Bridging and Conformational Control of Porphyrin Units through Non-Traditional Rigid Scaffolds

Article abstract of DOI:10.1002/chem.201904199

Connecting two porphyrin units in a rigid linear fashion, without any undesired electron delocalization or communication between the chromophores, remains a synthetic challenge. Herein, a broad library of functionally diverse multi-porphyrin arrays that incorporate the non-traditional rigid linker groups cubane and bicyclo[1.1.1]pentane (BCP) is described. A robust, reliable, and versatile synthetic procedure was employed to access porphyrin-cubane/BCP-porphyrin arrays, representing the largest non-polymeric structures available for cubane/BCP derivatives. These reactions demonstrate considerable substrate scope, from utilization of small phenyl moieties to large porphyrin rings, with varying lengths and different angles. To control conformational flexibility, amide bonds were introduced between the bridgehead carbon of BCP/cubane and the porphyrin rings. Through varying the orientation of the substituents around the amide bond of cubane/BCP, different intermolecular interactions were identified through single crystal X-ray analysis. These studies revealed non-covalent interactions that are the first-of-their-kind including a unique iodine-oxygen interaction between cubane units. These supramolecular architectures indicate the possibility to mimic a protein structure due to the sp³ rigid scaffolds (BCP or cubane) that exhibit the essential conformational space for protein function while simultaneously providing amide bonds for molecular recognition.

Full text of DOI:10.1002/chem.201904199

A Journal of
Accepted Article
Title: Bridging and Conformational Control of Porphyrin Units through
Non-Traditional Rigid Scaffolds
Authors: Nitika Grover, Gemma M. Locke, Keith J. Flanagan, Michael
H. R. Beh, Alison Thompson, and Mathias O. Senge
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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to this Accepted Article as a result of editing. Readers should obtain
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content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201904199
Link to VoR: http://dx.doi.org/10.1002/chem.201904199
Supported by

10.1002/chem.201904199
Chemistry - A European Journal
FULL PAPER
Bridging and Conformational Control of Porphyrin Units through
Non-Traditional Rigid Scaffolds
Nitika Grover,‡,a Gemma M. Locke,‡,a Keith J. Flanagan,a Michael H. R. Beh,a,b Alison Thompsonb and
Mathias O. Senge*a,c,d
Abstract: Connecting two porphyrin units in a rigid linear fashion,
without any undesired electron delocalization or communication
between the chromophores, remains a synthetic challenge. Herein, a
broad library of functionally diverse multi-porphyrin arrays that
incorporate the non-traditional rigid linker groups cubane and
bicyclo[1.1.1]pentane (BCP) is described. A robust, reliable, and
versatile synthetic procedure was employed to access porphyrin-
cubane/BCP-porphyrin arrays, representing the largest non-polymeric
structures available for cubane/BCP derivatives. These reactions
demonstrate considerable substrate scope, from utilization of small
phenyl moieties to large porphyrin rings, with varying lengths and
different angles. To control conformational flexibility, amide bonds
were introduced between the bridgehead carbon of BCP/cubane and
the porphyrin rings. Through varying the orientation of the substituents
around the amide bond of cubane/BCP, different intermolecular
interactions were identified through single crystal X-ray analysis.
These studies revealed non-covalent interactions that are the first-of-
their-kind including a unique iodine-oxygen interaction between
cubane units. These supramolecular architectures indicate the
possibility to mimic a protein structure due to the sp3 rigid scaffolds
(BCP or cubane) that exhibit the essential conformational space for
protein function while simultaneously providing amide bonds for
molecular recognition.
Introduction
these multi-porphyrin arrays using approaches such as: (a)
connecting the porphyrin units via phenylene, ethynyl, ethenyl or
alkane linkers2 or (b) connecting two or more meso-meso-linked
porphyrin units via oxidative fusing reactions.3 However, most of
the porphyrin arrays reported have problems such as poor
solubility, synthetic inaccessibility, and conformational
heterogeneity. In meso-meso-linked porphyrin arrays, the
porphyrin units are orthogonal to one another which can cause a
significant energy/charge sink. Furthermore, porphyrin arrays
joined directly by π-conjugated linkers exhibit significantly altered
UV-Vis spectra, indicating very strong electronic coupling, i.e. loss
of the characteristic of individual units due to delocalization of π-
electrons. Hence, it is necessary to design a molecule which can
predictably exhibit a desired energy- and/or electron-transfer
process that is achievable without effecting electronic
delocalization and/or an energy sink.1-3 A straightforward strategy
for avoiding any undesirable overlap of the π-systems may be to
attach two porphyrin skeletons through non-traditional rigid
scaffolds such as bicyclo[1.1.1]pentane (BCP) or cubane. These
saturated entities are transparent to UV-Vis light and exhibit
specific three-dimensional (3D) arrangements of the bridgehead
carbons. This positions the chromophoric units in a rigid and linear
fashion without any electron delocalization or conjugation such as
to potentially reduce the drawbacks previously outlined.4
Defined molecular architectures are a prerequisite for the logical
construction of multifunctional chemical systems. In carbon-
based covalent systems the individual effector units are typically
linked by either conjugating sp- or sp2-hybridized units or by
flexible sp3-hybridized bridges. The use of short, robust, and
spatially defined aliphatic linker units opens new avenues with
their potential application as molecular isolators, resistors and
rigid scaffolds, alongside the benefit of their inherent materials
properties.
Synthetic chemists are continually seeking to prepare new
rigid multi-porphyrin architectures due to their potential
applications as organic conducting materials, near-infrared (near-
IR) dyes, nonlinear optical materials, and molecular wires.1
number of synthetic strategies have been employed to access
A
[a]
[b]
Dr. N. Grover, G. M. Locke, Dr. K. J. Flanagan, M. H. R. Beh, Prof.
Dr. M. O. Senge
School of Chemistry, SFI Tetrapyrrole Laboratory
Trinity College Dublin, The University of Dublin
Trinity Biomedical Sciences Institute
152–160 Pearse Street, Dublin 2 (Ireland)
E-mail: sengem@tcd.ie, Twitter: @mathiassenge
M. H. R. Beh, Prof. A. Thompson
Department of Chemistry,
Dalhousie University
PO BOX 15000, Halifax, Nova Scotia B3H 4R2, Canada.
Prof. Dr. M. O. Senge
Physik Department E20, Technische Universität München,
James-Franck-Str. 1, 85748 Garching, Germany.
Prof. Dr. M. O. Senge
[c]
[d]
Institute for Advanced Study (TUM-IAS), Technische Universität
München, Lichtenberg-Str. 2a, 85748 Garching, Germany.
Figure 1. Schematic representation of synthesized porphyrin arrays.
‡ These authors contributed equally.
Supporting information for this article is given via a link at the end of
the document.
Herein, we report the first synthesis of porphyrin dimers that
utilize either BCP or cubane as a rigid linear scaffold (Figure 1).
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10.1002/chem.201904199
Chemistry - A European Journal
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This library of BCP/cubane porphyrin arrays contains some of the
largest non-polymeric structures available for cubane and BCP.
1,4-Disubstituted cubane is a well-known bioisostere of
para-substituted phenylene rings due to the similar distance
across the cube body diagonal of 2.72 Å vs. 2.79 Å for a benzene
ring.5 BCP is the smallest member of the bicyclic alkane family, in
terms of actual size rather than in terms of atoms present. Indeed,
BCP exhibits the shortest non-bonded distance between
bridgehead carbon atoms of 1.85 Å, which is closer in bond length
to ethyne (1.20 Å).6 The 3D, compact, electronically isolating, and
saturated structures of cubane and BCP enable them to avoid
undesirable π-π stacking which may lead to improved solubility of
chromophoric arrays. Despite their desirable well-defined
dimensions and rigid-rod geometries, the chemistry of these
moieties is undeveloped, particularly in terms of functionalization
or C–H-activation at the bridgehead carbons.7
through non-traditional BCP/cubane connectors as a test case for
multichromophoric and/or electroactive systems in general.
H
O
N
I
N
O
I
a
H
H
O
N
I
N
O
I
H
R
R
HN
O
O
O
OCH3
OCH3
N
O
N
O
I
I
b
H
H
HN
O
O
O
O
OCH3
O
OCH3
or
N
O
I
N
O
I
H
H
NH
OCH3
BCP and cubane are transparent to UV-Vis light and most
often their application is restricted to bioisosteres8 and crystal
engineering.9 The structural pre-organization and high thermal
stability of these compounds make them attractive candidates by
which to link two chromophoric units, but their use has been
neglected so far.7a,10 The limited use of these non-traditional
scaffolds is due to perceived complex synthetic procedures and
limited commercial supply chain of precursors. In addition,
appending rigid sp3 linkers as connectors between two
chromophoric units is synthetically demanding.
N
N
N
N
Zn
HN
O
H3CO
c
O
N
R
I
O
OCH3
N
N
Zn
HN
O
N
N
N
or
Zn
R =
N
N
M2+
O
O
N
N
or
=
d
M2+
N
N
N
N
Zn
Zn
N
N
N
N
Recent synthetic developments by Baran, Aggarwal and
ourselves include methods based on decarboxylative sp3 C–C
coupling to functionalize the bridgehead carbons of cubane and
BCP.11 Knochel and co-workers have also reported an efficient
method to synthesize 1,3-bisaryl substituted BCPs.12 Additionally,
amide bonds have been introduced at the bridgehead carbons of
cubane and BCP,13 however most of these reported moieties
Figure 2. Schematic representation of potential interactions between amide-
connected BCP/cubane derivatives: (a) H-bonding interactions; (b)
iodine•••oxygen interactions; (c) intermolecular axial interactions; (d) potential
interaction site with external metal ions.
w
ere used as bioisosteres8 or in crystal engineering.9 Yet, these
Results and Discussion.
compounds also have the potential to be utilized as molecular
building blocks. Moreover, cubane/BCP could be implemented as
rigid scaffolds linking two chromophores while providing a
synthetic handle for molecular recognition of small molecules or
ions.
Synthesis and characterization
The amide bond is crucially important as one of the main chemical
linkages found in biologically and pharmaceutically active
compounds.14 Amide bonds exhibit a planar trans configuration of
the N−H and C=O moieties and undergo very little rotation or
twisting around the bond due to amido-imido tautomerization. The
semi-rigid nature of amide bonds enables conformational control
over the molecular architecture of the compound they are part of
courtesy of hydrogen bonds and the coordination of metal ions
(Figure 2). To this end, the synthetic design of the current project
focused on the functionalization of the bridgehead BCP/cubane
carbons through amide bonds. Firstly, we started with the
synthesis of small rigid building blocks. Carboxylic acid
derivatives of cubane (1 and 2) were reacted15 with substituted
aryl amines 3−12 to access the amide derivatives 13−29. The use
of HATU/HOAt as an activating agent in presence of DIPEA in
DMF at 25 °C provided the most suitable synthetic reaction
condition by which to access amide substituted cubanes (13−29).
Building upon the progress made in synthetically accessing
these non-traditional rigid scaffolds, we envisioned appending
BCP/cubane between two porphyrin units in a conformationally
controlled manner. The utilization of semi-rigid amide bonds for
the attachment of a porphyrin skeleton to a rigid scaffold
introduces a controlled conformational flexibility into porphyrin
dyad(s). This allows significant modulation of the photophysical
properties in the porphyrin dyad(s) through the coordination of
transition metal(II) ions (Figure 2). By varying the distance and
angles between the two chromophores it is hoped that the extent
of the impact that cation coordination has on the photophysical
properties of a multi-chromophoric tweezer-like system can be
investigated.
