyllithium (obtained by a reaction of
influenced by the binding of a Me2V guest inside the cavity.[8] 2-bromoanisole with n-butyllithium) to one of the available
meso-positions of 2.[11a,12] After oxidation with DDQ, compound
3 was obtained in 40 % yield. The remaining free meso-position
of this compound is unsuitable for a similar reaction with an
appropriate lithium compound to prepare the desired mono-
functionalized porphyrin, because a reaction of the lithium salt
with the free meso-position yields a Meisenheimer-type com-
plex. The negative charge of this complex is localized and stabi-
lized at the opposite meso-position of the porphyrin, which
therefore should be unsubstituted.[13] As an alternative, we se-
lected a Suzuki cross-coupling reaction to introduce the final
meso-aryl ring. To this end, the free meso-position of 3 was first
regioselectively brominated with NBS, giving compound 4 in
quantitative yield.[14] A subsequent cross-coupling of 4 with
5-bromo-2-methoxyphenyl boronic acid, in the presence of a
palladium catalyst, gave porphyrin 5 in 83 % yield.[15] To pre-
vent additional cross-coupling reactions at the bromo-function-
alized phenyl ring, product formation of 5 was monitored with
the help of mass spectrometry (MS), and the reaction was car-
ried out at a moderate temperature. At the moment that MS
showed full conversion of 4, the reaction was stopped. As a
final step, the methoxy groups of 5 were deprotected using
We here describe the synthesis of 3 double porphyrin cages,
which differ in the length of the linker that connects the two
separate porphyrin rings. Furthermore, we report the ditopic
coordination of dabco to the zinc derivatives of the double
cage compounds, yielding stable 1:1 sandwich complexes.
Results and Discussion
Synthesis. Conventionally, porphyrin cage compounds are
prepared via a fourfold nucleophilic substitution reaction of
tetratosyl-functionalized molecular clip 7 (Scheme 1) with
tetrakis-meso-ortho-hydroxyphenyl porphyrin.[9] For the synthe-
sis of the double porphyrin cages, the latter compound needed
to be equipped on one of the meso-aryl substituents with a
functional group that would allow further conversion to a linker
between the two cages. To synthesize such a mono-functional-
ized porphyrin, we designed the synthetic route that is de-
picted in Scheme 1. It starts with an acid-catalyzed condensa-
tion of paraformaldehyde with pyrrole to provide dipyrrometh-
ane 1 in 57 % yield.[10] A MacDonald [2+2] condensation of this
compound with 2-methoxybenzaldehyde and subsequent
oxidation of the porphyrinogen gave 5,15-bis(2-methoxy- boron tribromide to give the desired mono-bromo-functional-
phenyl)porphyrin 2 in 35 % yield.[11] The attachment of the ized tetrahydroxy porphyrin 6 in 89 % yield. Compound 6 was
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then coupled to clip 7[9] to give the mono-bromo-substituted cycloaddition (CuAAC) reaction, the bromide substituent was
porphyrin cage compound 8 in 16 % yield. To protect the por- converted into an alkyne via a Suzuki–Miyaura cross coupling
phyrin of 8 from undesired metal insertion in following synthe- reaction. Using potassium triisopropylsilylacetylene trifluoro-
sis steps, it was metallated by inserting a zinc(II) center, provid- borate as the alkyne source,[16] compound 10 was obtained in
ing compound 9 in quantitative yield. To convert 9 into a suit- 93 % yield. Subsequent deprotection of the alkyne with tet-
able precursor for a copper-catalyzed azide-alkyne 1,3-dipolar rakis-n-butylammonium fluoride provided mono-acetylene-
Scheme 1. Synthesis of double porphyrin cage compounds.
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functionalized porphyrin cage 11 in 73 % yield. Using CuAAC, spectrum revealed couplings of both the nitrogen signals
this compound was subsequently reacted with α,ω-diazido- 15N-61 at 346.54 and 346.45 ppm with triazole proton signal H-
alkane linkers of different length to obtain a series of three 58 at 7.77 ppm. Also the signals of 15N-59 at 244.89 and
double cage compounds with various spacers lengths between 244.77 ppm coupled with this triazole signal, as well as to
the two cages. To facilitate the characterization of the new com- proton signals at 4.32 and 2.47 ppm belonging to CH2-62 and
pounds by NMR, 15N-enriched α,ω-diazidoalkanes were synthe- CH2-63, respectively. Via a ROE contact between H-58 and the
sized according to a literature procedure using 15N-enriched so- phenyl proton H-22 in the 2D ROESY spectrum, the resonance
dium azide, in which the 15N isotope is located at one of the of the latter proton in the 1H NMR spectrum could be assigned
two terminal azide positions.[17] CuAAC reactions of 11 with (8.40 ppm). C-22 displays a 13C-HMBC coupling to H-24 (8.28–
the respective diazides provided zinc double porphyrin cages 8.21 ppm), which in turn displays two COSY cross coupling
Zn2C3DC, Zn2C5DC and Zn2C11DC in yields of 35, 31 and 62 %, peaks with H-25. The fact that for this proton two well-sepa-
respectively. The rather low yields of the double click reactions rated resonances are observed confirms the abovementioned
are attributed to steric hindrance between the two approaching existence of two different species. The two signals integrate
porphyrin cages. During purification by column chromatogra- equally, meaning that the two species are present in a 1:1 ratio.
phy, it was possible to retrieve unreacted 11, which could be In addition to H-25, also H-45, H-46, and H-48 in the same quad-
re-employed in subsequent click reactions. After treatment of rant of the molecule (denoted “I” in Figure 2) give two distinct
the Zn2CxDC (x = 3, 5 or 11) compounds with aqueous hydro- signals in the NMR spectrum, all confirming the existence of
chloric acid, free base double porphyrin cage compounds two different species. Conversely, the analogous proton signals
H4C3DC, H4C5DC and H4C11DC were obtained in yields of 68, in the other three quadrants of the molecule (II, III and IV) do
81, and 92 %, respectively.
not show such a splitting of signals.
Structural characterization. The double porphyrin cage
The observation that H4C3DC exists as two equally abundant
compounds were characterized with the help of 1H, 13C and species is the result of the fact that this compound, as well as
15N NMR spectroscopy in chloroform solution. All proton and the other double porphyrin cage compounds, are mixtures of
carbon resonances could be readily assigned with the help of two diastereoisomers. The monofunctionalized single porphyrin
2D techniques (see Figure 2 for the assignment of H4C3DC). The cage compounds 8–11 are all racemates of two enantiomers.
NMR measurements revealed the presence of several structural Although their chiral nature is at first sight not easily recogniza-
isomers of the double porphyrin cage compounds. The 15N ble, their macrocyclic three-dimensional (3D) structure gives
spectrum of H4C3DC showed the presence of four singlets for rise to the existence of two non-superimposable mirror-image
the 15N-labeled nitrogen atoms present in the triazole rings of structures, i.e., enantiomers (Figure 3A). The compounds exhibit
the spacer between the two porphyrin cages (Figure 2B). The
fact that two sets of two singlets are observed for the two
different types of 15N-labeled nitrogen atoms indicates that two
1
different species of H4C3DC must be present. A H-15N HBMC
Figure 3. (A) Representations of the two enantiomers of monofunctionalized
single cage compounds 8–11. Top: 3D representations. Bottom: schematic
view of the porphyrin (black square) seen from the top. The black lines left
and right from the square indicate the location of the o-xylylene side walls
of the cage, the cyan dot the functional group at the top. (B) Representations
(top views and 3D views) of the two diastereoisomers that are obtained by
the coupling of the enantiomers of monofunctionalized single cage com-
pound 11.
Figure 2. (A) 1H NMR spectrum of H4C3DC in CDCl3 and proton/carbon num-
bering of the compound. The Roman numbers I, II, III and IV and the related
colors indicate the four symmetry quandrants within the porphyrin cage
structure. (B) 15N spectrum of H4C3DC in CDCl3.
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planar chirality,[18] and the 3D chiral morphology leads in this
specific case to the emergence of two chiral centers, i.e., the
two quaternary bridgehead carbon atoms in the diphenyl-
glycoluril framework (C-52, see Figure 2A).[19] The subsequent
connection of two molecules of (rac)-11 via click chemistry
leads to the expected formation of two diastereoisomers in
equal quantities (Figure 3B). So far, we have not succeeded in
separating the diastereoisomers via chromatographic methods.
Besides H4C3DC, also H4C5DC displayed two sets of signals for
1
protons H-25, H-45, H-46 and H-48 in its H NMR spectrum. In
contrast, H4C11DC did not display double resonance sets for
these protons. This is presumably the result of the spacer length
in this double cage compound. The longer spacer increases the
distance between the two cages so much that they no longer
experience chemical environments that are different enough
to cause double resonances for the same protons in the NMR
spectrum.
Insertion of a zinc center in the porphyrin led to broadening
of the proton signals of the double zinc porphyrin cage com-
pounds Zn2CxDC in their 1H NMR spectra in CDCl3. The addition
of deuterated pyridine to these solutions caused a sharpening
of the signals, which suggests that the signal broadening is
caused by coordination interactions (intramolecular or inter-
molecular) between the triazole nitrogen or carbonyl oxygen
atoms and the porphyrin zinc centers, which are broken by co-
ordination of the deuterated pyridine to the zinc centers. To
characterize the Zn2CxDC compounds, we recorded their NMR
spectra at 60 °C in [D6]DMSO, a solvent that also prohibits such
intramolecular or intermolecular coordination. The spectra in-
deed displayed sharp resonances, which could be completely
assigned to the two diastereoisomers that were also observed
for the H4CxDC compounds.
Figure 4. (A) Changes in UV/Vis spectra of Zn2C3DC upon the addition of
dabco, in CHCl3/CH3CN, 1:1 (v/v). (B) Titration curves extracted from the spec-
tral changes in (A), monitoring the absorbance of the bands at 426 (red) and
431 nm (blue). The solid lines through the data points represent fits assuming
a standard 1:2 binding model.
the open-folded complex between Zn2C3DC and axially coordi-
nated acetonitrile molecules. Moreover, due to effective molar-
ity and binding statistics effects, this complex is highly stable
and only upon the addition of a large excess of the ligand, the
emergence of a red-shifted Soret band at 431 nm reflects the
formation of a 1:2 Zn2C3DC:dabco complex, which is again
open-folded.[20] UV/Vis titrations of Zn2C5DC and Zn2C11DC
with dabco gave similar results (see Supporting Information).
The obtained titration curves were fitted with a standard 1:2
binding model (Figure 4B). The association constants Ka and
binding free energies ΔGθ were extracted from the fits and are
summarized in Table 1.[22] The Ka-values obtained for all the
double zinc porphyrin cage compounds are comparable to
those obtained previously for the coordination of dabco to
other bis-zinc porphyrin compounds, which range between 104
Coordination complexes of the double zinc porphyrin
cage compounds with dabco. The ability of the double zinc
porphyrin cages to coordinate the ditopic ligand dabco was
investigated. The coordination of this ligand to zinc porphyrins
and the typical spectral changes it induces in NMR and optical
spectra have been reported extensively.[20] To enable future fol-
low-up studies with chloroform-insoluble viologen guests, the
ligand coordination studies were carried out in a solvent mix-
ture of chloroform and acetonitrile (1:1, v/v). While in chloro-
form the Zn2CxDC compounds all displayed a Soret band at
421 nm, in CHCl3/CH3CN this band shifts to 426 nm, which we
attribute to axial coordination of acetonitrile to the zinc centers.