As cubane and BCP are rigid and relatively inert scaffold,
the amide bonds are the only variable in the system and a true
measurement of their role in the conformational changes can thus
be undertaken. We herein present porphyrin units bridged
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10.1002/chem.201904199
Chemistry - A European Journal
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Generally, meta-/para-ethynyl-substituted anilines reacted more
efficiently with cubane-1,4-dicarboxylic acid (2) compared to
those with iodo substituents. Attempts to purify the crude cubane
compounds (13–18) via column chromatography, using silica gel,
were mostly unfruitful due to degradation of the product on the
silica gel. However, recrystallization from CH2Cl2 and excess
hexane proved very effective in removing any remaining aniline
and other impurities.
Ph
I
NH2
=
NH2
NH2
Ar
H2N
NH2
N
N
N
3
6
4
5
I
Ph
NH2
M
N
p-Tol
p-Tol
7, M = 2H
8, M = Zn
Ph
N
N
N
N
N
p-Tol
Ph
Zn
NH2
Ph
Zn
NH2
Ph
N
N
NH2
N
N
N
To demonstrate the potential value of this method, we next
examined the scope of meso-amine-substituted porphyrins in
Zn
-Tol
p
9
10
p-Tol
N
N
p-Tol
p-Tol
11
amide coupling reactions with cubane
1 and 2. 5-(4'-
NH2
N
N
N
aminophenyl)-10,15,20-triphenylporphyrin (7) and its zinc(II)
complex (8) were synthesized by mono-nitration of TPP followed
by reduction using procedures reported in the literature.16 Table 1
outlines the different reaction conditions employed to optimize the
amide coupling reaction between 1 and 7. The use of HATU/HOAt
in presence of DIPEA furnished the amide-coupled cubane-
porphyrin array 21 in 79% isolated yield. However, the use of
other activating agents such as DIC and ethylchloroformate in the
presence of TEA or DMAP also resulted in the formation of
product 21, albeit in lower yields of 43% and 31%, respectively
(Table 1). Reaction of porphyrin 8 with cubane 1 shows the neat
conversion of porphyrin 8 into the cubane porphyrin array 19 in
52% yield.
Ph
Zn
N
p-Tol
12
NH
I
HN
O
I
HN
O
CO2Me
I
CO2Me
O
NH
O
I
14, 37%
15, 39%
13, 61%
NH
O
NH
O
O
O
NH
O
O
NH
NH
NH
16, 31%
17, 67%
18, 47%
I
p-Tol
Ph
N
N
N
N
N
N
Ph
Zn
HN
Ph
M
HN
O
CO2Me
CO2R
N
N
O
23, 75%
p-Tol
p-Tol
Ph
19, M = Zn, R = Me, 52%
20, M = Zn, R = H, Quantitative
21, M = 2H, R = Me, 79%
22, M = 2H, R = H, Quantitative
Table 1. Test C−H activation reactions for the amide coupling of 4-
(methoxycarbonyl)cubane-1-carboxylic acid (1) with 5-(4'-aminophenyl)-
10,15,20-triphenylporphyrin (7).
N
N
N
Zn
N
Ph
HN
O
CO2Me
24, 56%
p-Tol
Ph
Ph
N
N
N
N
M1
Ph
HN
O
O
Ph
N
N
N
N
NH
M2
Ph
Ph
Ph
p-Tol
25, M1 = M2 = Zn, 28%
26, M1 = M2 = 2H, 56%
27, M1 = Zn, M2 = 2H, 55%
N
N
Ph
Zn
N
N
p-Tol
N
p-Tol
N
Zn
N
N
p-Tol
O
HN
O
NH
Cubane
(equiv.)
Activating
Agent
(equiv.)
Base
Sol.
Time
(h)
Yield
O
HN
O
p-Tol
NH
N
Zn
N
28, 36%
N
N
p-Tol
2.0
2.0
6.0
3.0
DIC (1.3)
ECFa (1.3)
DIC (1.3)
DMAP
NEt3
THF
48
65
75
65
25
N
p-Tol
Ph
N
Zn
N
N
29, 50%
CHCl3
THF
120
48
p-Tol
Ph
DMAP
DIPEA
Scheme 1. Amide coupling of cubane moieties 1 and 2 with amines 7−12.
HATU/HOAt
(1.3/1.3)
DMF
24
The reaction of 4-methoxycarbonylcubane-1-carboxylic acid (1)
with 4-iodoaniline (3) proceeded smoothly in yield of 61%.
Similarly, we could couple 4-ethynylaniline (4) and 4-
methoxycarbonylcubane-1-carboxylic acid (1) to access cubane
14 in a 37% yield. Further, cubane-1,4-dicarboxylic acid was
reacted with anilines 3 and 4 in above mentioned reaction
conditions to afford the cubanes 15 and 17 in yields of 39% and
67%. The preliminary substrate scope was investigated by
incorporating various combinations of structural motifs such as
meta-iodo/ethynyl-substituted anilines to access the amide
substituted cubanes 16 and 18. (Scheme 1).
aECF = Ethylchloroformate
Notable compounds 19 and 21 were subjected to further
functionalization. Base hydrolysis of zinc and free base
substituted porphyrin 19 and 21 yielded the carboxylic acid
derivatives of cubane-porphyrin array 20 and 22 respectively, in
quantitative yields. Similarly, the reaction of cubane-1,4-
dicarboxylic acid (2) with 7 and 8 resulted in access to the very
first porphyrin-cubane-porphyrin arrays 25 and 26, respectively.
Next we attempted the synthesis of Zn(II)porphyrin–cubane–free
base porphyrin array 27 via amide coupling reaction of amine
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substituted porphyrin 7 and carboxylic acid substituted cubane
porphyrin 20. Use of optimized reaction conditions resulted in
unsymmetric dimer 27 in a 55% yield.
To overcome the low solubility of phenyl substituted
porphyrins we changed to more soluble 4′-methylphenyl
substituted amine porphyrins for further reactions. [5-(4'-
Aminophenylacetylene)-10,20-bis(4'-methylphenyl)-15-
phenylporphyrinato]zinc(II) (9), [5-(4'-(4″-ethynylaniline)phenyl)-
10,20-bis(4'-methylphenyl)-15-phenylporphyrinato]zinc(II) (10),
[5-(3'-aminophenylacetylene)-10,20-bis(4'-methylphenyl)-15-
iodo/ethynyl groups, enabling H-bonding interactions between the
moieties, ultimately reducing the basicity and reactivity of the
amine. On the other hand, the cubane porphyrin dimer 29 was
accessed in a 50% yield due to the replacement of the small H-
bonding moieties with a porphyrin, preventing the reduced amine
basicity.
1) (COCl)2, DCM, 2h
O
O
NH
NH
O
Ar
0
40 ºC
CO2Me Or
RO2
C
CO2H
NH
Ar
Ar
2) NEt3, DCM, 2h
0
40 ºC
NH2
R = Me, 30
R = H, 31
Ar
phenylporphyrinato]zinc(II)
(11)
and
[5-(2'-
aminophenylacetylene)-10,20-bis(4'-methylphenyl)-15-
NH2
NH2
NH2
NH2
NH2
I
=
Ar
phenylporphyrinato]zinc(II) (12) were synthesized via modified
Sonogashira reaction conditions by reacting the corresponding
ethynyl anilines with [5-iodo-10,20-bis(4′-methylphenyl)-15-
phenylporphyrinato]zinc(II) in the presence of Pd(PPh3)2Cl2 (0.15
equiv.) and CuI (0.3 equiv.) in THF/NEt3. Amide coupling of 9 and
cubane 1 proceed efficiently and provide convenient access to
porphyrin 23 in isolated yield of 75%. Similarly, porphyrin 24 was
achieved in 56% yield by reacting porphyrin 10 with cubane 1.
Additionally, we tried the synthesis of cubane linked porphyrin
dimers by using meta- and ortho-substituted aniline 11 and 12.
Reaction of 11 and cubane 2 resulted into the formation of dimer
28 in 36% yield whereas ortho-dimer 29 was synthesized in 50%
yield via reaction of ortho-amine substituted porphyrin 12 and
cubane 2. This robust reaction demonstrated considerable scope,
from the utilization of small benzene rings to large porphyrin
systems with varying lengths and at different angles with respect
to the cubane plane.
The successful functionalization of cubane motivated us to
next attempt functionalization of the BCP using the same amide
coupling method. However, initial attempts to synthesize the
required BCP building blocks using HATU/HOAt, EDC, or DIC
were unsuccessful. This may be due to unstable BCP
intermediates capable of undergoing rearrangement to result in
ring-opened moieties. The BCP carboxylic acid was instead
reacted with (COCl)2/TEA, followed by the desired amine. Initially,
this reaction was conducted at room temperature similar to the
cubane analogues above, however, this was met with limited
success as the product was detected only in a small amounts by
1H NMR spectroscopy and mass spectrometry. This limited
success was mitigated by the use of an elevated reaction
temperature of 40 C for both steps, which resulted in a significant
increase in the product yields (49–77%) (Scheme 2). The crude
reaction mixtures were purified via recrystallization using a small
amount of CH2Cl2 and excess hexane to access the desired
products as white powders. The reaction of BCP 30 with aniline 3
and 4 resulted into the formation of 32 and 33 in 57% and 61%
yield. Next, the meta-phenyl substituted BCPs 34 and 35 were
synthesized via amide coupling reaction of BCP 30 and aniline 5
and 6, respectively. Amide coupling of BCP 31 and anilines 3–6
resulted into the formation of amide substituted BCPs 36–39. We
had found that the amide coupling reactions proceed optimally
with meta-/para-substituted aniline in presence of (COCl)2/TEA.
Unfortunately, amide coupling with ortho-substituted anilines
resulted in degradation. The ineffective ortho-substituted aniline
coupling may be caused by the proximity of the amine and
I
5
6
3
4
O
O
I
O
CO2Me
CO2Me
CO2Me
NH
I
NH
NH
34, 52%
32, 57%
33, 61%
O
CO2Me
O
NH
O
O
I
NH
NH
NH
I
NH
O
35, 49%
36, 72%
37, 77%
O
NH
O
O
NH
O
I
NH
NH
I
38, 52%
39, 68%
Scheme 2. Amide coupling at bridgehead carbon of BCP moiety and substrate
scope.
The synthesized BCP-based building blocks 32–39 were further
subjected to Pd-catalyzed cross-coupling reactions to yield
porphyrin-BCP conjugates (44–53), as shown in Scheme 3. Pd-
catalyzed cross-coupling reactions are versatile and
straightforward approaches for porphyrins to form carbon-carbon
bonds with a wide range of functionalities.1b,17 In contrast to
cubane,18 the BCP ring is more tolerant towards Pd-catalyzed
cross-coupling reactions.19 The first BCP-porphyrin array 44 was
afforded using Suzuki−Miyaura cross-coupling reaction of [5-
(4′,4′,5′,5′-tetramethyl-1′,3′,2′-dioxaborolan-2′-yl)-10,20-bis(4′-
methylphenyl)-15-phenylporphyrinato]zinc(II) (41)20 and BCP (33).
The same synthetic strategy was employed to access the meta
linked BCP porphyrin array 47 in 78% yield. Neat conversion of
41 into 44 and 47 encouraged us to try further attempts to
synthesize the porphyrin-BCP-porphyrin arrays. The BCP
porphyrins 50 and 52 were synthesized through Suzuki−Miyaura
cross-coupling reactions with [5-(4′,4′,5′,5′-tetramethyl-1′,3′,2′-
dioxaborolan-2′-yl)-10,20-bis(4′-methylphenyl)-15-
phenylporphyrinato]zinc(II) (41)20 and BCPs 36 and 39,
respectively. The isolated yields of meta-derivatives 47 and 52
were higher as compared to those of corresponding para
derivatives (44 and 50).
The porphyrin arrays 45 and 46 were synthesized using
Sonogashira cross-coupling reactions of [5-ethynyl-10,20-bis(4′-
methylphenyl)-15-phenylporphyrinato]zinc(II) (42) and [5-(4’-
ethynylphenyl)-10,20-bis(4′-methylphenyl)-15-
phenylporphyrinato]zinc(II) (43) and BCP 32. The Sonogashira
reactions did not proceed well for the synthesis of meta-
derivatives 48 and 53, while a copper-free modified Sonogashira
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10.1002/chem.201904199
Chemistry - A European Journal
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reaction
of
[5-iodo-10,20-bis(4′-methylphenyl)-15-
UV-Vis spectra of the chromophore arrays were recorded in
CHCl3 or THF at room temperature. The free base dimers 26 and
51 illustrate a typical etio-type porphyrin spectrum, having the
Soret and four Q-bands in decreasing intensity. The symmetrical
zinc dimers 25, 28, 29, 50, 52, and 53 showed an absorbance
maximum at 422 nm. The full width at half maxima (FWHM) of
these dimers is nearly equal to 5,10,15,20-tetraphenylporphyrin
(H2TPP) or its zinc(II) complex (ZnTPP), displaying no evidence
of exciton coupling between two porphyrin units, which supports
the suggested potential trans conformation of one porphyrin unit
with respect to another unit.22 The absorption spectra of ethynyl-
linked porphyrin dimers such as 28, 29, and 53 exhibited a 15–18
nm bathochromic shift compared to the phenylene-linked dimers
25 and 50 due to the π-extended ethynyl or phenylethynyl
moieties. The UV-Vis spectra of ethynyl-linked dimers (28, 29,
and 53) exhibit nearly the same FWHM and λmax as compared to
the precursor amine porphyrin (11 and 12). Similar λmax values of
monomers and dimers indicate the lack of through space or
through bond electronic communication between porphyrin units,
i.e. a trans orientation of the synthesized dimers.
phenylporphyrinato]zinc(II) (40)21 with BCPs 35 and 38
proceeded well to access the porphyrin-BCP arrays 48 and 53, in
73% and 46% yield, respectively. Detailed synthetic procedures
are described in the Supporting Information (SI). All newly
synthesized compounds were characterized by 1H NMR, 13C
NMR, UV-Vis, and IR spectroscopic methods as well as via
MALDI-TOF-MS spectrometry (see Figures S1-S135 in SI).
p-Tol
p-Tol
Pd(PPh3)4, K3PO4, DMF
or
Pd(PPh3)2Cl2, CuI, TEA/THF
O
N
N
N
N
N
N
CO2Me
X
Zn
NH
Ph
Zn
Ph
Ar
N
O
NH
O
N
Ar
Or
NH
O
Ar
Ar
p-Tol
p-Tol
Or
p-Tol
40, X = I
41, X = Bpin
42, X = C2
43, X = PhC2
CO2Me
p-Tol
NH
N
N
N
H
O
NH
O
Ar
Zn
p-Tol
H
N
N
N
N
NH
Zn
Ar
Ph
N
p-Tol
p-Tol
I
Ar
I
=
Single crystal X-ray analysis
-Tol
N
p
-Tol
p
O
O
The structure of compounds [5-(2'-aminophenylacetylene)-10,20-
bis(4'-methylphenyl)-15-phenylporphyrinato]zinc(II) (12), cubane
13, BCP 33, 35, 38, 45, 46 and dimethyl bicyclo[1.1.1]pentane-
1,3-dicarboxylate were determined using single crystal X-ray
diffraction analysis. Structural parameter tables and refinement
details (Table S1 and S2) are provided in the SI.23,24
N
N
CO2Me
N
N
N
CO2Me
Zn
NH
Ph
Zn
NH
Ph
N
N
44, 65%
45, 72%
N
p-Tol
p-Tol
Ph
-Tol
p
-Tol
p
N
O
Zn
N
N
N
N
CO2Me
N
Zn
NH
p-Tol
Ph
O
The crystal structure of cubane scaffold 13 illustrates two types of
intermolecular non-covalent interactions (Figure 3). The structure
exhibits a head-to-tail N1ꞏꞏꞏO1=C interaction at a distance of
2.853 Å with an angle of 175.4°. Furthermore, the iodo atom at
the para-position of the phenylene moiety exhibits a head-to-tail
halogen bond interaction with O2=C of the ester group with a
distance of 3.074 Å and an angle of 170.1°. The observed halogen
and hydrogen bond interactions are nearly orthogonal to each
other. Interestingly, the combined and repetitive intermolecular
N
CO2Me
NH
46, 58%
p-Tol
47, 78%
Ph
Ph
-Tol
p
N
-Tol
p
N
N
Zn
N
N
Zn
N
N
p-Tol
N
p-Tol
O
CO2Me
48, 73%
O
NH
CO2Me
NH
p-Tol
49, 52%
p-Tol
halogen and hydrogen bond interactions result in
a
N
N
N
O
M
NH
supramolecular 3D network between the cubane molecules
directed by the substituents at 1,4-bridgehead positions. There
are only a few reports of oxygen-iodine interactions,25 but the
specific 3D-orientation of cubane potentially favors this packing
pattern enabling it to access this unusual interaction.
Ph
N
N
N
M
N
NH
O
Ph
N
50, M = Zn, 52%
51, M = 2H, 60%
p-Tol
p-Tol
Ph
p-Tol
N
Ph
N
Zn
N
p-Tol
N
The crystal structures of BCP 33, 35, and 38 exhibit non-
covalent interactions between amide N-donors and C=O
acceptors within the crystal lattices. The nature of these
interactions are dependent upon the substitution pattern at the
phenylene ring. The crystal structure of para-substituted BCP
compound 33 reveals repetitive head-to-head N1ꞏꞏꞏO1=C
hydrogen bond interactions at distances of 2.970 Å (Figure 4). In
contrast to 33, the crystal structure of meta-substituted BCP 35
exhibits head-to-tail N1ꞏꞏꞏO2=C interactions at distances of 3.061
Å, leading to the formation of a non-covalently attached inversion-
centered dimer (Figures S138 and S139 in SI).
N
N
p-Tol
Zn
N
N
p-Tol
O
O
NH
NH
NH
NH
O
O
p-Tol
N
N
Zn
p-Tol
N
N
53, 46%
N
N
p-Tol
Zn
N
Ph
N
52, 73%
p-Tol
Ph
Scheme 3. Suzuki [Pd(PPh3)4, K3PO4, DMF
(Pd(PPh3)2Cl2, CuI, TEA/THF) reaction conditions and substrate scope.
] or Sonogashira coupling
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Figure 3. (a) Molecular structure of cubane 13. (b) Molecular arrangement of compound 13 in the crystal shows the non-covalent interactions between N1•••O1=C
and C=O2•••I1.
packing of this molecule further shows intermolecular head-to-tail
non-covalent DꞏꞏꞏA interactions between the acceptor Zn(II) metal
of the porphyrin and donor oxygen atom of the carbonyl group in
the amide moiety at a distance of 2.191 Å (Figure 5). This
particular interaction supports the proposed mechanism of
binding between a transition metal(II) and the C=O moiety of the
amide bond (vide infra). Similarly, the crystal structure of [5-(2'-
aminophenylacetylene)-10,20-bis(4'-methylphenyl)-15-
phenylporphyrinato]zinc(II) (12) also exhibits head-to-tail DꞏꞏꞏA
interactions, in this case between the donor N-atom of the amine
group from one porphyrin to the Zn(II) center of another (Figures
S145 and S146 in SI). This interaction is further supported by 1H
NMR spectra where the ortho-amine protons resonate at -0.58
ppm due to the shielding effect of the porphyrin ring current.
Along with the above mentioned non-covalent interactions, we
also observed a unique example of a porphyrin-based ion pair
complex, i.e. a pair of opposite charges held together by Columbic
interactions in the same solvent-shell.26 Although charge-
separated ion pair complexes are quite common in transition-
metal organometallic chemistry, ion pair complexes of phlorins
and porphodimethene-based systems are also known, this type
of interaction has not previously been observed for systems with
intact porphyrin cores.27 The crystal structure of porphyrin 45 is
Figure 4. (a) Molecular structure of compound 33. (b) Molecular arrangement
of compound 33 in the crystal shows the non-covalent interaction between
unique as it exhibits an ion pair interaction between an axial
N1•••O1.
chloride ligand and a [Et3NH]+ counter ion in the same unit cell
without disturbing the aromatic 18π-electron pathway (Figure 6).
Axial coordination results in displacement of the Zn(II) ion from
the 24-atom mean plane by 0.51 Å. The chloride and
Similarly, the crystal structure of bis-meta-substituted BCP
38 shows head-to-tail interactions at distances of 2.910 Å and
triethylammonium ions exhibit an ion pair interaction at a distance
forms a supramolecular 3D network/array (Figure S141 in SI).
of 3.043 Å. This is further supported by the 1H and 13C NMR
In nature, the 3D structures of proteins and other
biomolecules are controlled using H-bonding interactions
between trans N–H and C=O moieties of amino acids and these
spectra of compound 45 where the ratio of the porphyrin
derivative and [Et3NH]+ was found to be 1:1. To best of our
knowledge, it is the first example of a porphyrin-based charge-
3D architectures are responsible for their specific biological
separated ion pair complex. Figure 6 illustrates an example of the
functions. The substituents surrounding the amide bonds direct
[Et3NH]+ [porphyrin(ZnCl)]‒ ion pair in which a negatively charged
the non-covalent interactions in all of the above-mentioned crystal
porphyrin electrostatically interacts with positively charged
structures, and this indicates the possibility of potentially
triethylamine. In the crystal structure of 45, Zn(II) binds to the Cl‒
mimicking protein architecture with sp3 rigid scaffolds (BCP or
cubane). This would provide the conformational space essential
and the oxidation state of the Zn metal ion remains unchanged,
the chloride ion shows noncovalent interaction with [Et3NH]+. Most
for protein function, while simultaneously providing amide bonds
of the reported examples of chloride coordinated Zn(II)
for “substrate” coordination.
The crystal structure of the BCP-porphyrin 46 illustrates the
planar conformation of the macrocyclic core while the crystal
porphyrinoids either fall into the class of 16π electron
macrocycles
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Figure 5. (a) Molecular structure of compound 46. (b) Intermolecular head-to-tail interaction between the Zn metal of the porphyrin unit (acceptor) and the C=O
donor moiety of the amide bond.
or N-substituted porphyrins.27 In the case of N-substituted
porphyrins, the negative charge of the chloride is counter-
Conclusions
balanced by the positive charge on the tertiary core-N-atom
whereas in present case charge is counter-balanced by [Et3NH]+
and the porphyrin core remains intact making this an unique
example.
Structure elucidation of BCP-porphyrin 45 revealed the nearly
coplanar nature of the BCP-appended arm with respect to the
porphyrin plane. In contrast, BCP-porphyrin 46, which has a larger
distance between the BCP and porphyrin moieties, showed
orthogonal rotation of the phenyl rings with respect to the
porphyrin plane. Hence, 45 and its analogues show more promise
towards the synthesis of cubane/BCP-linked porphyrin systems
for electron/energy studies owing to their extended conjugation.
Similarly, the crystal structure of [5-(2'-aminophenylacetylene)-
We have designed, synthesized, and characterized bridgehead
substituted bicyclo[1.1.1]pentane and cubane derivatives via
amide coupling reactions. This work demonstrates a broad
substrate scope with over 35 new derivatives of cubane/BCP that
were synthesized in moderate to good yields. The single crystal
X-ray structures of small rigid linker motifs (13, 33, 35, and 38)
revealed supramolecular 3D networks with combined and
repetitive inter- and intramolecular H-bonding interactions.
Significantly, the crystal structure of cubane 13 showed an
unusual C=O2ꞏꞏꞏI1 interaction along with the usual N1ꞏꞏꞏO1=C
interaction to result in a 3D cage-like structure. The formation of
3D supramolecular network dependent on the structurally pre-
organized BCP/cubane scaffold in association with the semi-rigid
amide moieties.