When dabco is added to a solution of Zn2C3DC, the band at
426 nm initially does not shift, but sharpens and increases in
intensity (Figure 4A), which indicates the formation of a more
well-defined species. After the addition of several equivalents
of dabco, the spectral changes remain virtually unchanged up
to the addition of several hundreds of equivalents of the ligand
(Figure 4B). In the presence of a larger excess of dabco, the
band at 426 nm again decreases in intensity, with a concomi-
tant emergence of a new band at 431 nm, which increases in
intensity as up to 5 × 105 equivalents of dabco are added.
–1
–1
- 108
M
for Ka (1:1) and 102 – 103
M
for Ka (1:2) in various
solvents.[20] Due to possible competition for axial ligation to the
zinc centers between dabco and the acetonitrile solvent, the
association constants determined here are on the lower end of
the commonly reported range.[23] While the Ka(1:1)-values of
the complexes of dabco with Zn2C5DC and Zn2C11DC are quite
similar, the Ka(1:1)-value of the complex with Zn2C3DC is signifi-
cantly higher. We attribute this difference to a more favorable
effective molarity effect for the second zinc porphyrin in the
The initial sharpening of the Soret band is attributed to the latter complex: once the first zinc porphyrin of Zn2C3DC has
formation of a 1:1 sandwich complex between Zn2C3DC and coordinated a dabco ligand, the second zinc porphyrin is in
dabco.[21] Such a complex is better defined and more rigid than close proximity as a result of the relatively short spacer between
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the two porphyrins. This effect is favorable for 1:1 complexation complex, the signal of the methylene-protons of bound dabco
and the generation of a high Ka(1:1)-value, but since the differ- are expected around –3 ppm. This absence may again be due
ence in Ka(1:1)-value between the complexes of dabco with to signal broadening as a result of rapid exchange.[20b,20c,24]
Zn2C5DC and Zn2C11DC is much less prominent, probably also
other factors play a role. Molecular modelling calculations of
the complexes (Spartan™, PM3/semi-empirical) revealed that
the short C3-spacer allows an almost perfect fit for the dabco
ligand between the zinc porphyrins of Zn2C3DC. The longer C5
and C11 spacers of the other two double zinc porphyrin cages
require progressive folding of their chain to still allow a ditopic
binding of the ligand (Figure 5), which may be a factor that
leads to a lowering of the binding strength of the ligand.
Table 1. Association constants Ka [M – 1] and binding free energies ΔGθ
(kJ mol–1) for the 1:1 and 1:2 complexes between Zn2CxDC and dabco in
CHCl3/CH3CN, 1:1 (v/v). The error represents the standard deviation ( 1 S.D.)
over a triplo of measurements.
1:1 Complex
2:1 Complex
Ka
ΔGθ
Ka
ΔG
Zn2C3DC
Zn2C5DC
Zn2C11DC
1.95 0.3 × 106 –35.9 0.8
2.34 0.3 × 105 –30.6 0.2
3.31 0.3 × 105 –31.5 0.2
130 30
740 90
350 25
–12.1 0.5
–16.4 0.3
–14.5 0.2
Figure 6. 1H NMR titration of Zn2C3DC with 0 to 8 equiv. of dabco (500 MHz,
298 K, CDCl3/CD3CN, 1:1 (v/v)). The blue box and arrow indicate the location
of the signal of dabco in the 1:1 sandwich complex, and the red arrow the
signal of non-coordinated dabco.
To decrease the exchange dynamics, NMR studies were car-
ried out at lower temperature (Figure 7). At temperatures lower
than 278 K the broad resonance at –4.5 ppm sharpened into a
well-defined peak at –4.46 ppm, which shifted slightly upfield
Figure 5. Computer-modeled structures of the sandwich complexes of double
zinc porphyrin cages (indigo) (A) Zn2C3DC, (B) Zn2C5DC and (C) Zn2C11DC
with dabco (red). The alkyl spacers between the cages are indicated in yellow.
To corroborate the formation of the 1:1 and 1:2 complexes
identified by the UV/Vis titration experiments, NMR studies
were carried out for the complex formation between dabco
and Zn2C3DC, at various temperatures in CDCl3/CD3CN, 1:1
(v/v). Figure 6 shows the changes in the 1H NMR spectra at
298 K when up to 8 equivalents of dabco were added to a
1 mM
solution of Zn2C3DC. The addition of one equivalent of
the ligand caused an upfield shift of the porphyrin ꢀ-pyrrole
signals from 8.9–8.5 to 8.5–8.3 ppm, while a new, very broad
signal appeared at –4.5 ppm. The latter signal is characteristic
for a dabco ligand bound in a sandwich-like geometry between
two zinc porphyrins.[20] Its broadness is probably caused by
rapid exchange between the bound and unbound components
on the NMR timescale. In the presence of two or more equiva-
lents of dabco, a broad signal corresponding to uncomplexed
ligand (at 2.6 ppm) appeared, while the signal at –4.5 ppm
disappeared. Remarkably, no signal corresponding to a dabco
ligand in an open-folded 1:2 complex was observed. In such a
Figure 7. Variable temperature 1H NMR spectra of the 1:1 sandwich complex
between Zn2C3DC and dabco (400 MHz, CDCl3/CD3CN, 1:1 (v/v)). The arrow
indicates the location of the signal of dabco in the 1:1 sandwich complex.
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to –4.6 ppm at 238 K, while simultaneously the signals of Conclusions
Zn2C3DC gradually broadened.
We have presented a multistep route for the synthesis of cova-
To investigate the binding of dabco into further detail, up
to 4 equivalents of the ligand were added to the solution of
Zn2C3DC and NMR spectra were recorded at 248 K (Figure 8).
In the presence of 0.25 equivalents of dabco, the signals of
Zn2C3DC sharpened, indicating a decrease in dynamics of the
cage molecule. When the amount of dabco was increased to 1
equivalent, the resonance of the sandwiched ligand at
–4.58 ppm slightly broadened. The addition of more equiva-
lents of dabco led to the emergence of a signal of the mono-
coordinated ligand in the open-folded 1:2 complex at
–2.92 ppm (α-protons of the ligand), while simultaneously the
resonance at –4.58 ppm decreased in intensity. With the use of
2D NMR techniques we were unable to locate the signals of the
ꢀ-protons of the mono-coordinated dabco ligand or the signal
of the free ligand, which is probably due to the broadness of
the signals and the poor signal-to-noise ratio under these con-
ditions. Due to the gradual broadening of the dabco resonan-
ces, no reliable baseline correction could be applied and, there-
fore, no reliable ratio of the 1:1 and 1:2 complexes could be
determined by integration of the signals. The signals of
Zn2C3DC broadened and became less defined upon the addi-
tion of more equivalents of dabco, which indicates an increase
in the dynamics of the double cage compound. Although the
NMR signals become better resolved at temperatures lower
than 288 K, it can be expected that the complexes also exist at
298 K, albeit more dynamic and in abundancies that are gov-
erned by the association constants at that temperature. Thus,
the NMR results corroborate the binding geometries as pro-
posed by the UV/Vis experiments.
lently linked double porphyrin cage compounds. For the syn-
thesis of these compounds, a mono-bromo-substituted por-
phyrin was synthesized in 6 steps starting from paraformalde-
hyde and pyrrole. Upon connection of the porphyrin to a cavity
molecule based on diphenylglycoluril, a racemate of two pla-
nar-chiral porphyrin cage molecules was obtained. After con-
verting the bromo-substituent of these cage compounds into
an acetylene function, double porphyrin cage compounds
could be prepared via “click” reactions with α,ω-diazidoalkanes
of different lengths. With the help of extensive NMR spectro-
scopy experiments the double cage compounds could be fully
characterized. The presence of multiple resonances for several
protons of the double cages with C3 and C5 spacers proved
their existence as two diastereoisomers, while the absence of
such multiple resonances in the case of the double cage com-
pound with the C11 spacer indicated that the two cavities of
that compound are so remote that they are no longer affected
by each other's chirality. The ability of the zinc double por-
phyrin cage compounds to form sandwich complexes with the
ditopic ligand dabco was confirmed by UV/Vis and NMR titra-
tion studies. These revealed that the zinc double cage with the
short C3 spacer formed the strongest 1:1 sandwich complex
with the ligand, probably as a result of a favourable effective
molarity effect and binding geometry. As expected, the 1:2
open complexes displayed association constants of about 3 or-
ders of magnitude lower than those of the respective 1:1 com-
plexes. The formation of the 1:1 and 1:2 complexes were corrob-
orated by variable temperature 1H NMR titrations. Future re-
search will focus on the possibilities to transfer information be-
tween the receptor cavities of the sandwich complexes during
catalytic reactions. We will equip the double porphyrin cage
compounds with one zinc and one catalytic manganese center,
and investigate the influence of the binding of guests in the
zinc porphyrin cage, via the coordinated dabco ligand, on the
processive epoxidation of threaded polyalkenes by the manga-
nese cage of the system.
Experimental Section
Materials and methods. All commercially obtained chemicals were
used without further purification, unless stated otherwise. Dry n-
pentane was stored under argon in a glovebox, THF was distilled
under nitrogen from potassium, CH2Cl2 was distilled under nitrogen
from calcium hydride, and MeCN was distilled under argon from
calcium chloride. For TLC analysis, TLC Silicagel 60 F254 (Merck) and
for column chromatography, Silica gel 0.035–0.070 mm 60A (Acros),
SilicaFlash® P60 40–63 μm (SiliCycle) or Silicagel 60 H (Merck) were
used. 1H, 13C NMR and 15N NMR spectra were recorded on Bruker
Avance III 400 or 500 MHz spectrometers at 25 °C unless stated
otherwise. Chemical shifts are reported in parts per million (ppm)
relative to tetramethylsilane (TMS, 0.00 ppm) as the internal refer-
ence. NMR data are presented as follows: chemical shift (∂) in ppm,
multiplicity (s = singlet, bs = broad singlet, d = doublet, t = triplet,
q=quartet, td = triplet of doublets, m = multiplet and/or multiple
resonances), integration, assignment and coupling constant (J) in
Hertz (Hz). All NMR signals were assigned on the basis of 1H, 13C
Figure 8. 1H NMR titration of Zn2C3DC with 0 to 4 equiv. of dabco (500 MHz,
248 K, CDCl3/CD3CN, 1:1 (v/v)). The blue and purple arrows indicate the loca-
tions of the signals of dabco in the 1:1 sandwich complex (–4.58 ppm) and
in the 2:1 open-folded complex (–2.92 ppm), respectively.
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NMR, 15N NMR, COSY, ROESY, HSQC, and HMBC experiments. The 1H-NMR (CDCl3, 400 MHz): ∂ 7.91 (bs, 2H, NH), 6.68 (td, 2H, ArH-5,
numbering of the proton, carbon, and nitrogen atoms used in the
assignments is depicted in Figure 9. Phase and baseline correction
was applied to all NMR spectra. As several porphyrin compounds
were obtained as a mixture of atropisomers that were inseparable
by column chromatography, the reported chemical shifts represent
the averaged shifts over all of these atropisomers. Assigning all
inequivalent 13C-signals was not possible due to the limited resolu-
tion of the 2D spectra and overlapping proton signals, therefore
ranges are reported for several almost identical 13C atoms. LCQ
mass spectra were recorded in methanol on a Thermo Finnigan LCQ
Advantage Max mass spectrometer, and MALDI-TOF mass spectra
were measured in reflective mode with dithranol as matrix on a
Bruker Microflex LRF MALDI-TOF mass spectrometer. Accurate
MALDI-TOF mass spectra were obtained on a Brukerdaltonics auto-
flex (ST-A2130) MALDI-TOF mass spectrometer with cesium triiodide
as matrix in reflective mode. Accurate masses were obtained from
a solution of the compound in methanol on a JEOL AccuTOF CS
JMS-T100CS. Compound 7 was synthesized according to a literature
procedure.[9]
J = 2.6, 1.5 Hz), 6.15 (q, 2H, ArH-4, J = 2.9 Hz), 6.05–6.02 (m, 2H,
ArH-3), 3.99 (s, 2H, CH2-1); 13C{1H}-NMR (CDCl3, 100 MHz): ∂ 129.03
(ArC-2), 117.24 (ArC-5), 108.38 (ArC-4), 106.36 (ArC-3), 26.38 (CH2-1).
5,15-Bis(2-methoxyphenyl)porphyrin (2). Argon was led through
CH2Cl2 (1.85 L) for 30 min and compound 1 (1.205 g, 8.24 mmol),
2-methoxybenzaldehyde (1.122 g, 8.24 mmol) and TFA (0.140 mL,
1.82 mmol) were added. The reaction mixture was stirred in the
dark at r.t. for 16 h. Then a solution of DDQ (2.685 g, 11.83 mmol)
in CH2Cl2 (70 mL) was added. After stirring for 2 h the mixture was
quenched with Et3N (6 mL) and concentrated in vacuo. The residue
was purified over a silica gel column using chloroform as the eluent.
The crude product was dissolved in CH2Cl2, filtered, and precipi-
tated in n-heptane. After washing the precipitate with n-pentane
(4×), drying in vacuo yielded 2 (749.1 mg, 1.43 mmol, 35 %) as a
purple solid containing 2 atropisomers.
1H-NMR (CDCl3, 500 MHz): ∂ 10.23 (s, 2H, ArH-1,11), 9.33 (d, 4H, ꢀ-
pyrrole-H-3,9,13,19, J = 4.5 Hz), 8.97 (d, 4H, ꢀ-pyrrole-H-4,8,14,18,
J = 4.5 Hz), 8.06 (d, 2H, ArH-28,40, J = 7.2 Hz), 7.80 (t, 2H, ArH-30,42,
J = 7.9 Hz), 7.41 (t, 2H, ArH-29,41, J = 7.5 Hz), 7.38 (d, 2H, ArH-31,43,
J = 8.0 Hz), 3.61 (s, 6H, OMe-46,48), –3.07 (s, 2H, NH); 13C{1H}-NMR
(CDCl3, 126 MHz): ∂ 159.45 (ArC-32,44), 147.28 (ArC-5,7,15,17),
145.18 (ArC-2,10,12,20), 135.80 (ArC-28,40), 131.33 (ArC-3,9,13,19),
130.68 (ArC-4,8,14,18), 130.29 (ArC-27,39), 129.89 (ArC-30,42), 119.61
(ArC-29,41), 115.01 (ArC-6,16), 111.07 (ArC-31,43), 104.78 (ArC-1,11),
55.81 (OMe-46,48); UV/Vis (CHCl3): λ/nm (log (ε/M–1 cm–1)) 408
(5.53), 502 (4.21); Accurate mass: m/z 523.21361 [M + H]+; calcd. for
C34H27N4O2 523.213040; Anal. Calcd for C34H26N4O2: C, 78.14; H,
5.01; N, 10.72; found C, 77.99; H, 4.92; N, 10.68.
5,10,15-Tris(2-methoxyphenyl)porphyrin (3). 2-Bromoanisole
(2.763 g, 14.77 mmol) was added to dry n-pentane (50 mL). n-Butyl-
lithium (1.6
M in hexanes, 8 mL, 12.79 mmol) was added and the
reaction mixture was stirred for 30 min at r.t. until a white precipi-
tate was formed. The mixture was filtered under Schlenk conditions
and the white residue was washed with dry n-pentane (4 × 40 mL),
after which it was dissolved in distilled THF (150 mL). Compound 2
(390 mg, 0.75 mmol) was added and the reaction mixture was
stirred at r.t. for 16 h, after which water (3.5 mL) was added, fol-
lowed by DDQ (761.32 mg, 3.35 mmol). After stirring for 1 h at r.t.
the reaction mixture was evaporated to dryness and the residue
was purified over a silica gel column using chloroform as the eluent.
The crude product was subsequently purified by silica gel column
chromatography using DCM/n-heptane (75:25, (v/v)) as the eluent
to yield 3 (187.7 mg, 0.29 mmol, 40 %) as a purple solid containing
3 atropisomers.
Figure 9. Carbon, proton, and nitrogen numbering of 5-(5-bromo-2-methoxy-
phenyl)-10,15,20-tris(2-methoxyphenyl) porphyrin 5 (left) and the double
cage compounds M2CnDC (M = 2H or Zn, n = 3, 5 or 11) (right) used for all
NMR analyses. For the double cage compounds, R represents the mirror im-
age of the cage molecule, with the restriction that for Zn2C3DC the attach-
ment starts at carbon number 63, for Zn2C5DC at carbon atom 64, and for
Zn2C11DC at carbon atom 67 (the latter is shown). The CH2-groups of the
diphenylglycoluril framework (carbon atoms 45, 46, 48 and 50) all have two
inequivalent geminal protons, marked as a and b. The location of the signals
of these protons could only be identified for CH2-50, with the help of ROESY
experiments.
1H-NMR (CDCl3, 500 MHz): ∂ 10.11 (s, 1H, ArH-1), 9.25 (d, 2H, ꢀ-
pyrrole-H-3,19, J = 4.6 Hz), 8.90 (d, 2H, ꢀ-pyrrole-H-4,18, J = 4.4 Hz),
8.79–8.75 (m, 4H, ꢀ-pyrrole-H-8,9,13,14), 8.04 (d, 1H, ArH-34, J =
7.3 Hz), 8.02–7.92 (m, 2H, ArH-28,40), 7.80–7.70 (m, 3H, ArH-
30,36,42), 7.39–7.35 (m, 3H, ArH-29,35,41), 7.35–7.26 (m, 3H, ArH-
31,37,43), 3.61–3.51 (m, 9H, OMe-46,47,48), –2.89 (s, 2H, NH);
13C{1H}-NMR (CDCl3, 126 MHz): ∂ 159.56–159.37 (ArC-32,38,44),
149.00–144.00 (broad, ArC-2,5,7,10,12,15,17,20), 135.78–135.50 (ArC-
28,34,40), 131.49–130.77 (ArC-27,33,39), 131.20–130.10 (broad, ArC-
3,4,8,9,13,14,18,19), 129.76–129.68 (ArC-30,36,42), 119.46–119.26
(ArC-29,35,41), 115.87–115.19 (ArC-6,11,16), 111.05–110.81 (ArC-
31,37,43), 104.40 (ArC-1), 55.81 (OMe-46,47,48); UV/Vis (CHCl3):
λ/nm (log (ε/M–1 cm–1)) 413 (5.74), 508 (4.25); Accurate mass: m/z
629.25449 [M + H]+; calcd. for C41H33N4O3: 629.25526.
Syntheses. For the NMR assignments of proton, carbon and nitro-
gen signals, the atom numbering depicted in Figure 9 will be used.
Di(1H-pyrrol-2-yl)methane (1). This compound was synthesized
according to modified literature procedures.[10] To distilled pyrrole
(153 mL, 2.21 mol) a 37 % aq. formaldehyde solution (9 mL,
90.42 mmol) was added. Argon was led through the solution for
15 min, after which TFA was added (0.82 mL, 10.21 mmol). The
reaction mixture was stirred at r.t. for 5 min. The orange solution
was diluted with CH2Cl2 (150 mL) and washed with sat. aq. Na2CO3
(3 × 100 mL) and water (100 mL). The organic layer was concen-
trated in vacuo. The excess of pyrrole was removed by vacuum
distillation at 35 °C. Silicagel column chromatography using DCM/
n-heptane (60:40 (v/v)) as the eluent afforded 1 (7.469 g, 51 mmol,
57 %) as a white fluffy solid.
5-Bromo-10,15,20-tris(2-methoxyphenyl)porphyrin (4). Com-
pound 3 (385.4 mg, 0.61 mmol) was dissolved in chloroform (25 mL)
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and NBS (128.15 mg, 0.72 mmol) was added. After stirring at r.t. for
25 min the reaction mixture was quenched by the addition a solu-
tion of Na2SO3 (177.33 mg, 1.41 mmol) in water (10 mL). After
15 min of stirring the reaction mixture was diluted with chloroform
(50 mL) and washed with water. The organic layer was dried with
Na2SO4, filtered and the solvents evaporated to dryness. The crude
product was purified by silica gel column chromatography using
DCM/n-heptane (50:50 going to 75:25, (v/v)) as an eluent to yield 4
(467.7 mg, 0.66 mmol, 100 %) as a purple solid containing 3 atropi-
somers.
1H-NMR (CDCl3, 500 MHz): ∂ 9.60 (d, 2H, ꢀ-pyrrole-H-3,19, J = 4.8 Hz),
8.80 (bs, 2H, ꢀ-pyrrole-H-4,18), 8.68 (bs, 4H, ꢀ-pyrrole-H-8,9,13,14),
8.03–7.89 (m, 3H, ArH-28,34,40), 7.79–7.70 (m, 3H, ArH-30,36,42),
7.38–7.33 (m, 3H, ArH-29,35,41), 7.33–7.26 (m, 3H, ArH-31,37,43),
3.62–3.52 (m, 9H, OMe-46,47,48), –2.63 (s, 2H, NH); 13C{1H}-NMR
(CDCl3, 126 MHz): ∂ 159.50–159.20 (ArC-32,38,44), 135.62–135.38
(ArC-28,34,40), 130.74 (ArC-27,33,39), 129.91–129.84 (ArC-30,36,42),
119.41 (ArC-29,35,41), 116.53–116.29 (ArC-6,11,16), 110.97–110.77
(ArC-31,37,43), 102.43 (ArC-1), 55.79 (OMe-46,47,48); UV/Vis (CHCl3):
λ/nm (log (ε/M–1 cm–1)) 421 (5.54), 517 (4.21); Accurate mass: m/z
707.16436 (M(79Br)+H)+, 709.16321 (M(81Br)+H)+; calcd. for
C41H32BrN4O3 707.16578 (79Br); 709.16373 (81Br); Anal. Calcd for
C41H31BrN4O3: C, 69.59; H, 4.42; N, 7.92; found C, 69.16; H, 4.34; N,
7.76.