10,20-bis(4'-methylphenyl)-15-phenylporphyrinato]zinc(II)
(12)
also exhibits head-to-tail DꞏꞏꞏA interactions, in this case between
the donor N-atom of the amine group from one porphyrin to the
Zn(II) center of another (Figures S145 and S146 in SI). This
interaction is further supported by 1H NMR spectra where the
ortho-amine protons resonate at -0.58 ppm due to the shielding
effect of the porphyrin ring current.
The crystal structure of porphyrin 45 illustrates a unique example
of porphyrin based ion-pair complex. Additionally, porphyrin 46
exhibits non-covalent DꞏꞏꞏA interactions between the acceptor
Zn(II) metal of the porphyrin and the donor oxygen atom of the
carbonyl group in the amide moiety in solid-state. A follow-up
study on selective detection of small molecular motifs via this type
of arrays is underway and will be reported separately.
Experimental Section
General information, instrumentation, synthesis of precursors,
crystallographic studies, and complete synthetic details of all
synthesized compounds are given in supporting information (SI).
General Procedures
General procedure 1 for amide condensation reactions. 4-
(Methoxycarbonyl)cubane-1-carboxylic acid (1) (1.0 equiv.) or
cubane-1,4-dicarboxylic acid (2) (1.0 equiv.) was placed in oven-
dried microwave vial and heated under vacuum. The reaction
flask was purged with argon, anhydrous DMF (0.25 mL) was
added and the reaction mixture was heated slightly to dissolve the
cubane. HATU (1.3/2.6 equiv.), HOAt (1.3/2.6 equiv.) and DIPEA
(4.0/8.0 equiv.) were then added and the reaction mixture was left
to stir at rt. for 30 minutes under argon. The amine (2.0 equiv.)
Figure 6. (a) Molecular structure of compound 45. (b) Charge separated ion
pair complex of porphyrin 45 and [HNEt3]+.
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was added under an argon flow to the flask alongside additional
anhydrous DMF (0.25 mL). The reaction mixture was stirred at rt.
for a further 24 h and then diluted with H2O.
(methoxycarbonyl)cubane-1-carboxylic acid (50 mg, 240 μmol),
4-iodoaniline (160 mg, 730 μmol), HATU (119 mg, 310 μmol),
HOAt (42.5 mg, 310 μmol) and DIPEA (17 μL) in anhydrous DMF
(0.5 mL). The product was extracted with a mixture of CH2Cl2
/MeOH (×3), dried over MgSO4 and the solvent removed under
reduced pressure, the crystals were washed with CH2Cl2 to
remove any remaining aniline and dried under reduced pressure.
The product was obtained as white crystals. Yield = 120 mg, 61%;
m.p. = 240–245 °C; Rf = 0.35 (SiO2, EtOAc:hexane, 2:3, v/v); 1H
NMR (600 MHz, DMSO-d6): δ = 9.77 (s, 1H), 7.63 (d, J = 8.6 Hz,
2H), 7.50 (d, J = 8.6 Hz, 2H), 4.29–4.22 (m, 3H), 4.18–4.15 (m,
3H), 3.64 (s, 3H) ppm; 13C NMR (151 MHz, DMSO-d6) δ = 171.3,
169.5, 138.8, 137.2, 121.8, 86.8, 57.8, 54.9, 51.3, 46.5, 46.0 ppm;
General procedure 2 for amide condensation reactions. In an
oven-dried microwave vial, a drop of DMF was added to the
solution
of
3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-
carboxylic acid (1.0 equiv.) (30) or bicyclo[1.1.1]pentane-1,3-
dicarboxylic acid (1.0 equiv.) (31) in CH2Cl2. Oxalyl chloride (1.2
equiv./2.2 equiv.) was added dropwise to above solution at 0 °C.
The reaction mixture was warmed to 40 °C and stirred for 2 h
under inert atmosphere. The reaction mixture was cooled to 0 °C.
NEt3 (3.0/6.0 equiv.) followed by substituted aniline (1.1/2.0
equiv.) were added slowly to the reaction mixture. The reaction
vial was warmed to 40 °C and stirred for 2 h under argon. The
solvent was evaporated in vacuo, crude reaction mixture was
recrystallized from CH2Cl2/hexane. The desired product was
separated as white crystalline material.
IR (neat)/cm-1: ν
̃ = 1720 (m), 1644 (m), 1581 (m), 1512 (m), 1390
(m), 1322 (m), 1219 (w), 1169 (w), 1088 (m), 824 (s), 792 (s), 710
(m), 598 (m); HRMS (APCI) m/z calcd. for C17H13INO3 [M-H]-
405.994565, found 405.993716.
Methyl-4-((4'-ethynylphenyl)carbamoyl)cubane-1-
General procedure
3 to synthesize meso-ethynylamine
carboxylate (14). Synthesized via General Procedure 1 from 4-
(methoxycarbonyl)cubane-1-carboxylic acid (15 mg, 70 μmol),
HATU (43.5 mg, 114 μmol), HOAt (15.5 mg, 114 μmol), DIPEA
(61 μL), 4-ethynylaniline (25 mg, 210 μmol) in anhydrous DMF
substituted porphyrins (9‒12). Iodo porphyrin (1.0 equiv.) was
placed in an oven-dried Schlenk flask and heated under vacuum.
The reaction flask was purged with argon and a mixture of
THF/NEt3 (3:1) was added. Argon was bubbled through the
solution for 15 min then ethynylaniline (5.0 equiv.), PdCl2(PPh3)2
(0.15 equiv.) and CuI (0.3 equiv.) were added. The reaction
mixture was heated to 70 °C and allowed to stir for 4 h. The
reaction mixture was diluted with CH2Cl2 (10 mL) followed by
removal of solvents in vacuo. Crude reaction mixture was purified
by silica gel column chromatography.
(0.5 mL). The product was extracted with
a mixture of
CH2Cl2/MeOH (×3), dried over MgSO4 and the solvent removed
under reduced pressure, the crystals were washed with CH2Cl2 to
remove any remaining aniline and dried under reduced pressure
to afford white crystals. Yield = 8 mg, 37%; m.p. = 243–247 °C; Rf
= 0.67 (SiO2, EtOAc:hexane, 1:1, v/v); 1H NMR (600 MHz, DMSO-
d6) δ = 9.86 (s, 1H), 7.69 (d, J = 8.5 Hz, 2H), 7.41 (d, J = 8.5 Hz,
2H), 4.26 (t, J = 4.6 Hz, 3H), 4.17 (t, J = 4.7 Hz, 3H), 4.07 (s, 1H),
3.64 (s, 3H) ppm; 13C NMR (151 MHz, DMSO-d6): δ = 171.2,
169.6, 139.6, 132.2, 119.3, 116.1, 83.6, 79.8, 57.8, 54.8, 51.3,
General procedure 4 for Sonogashira cross-coupling using
meso-ethynyl porphyrin. An oven-dried Schlenk tube charged
with ethynyl porphyrin (1.0 equiv.) and iodo-substituted cubane or
BCP was heated under vacuum. THF (5 mL) followed by NEt3 (2.5
mL) were added to reaction vessel. Argon was bubbled through
the solution for 10–15 min. and PdCl2(PPh3)2 (0.2 equiv.) and CuI
(0.3 equiv.) were added. The resulting reaction mixture was
heated at 40 °C and progress of the reaction was monitored by
TLC. Reaction mixture was filtered through a celite pad. Solvent
was evaporate in vacuo, crude reaction mixture was purified by
silica gel column chromatography.
46.6, 46.0 ppm; IR (neat)/cm-1: ν
̃ = 3252 (m), 2993 (w), 2950 (w),
1721 (s), 1645 (s), 1585 (s), 1509 (s), 1401 (m), 1336 (s), 1288
(m), 1221 (m), 1090 (s), 931 (w), 833 (s), 721 (s), 671 (m); HRMS
(APCI) m/z calcd. for C19H16NO3 [M+H]+ 306.112470; found
306.113336.
N1,N4-Bis(4'-iodophenyl)cubane-1,4-dicarboxamide
Synthesized via General Procedure from cubane-1,4-
(15).
1
dicarboxylic acid (46 mg, 240 μmol), 4-iodoaniline (263 mg, 1.2
mmol), HATU (119 mg, 310 μmol), HOAt (42.5 mg, 310 μmol) and
DIPEA (17 μL) in anhydrous DMF (0.5 mL). The reaction mixture
was diluted with H2O and CH2Cl2 causing white crystals to crash
out of the solution. The product was collected by vacuum filtration,
washed with CH2Cl2 to remove unreacted aniline, and dried under
reduced pressure to obtain white crystals. Yield = 55 mg, 39%;
m.p. = 257–259 °C; Rf = 0.37 (SiO2, hexane:EtOAc, 1:3, v/v); 1H
NMR (400 MHz, DMSO-d6): δ = 9.77 (s, 2H), 7.64 (d, J = 8.6 Hz,
4H), 7.52 (d, J = 8.6 Hz, 4H), 4.24 (s, 6H) ppm; 13C NMR (151
MHz, DMSO-d6) : δ = 169.9, 138.9, 137.2, 121.8, 86.7, 57.6, 46.3
General procedure 5 for Suzuki cross-coupling. To an oven-
dried Schlenk tube charged with porphyrin (2.1 equiv.), BCP linker
(1.0 equiv.) and K3PO4 (10.0 equiv.) anhydrous DMF (5 mL) was
added under inert atmosphere. The above solution was purged
with argon for further 15 min followed by addition of 0.2 equiv. of
Pd(PPh3)4. The reaction mixture was heated to 100 °C and
allowed to stir for 18 h. The solvent was removed in vacuo, crude
reaction mixture was dissolved in CH2Cl2 washed with NaHCO3
followed by brine. Organic layer was extracted with CH2Cl2.
Extracted organic phases were combined and solvent was
evaporated. The resulting crude reaction mixture was purified by
silica gel column chromatography.
ppm; IR (neat)/cm-1: ν
̃ = 3342 (w), 2985 (w), 1738 (w), 1645 (s),
1588 (m), 1505 (s), 1390 (s), 1324 (m), 1289 (w), 1243 (m), 1217
(w), 1061 (w), 1007 (m), 955 (w), 809 (s), 795 (m), 669 (m), 610
(w); HRMS (APCI) m/z calcd. for C22H15I2N2O2 [M-H]- 592.922847;
found 592.922494.
Synthesis of Cubane Linkers (13‒18)
Methyl-4-((4'-iodophenyl)carbamoyl)cubane-1-carboxylate
(13). Synthesized via General Procedure
1
from 4-
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N1,N4-Bis(3'-iodophenyl)cubane-1,4-dicarboxamide
(16).
N1,N4-Bis[4′-{(10″,15″,20″-triphenylporphyrinato)zinc(II)-5″-
yl}-phenyl]cubane-1,4-dicarboxamides (25). Synthesized via
General Procedure 1 from cubane-1,4-dicarboxylic acid (15 mg,
Synthesized via General Procedure
2 from cubane-1,4-
dicarboxylic acid (46 mg, 240 μmol), Oxalyl chloride (45 μL, 530
μmol), NEt3 (0.13 mL, 960 μmol) and 3-iodoaniline (64 μL, 530
μmol) in DMF (0.25 mL) and CH2Cl2 (1.5 mL). Solvents were
evaporated in vacuo and resulting solid was washed with CH2Cl2
to give the product as white crystals. Yield = 44 mg, 31%; m.p. =
243–248 °C; Rf = 0.37 (SiO2, EtOAc:hexane 3:1, v/v); 1H NMR
(600 MHz, DMSO-d6): δ = 9.75 (s, 2H), 8.13 (s, 2H), 7.70 (d, J =
8.2 Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.12 (t, J = 8.2 Hz, 2H), 4.25
(s, 6H) ppm; 13C NMR (151 MHz, DMSO-d6): δ = 169.9, 140.5,
131.7, 130.7, 127.7, 118.7, 94.4, 57.5, 46.3 ppm; IR (neat)/cm-1:
80
μmol),
[5-(4’-aminophenyl)-10,15,20-
triphenylporphyrinato]zinc(II) (8) (110 mg, 160 μmol), HATU (79
mg, 210 μmol), HOAt (28.5 mg, 210 μmol) and DIPEA (111 μL) in
anhydrous DMF (0.5 mL). H2O was added and the product was
extracted with CH2Cl2/MeOH (×3), washed with H2O (×4), dried
over MgSO4 and the solvent removed under reduced pressure.
The crude material was purified by column chromatography (SiO2,
CH2Cl2:(CH₃)2CO, 100:0 to 98.8:0.02). The product was obtained
as purple crystals. Yield = 35 mg, 28%; m.p. = >350 °C; Rf = 0.71
(SiO2, CH2Cl2:(CH₃)2CO, 20:1, v/v); 1H NMR (600 MHz,
CDCl3/THF-d8): δ = 8.90 (dd, J = 14.4, 4.5 Hz, 8H), 8.86 (s, 8H),
8.21–8.19 (m, 16H), 7.99 (s, 2H), 7.98 (s, 4H), 7.75–7.70 (m, 18H),
4.58 (s, 6H) ppm; 13C NMR (151 MHz, CDCl3/THF-d8): δ = 169.9,
150.2, 150.1, 143.4, 139.6, 137.2, 135.2, 135.2, 134.6, 134.6,
131.7, 127.3, 126.5, 120.8, 120.1, 117.8, 60.5, 58.9, 47.2 ppm; IR
ν̃ = 3200 (w), 2996 (w), 1738 (w), 1642 (s), 1580 (s), 1537 (m),
1474 (s), 1406 (m), 1333 (m), 1287 (w), 1242 (w), 1197 (w), 1092
(w), 996 (w), 947 (w), 901 (w), 865 (w), 845 (w), 772 (s), 721 (w),
681 (m), 657 (w), 615 (w), 572 (w); HRMS (APCI) m/z calcd. for
C22H17I2N2O2 [M+H]+ 594.937400; found 594.937107.
N1,N4-Bis(4'-ethynylphenyl)cubane-1,4-dicarboxamide (17).
(neat)/cm-1: ν
̃ = 1736 (w), 1660 (w), 1594 (w), 1486 (m), 1439 (w),
1398 (w), 1338 (w), 1235 (w), 1203 (w), 1174 (w), 1067 (w), 993
(s), 796 (s), 749 (m), 718 (m), 701 (s), 569 (w); UV-Vis (CHCl3):
Synthesized via General Procedure
1 from cubane-1,4-
dicarboxylic acid (30 mg, 157 μmol), HATU (156 mg, 410 μmol),
HOAt (56 mg, 410 μmol), DIPEA (219 μL) and 4-ethynylaniline
(55 mg, 470 μmol) in DMF (0.5 mL). The reaction mixture was
diluted with CH2Cl2 causing the product to crash out of the solution.
The product was collected by vacuum filtration, washed with
CH2Cl2 to remove any leftover aniline, and dried under reduced
pressure to obtain white crystals. Yield = 39 mg, 67%; m.p. = 247–
λ
max (log ε) 422 (6.19), 549 (4.80), 589 nm (4.15); HRMS (MALDI-
TOF) m/z calcd. for C98H62N10O2Zn2 [M]+ 1538.3640; found
1538.3662.
N1,N4-Bis[4′-{(10″,15″,20″-triphenylporphyrin)-5″-yl}-
phenyl]cubane-1,4-dicarboxamides (26). Synthesized via
General Procedure 1 from cubane 2 (50 mg, 69 μmol), 5-(4’-
aminophenyl)-10,15,20-triphenylporphyrin (7) (129 mg, 210 μmol),
HATU (34.1 mg, 90 μmol), HOAt (12.2 mg, 90 μmol) and DIPEA
1
252 °C; Rf = 0.74 (SiO2, EtOAc:hexane, 3:1, v/v); H NMR (600
MHz, DMSO-d6): δ = 9.84 (s, 2H), 7.71 (d, J = 8.5 Hz, 4H), 7.42
(d, J = 8.5 Hz, 4H), 4.26 (s, 6H), 4.08 (s, 2H) ppm; 13C NMR (151
MHz, DMSO-d6): δ = 169.9, 139.6, 132.2, 119.3, 116.1, 83.6, 79.8, (48 μL) in anhydrous DMF (0.5 mL). H2O was added and the
57.5, 46.3 ppm; IR (neat)/cm-1: ν
̃
= 3283 (m), 3218 (w), 3086 (w),
product was extracted with CH2Cl2 (×3), washed with H2O (×4),
dried over MgSO4 and the solvent removed under reduced
pressure. The crude material was purified by column
chromatography (SiO2, CH2Cl2:(CH₃)2CO, 100:0 to 98.8:0.02).
The product was obtained as purple crystals. Yield = 55 mg, 56%;
3001 (w), 1650 (s), 1590 (s), 1510 (s), 1404 (s), 1338 (s), 1290
(m), 1252 (s), 1090 (m), 944 (m), 877 (m), 840 (s), 770 (m), 667
(m), 619 (s); HRMS (APCI) m/z calcd. for C26H19N2O2 [M+H]+:
391.144104, found 391.143171.
1
m.p. = > 350 °C; Rf = 0.52 (SiO2, CH2Cl2:EtOAc, 40:1, v/v); H
N1,N4-Bis(3′-ethynylphenyl)cubane-1,4-dicarboxamide (18).
Synthesized via General Procedure
NMR (600 MHz, CDCl3): δ = 8.87 (d, J = 3.4 Hz, 8H), 8.85 (s, 8H),
8.23-8.22 (m, 16H), 8.02 (d, J = 7.8 Hz, 2H), 7.78-7.75 (m, 20H),
7.58 (s, 2H), 4.63 (s, 6H), -2.76 (s, 4H) ppm; 13C NMR (151 MHz,
CDCl3): δ = 189.7, 142.3, 135.4, 134.7, 127.9, 126.8, 120.4, 118.1,
1 from cubane-1,4-
dicarboxylic acid (15 mg, 78 μmol), HATU (77 mg, 200 μmol),
HOAt (27 mg, 200 μmol), DIPEA (108 μL) and 3-ethynylaniline
(27 μL , 234 μmol) in anhydrous DMF (1 mL). The reaction mixture
was diluted with H2O and CH2Cl2 causing white crystals to crash
out of the solution. The product was collected by vacuum filtration,
washed with CH2Cl2 to remove any leftover aniline, and dried
under reduced pressure to obtain white crystals. Yield = 36 mg,
47.3; IR (neat)/cm-1: ν
̃ = 1674 (w), 1584 (w), 1494 (w), 1397 (w),
1317 (w), 1190 (w), 965 (m), 798 (s), 753 (m), 722 (m), 701 (s);
UV-Vis (CH2Cl2): λmax (log ε) 422 (6.01), 518 (4.65), 554 (4.40),
593 (4.29), 649 nm (4.21); HRMS (MALDI-TOF) m/z calcd. for
C98H67N10O2 [M+H]+: 1415.5448, found 1415.5514.
50%; m.p.
= 297–302 °C (charred); Rf = 0.69 (SiO2,
EtOAc:hexane, 3:1, v/v); 1H NMR (600 MHz, DMSO-d6): δ = 9.76
N1-[4′-{(10″,20″,15″-triphenylporphyrinato)zinc(II)-5′-
yl}phenyl]-N4-[4′-{(10″,20″,15″-triphenylporphyrin)-5′-
(s, 2H), 7.86 (s, 2H), 7.69 (d, J = 7.9 Hz, 2H), 7.33 (t, J = 7.9 Hz,
2H), 7.16 (d, J = 7.9 Hz, 2H), 4.26 (s, 6H), 4.17 (s, 2H) ppm; 13
C
yl}phenyl]cubane-1,4-dicarboxamide (27). Synthesized via
General Procedure 1 from compound 22 (30 mg, 37 μmol), 5-(4-
aminophenyl)-10,15,20-triphenylporphyrinato zinc(II) (8) (31 mg,
45 μmol), HATU (43.5 mg, 114 μmol), HOAt (15.5 mg, 114 μmol)
and DIPEA (61 μL) in anhydrous DMF (0.5 mL). The reaction
mixture washed with brine and the products were extracted with
a mixture of CH2Cl2/THF (×3), dried over MgSO4 and the solvent
removed under reduced pressure. The crude material was
purified by column chromatography (SiO2, CH2Cl2:(CH₃)2CO,
NMR (151 MHz, DMSO-d6) δ = 169.9, 139.3, 129.1, 126.4, 122.4,
121.8, 120.2, 83.4, 80.4, 57.5, 46.3, 45.9 ppm; IR (neat)/cm-1: ν
3312 (w), 3218 (w), 3048 (w), 2999 (w), 1649 (m), 1603 (m),
1524(m), 1480 (s), 1406 (s), 1331 (s), 1298 (m), 1225 (m), 1086
(w), 950 (m), 859 (m), 782 (s), 683 (s), 599 (s); HRMS (APCI) m/z
calcd. for C26H19N2O2 [M+H]+ 391.144104; found 391.143981.
̃
=
Synthesis of Cubane Porphyrin Dimers (25–29)
This article is protected by copyright. All rights reserved.

10.1002/chem.201904199
Chemistry - A European Journal
FULL PAPER
100:0 to 98.8:0.02). The product was recrystallized from
CH2Cl2/CH3OH and obtained as purple crystals. Yield = 28 mg,
51%; m.p. = >350 °C; Rf = 0.64 (SiO2, (CH₃)2CO: CH2Cl2, 1:20,
v/v); 1H NMR (600 MHz, DMSO-d6): δ = 10.21 (s, 1H), 10.16 (s,
1H), 8.92 (s, 2H), 8.86–8.84 (m, 8H), 8.80–8.78 (m, 6H), 8.25–
8.15 (m, 20H), 7.83 (dd, J = 25.5, 5.4 Hz, 18H), 4.52 (s, 6H), -2.88
(s, 2H) ppm; 13C NMR (151 MHz, DMSO-d6): δ = 170.1, 149.5,
149.3, 149.2, 142.8, 141.2, 134.6, 134.4, 134.2, 134.2, 131.5,
128.1, 127.4, 127.0, 126.6, 120.3, 120.0, 117.9, 117.7, 46.6 ppm;
δ = 9.61 (d, J = 4.4 Hz, 4H), 8.91 (d, J = 4.4 Hz, 4H), 8.75 (dd, J
= 11.1, 4.4 Hz, 10H), 8.43 (d, J = 8.1 Hz, 2H), 8.15 (d, J = 6.4 Hz,
4H), 8.03 (d, J = 7.6 Hz, 8H), 7.95 (d, J = 6.8 Hz, 2H), 7.74 (dt, J
= 13.9, 7.0 Hz, 6H), 7.51 (d, J = 7.5 Hz, 8H), 7.37 (t, J = 6.8 Hz,
2H), 7.22 (t, J = 6.8 Hz, 2H), 3.81 (s, 6H), 2.60 (s, 12H) ppm; 13
C
NMR (151 MHz, THF-d8): δ = 170.0, 153.0, 151.8, 150.9, 146.7,
144.3, 141.1, 138.1, 135.4, 135.3, 133.7, 132.6, 132.4, 132.3,
130.8, 130.3, 128.2, 127.4, 124.0, 123.2, 120.7, 114.8, 101.1,
98.11, 91.6, 86.1, 59.7, 47.8, 21.6 ppm; IR (neat)/cm-1: ν
̃ = 3380
IR (neat)/cm-1: ν
̃
= 1658 (w), 1596 (w), 1489 (m), 1400 (w), 1320
(w), 2920 (w), 2187 (w), 1652 (m), 1574 (m), 1510 (m), 1313 (m),
1206 (m), 1063 (m), 995 (s), 944 (m), 794 (s), 755 (s), 715 (m),
596 (m); UV-Vis (THF): λmax (log ε) = 439 (5.92), 574 (4.53), 622
nm (4.72); HRMS (MALDI-TOF) m/z calcd. for C106H70N10O2Zn2
[M]+ 1642.4266; found 1642.4304.