NaHCO3 (2 × 70 mL) and dried with MgSO4, filtered, and the sol-
vents evaporated to dryness. The crude product was purified by
silica gel column chromatography using ethyl acetate/chloroform
(50:50 (v/v)) as an eluent, yielding 6 (549.4 mg, 0.73 mmol, 89 %)
as a purple solid containing 8 atropisomers.
1H-NMR (CDCl3, 500 MHz): ∂ 8.96–8.88 (m, 8H, ꢀ-pyrrole-H-
3,4,8,9,13,14,18,19), 8.13–8.08 (m, 1H, ArH-22), 7.98–7.94 (m, 3H,
ArH-28,34,40), 7.83 (t, 1H, ArH-24, J = 8.8 Hz), 7.73 (t, 3H, ArH-
30,36,42, J = 8.1 Hz), 7.37–7.32 (m, 6H, ArH-29,31,35,37,41,43), 7.23
(d, 1H, ArH-25, J = 2.5 Hz), 4.92 (bs, 4H, OH), –2.78 (s, 2H, NH);
13C{1H}-NMR (CDCl3, 126 MHz): ∂ 155.40 (ArC-32,38,44), 154.72 (ArC-
26), 137.07 (ArC-22), 135.01 (ArC-28,34,40), 133.57 (ArC-24), 133.00–
131.00 (broad ArC-3,4,8,9,13,14,18,19), 130.76 (ArC-30,36,42), 129.35
(ArC-21), 127.22 (ArC-27,33,39), 119.77–119.73 (ArC-29,35,41), 117.36
(ArC-25), 115.71–115.55 (ArC-31,37,43), 114.01–113.73 (ArC-6,11,16),
111.95–111.91 (ArC-23), 111.53–111.30 (ArC-1); UV/Vis (CHCl3): λ/nm
(log (ε/M–1 cm–1)) 419 (5.32), 513 (4.20); Accurate mass: m/z
757.14343 (M(79Br)+H)+, 759.14233 (M(81Br)+H)+; calcd. for
C44H30BrN4O4: 757.14504 (79Br), 759.14300 (81Br); Anal. Calcd for
C44H29BrN4O4: C, 69.75; H, 3.86; N, 7.40; found C, 69.31; H, 3.91;
N, 7.13.
Mono-bromo porphyrin cage compound (8). To compound 7
(549.09 mg, 0.41 mmol), potassium carbonate (1.406 g,
10.19 mmol), compound 6 (306.97 mg, 0.41 mmol), and acetonitrile
(750 mL) were added. Argon was led through the reaction mixture
for 30 min, and the solution was subsequently refluxed for 16 h.
After cooling, the mixture was filtered through Celite and the filtrate
was evaporated to dryness. The crude product was purified by col-
umn chromatography (alumina Brockmann III) using chloroform as
the eluent. Precipitation from DCM/n-heptane followed by washing
with n-pentane (4 ×) and drying in vacuo yielded 8 (92.6 mg,
0.07 mmol, 16 %, racemate of two enantiomers) as a purple solid.
5-(5-Bromo-2-methoxyphenyl)-10,15,20-tris(2-methoxyphenyl)-
porphyrin (5). Compound 4 (690 mg, 0.98 mmol), (5-bromo-2-
methoxyphenyl)boronic acid (1.125 g, 4.88 mmol), triphenylarsine
(119.9 mg, 0.39 mmol), bis(triphenyl-phosphine)palladium (II) di-
chloride (137 mg, 0.20 mmol), and tripotassium phosphate (1.035 g,
4.88 mmol) were dissolved in distilled THF (175 mL). The reaction
mixture was stirred at 42.5 °C for 4 h (reaction progress monitored
with the help of MALDI-TOF). After cooling to r.t., the mixture was
evaporated to dryness and the residue purified by a silica gel col-
umn using DCM as the eluent. Subsequently, the crude product
was purified by silica gel column chromatography using DCM/n-
heptane (60:40 going to 80:20 (v/v)) as the eluent to yield 5
(660.5 mg, 0.81 mmol, 83 %) as a purple solid containing 8 atropiso-
mers.
1H-NMR (CDCl3, 500 MHz): ∂ 8.80–8.74 (m, 4H, ꢀ-pyrrole-H-3,4,13,14),
8.70–8.64 (m, 4H, ꢀ-pyrrole-H-8,9,18,19), 8.21 (d, 1H, ArH-22,
J = 2.5 Hz), 8.10–8.03 (m, 3H, ArH-28,34,40), 7.86 (dd, 1H, ArH-24,
J = 8.9, 2.5 Hz), 7.78–7.73 (m, 3H, ArH-30,36,42), 7.41–7.36 (m, 3H,
ArH-29,35,41), 7.35–7.32 (m, 3H, ArH-31,37,43), 7.21 (d, 1H, ArH-25,
J = 8.9 Hz), 6.98–6.91 (m, 6H, ArH-55,56), 6.83–6.80 (m, 4H, ArH-54),
6.19 (s, 3H, ArH-48(II, III, IV)), 6.18 (s, 1H, ArH-48(I)), 4.31–4.23 (m,
4H, CH2-45a), 4.23 (d, 4H, CH2-50a, J = 15.9 Hz), 4.10–4.00 (m, 4H,
CH2-45b), 3.74 (d, 4H, CH2-50b, J = 15.6 Hz), 3.55–3.48 (m, 4H, CH2-
46a), 3.39–3.30 (m, 4H, CH2-46b), –2.75 (s, 2H, NH); 13C{1H}-NMR
(CDCl3, 126 MHz): ∂ 158.72 (ArC-32,38,44), 158.01 (ArC-26), 156.99
(C=O-51), 146.58–146.49 (ArC-47), 138.01 (ArC-22), 135.77 (ArC-
28,34,40), 134.03 (ArC-21), 133.64 (ArC-53), 132.34 (ArC-24), 131.80–
131.76 (ArC-27,33,39), 129.93–129.83 (ArC-49), 129.64 (ArC-30,36,42),
128.52–128.45 (ArC-55,56), 128.11 (ArC-54), 119.88–119.84 (ArC-
29,35,41), 115.59–115.39 (ArC-6,11,16), 115.18 (ArC-48), 113.51 (ArC-
25), 113.16 (ArC-1), 112.33 (ArC-23), 111.93–111.87 (ArC-31,37,43),
84.77 (C-52), 67.43 (CH2-46), 66.86 (CH2-45), 44.41 (CH2-50); UV/Vis
(CHCl3): λ/nm (log (ε/M–1 cm–1)) 421 (5.46), 516 (4.18); Accurate
mass: m/z 1423.39108 (M(79Br)+H)+, 1425.39106 (M(81Br)+H)+; calcd.
for C84H64BrN8O10: 1423.39288 (79Br), 1425.39083 (81Br).
1H-NMR (CDCl3, 500 MHz):
∂ 8.78–8.68 (m, 8H, ꢀ-pyrrole-H-
3,4,8,9,13,14,18,19), 8.20–8.07 (m, 1H, ArH-22), 8.06–7.91 (m, 3H,
ArH-28,34,40), 7.84 (d, 1H, ArH-24, J = 9.0 Hz), 7.75 (t, 3H, ArH-
30,36,42, J = 7.9 Hz), 7.36–7.32 (m, 3H, ArH-29,35,41), 7.32–7.28 (m,
3H, ArH-31,37,43), 7.21–7.14 (m, 1H, ArH-25), 3.63–3.50 (m, 12H,
OMe-45,46,47,48), –2.65 (s, 2H, NH); 13C{1H}-NMR (CDCl3, 126 MHz):
∂ 159.46 (ArC-32,38,44), 158.73 (ArC-26), 137.96–137.64 (ArC-22),
135.83–135.40 (ArC-28,34,40), 133.37 (ArC-21), 132.38 (ArC-24),
131.11 (ArC-27,33,39), 129.72 (ArC-30,36,42), 119.33 (ArC-29,35,41),
115.71 (ArC-6,11,16), 113.44 (ArC-1), 112.51 (ArC-25), 111.77
(ArC-23), 110.91 (ArC-31,37,43), 56.09 (OMe-45,[46,47,48]), 55.85
(OMe-[45],46,47,48); UV/Vis (CHCl3) λ/nm (log (ε/M–1 cm–1)) 419
(5.62), 514 (4.28); Accurate mass: m/z 813.20482 (M(79Br)+H)+,
815.20403 (M(81Br)+H)+; calcd. for C48H38BrN4O4: 813.20764 (79Br);
815.20560 (81Br); Anal. Calcd for C48H37BrN4O4: C, 70.85; H, 4.58; N,
6.89; found C, 70.55; H, 4.45; N, 6.80.
5-(5-Bromo-2-hydroxyphenyl)-10,15,20-tris(2-hydroxyphenyl)- Zinc mono-bromo porphyrin cage compound (9). The mono-
porphyrin (6). Compound 5 (660.5 mg, 0.81 mmol) was dissolved
in distilled DCM (40 mL) and this solution was cooled to –30 °C.
Then, BBr3 (1.55 mL, 16.2 mmol) was added. The reaction mixture
was warmed up to r.t. overnight before it was poured into an ice-
bromo porphyrin cage compound (8, 220 mg, 0.15 mmol, 1 equiv.)
was dissolved in chloroform (15 mL) and methanol (7.5 mL). Zinc(II)
acetate dihydrate (119.60 mg, 0.54 mmol, 3.5 equiv.) was added and
the reaction mixture was stirred at r.t. for 1 h. After evaporating the
water mixture (100 mL). Ethyl acetate (110 mL) and sat. aq. NaHCO3 mixture to dryness, the residue was purified by silica gel column
(250 mL) were added upon which the color of the mixture turned
from green to red. The organic layer was washed with sat. aq.
chromatography using chloroform as the eluent. Precipitation from
DCM/n-heptane followed by washing with n-pentane (4 ×) and dry-
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ing in vacuo yielded the product (9, 229.4 mg, 0.15 mmol, 100 %,
racemate of two enantiomers) as a pink/purple solid.