(w), 1179 (w), 1071 (w), 1002 (m), 994 (m), 796 (s), 718 (m), 700
(s), 563 (w); UV-Vis (CHCl3): λmax (log ε) = 422 (5.79), 451 (5.66),
550 (4.43), 671 nm (4.81); HRMS (MALDI-TOF) m/z calcd. for
C98H64N10O2Zn [M]+ 1476.4505; found 1476.4495.
N1,N4-Bis[3′-{(10″,20″-bis(4′-methylphenyl)-15″-
Synthesis of BCP Linkers (32–39)
phenylporphyrinato)zinc(II)-5″-yl}phenylacetylene]cubane-
1,4-dicarboxamide (28). Synthesized via General Procedure 1
from cubane-1,4-dicarboxylic acid (10.5 mg, 55 μmol) (2),
porphyrin 11 (85 mg, 110 μmol), HATU (54.4 mg, 143 μmol),
HOAt (19.5 mg, 143 μmol) and DIPEA (76 μL) in anhydrous DMF
(0.5 mL). The reaction mixture was then washed with brine and
the products were extracted with a mixture of CH2Cl2/MeOH (×3),
dried over MgSO4 and the solvent removed under reduced
pressure. The crude material was purified by column
chromatography (SiO2, CH2Cl2:(CH₃)2CO,100:0 to 98.8:0.02).
The product was recrystallized from CH2Cl2/CH3OH and obtained
as purple crystals. Yield = 32 mg, 36%; m.p. = >350 °C; Rf = 0.33
(SiO2, CH2Cl2:(CH₃)2CO, 20:1, v/v); 1H NMR (600 MHz, CDCl3): δ
= 9.77 (d, J = 4.4 Hz, 4H), 8.97 (d, J = 4.4 Hz, 4H), 8.80 (dd, J =
21.3, 4.5 Hz, 8H), 8.19 (s, 1H), 8.16 (d, J = 4.4 Hz, 4H), 8.08 (d,
J = 7.2 Hz, 8H), 7.80–7.77 (m, 3H), 7.74–7.69 (m, 8H), 7.59 (s,
1H), 7.55 (d, J = 7.2 Hz, 8H), 7.52–7.49 (m, 3H), 4.50 (s, 6H), 2.71
(s, 12H) ppm; 13C NMR (151 MHz, CDCl3): δ = 169.7, 152.3, 150.7,
150.0, 149.9, 143.2, 140.1, 138.1, 137.1, 134.6, 134.5, 132.8,
131.9, 131.7, 130.5, 129.5, 127.4, 127.3, 126.5, 125.4, 122.7,
122.5, 121.9, 119.7, 98.8, 95.2, 93.9, 67.7, 58.8, 47.1, 21.7 ppm;
UV-Vis (THF): λmax (log ε) = 443 (6.13), 557 (4.65), 624 nm (4.94);
Methyl-3-((4'-iodophenyl)carbamoyl)bicyclo[1.1.1]pentane-1-
carboxylate (32). Synthesized according to General Procedure 2
using compounds 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-
carboxylic acid (30) (52.0 mg, 0.306 mmol), oxalyl chloride (32.0
μL, 0.378 mmol), NEt3 (130 μL, 0.934 mmol), 4-iodoaniline (77.8
mg, 0.355 mmol). The solvent was removed in vacuo, crude
product was recrystallized from CH2Cl2/hexane to afford titled
compound as off-white powder. Yield = 65 mg, 57%; m.p. =
1
206 °C; Rf = 0.75 (SiO2, hexane:EtOAc, 7:3, v/v); H NMR (400
MHz; CDCl3): δ = 7.60 (d, J = 8.8 Hz, 2H), 7.34 (br s, 1H), 7.30 (d,
J = 8.8 Hz, 2H), 3.70 (s, 3H), 2.36 (s, 6H) ppm; 13C NMR (100
MHz; CDCl3): δ = 169.5, 167.4, 137.8, 136.8, 121.6, 87.9, 52.4,
51.9, 40.0, 36.5 ppm; IR(neat)/cm-1: ν
̃ = 3279 (w), 1723 (m), 1653
(s), 1593 (m), 1526 (s), 1392 (m), 1310 (s), 1214 (s), 1044 (m),
+
812 (s), 785 (s), 691 (s); HRMS(APCI): m/z = calc. for C14H15INO3
[M+H]+, 372.0091; found 372.0091.
Methyl-3-((4′-ethynylphenyl)carbamoyl)bicyclo[1.1.1]
pentane-1-carboxylate (33). Synthesized according to General
Procedure
2
using
compounds
3-
(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (30)
(80.0 mg, 0.47 mmol), oxalyl chloride (47.0 μL, 0.56 mmol), NEt3
(200 μL, 1.4 mmol), 4-ethynylaniline (60 mg, 0.47 mmol). The
solvent was removed in vacuo, crude product was recrystallized
from CH2Cl2/hexane to afford titled compound as an off-white
powder. Yield = 77 mg, 61%; m.p. = 216 °C; Rf = 0.25 (SiO2,
hexane:EtOAc, 7:3, v/v); 1H NMR (400 MHz; CDCl3): δ = 7.49 (d,
J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.23 (brs, 1H), 3.69 (s,
3H), 3.03 (s, 1H), 2.36 (s, 6H) ppm; 13C NMR (100 MHz; CDCl3):
δ = 169.5, 167.1, 137.6, 133.0, 119.3, 118.1, 83.2, 52.4, 52.0,
IR (neat)/cm-1: ν
̃ = 1650 (w), 1598 (w), 1519 (w), 1483 (m), 1401
(w), 1339 (m), 1305 (w), 1207 (m), 1180 (w), 1064 (w), 996 (s),
845 (w), 792 (s), 714 (m), 701 (m), 682 (m), 569 (m); HRMS
(MALDI-TOF) m/z calcd. for C106H70N10O2Zn2 [M]+ 1642.4266;
found 1642.4296.
N1,N4-Bis[2′-{(10″,20″-bis(4′-methylphenyl)-15″-
phenylporphyrinato)zinc(II)-5″-yl}phenylacetylene]cubane-
1,4-dicarboxamide (29). Synthesized via General Procedure 1
from cubane-1,4-dicarboxylic acid (8.4 mg, 44 μmol) (2),
porphyrin 12 (65 mg, 87 μmol), HATU (43.5 mg, 114 μmol), HOAt
(15.5 mg, 114 μmol) and DIPEA (61 μL) in anhydrous DMF (0.5
mL). The reaction mixture was then washed with brine and the
products were extracted with a mixture of CH2Cl2/MeOH (×3),
dried over MgSO4 and the solvent removed under reduced
pressure. The crude material was purified by column
chromatography (SiO2, CH2Cl2:(CH₃)2CO, 100:0 to 98.8:0.02).
The product was recrystallized from CH2Cl2/CH3OH and obtained
as purple crystals. Yield = 36 mg, 50%; m.p. = >350 °C; Rf = 0.75
(SiO2, CH2Cl2:(CH₃)2CO, 40:1, v/v); 1H NMR (600 MHz, THF-d8):
40.1, 36.7 ppm; IR(neat)/cm-1: ν
̃ = 3281 (w), 3242 (m), 1718 (m),
1651 (m), 1587 (m), 1506 (m), 1312 (s), 1217 (s), 1043 (w), 943
(s), 826 (s), 721 (m), 677 (m); HRMS(APCI): m/z = calc. for
(C16H14NO3 [M-H]-) 268.0974; found 268.0984. calc. for
(C16H15ClNO3 [M+Cl] -) 304.0746; found 304.0754.
Methyl-3-((3'-iodophenyl)carbamoyl)bicyclo[1.1.1]pentane-1-
carboxylate (34). Synthesized according to General Procedure 2
using compounds 3-(methoxycarbonyl)bicyclo[1.1.1]pentane-1-
carboxylic acid (30) (80.0 mg, 0.47 mmol), oxalyl chloride (47.0
μL, 0.56 mmol), NEt3 (200 μL, 1.4 mmol), 3-iodoaniline (57.0 μL,
0.47 mmol). The solvent was removed in vacuo, crude product
This article is protected by copyright. All rights reserved.

10.1002/chem.201904199
Chemistry - A European Journal
FULL PAPER
was recrystallized from CH2Cl2/hexane to afford titled compound
116.8, 83.9, 80.4, 52.3, 39.2 ppm; IR(neat)/cm-1: ν
̃ = 3292 (w),
as white powder. Yield = 90 mg, 52%; m.p. = 198 °C; Rf = 0.35
(SiO2, hexane:EtOAc, 7:3, v/v); H NMR (400 MHz; CDCl3): δ =
3269 (w), 1649 (s), 1589 (m), 1522 (m), 1504 (m), 1402 (w), 1324
(m), 1246 (w), 825 (s), 705 (w), 616 (m); HRMS(APCI): m/z = calc.
for C23H19N2O2 [M+H]+ 355.1441; found 355.1437.
1
7.93 (t, J = 1.7 Hz, 1H), 7.56 (d, J = 12 Hz, 1H), 7.48 (d, J = 7.9
Hz, 1H), 7.14 (brs, 1H), 7.07(t, J = 8Hz, 1H), 3.74 (s, 3H), 2.40 (s,
6H) ppm; 13C NMR (100 MHz; CDCl3): δ = 169.4, 167.2, 138.4,
133.7, 130.5, 128.3, 118.8, 94.1, 52.4, 51.9, 39.9 ppm;
N1,N3-Bis(3′-ethynylphenyl)bicyclo[1.1.1]pentane-1,3-
dicarboxamide (38). Synthesized according to General
Procedure
2
using compounds bicyclo[1.1.1]pentane-1,3-
IR(neat)/cm-1: ν
̃ = 3276 (w), 1653 (s), 1525 (m), 1588 (s), 1525
dicarboxylic acid (31) (50 mg, 0.320 mmol), oxalyl chloride (60.0
μL, 0.640 mmol), NEt3 (0.28 mL, 2.70 mmol) and 4-ethynylaniline
(78 mg, 0.64 mmol). Titled compound was obtained by
recrystallization from CH2Cl2. Yield = 59 mg, 52%; m.p. = 240 °C;
1H NMR (400 MHz; DMSO-d6): δ = 9.85 (s, 2H), 7.84 (d, J = 1.6
Hz, 2H), 7.70 (d, J = 9.5 Hz, 2H), 7.30 (t, J = 8.0 Hz, 2H), 7.14 (d,
J = 9.8 Hz, 2H), 4.15 (s, 2H), 2.34 (s, 6H) ppm; 13C NMR (101
MHz; DMSO-d6): δ = 168.5, 139.1, 131.8, 120.2, 116.8, 83.8, 80.1,
(m), 1415 (s), 1302 (s), 1212 (s), 1043 (m), 883 (m), 775 (s), 653
(s); HRMS(APCI): m/z = calc. for C14H13INO3 [M-H]- 369.9940;
found 369.9954.