1H-NMR (CDCl3, 500 MHz): ∂ 8.93–8.85 (m, 4H, ꢀ-pyrrole-H-3,4,13,14),
8.74–8.67 (m, 4H, ꢀ-pyrrole-H-8,9,18,19), 8.19 (d, 1H, ArH-22, J =
2.1 Hz), 8.01–7.96 (m, 2H, ArH-28,40), 7.95–7.91 (m, 1H, ArH-34), 7.87
(dd, 1H, ArH-24, J = 8.5, 2.1 Hz), 7.74–7.68 (m, 3H, ArH-30,36,42),
7.33–7.29 (m, 3H, ArH-31,37,43), 7.29–7.24 (m, 3H, ArH-29,35,41),
7.22 (d, 1H, ArH-25, J = 8.6 Hz), 6.97–6.91 (m, 6H, ArH-55,56), 6.44
(bs, 4H, ArH-54), 5.86–5.73 (m, 4H, ArH-48), 4.17–4.07 (m, 4H, CH2-
45a), 3.95–3.84 (m, 4H, CH2-45b), 3.55 (bs, 4H, CH2-50a), 3.47–3.39
(m, 4H, CH2-46a), 3.39–3.29 (m, 4H, CH2-50b), 3.17–3.05 (m, 4H, CH2-
46b), 1.07 (bs, 21H, TIPS); 13C{1H}-NMR (CDCl3, 126 MHz): ∂ 159.05
(ArC-26), 158.84–158.81 (ArC-32,44), 158.76 (ArC-38), 156.40–156.37
(C=O-51), 150.10–149.60 (ArC-2,5,7,10,12,15,17,20), 146.32–146.08
(ArC-47), 138.60 (ArC-22), 135.54 (ArC-28,40), 135.39 (ArC-34), 133.51
(ArC-24), 133.23 (ArC-53), 132.85 (ArC-21), 132.79–132.75 (ArC-
27,33,39), 131.50–130.50 (ArC-3,4,8,9,13,14,18,19), 129.37 (ArC-49),
129.31–129.22 (ArC-30,36,42), 128.51 (ArC-55,56), 127.86 (ArC-54),
119.94–119.82 (ArC-29,35,41), 116.07 (ArC-11), 115.91–115.88 (ArC-
6,16), 114.87 (ArC-23), 114.78 (ArC-48), 114.38 (ArC-1), 112.39–
112.27 (ArC-31,37,43), 111.92 (ArC-25), 107.10 (ArC-57), 88.95 (ArC-
58), 84.37 (C-52), 67.37–67.19 (CH2-46), 67.02–66.96 (CH2-45), 43.76
(CH2-50), 18.69 (TIPS-C), 11.33 (TIPS-C); MALDI-TOF: m/z 1587.5 [M
+ H]+; calcd. for C95H83N8O10SiZn: 1587.5.
1H-NMR (CDCl3, 500 MHz): ∂ 8.94–8.87 (m, 4H, ꢀ-pyrrole-H-3,4,13,14),
8.80–8.73 (m, 4H, ꢀ-pyrrole-H-8,9,18,19), 8.23 (d, 1H, ArH-22,
J = 2.5 Hz), 8.12–8.03 (m, 3H, ArH-28,34,40), 7.85 (dd, 1H, ArH-24,
J = 8.9, 2.6 Hz), 7.78–7.72 (m, 3H, ArH-30,36,42), 7.40–7.35 (m, 3H,
ArH-29,35,41), 7.35–7.31 (m, 3H, ArH-31,37,43), 7.21 (d, 1H, ArH-25,
J = 8.9 Hz), 6.99–6.90 (m, 6H, ArH-55,56), 6.77–6.72 (m, 4H, ArH-54),
6.11 (s, 3H, ArH-48(II, III, IV)), 6.10 (s, 1H, ArH-48(I)), 4.26–4.16 (m,
4H, CH2-45a), 4.09 (d, 4H, CH2-50a, J = 15.6 Hz), 4.06–3.94 (m, 4H,
CH2-45b), 3.66 (d, 4H, CH2-50b, J = 15.8 Hz), 3.55–3.46 (m, 4H, CH2-
46a), 3.32–3.23 (m, 4H, CH2-46b); 13C{1H}-NMR (CDCl3, 126 MHz):
∂ 158.75 (ArC-32,38,44), 158.04 (ArC-26), 156.84 (O=C-51), 150.23–
149.45 (ArC-2,5,7,10,12,15,17,20), 146.51–146.42 (ArC-47), 137.89
(ArC-22), 135.56 (ArC-28,34,40), 134.78 (ArC-21), 133.58 (ArC-53),
132.53 (ArC-27,33,39), 132.10 (ArC-24), 131.70–130.50 (ArC-
3,4,8,9,13,14,18,19), 129.89–129.79 (ArC-49), 129.41 (ArC-30,36,42),
128.54–128.46 (ArC-55,56), 128.05 (ArC-54), 119.85 (ArC-29,35,41),
116.51–116.28 (ArC-6,11,16), 115.19 (ArC-48), 114.11 (ArC-1), 113.68
(ArC-25), 112.33 (ArC-23), 112.11–112.04 (ArC-31,37,43), 84.68 (C-52),
67.45 (CH2-46), 66.94 (CH2-45), 44.26 (CH2-50); UV/Vis (CHCl3) λ/nm
(log (ε/M–1 cm–1)) 422 (5.64), 549 (4.29); MALDI-TOF; m/z: 1485.3
(M(79Br)+H)+, 1487.3 (M(81Br)+H)+; calcd. for C84H62BrN8O10Zn
1485.3 (79Br); 1487.3 (81Br).
Acetylene functionalized zinc porphyrin cage compound 11. Ar-
gon was led through THF (75 mL) for 30 min and compound 10
(372 mg, 0.23 mmol) and tetrabutylammonium fluoride trihydrate
(739.5 mg, 2.34 mmol) were added. The reaction mixture was stirred
in the dark at r.t. for 4 h and was then evaporated to dryness. The
residue was dissolved in DCM and this solution was washed with
water (3 × 50 mL), dried with Na2SO4, filtered and the solvents evap-
orated to dryness. The crude product was purified by silica gel col-
umn chromatography using 0.5 % MeOH in CHCl3 (v/v) as the elu-
ent. Precipitation from DCM/n-heptane followed by washing with
n-pentane (4 ×) and drying in vacuo yielded 11 (244 mg, 0.17 mmol,
73 %, racemate of two enantiomers) as a pink/purple solid.
Potassium triisopropylsilylacetylene trifluoroborate (TIPSA
BF3K). This compound was synthesized according to a modified
literature procedure.[16]A solution of triisopropylsilylacetylene
(2.0 mL, 8.9 mmol) was dissolved in degassed THF (20 mL) and
cooled to –78 °C. n-Butyllithium (5.6 mL, 8.9 mmol) was added drop-
wise and the reaction mixture was stirred for 1 hour. Trimethoxy-
borate (1.5 mL, 13 mmol) was added dropwise, the mixture was
stirred for 1 hour and then warmed up to –20 °C over the course
of 1 hour. Subsequently, a saturated solution of potassium bifluor-
ide (4.30 g, 55.1 mmol) in water was added under vigorous stirring.
The mixture was stirred at –20 °C for 1 hour, after which it was
warmed to room temperature. The solvent was evaporated and the
resulting white residue was dried under vacuum for 2 hours. The
residue was washed with subsequently acetone and hot acetone
and the filtrate was evaporated to yield a white solid, which was
re-precipitated from hot acetone/petroleum ether (80–100). After
cooling the suspension to –20 °C, the precipitate was filtered off
and the residue was washed with n-pentane. After drying in air and
under vacuum, the product was obtained as a white, fluffy solid
(1.0 g, 3.6 mmol, 40 %).
1H-NMR (CDCl3, 500 MHz): ∂ 8.91–8.87 (m, 4H, ꢀ-pyrrole-H-3,4,13,14),
8.77–8.71 (m, 4H, ꢀ-pyrrole-H-8,9,18,19), 8.24 (d, 1H, ArH-22,
J = 2.2 Hz), 8.10–8.03 (m, 3H, ArH-28,34,40), 7.89 (dd, 1H, ArH-24,
J = 8.6, 2.2 Hz), 7.77–7.72 (m, 3H, ArH-30,36,42), 7.38–7.34 (m, 3H,
ArH-29,35,41), 7.34–7.32 (m, 3H, ArH-31,37,43), 7.27 (d, 1H, ArH-25,
J = 8.7 Hz), 6.97–6.92 (m, 6H, ArH-55,56), 6.74–6.68 (m, 4H, ArH-54),
6.09–6.05 (m, 4H, ArH-48), 4.28–4.15 (m, 4H, CH2-45a), 4.07–3.96 (m,
8H, CH2-45b, CH2-50a), 3.63 (d, 4H, CH2-50b, J = 16.0 Hz), 3.54–3.47
(m, 4H, CH2-46a), 3.32–3.22 (m, 4H, CH2-46b), 3.05 (s, 1H, alk-
yneH-58); 13C{1H}-NMR (CDCl3, 126 MHz): ∂ 159.22 (ArC-26), 158.80–
158.74 (ArC-32,38,44), 156.80 (C=O-51), 150.18–149.55 (ArC-
2,5,7,10,12,15,17,20), 146.49–146.35 (ArC-47), 139.07 (ArC-22),
135.58–135.59 (ArC-28,34,40), 133.54 (ArC-24), 133.50 (ArC-53),
132.81 (ArC-21), 132.67–132.59 (ArC-27,33,39), 131.60–130.56 (ArC-
3,4,8,9,13,14,18,19), 129.83–129.67 (ArC-49), 129.36 (ArC-30,36,42),
128.53–128.47 (ArC-55,56), 128.04 (ArC-54), 119.85 (ArC-29,35,41),
116.32–116.13 (ArC-6,11,16), 115.16–114.97 (ArC-48), 114.46 (ArC-1),
113.37 (ArC-23), 112.18–112.07 (ArC-31,37,43), 111.70 (ArC-25),
84.66 (C-52), 83.76 (alkyneC-57), 76.12 (alkyneC-58), 67.45–67.40
(CH2-46), 66.95–66.93 (CH2-45), 44.21 (CH2-50); MALDI-TOF: m/z
1431.3 [M + H]+; calcd. for C86H63N8O10Zn: 1431.4.
1H-NMR ([D6]Acetone, 400 MHz): ∂ 1.08–1.10 (m, 18H, CH(CH3)2),
0.93–1.03 (m, 3H, CH(CH3)2); 19F-NMR ([D6]acetone, 380 MHz): ∂
135.5 (1:1:1:1, J = 34 Hz); 29Si-NMR ([D6]acetone, 80 MHz): ∂ (ppm)
–5.63 (s); 11B-NMR ([D6]acetone, 133 MHz) δ –2.15 (q, J = 36 Hz).
TIPS-protected acetylene functionalized zinc porphyrin cage
compound 10. Compound 9 (288 mg, 0.19 mmol), potassium triiso-
propylsilylacetylene trifluoroborate (111.7 mg, 0.39 mmol), cesium
carbonate (315.8 mg, 0.97 mmol), and [1,1′-bis(diphenylphosphino)
ferrocene]dichloropalladium(II) (39.8 mg, 0.05 mmol) were dissolved
in THF (42.75 mL) and water (2.25 mL) under an argon atmosphere.
The reaction mixture was refluxed for 16 h. After cooling to r.t., the
mixture was diluted with DCM and the solution was subsequently
washed with water (4 × 50 mL). The organic layer was dried with
MgSO4, filtered, and the solvents evaporated to dryness. The crude
product was purified by silica gel column chromatography using
1 % MeOH in CHCl3 (v/v) as the eluent yielding 10 (285.4 mg,
0.18 mmol, 93 %, racemate of two enantiomers) as a pink/purple
solid.
1,3-Diazidopropane. This compound was synthesized according to
a modified literature procedure.[17] Sodium azide-1-15N (490 mg,
7.43 mmol) and 1,3-dibromopropane (0.25 mL, 2.48 mmol) were dis-
solved in DMF (16 mL) and the reaction mixture was heated at 85 °C
for 20 h. After cooling to r.t., water (100 mL) was added to the mix-
ture and the resulting solution was extracted with diethyl ether. Sub-
sequently the organic layer was washed with water (5 × 100 mL) and
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brine (2 × 100 mL), dried with Na2SO4, filtered, and evaporated to
almost dryness to yield the product as a clear solution in diethyl
ether (96 %, based on 1H NMR integrals). Due to its instability the
product was directly used in the following synthesis step.
1H NMR (CDCl3, 500 MHz): ∂ 3.42 (t, 4H, N3CH2CH2CH2N3, J = 6.5 Hz),
1.87–1.80 (m, 2H, N3CH2CH2CH2N3); 13C NMR (CDCl3, 126 MHz):
∂ 48.58 (N3CH2CH2CH2N3), 28.47 (N3CH2CH2CH2N3); 15N NMR†
(CDCl3, 51 MHz): ∂ 247.78 (s, N*NN*CH2CH2CH2N*NN*), 211.36 (s,
N*NN*CH2CH2CH2N*NN*), 69.69 (s, N*NN*CH2CH2CH2N*NN*); †50 %
of the indicated N atoms are 15N-labeled.
1H-NMR ([D6]DMSO at 333.15 K, 500 MHz): ∂ 8.79 (dd, 2H, ꢀ-pyrrole-
H, J = 4.6, 1.2 Hz), 8.75–8.70 (m, 6H, ꢀ-pyrrole-H), 8.58–8.49 (m, 8H,
ꢀ-pyrrole-H) 8.50–8.47 (m, 2H, Triazole-H-58), 8.33 (t, 2H, ArH-22, J =
2.4 Hz), 8.19 (dd, 1H, ArH-24*, J = 8.5, 2.3 Hz), 8.18 (dd, 1H, ArH-24*,
J = 8.5, 2.3 Hz) 7.92–7.82 (m, 6H, ArH-28, 34, 40), 7.79–7.66 (m, 6H,
ArH-30, 36, 42), 7.56–7.48 (m, 6H, ArH-31, 37, 43), 7.46 (d, 1H, ArH-
25*, J = 8.7 Hz), 7.39 (d, 1H, ArH-25*, J = 8.9 Hz), 7.37–7.19 (m, 6H,
ArH-29, 35, 41), 7.05–6.94 (m, 12H, ArH-55, 56), 6.84–6.78 (m, 6H,
ArH-48(II,III,IV)), 6.20 (s, 1H, ArH-48(I)*), 6.19 (s, 1H, ArH-48(I)*), 4.43
(t, 4H, CH2-62, J = 6.8 Hz), 4.22–4.03 (m, 24H, CH2-45, CH2-50a), 3.65
(d, 8H, CH2-50b, J = 15.7 Hz), 3.51–3.40 (m, 8H, CH2-46a), 3.28–3.22
(m, 8H, CH2-46b), 2.51–2.46 (m, 2H, CH2-63); 13C NMR‡ ([D6]DMSO
at 333.15 K, 126 MHz): ∂ 158.40 (ArC-32, 38, 44), 156.00 (C=O-51),
155.86 (C=O-51), 149.37 (ArC-2, 5, 7, 10, 12, 15, 17, 20), 148.57 (ArC-
2, 5, 7, 10, 12, 15, 17, 20), 146.07 (C-57), 145.69 (ArC-47), 134.53
(ArC-28, 34, 40), 133.06 (ArC-53), 132.40 (ArC-27, 33, 39), 131.70 (ArC-
22), 130.21 (ArC-3, 4, 8, 9, 13, 14, 18, 19), 129.89 (ArC-3, 4, 8, 9, 13,
14, 18, 19), 129.81 (ArC-49), 128.83 (ArC-30, 36, 42), 127.79 (ArC-55,
56), 127.40 (ArC-54), 125.67 (ArC-24), 120.44 (CH-58), 119.16 (ArC-
29, 35, 41), 114.79 (ArC-48(II,III,IV)), 114.46 (ArC-48(I)), 112.62 (ArC-
25), 112.60 (ArC-31, 37, 43), 84.00 (C-52), 83.83 (C-52), 67.06 (CH2-
46), 66.66 (CH2-45), 46.44 (CH2-62), 43.18 (CH2-50), 29.28 (CH2-63);
15N{1H} NMR† ([D6]DMSO at 333.15 K, 51 MHz): ∂ 346.64 (Triazole-
N-61*), 346.56 (Triazole-N-61*), 248.62 (Triazole-N-59*), 248.57 (Tri-
azole-N-59*); UV/Vis (CHCl3/CH3CN 1:1, v/v) λ/nm (log (ε/M–1 cm–1))
426 (5.71), 559 (4.34), 597 (3.91); Accurate MALDI-TOF: m/z
2988.7613 (M)+; calcd. for C175H130N2015N2O2064Zn2: 2988.8355.
*Peaks belonging to the two different diastereoisomers that could
not be separated. ‡13C-NMR shifts obtained via HSQC and HMBC
spectra as no 13C{1H}-NMR spectrum was recorded. †50 % of the
indicated N atoms are 15N-labeled. For UV/Vis spectra, see text.
1,5-Diazidopentane. This compound was synthesized according to
a modified literature procedure.[17] Sodium azide-1-15N (486 mg,
7.37 mmol) and 1,5-dibromopentane (0.35 mL, 2.57 mmol) were
dissolved in DMF (15 mL) and the reaction mixture was heated at
80 °C for 16 h. After cooling to r.t., water (100 mL) was added to
the mixture and the resulting solution was extracted with diethyl
ether (2 × 150 mL). Subsequently the organic layer was washed
with brine (2 × 100 mL), dried with Na2SO4, filtered and the evapo-
rated to almost dryness to yield the product as a clear solution in
diethyl ether (75 %, based on 1H NMR integrals). Due to its instabil-
ity the product was directly used in the following synthesis step.
1H NMR (CDCl3, 500 MHz): ∂ 3.29 (t, 4H, N3CH2(CH2)3CH2N3, J =
6.8 Hz), 1.60–1.52 (m, 4H, N3CH2CH2CH2CH2CH2N3), 1.45–1.35 (m,
2H, N3(CH2)2CH2(CH2)2N3); 15N NMR† (CDCl3, 51 MHz): ∂ 242.94 (s,
N*NN*CH2(CH2)3CH2N*NN*), 205.87 (s, N*NN*CH2(CH2)5CH2N*NN*),
66.78 (s, N*NN*CH2(CH2)3CH2N*NN*); †50 % of the indicated
N atoms are 15N-labeled.
1,11-Diazidoundecane. This compound was synthesized according
to a modified literature procedure.[17] Sodium azide-1-15N (500 mg,
7.58 mmol, 3 equiv.) and 1,11-dibromoundecane (0.60 mL,
2.53 mmol, 1 equiv.) were dissolved in DMF (15 mL). The reaction
mixture was stirred at 80 °C for 20 h. After cooling to r.t., water
(150 mL) was added to the mixture and the resulting solution was
extracted with diethyl ether (2 × 100 mL). Subsequently, the organic
layer was washed with water (10 × 200 mL) and brine (2 × 200 mL),
dried with Na2SO4, filtered and evaporated to almost dryness to
yield the product as a clear solution in diethyl ether (45 %, based
on 1H NMR integrals). Due to its instability the product was directly
used in the following synthesis step.
Double porphyrin cage compound Zn2C5DC. To a mixture of
compound 11 (134.1 mg, 0.09 mmol) and copper(I) iodide (10.2 mg,
0.05 mmol) in freshly distilled THF (19 mL) and freshly distilled
MeCN (19 mL), DIPEA (15.80 μL, 0.09 mmol) was added. A solution
of 1,5-diazidopentane-15N-enriched in diethyl ether (51.2 μL, 0.83
M,
0.04 mmol) was added and the reaction mixture was stirred in the
dark at r.t. for 7 days. On days 2 and 4 additional CuI (20.26 mg and
10.44 mg, resp.) and DIPEA (2 × 15.80 μL) were added. The mixture
was concentrated in vacuo and the crude product was purified by
silica gel column chromatography using a gradient of 0.7–5 %
MeOH in CHCl3 (v/v) as the eluent. Precipitation from DCM/n-hept-
ane followed by washing with n-pentane (4 ×) and drying in vacuo
yielded Zn2C5DC (39.7 mg, 0.01 mmol, 31 %) as a pink/purple solid.
1H-NMR ([D6]DMSO at 333.15 K, 500 MHz): ∂ 8.80 (dd, 2H, ꢀ-pyrrole-
H, J = 4.7, 3.5 Hz), 8.76–8.72 (m, 6H, ꢀ-pyrrole-H), 8.59 (d, 2H,
ꢀ-pyrrole-H, J = 4.6 Hz) 8.55–8.52 (m, 6H, ꢀ-pyrrole-H), 8.48–8.45
(m, 2H, Triazole-H-58), 8.34 (t, 2H, ArH-22, J = 1.9 Hz), 8.20 (dd, 2H,
ArH-24, J = 8.6, 2.2 Hz), 7.91–7.86 (m, 6H, ArH-28, 34, 40), 7.79–7.67
(m, 6H, ArH-30, 36, 42), 7.54–7.46 (m, 6H, ArH-31, 37, 43), 7.44 (dd,
1H-NMR (CDCl3, 500 MHz): ∂ 3.26 (t, 4H, N3CH2(CH2)9CH2N3, J = 7 Hz),
1.62–1.56 (m, 4H, N3CH2CH2(CH2)7CH2CH2N3), 1.39–1.28 (m, 14H,
N3(CH2)2(CH2)7(CH2)2N3); 13C NMR (CDCl3, 126 MHz): ∂ 51.49 & 51.46
(N3CH2(CH2)9CH2N3), 29.44 & 29.41 (N3(CH2)3(CH2)5(CH2)3N3),, 28.8
(N3CH2CH2(CH2)7CH2CH2N3), 26.7 (N3(CH2)2CH2(CH2)5CH2(CH2)2N3;
15N NMR† (CDCl3, 51 MHz): δ = 248.5 (s, N*NN*CH2(CH2)9CH2N*NN*),
210.5 (s, N*NN*CH2(CH2)9CH2N*NN*), 71.9 (s, N*NN*CH2-
†
(CH2)9CH2N*NN*); 50 % of the indicated N atoms are 15N-labeled.
Double porphyrin cage compound Zn2C3DC. To a mixture of com-
pound 11 (135.5 mg, 0.09 mmol) and copper(I) iodide (9.36 mg, 2H, ArH-25*, J = 8.8, 5.9 Hz), 7.38–7.27 (m, 6H, ArH-29, 35, 41), 7.04–
0.05 mmol) in freshly distilled THF (19 mL) and freshly distilled MeCN
6.95 (m, 12H, ArH-55, 56), 6.83–6.78 (m, 8H, ArH-54), 6.27–6.23 (m,
6H, ArH-48(II,III,IV)), 6.18 (s, 1H, ArH-48(I)*), 6.16 (s, 1H, ArH-48(I)*),
4.41 (t, 4H, CH2-62, J = 6.9 Hz), 4.20–4.00 (m, 24H, CH2-45, CH2-50a),
3.68–3.57 (m, 8H, CH2-50b), 3.53–3.40 (m, 8H, CH2-46a), 3.27–3.20
(19 mL), DIPEA (15.80 μL, 0.09 mmol) was added. A solution of 1,3-
diazidopropane-15N-enriched in diethyl ether (74.3 μL, 0.57
M,
0.04 mmol) was added and the reaction mixture was stirred in the
dark at r.t. for 9 days. On days 2 and 4 additional CuI (12.08 mg and (m, 8H, CH2-46b), 1.85 (p, 4H, CH2-63, J = 7.3 Hz), 1.30–1.22 (m, 2H,
21.15 mg, resp.) and DIPEA (2 × 15.80 μL) were added. The mixture
was diluted with DCM (50 mL) and washed with water (3 × 50 mL).