Methyl-3-((3′-ethynylphenyl)carbamoyl)bicyclo[1.1.1]
pentane-1-carboxylate (35). Synthesized according to General
Procedure
2
using
compounds
3-
(methoxycarbonyl)bicyclo[1.1.1]pentane-1-carboxylic acid (30)
(80.0 mg, 0.47 mmol), oxalyl chloride (47.0 μL, 0.56 mmol), NEt3
(200 μL, 1.4 mmol), 3-ethynylaniline (58 μL, 0.47 mmol). The
solvent was removed in vacuo, crude product was recrystallized
from CH2Cl2/hexane to afford titled compound as white powder.
Titled compound was obtained by recrystallization from CH2Cl2
/hexane. Yield = 62 mg, 49%; m.p. = 185 °C; Rf = 0.30 (SiO2,
hexane:EtOAc 7:3, v/v); 1H NMR (400 MHz; DMSO-d6): δ = 9.73
(s, 1H), 7.81 (t, J = 1.7 Hz, 1H), 7.65 (d, J = 9.4 Hz, 1H), 7.33 (t,
J = 7.9 Hz, 1H), 7.17 (dt, J = 7.8, 1.2 Hz, 1H), 4.17 (s, 1H), 3.64
(s, 3H), 2.30 (s, 6H) ppm; 13C NMR (101 MHz; DMSO-d6): δ =
169.8, 167.9, 139.2, 129.5, 127.2, 123.1, 122.3, 120.8, 83.7, 81.0,
52.4, 52.0, 40.6, 40.4, 40.1, 39.9, 39.8, 39.6, 39.4, 36.8 ppm;
52.4; IR (neat)/cm-1: ν
̃ = 3286 (w), 1651 (s), 1583 (m), 1540 (m),
1426 (s), 1307 (w), 1317 (w), 1217 (w), 792 (s), 686 (m) 643 (s);
HRMS(APCI): m/z = calc. for C23H19N2O2 [M+H]+ 355.1441; found
355.1441.
N1,N3-Bis(3’-iodophenyl)bicyclo[1.1.1]pentane-1,3-
dicarboxamide (39). Synthesized according to General
Procedure
2
using compounds bicyclo[1.1.1]pentane-1,3-
dicarboxylic acid (31) (50 mg, 0.320 mmol), oxalyl chloride (60.0
μL, 0.640 mmol), NEt3 (0.28 mL, 2.70 mmol) and 3-iodoaniline
(140 mg, 0.64 mmol). Titled compound was obtained by
recrystallization from CH2Cl2. Yield = 68%; m.p. = 320 °C; 1H NMR
(400 MHz; DMSO-d6): δ = 9.77 (s, 2H), 8.11 (t, J = 1.8 Hz, 2H),
7.79 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.12 (t, J = 8.0
Hz, 2H), 2.33 (s, 6H) ppm; 13C NMR (101 MHz; DMSO-d6): δ =
167.9, 140.0, 132.0, 130.6, 128.0, 119.1, 94.4, 51.8, 45.7 ppm;
IR(neat)/cm-1: ν
̃ = 3374 (w), 3193 (w), 1713 (m), 1672 (m), 1603
(m), 1406 (m), 1307 (s), 1213 (s), 1054 (w), 862 (w), 791 (s), 686
(s), 630 (s); HRMS(APCI): m/z = calc. for C16H14NO3 [M-H]-
268.0974; found. 268.0985.
IR(neat)/cm-1: ν
̃ = 3272 (w), 1652 (s), 1586 (m), 1522 (m), 1414
(m), 1310 (w), 1243 (w), 882 (w), 776 (s), 681 (s); HRMS(APCI):
m/z = calc. for C19H15I2N2O2 [M-H]- 556.9223; found 556.9074.
N1,N3-Bis(4′-iodophenyl)bicyclo[1.1.1]pentane-1,3-
dicarboxamide (36). Synthesized according to General
Procedure
2
using compounds bicyclo[1.1.1]pentane-1,3-
Synthesis of BCP Porphyrin Dimers (50–52)
dicarboxylic acid (31) (70 mg, 0.45 mmol), oxalyl chloride (85.0
μL, 0.99 mmol), NEt3 (0.37 mL, 2.7 mmol) and 4-iodoaniline (207
mg, 0.98 mmol). The reaction solvent was removed in vacuo and
the resulting residue was washed with CH2Cl2, and the insoluble
material was collected to yield the desired product as a white solid.
Yield = 180 mg, 72%; m.p. = 301 °C; 1H NMR (400 MHz; DMSO-
d6): δ = 9.72 (s, 2H), 7.63 (d, J = 8 Hz, 4H), 7.49 (d, J = 12 Hz,
4H), 2.31 (s, 6H) ppm; 13C NMR (100 MHz; DMSO-d6): δ = 168.3,
N1,N3-Bis[4′-{(10″,15″,20″-triphenylporphyrinato)zinc(II)-5″-
yl}-phenyl]bicyclo[1.1.1]pentane-1,3-dicarboxamides
(50).
Synthesized according to General Procedure 5 using BCP 36 (30
mg, 0.028 mmol), [5-(4′,4′,5′,5′-tetramethyl-1′,3′,2′-dioxaborolan-
2′-yl)-10,20-bis(4′-methylphenyl)-15-phenylporphyrinato]zinc(II)
(41) (40 mg, 0.055 mmol), K3PO4 (140 mg, 0.34 mmol) and
Pd(PPh3)4 (13 mg, 0.0056 mmol). Crude reaction mixture was
purified using silica gel column chromatography to yield desired
compound. Yield = 22 mg, 52%; m.p = 207 °C; Rf = 0.8 (SiO2,
CH2Cl2:EtOAc, 8:2, v/v); 1H NMR (400 MHz; CDCl3): δ = 8.89 (d,
J = 4.6 Hz, 4H), 8.85 (d, J = 4.6 Hz, 4H), 8.84 (s, 8H), 8.19 (d, J
= 7.6 Hz, 16H), 8.04 (d, J = 8.1 Hz, 4H), 7.73-769 (m, 20H), 2.71
(s, 6H) ppm; 13C NMR (101 MHz; CDCl3): δ = 169.6, 167.1, 150.4,
150.2, 149.8, 139.7, 137.1, 134.5, 134.4, 134.3, 132.2, 132.1,
131.9, 131.5, 129.8, 127.3, 126.5, 89.9, 89.7, 52.5, 52.0, 40.1,
138.9, 137.6, 122.4, 87.5, 52.1, 39.2 ppm; IR(neat)/cm-1: ν
̃ = 3321
(w), 1666 (s), 1584 (w), 1502 (s), 1387 (m), 1307 (m), 1004 (m),
814 (s), 661 (m); HRMS(APCI): m/z = calc. for C19H17I2N2O2
[M+H]+ 558.9374; found 558.9370.
N1,N3-Bis(4′-ethynylphenyl)bicyclo[1.1.1]pentane-1,3-
dicarboxamide (37). Synthesized according to General
Procedure
2
using compounds bicyclo[1.1.1]pentane-1,3-
dicarboxylic acid (31) (50 mg, 0.32 mmol), oxalyl chloride (60.0
μL, 0.64 mmol), NEt3 (0.28 mL, 2.7 mmol) and 4-ethynylaniline
(78 mg, 0.64 mmol). Titled compound was obtained by
recrystallization from CH2Cl2. Yield = 87 mg, 77%; m.p. = 326 °C;
1H NMR (400 MHz; DMSO-d6): δ = 9.84 (s, 2H), 7.70 (d, J = 8.5
Hz, 4H), 7.43 (d, J = 8.5 Hz, 4H), 4.10 (s, 2H) 2.35 (s, 6H) ppm;
13C NMR (100 MHz; DMSO-d6): δ = 168.4, 139.7, 132.7, 120.1,
21.5 ppm; IR (neat)/cm-1: ν
̃ = 2921 (w), 1736 (w), 1666 (w), 1529
(w), 1483 (w), 1339 (w), 1298 (w), 1208 (m), 998 (s), 796 (s), 719
(m); UV-Vis (CHCl3): λmax (log ε) = 424 (6.80), 551 (5.41), 590 nm
(4.82); HRMS(MALDI-TOF): m/z = calc. for C95H62N10O2Zn2 [M]+
1502.3640; 1502.3638 found.
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N1,N3-Bis[4′-{(10″,20″-bis(4-methylphenyl)-15″-
Keywords: Porphyrin arrays • Molecular tweezers •
Supramolecular • Cubane • Bicyclo[1.1.1]pentane
phenylporphyrin)-5″-yl}-phenyl]bicyclo[1.1.1]pentane-1,3-
dicarboxamides (51). Synthesized according to General
Procedure 5 using BCP 36 (23 mg, 0.042 mmol), [5-(4′,4′,5′,5′-
tetramethyl-1′,3′,2′-dioxaborolan-2′-yl)-10,20-bis(4′-
[1]
(a) T. Tanaka, A. Osuka, Chem. Soc. Rev., 2015, 44, 943–969; (b) M. O.
Senge, Chem. Commun., 2011, 47, 1943–1960; (c) T. Tanaka, B. S. Lee,
N. Aratani, M.-C. Yoon, D. Kim, A. Osuka, Chem. Eur. J., 2011, 17,
14400–14412; (d) N. Aratani, D. Kim, A. Osuka, Acc. Chem. Res., 2009,
42, 1922–1934.
methylphenyl)-15-phenylporphyrinato]zinc(II) (41) (58 mg, 0.083
mmol), K3PO4 (200 mg, 0.50 mmol), Pd(PPh3)4 (20 mg, 8.4 μmol).
Reaction mixture was heated at 100 °C for 12 h. The crude
reaction mixture was purified using silica gel column
chromatography, desired compound was eluted via using CH2Cl2:
(CH3)2CO, 8:2. Yield = 34 mg, 60%; m.p = 331 °C; Rf = 0.2 (SiO2,
CH2Cl2:EtOAc, 8:2, v/v); 1H NMR (600 MHz, CDCl3) δ = 8.92–8.85
(m, 16H), 8.25 (t, J = 7.6 Hz, 8H), 8.11 (d, J = 7.7 Hz, 8H), 8.03
(d, J = 7.9 Hz, 4H), 7.81–7.76 (m, 6H), 7.66 (s, 2H), 7.59 (d, J =
7.7 Hz, 8H), 2.77 (s, 6H), 2.74 (s, 12H), -2.74 (s, 4H) ppm; 13C
NMR (151 MHz, CDCl3) δ = 167.4, 144.2, 142.2, 139.3, 139.2,
138.8, 137.4, 136.9, 135.2, 134.5, 134.5, 127.4, 126.6, 120.3,
[2]
(a) S. Prathapan, T. E. Johnson, J. S. Lindsey, J. Am. Chem. Soc., 1993,
115, 7519–7520; (b) R. Paolesse, R. K. Pandey, T. P. Forsyth, l.
Jaquinod, K. R. Gerzevske, D. J. Nurco, M. O. Senge, S. Licoccia, T.
Boschi, K. M. Smith, J. Am. Chem. Soc., 1996, 118, 3869–2882; (c) M.
O. Senge, W. W. Kalisch, K. Ruhlandt-Senge, Chem. Commun., 1996,
2149–2150; (d) P. S. Bols, H. L. Anderson, Acc. Chem. Res., 2018, 51,
2083–2092.
[3]
(a) A. Tsuda, A. Osuka, Science, 2001, 293, 79–82; (b) N. K. S. Davis,
A. L. Thompson, H. L. Anderson, J. Am. Chem. Soc., 2011, 133, 30–31;
(c) M. O. Senge, X. Feng, Tetrahedron Lett., 1999, 40, 4165–4168; (d)
W. Auwärter, D. Écija, F. Klappenberger, J. V. Barth, Nat. Chem., 2015,
7, 105–120.