CH2-64); 13C NMR‡ ([D6]DMSO at 333.15 K, 126 MHz): ∂ 158.27 (ArC-
32, 38, 44), 157.92 (ArC-26), 155.88 (C=O-51), 155.72 (C=O-51),
The organic layer was evaporated and the crude product was purified 149.20 (ArC-2, 5, 7, 10, 12, 15, 17, 20), 148.47 (ArC-2, 5, 7, 10, 12, 15,
by silica gel column chromatography using a gradient of 1–5 % of
MeOH in CHCl3 (v/v) as the eluent. Precipitation from DCM/n-heptane
followed by washing with n-pentane (4×) and drying in vacuo
yielded Zn2C3DC (44.8 mg, 0.02 mmol, 35 %) as a pink/purple solid.
17, 20), 145.84 (C-57), 145.55 (ArC-47(II, III, IV)), 145.42 (ArC-47(I)),
134.60 (ArC-28, 34, 40), 132.92 (ArC-53), 132.42 (ArC-21), 132.24
(ArC-27, 33, 39), 131.75 (ArC-22), 130.28 (ArC-3, 4, 8, 9, 13, 14, 18,
19), 129.91 (ArC-3, 4, 8, 9, 13, 14, 18, 19), 129.66 (ArC-49(II, III, IV)),
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129.51 (ArC-49(I)), 128.89 (ArC-30, 36, 42), 127.84 (ArC-55, 56), 127.41
(ArC-54), 125.68 (ArC-24), 122.16 (ArC-23), 120.17 (CH-58), 119.21 stirred at r.t. for 2 h. Subsequently, the organic layer was washed
(ArC-29, 35, 41), 115.13 (ArC-6, 11, 16), 114.82 (ArC-48(II,III,IV)), with sat. aq. NaHCO3 (200 mL) and water (200 mL), dried with
aq. HCl (6 M, 200 mL) was added and the reaction mixture was
114.67 (ArC-1), 114.47 (ArC-48(I)*), 114.36 (ArC-48(I)*), 112.67 (ArC- Na2SO4, filtered, and the solvents evaporated to dryness. The crude
25, 31, 37, 43), 83.83 (C-52), 83.71 (C-52), 67.07 (CH2-46), 66.69 (CH2- product was purified by silica gel column chromatography using
45), 48.68 (CH2-62), 43.19 (CH2-50), 28.33 (CH2-64), 28.27 (CH2-63); 1.5 % MeOH in CHCl3 (v/v) as the eluent. Precipitation from DCM/
15N{1H} NMR† ([D6]DMSO at 333.15 K, 51 MHz): ∂ 345.74 (Triazole-
n-heptane followed by washing with n-pentane (4 ×) and drying in
N-61*), 345.72 (Triazole-N-61*), 250.74 (Triazole-N-59*), 250.66 (Tri- vacuo yielded H4C3DC (43.16 mg, 15 μmol, 68 %) as a purple solid.
azole-N-59*); UV/Vis (CHCl3/CH3CN 1:1, v/v) λ/nm (log (ε/M–1 cm–1))
1H-NMR (CDCl3, 500 MHz): ∂ 8.80–8.76 (m, 4H, ꢀ-pyrrole-H), 8.76–
426 (5.95), 558 (4.57), 598 (3.94); Accurate MALDI-TOF: m/z
8.70 (m, 4H, ꢀ-pyrrole-H), 8.69–8.65 (m, 4H, ꢀ-pyrrole-H), 8.65–8.59
3016.8603 (M)+; calcd. for C177H134N2015N2O2064Zn2: 3016.8668.
(m, 4H, ꢀ-pyrrole-H), 8.40 (dd, 2H, ArH-22, J = 4.3, 2.4 Hz), 8.28–8.21
*Peaks belonging to the two different diastereoisomers that could
(m, 2H, ArH-24), 8.08–7.97 (m, 6H, ArH-28, 34, 40), 7.79–7.75 (m, 2H,
not be separated. ‡13C-NMR shifts obtained via HSQC and HMBC
Triazole-H-58), 7.76–7.63 (m, 6H, ArH-30, 36, 42), 7.38–7.22 (m, 12H,
spectra as no 13C{1H}-NMR spectrum was recorded. †50 % of the
ArH-29, 31, 35, 37, 41, 43), 7.26 (1H, ArH-25#), 7.20 (1H, ArH-25◊),
indicated N atoms are 15N-labeled.
7.01–6.90 (m, 12H, ArH-55, 56), 6.85–6.77 (m, 8H, ArH-54), 6.23–6.17
Double porphyrin cage compound Zn2C11DC. To a solution of
(m, 6H, ArH-48(II,III,IV)), 6.16 (s, 1H, ArH-48(I)#), 6.13 (s, 1H, ArH-
compound 11 (134.8 mg, 0.09 mmol) and copper(I) iodide (11.4 mg, 48(I)◊), 4.32 (t, 4H, CH2-62, J = 6.1 Hz), 4.28–4.20 (m, 6H, CH2-45a(II,
0.06 mmol) in freshly distilled THF (19 mL) and freshly distilled
MeCN (19 mL), DIPEA (15.80 μL, 0.09 mmol) was added. A solution
of 1,11-diazidoundecane-15N-enriched in diethyl ether (304 μL,
III, IV)), 4.23 (d, 8H, CH2-50a, J = 16.2 Hz), 4.20 (1H, CH2-45a(I)#), 4.12
(1H, CH2-45a(I)◊), 4.08–4.00 (m, 6H, CH2-45b(II, III, IV)), 3.96 (1H, CH2-
45b(I)#), 3.88 (1H, CH2-45b(I)◊), 3.80–3.67 (m, 8H, CH2-50b, J =
15.4 Hz), 3.55–3.42 (m, 6H, CH2-46a(II, III, IV)), 3.47 (1H, CH2-46a(I)#),
0.14 M, 0.04 mmol) was added and the reaction mixture was stirred
in the dark at r.t. for 6 days. On days 3 and 5 additional CuI 3.39–3.28 (m, 6H, CH2-46b(II, III, IV)), 3.37 (1H, CH2-46a(I)◊), 3.33 (1H,
(16.78 mg and 19.24 mg, resp.) and DIPEA (2 × 15.80 μL) were
added. The mixture was concentrated in vacuo and the crude prod-
ucts was purified by silica gel column chromatography using a gra-
dient of 0.5 %-5 % MeOH in CHCl3 (v/v) as the eluent. Precipitation
from DCM/n-heptane followed by washing with n-pentane (4 ×)
and drying in vacuo yielded Zn2C11DC (81.9 mg, 0.03 mmol, 62 %)
as a pink/purple solid.
CH2-46b(I)#), 3.27 (1H, CH2-46b(I)◊), 2.52–2.41 (m, 2H, CH2-63), –2.74
(s, 2H, NH); 13C NMR (CDCl3, 126 MHz): ∂ 158.86 (ArC-26), 158.76
(ArC-32, 38, 44), 157.07 (C=O-51), 147.84 (C-57), 146.62 (ArC-47),
135.78 (ArC-28, 34, 40), 133.21 (ArC-22), 131.90 (ArC-27, 33, 39),
132.20 (ArC-21), 129.85 (ArC-49), 129.63 (ArC-30, 36, 42), 128.53
(ArC-55, 56), 128.20 (ArC-54), 127.13 (ArC-24), 122.10 (ArC-23),
120.07 (CH-58), 119.83 (ArC-29, 35, 41), 115.30 (ArC-6, 11, 16) 115.27
(ArC-48(II,III,IV)), 115.01 (ArC-48(I)), 114.50 (ArC-1), 112.20 (ArC-25),
111.92 (ArC-31, 37, 43), 84.78 (C-52), 67.44 (CH2-46(II, III, IV)), 67.20
(CH2-46(I)#), 67.13 (CH2-46(I)◊), 66.90 (CH2-45(II, III, IV)), 66.87 (CH2-
45(I)#), 66.78 (CH2-45(I)◊), 46.65 (CH2-62), 44.43 (CH2-50), 30.54 (CH2-
63); 15N{1H}-NMR† (CDCl3, 51 MHz): ∂ 346.55 (Triazole-N-61*), 346.44
(Triazole-N-61*), 244.89 (Triazole-N-59*), 244.77 (Triazole-N-59*);
UV/Vis (CHCl3/CH3CN 1:1, v/v) λ/nm (log (ε/M–1 cm–1)) 418 (5.81),
514 (4.50), 546 (4.00), 590 (4.00), 6.43 (3.67); Accurate mass: m/z
2867.01780 (M+2H)+; calcd. for C175H136N2015N2O20: 2867.02419.
◊/#Peaks belonging to the two diastereoisomers. *Peaks belonging
to the two different diastereoisomers that could not be separated.
†50 % of the indicated N atoms are 15N-labeled.
1H-NMR ([D6]DMSO at 333.15 K, 500 MHz): ∂ 8.80 (dd, 2H, ꢀ-pyrrole-
H, J = 4.6, 2.1 Hz), 8.76–8.70 (m, 6H, ꢀ-pyrrole-H), 8.59 (t, 2H, ꢀ-
pyrrole-H, J = 4.2 Hz) 8.56–8.49 (m, 6H, ꢀ-pyrrole-H), 8.47–8.44 (m,
2H, Triazole-H-58), 8.36–8.34 (m, 2H, ArH-22), 8.23 (dt, 2H, ArH-24,
J = 8.7, 1.7 Hz), 7.92–7.88 (m, 6H, ArH-28, 34, 40), 7.79–7.68 (m, 6H,
ArH-30, 36, 42), 7.56 (d, 2H, ArH-25, J = 8.8 Hz), 7.54–7.41 (m, 6H,
ArH-31, 37, 43), 7.38–7.27 (m, 6H, ArH-29, 35, 41), 7.04–6.95 (m, 12H,
ArH-55, 56), 6.83–6.79 (m, 8H, ArH-54), 6.26–6.20 (m, 8H, ArH-48),
4.24 (t, 4H, CH2-62, J = 6.9 Hz), 4.21–4.04 (m, 24H, CH2-45, CH2-50a),
3.69–3.59 (m, 8H, CH2-50b), 3.53–3.38 (m, 8H, CH2-46a), 3.29–3.18
(m, 8H, CH2-46b), 1.79–1.71 (m, 4H, CH2-63), 1.19–1.11 (m, 14H, CH2-
64, 65, 66, 67); 13C NMR‡ ([D6]DMSO at 333.15 K, 126 MHz): ∂ 158.56
(ArC-32, 38, 44), 158.23 (ArC-26), 156.16 (C=O-51), 156.03 (C=O-51),
149.51 (ArC-2, 5, 7, 10, 12, 15, 17, 20), 148.75 (ArC-2, 5, 7, 10, 12, 15,
Double porphyrin cage compound H4C5DC. This compound was
synthesized as described for H4C3DC, using Zn2C5DC (45.53 mg,
17, 20), 146.13 (C-57), 145.80 (ArC-47), 134.57 (ArC-28, 34, 40), 15.1 μmol), CHCl3 (75 mL) and aq. HCl (6
M, 200 mL) Compound
133.23 (ArC-53), 132.81 (ArC-21), 132.56 (ArC-27, 33, 39), 131.70 H4C5DC was obtained as a purple solid (35.66 mg, 12.3 μmol, 81 %).