120.1, 119.1, 118.1, 52.4, 42.0, 21.6 ppm; IR (neat)/cm-1: ν
̃ = 2981
(w), 2832 (w), 1710 (m), 1595 (m), 1367 (w), 1219 (m), 1140 (m),
1093 (m), 1047 (m), 942 (m), 807 (s), 757 (s), 691 (m), 652 (m);
UV-Vis (CHCl3): λmax (log ε) = 423 (5.92), 519 (4.52), 555 (4.25),
594 nm (4.04), 651 nm (4.06); HRMS(MALDI-TOF): m/z = calc.
for C99H75N10O2 [M+H]+ 1434.5996; 1435.6091 found.
[4]
[5]
(a) K. F. Biegasiewicz, J. R. Griffiths, G. P. Savage, J. Tsanaktsidis, R.
Priefer, Chem. Rev., 2015, 115, 6719–6745; (b) M. D. Levin, P.
Kaszynski, J. Michl, Chem. Rev., 2000, 100, 169–234.
(a) P. E. Eaton, Angew. Chem. Int. Ed., 1992, 31, 1421–1436; (b) B. A.
Chalmers, H. Xing, S. Houston, C. Clark, S. Ghassabian, A. Kuo, B. Cao,
A. Reitsma, C. P. Murray, J. E. Stok, G. M. Boyle, C. J. Pierce, S. W.
Littler, D. A. Winkler, P. V. Bernhardt, C. Pasay, J. J. De Voss, J.
McCarthy, P. G. Parsons, G. H. Walter, M. T. Smith, H. M. Cooper, S. K.
Nilsson, J. Tsanaktsidis, G. P. Savage, C. M. Williams, Angew. Chem.
Int. Ed., 2016, 55, 3580–3585.
N1,N3-Bis[3′-{(10″,15″,20″-triphenylporphyrinato)zinc(II)-5″-
yl}-phenyl]bicyclo[1.1.1]pentane-1,3-dicarboxamides
(52).
Synthesized according to General Procedure 5 using BCP 39 (19
mg, 0.033 mmol), [5-(4′,4′,5′,5′-tetramethyl-1′,3′,2′-dioxaborolan-
2′-yl)-10,20-bis(4′-methylphenyl)-15-phenylporphyrinato]zinc(II)
(41) (50 mg, 0.066 mmol), K3PO4 (70 mg, 0.33 mmol) and
Pd(PPh3)4 (0.0066 mmol, 7.6 mg). Reaction mixture was heated
at 100 °C for 4 h. The crude reaction mixture was subjected to
silica gel column chromatography and titled compound was eluted
via CH2Cl2:EtOAc, 9:1. Yield = 37 mg, 73%; m.p = 220 °C; Rf =
0.35 (SiO2, CH2Cl2:EtOAc, 8:2, v/v); 1H NMR (400 MHz,
CDCl3/CD3OD) δ = 8.85–8.81 (m, 16H), 8.32(brs, 2H), 8.17 (d, J
= 4.3 Hz, 4H), 8.03 (d, J = 7.1 Hz, 10H), 7.95 (d, J = 7.6 Hz, 2H),
7.71–7.62 (m, 8H), 7.47 (d, J = 7.2 Hz, 8H), 2.65 (s, 12H), 2.44 (s,
6H) ppm; 13C NMR (101 MHz, CDCl3/CD3OD) δ = 150.1, 149.9,
149.7, 144.1, 140.3, 136.7, 134.4, 131.5, 131.4, 131.2, 127.0,
[6]
[7]
A. M. Dilmaç, E. Spuling, A. de Meijere, S. Bräse, Angew. Chem. Int. Ed.,
2017, 56, 5684–5718.
(a) G. M. Locke, S. S. R. Bernhard, M. O. Senge, Chem. Eur. J., 2019,
25, 4590–4647; (b) P. K. Mykhailiuk, Org. Biomol. Chem., 2019, 17,
2839–2849.
[8]
(a) T. A. Reekie, C. M. Williams, L. M. Rendina, M. Kassiou, J. Med.
Chem., 2019, 62, 1078–1095; (b) N. D. Measom, K. D. Down, D. J. Hirst,
C. Jamieson, E. S. Manas, V. K. Patel, D. O. Somers, ACS Med. Chem.
Lett., 2017, 8, 43–48; (c) Y. L. Goh, Y. T. Cui, V. Pendharkar, V. A.
Adsool, ACS Med. Chem. Lett., 2017, 8, 516−520; (d) K. C. Nicolaou, J.
Yin, D. Mandal, R. D. Erande, P. Klahn, M. Jin, M. Aujay, J. Sandoval, J.
Gavrilyuk, D. Vourloumis, J. Am. Chem. Soc., 2016, 138, 1698−1708.
(a) A. R.-Fortea, J. Kaleta, C. Mézière, M. Allain, E. Canadell, P. Wzietek,
J. Michl, P. Batail, ACS Omega, 2018, 3, 1293−1297; (b) K. J. Flanagan,
S. S. R. Bernhard, S. Plunkett, M. O. Senge, Chem. Eur. J., 2019, 25,
6941−6954.
[9]
126.6, 126.2, 120.0, 52.1, 39.0, 21.3 ppm; IR (neat)/cm-1: ν
̃ = 2920
(w), 1650 (w), 1603 (w), 1518 (w), 1477 (w), 1388(w), 1204 (w),
1065 (w), 992 (s), 794 (s), 721 (m), 693 (m); UV-Vis (CHCl3): λmax
(log ε) = 422 (6.80), 551 (5.55), 589 nm (5.08); HRMS(MALDI-
TOF): m/z calc. for C99H70N10O2Zn2 [M]+ 1562.4770; 1562.4253
found.
[10] A. de Meijere, L. Zhao, V. N. Belov, M. Bossi, M. Noltemeyer, S. W. Hell,
Chem. Eur. J., 2007, 13, 2503–2516.
[11] (a) J. M. Smith, S. J. Harwood, P. S. Baran, Acc. Chem. Res., 2018, 51,
1807–1817; (b) A. Fawcett, J. Pradeilles, Y. Wang, T. Mutsuga, E. L.
Myers, V. K. Aggarwal, Science, 2017, 357, 283–286; (c) S. S. R.
Bernhard, G. M. Locke, S. Plunkett, A. Meindl, K. J. Flanagan, M. O.
Senge, Chem. Eur. J., 2018, 24, 1026–1030.
[12] I. S. Makarov, C. E. Brocklehurst, K. Karaghiosoff, G. Koch, P. Knochel,
Angew. Chem. Int. Ed., 2017, 56, 12774–12777.
Acknowledgements
[13] (a) J. Wlochal, R. D. M. Davies, J. Burton, Org. Lett., 2014, 16, 4094–
4097; (b) M. J. Soth, G. Liu, K. Le, J. Cross, J. Philip (Board of regents,
the university of Texas system) US Patent WO 2018/107072 A1.
[14] (a) A. Graul, J. Castaner, Drugs Future, 1997, 22, 956–968; (b) R. B.
Merrifield, J. Am. Chem. Soc., 1963, 85, 2149–2154; (c) J. W. Bode, Curr.
Opin. Drug Disc. Dev., 2006, 9, 765–775.
This work was supported by grants from the Science Foundation
Ireland (SFI IvP 13/IA/1894), Irish Research Council
(GOIPG/2015/3700), the Ireland-Canada University Foundation
(M.H.R.B., Dobbin Atlantic Scholarship), and through an August-
Wilhelm Scheer Gastprofessor award (M.O.S., TUM).
[15] E. Valeur, M. Bradley, Chem. Soc. Rev., 2009, 38, 606–631.
[16] W. J. Kruper, T. A. Chamberlin, M. Kochanny, J. Org. Chem., 1989, 54,
2753–2756.
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[17] (a) L. J. Esdaile, M. O. Senge, D. P. Arnold, Chem. Commun., 2006,
4192–4194; (b) J. M. O’Brien, E. Sitte, K. J. Flanagan, H. Kühner, L. J.
Hallen, D. Gibbons, M. O. Senge, J. Org. Chem., 2019, 84, 6158–6173;
(c) S. Hiroto, Y. Miyake, H. Shinokubo, Chem. Rev., 2017, 117, 2910–
3043.
[18] S. Plunkett, K. J. Flanagan, B. Twamley, M. O. Senge, Organometallics,
2015, 34, 1408−1414.
[19] J. D. D. Rehm, B. Ziemer, G. Szeimies, Eur. J. Org. Chem., 2001, 2001,
1049−1052.
[20] A. G. Hyslop, M. A. Kellett, P. M. Lovine, M. J. Therien, J. Am. Chem.
Soc., 1998, 120, 12676–12677.
[21] A. Ryan, A. Gehrold, R. Perusitti, M. Pintea, M. Fazekas, O. B. Locos, F.
Blaikie, M. O. Senge, Eur. J. Org. Chem., 2011, 5817–5844.
[22] Similar observations were made for m-phthalic diamide-linked zinc(II)
bisporphyrinates: J. Jiang, X. Fang, B. Liu, C. Hu, Inorg. Chem., 2014,
53, 3298−3306.
[23] Crystals were grown according to established procedures,23a,b data
collection and refinements,23c-e and graphical illustrations utilized
standard software: (a) H. Hope, Prog. Inorg. Chem., 1994, 41, 1–19; (b)
M. O. Senge, Z. Naturforsch., 2000, 55b, 336–344; (c) Saint, Version
8.37a., Bruker AXS, Inc., Madison, WI, 2013; (d) SADABS, version
2016/2., Bruker AXS, Inc, Madison, WI, 2014; (e) APEX3, Version
2016.9-0., Bruker AXS, Inc., Madison, WI, 2016; (f) C. F. Macrae, I. J.
Bruno, J. A. Chisholm, P. R. Edgington, P. McCabe, E. Pidcock, L.
Rodriguez-Monge, R. Taylor, J. van de Streek, P. A. Wood J. Appl. Cryst.,
2008, 41, 466–470; (g) O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J.
A. K. Howard, H. Puschmann, J. Appl. Crystallogr., 2009, 42, 339–341;
(h) G. Sheldrick, Acta Cryst., 2015, A71, 3–8.
[24] CCDC 944514–1944521 contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge from The
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/structures.
[25] K. S. Shin, M. Brezgunova, O. Jeannin, T. Roisnel, F. Camerel, P. A.
Senzier, M. Fourmigué, Cryst. Growth Des., 2011, 11, 5337–5345.
[26] A. Macchioni, Chem. Rev., 2005, 105, 2039−2073.
[27] (a) Y. Yamamoto, Y. Hirata, M. Kodama, T. Yamaguchi, S. Matsukawa,
K. Akiba, D. Hashizume, F. Iwasaki, A. Muranaka, M. Uchiyama, P. Chen,
K. M. Kadish, N. Kobayashi, J. Am. Chem. Soc., 2010, 132,
12627−12638; (b) N. L. Bill, M. Ishida, S. Bahring, J. M. Lim, S. Lee, C.
M. Davis, V. M. Lynch, K. A. Nielsen, J. O. Jeppesen, K. Ohkubo, S.
Fukuzumi, D. Kim, J. L. Sessler, J. Am. Chem. Soc., 2013, 135,
10852−10862; (c) D. Kuila, D. K. Lavalee, C. K. Schauer, O. P. Anderson,
J. Am. Chem. Soc., 1984, 106, 448-450.
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
Synthesis and characterization of
novel porphyrin-cubane/BCP arrays
have been reported. The single crystal
analysis revealed supramolecular 3D
networks with combined and repetitive
inter- and intramolecular H-bonding
interactions.
Nitika Grover, Gemma M. Locke, Keith J.
Flanagan, Michael H. R. Beh, Alison
Thompson and Mathias O. Senge*
Page No. – Page No.
Bridging and Conformational Control
of Porphyrin Units through Non-
Traditional Rigid Scaffolds
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