(ArC-22), 130.23 (ArC-3, 4, 8, 9, 13, 14, 18, 19), 129.93 (ArC-49),
1H-NMR (CDCl3, 500 MHz): ∂ 8.80–8.76 (m, 4H, ꢀ-pyrrole-H), 8.76–
129.87 (ArC-3, 4, 8, 9, 13, 14, 18, 19), 128.84 (ArC-30, 36, 42), 127.79
8.70 (m, 4H, ꢀ-pyrrole-H), 8.69–8.60 (m, 8H, ꢀ-pyrrole-H), 8.36 (t, 2H,
(ArC-55, 56), 127.34 (ArC-54), 125.56 (ArC-24), 122.52 (ArC-23),
ArH-22, J = 2.0 Hz), 8.33–8.28 (m, 2H, ArH-24), 8.06–7.98 (m, 6H,
120.10 (CH-58), 119.16 (ArC-29, 35, 41), 115.52 (ArC-6, 11, 16), 114.70
ArH-28, 34, 40), 7.77–7.61 (m, 6H, ArH-30, 36, 42), 7.65 (2H, Triazole-
(ArC-48), 112.66 (ArC-25, 31, 37, 43), 84.08 (C-52), 67.02 (CH2-46),
H-58), 7.37–7.23 (m, 12H, ArH-29, 31, 35, 37, 41, 43), 7.28 (1H, ArH-
66.61 (CH2-45), 48.93 (CH2-62), 43.20 (CH2-50), 28.84 (CH2-63), 28.08
25#), 7.25 (1H, ArH-25◊), 6.98 –6.91 (m, 12H, ArH-55, 56), 6.84–6.78
(CH2-62), 28.02 (CH2-64), 27.67 (CH2-65), 25.18 (CH2-66, 67);
(m, 8H, ArH-54), 6.21–6.17 (m, 6H, ArH-48(II,III,IV)), 6.16 (s, 1H, ArH-
15N{1H} NMR† ([D6]DMSO at 333.15 K, 51 MHz): ∂ 345.55 (Triazole-
48(I)#), 6.14 (s, 1H, ArH-48(I)◊), 4.30 (t, 4H, CH2-62, J = 6.9 Hz), 4.27–
N-61), 251.23 (Triazole-N-59); UV/Vis (CHCl3/CH3CN 1:1, v/v) λ/nm
4.15 (m, 6H, CH2-45a(II, III, IV)), 4.23 (d, 8H, CH2-50a, J = 16.0 Hz),
(log (ε/M–1 cm–1)) 426 (5.93), 559 (4.56), 597 (4.03); Accurate MALDI-
4.20 (1H, CH2-45a(I)#), 4.18 (1H, CH2-45a(I)◊), 4.08–3.93 (m, 6H, CH2-
TOF: m/z 3100.9959 (M)+; calcd. for C183H146N2015N2O2064Zn2:
45b(II, III, IV)), 4.00 (1H, CH2-45b(I)#), 3.95 (1H, CH2-45b(I)◊), 3.74 (d,
3100.9607. *Peaks belonging to the two different diastereoisomers
8H, CH2-50b, J = 15.7 Hz), 3.53–3.41 (m, 6H, CH2-46a(II, III, IV)), 3.47
that could not be separated. ‡13C-NMR shifts obtained via HSQC
(1H, CH2-46a(I)#), 3.37–3.27 (m, 6H, CH2-46b(II, III, IV)), 3.44 (1H, CH2-
and HMBC spectra as no 13C{1H}-NMR spectrum was recorded.
46a(I)◊), 3.32 (2H, CH2-46b(I)*), 1.94–1.87 (m, 4H, CH2-63), 1.38–1.33
†50 % of the indicated N atoms are 15N-labeled.
(m, 2H, CH2-64), –2.74 (s, 2H, NH); 13C NMR (CDCl3, 126 MHz):
Double porphyrin cage compound H4C3DC. Compound Zn2C3DC
(65.93 mg, 22 μmol) was dissolved in CHCl3 (100 mL) after which
∂ 158.75 (ArC-26), 158.72 (ArC-32, 38, 44), 156.90 (C=O-51), 147.70
(C-57), 146.61 (ArC-47), 135.80 (ArC-28, 34, 40), 133.31 (ArC-22),
Eur. J. Org. Chem. 2020, 7087–7100
www.eurjoc.org
7098
© 2020 The Authors. European Journal of Organic Chemistry
published by Wiley-VCH GmbH

Full Paper
doi.org/10.1002/ejoc.202001211
EurJOC
European Journal of Organic Chemistry
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131.90 (ArC-27, 33, 39), 131.33 (ArC-21), 129.81 (ArC-49), 129.51
(ArC-30, 36, 42), 128.51 (ArC-55, 56), 128.12 (ArC-54), 126.80 (ArC-
24), 122.30 (ArC-23), 119.79 (ArC-29, 35, 41), 119.14 (CH-58), 115.31
(ArC-48(II,III,IV)), 115.30 (ArC-6, 11, 16), 114.99 (ArC-48(I)), 114.40
(ArC-1), 112.04 (ArC-25), 111.95 (ArC-31, 37, 43), 84.77 (C-52), 67.45
(CH2-46(II, III, IV)), 67.21 (CH2-46(I)*), 66.87 (CH2-45), 49.90 (CH2-62),
44.44 (CH2-50), 29.62 (CH2-63), 23.41(CH2-64); 15N{1H}-NMR†
(CDCl3, 51 MHz): ∂ 344.66 (Triazole-N-61*), 344.61 (Triazole-N-61*),
247.82 (Triazole-N-59*); UV/Vis (CHCl3/CH3CN 1:1, v/v) λ/nm
(log (ε/M–1 cm–1)) 420 (5.81), 515 (4.45), 5,46 (4.12), 590 (4.15), 642
(3.78); Accurate mass: m/z 2895.04174 (M+2H)+; calcd. for
C177H140N2015N2O20: 2895.05549. ◊/#Peaks belonging to the two dia-
stereoisomers. *Peaks belonging to the two different diastereoiso-
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†
mers that could not be separated. 50 % of the indicated N atoms
are 15N-labeled.
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Double porphyrin cage compound H4C11DC. This compound was
synthesized as described for H4C3DC, using Zn2C11DC (39.03 mg,
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12.6 μmol), CHCl3 (50 mL) and aq. HCl (6
M, 200 mL). Compound
H4C11DC was obtained as a purple solid (34.59 mg, 11.6 μmol,
92 %).
1H-NMR (CDCl3, 500 MHz): ∂ 8.80–8.77 (m, 4H, ꢀ-pyrrole-H), 8.76–8.72
(m, 4H, ꢀ-pyrrole-H), 8.71–8.61 (m, 8H, ꢀ-pyrrole-H), 8.35–8.33 (m, 2H,
ArH-22), 8.33–8.31 (m, 2H, ArH-24), 8.07–8.01 (m, 6H, ArH-28, 34, 40),
7.75–7.66 (m, 6H, ArH-30, 36, 42), 7.56–7.52 (m, 2H, Triazole-H-58),
7.38–7.273 (m, 12H, ArH-29, 31, 35, 37, 41, 43), 7.35 (2H, ArH-25), 6.99
–6.91 (m, 12H, ArH-55, 56), 6.84–6.78 (m, 8H, ArH-54), 6.21–6.15 (m,
8H, ArH-48), 4.29 (2H, CH2-45a(I)), 4.23 (6H, CH2-45a(II, III, IV)), 4.23 (d,
8H, CH2-50a, J = 15.6 Hz), 4.16 (t, 4H, CH2-62, J = 7.2 Hz), 4.12–3.97
(m, 6H, CH2-45b(II, III, IV)), 4.09 (2H, CH2-45b(I)), 3.74 (d, 8H, CH2-50b,
J = 15.8 Hz), 3.57–3.44 (m, 6H, CH2-46a(II, III, IV)), 3.55 (2H, CH2-46a(I)),
3.39 (2H, CH2-46b(I)), 3.36–3.28 (m, 6H, CH2-46b(II, III, IV)), 1.73 (4H,
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CH2-63), 1.19–1.08 (m, 14H, CH2-64, 65, 66, 67), –2.73 (s, 2H, NH); 13
C
NMR (CDCl3, 126 MHz): ∂ 158.77 (ArC-32, 38, 44), 158.72 (ArC-26),
157.03 (C=O-51), 147.48 (C-57), 146.68 (ArC-47), 135.88 (ArC-28, 34,
40), 133.20 (ArC-22), 131.99 (ArC-21), 131.82 (ArC-27, 33, 39), 129.82
(ArC-49), 129.73 (ArC-30, 36, 42), 128.66 (ArC-55, 56), 128.25 (ArC-54),
127.20 (ArC-24), 122.54 (ArC-23), 119.96 (ArC-29, 35, 41), 119.04 (CH-
58), 115.47 (ArC-48(II,III,IV)), 115.46 (ArC-48(I)), 115.29 (ArC-6, 11, 16)
114.54 (ArC-1), 112.28 (ArC-25), 112.15 (ArC-31, 37, 43), 84.80 (C-52),
67.62 (CH2-46(II, III, IV)), 67.37 (CH2-46(I)), 67.20 (CH2-45(I)), 67.04 (CH2-
45(II, III, IV)), 50.40 (CH2-62), 44.42 (CH2-50), 30.34 (CH2-63), 26.60
(CH2-64, 65, 66, 67); 15N{1H}-NMR† (CDCl3, 51 MHz): ∂ 343.68 (Triazole-
N-61), 249.14 (Triazole-N-59); UV/Vis (CHCl3/CH3CN 1:1, v/v) λ/nm
(log (ε/M–1 cm–1)) 420 (5.90), 515 (4.58), 548 (4.08), 590 (4.08), 644
(3.78); Accurate mass: m/z 2979.14800 (M+2H)+; calcd. for
C183H152N2015N2O20: 2979.14939. †50 % of the indicated N atoms are
15N-labeled.
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Acknowledgments
The authors acknowledge support from the Netherlands Re-
search School Combination Catalysis, the European Research
Council (ERC Advanced Grant ENCOPOL-74092) and from the
Dutch National Science Organization NWO (Gravitation pro-
gram 024.001.035).
Keywords: Porphyrin compounds · Host–guest chemistry ·
Axial ligands
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Received: September 4, 2020
Eur. J. Org. Chem. 2020, 7087–7100
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7100
© 2020 The Authors. European Journal of Organic Chemistry
published by Wiley-VCH GmbH