Synthesis of substituted [8]cycloparaphenylenes by [2 + 2 + 2] cycloaddition

Article abstract of DOI:10.1021/ol500194s

A new modular approach to the smallest substituted cycloparaphenylenes (CPPs) is presented. This versatile method permits access to substituted CPPs, choosing the substituent at a late stage of the synthesis. Variously substituted [8]CPPs have been synthesized, and their properties analyzed. The structural characteristics of substituted CPPs are close to those of unsubstituted CPPs. However, their optoelectronic behavior differs remarkably due to the larger torsion angle between the phenyl units.

Full text of DOI:10.1021/ol500194s

Letter
pubs.acs.org/OrgLett
Synthesis of Substituted [8]Cycloparaphenylenes by [2 + 2 + 2]
Cycloaddition
Anne-Florence Tran-Van,† Elena Huxol,† Jonathan M. Basler,† Markus Neuburger,† Jean-Joseph Adjizian,‡
Chris P. Ewels,‡ and Hermann A. Wegner*,§
†Department of Chemistry, Basel University, St Johanns-Ring 19, CH-4056 Basel, Switzerland
‡IMN, CNRS, Universite
́ ̀
de Nantes, 2, rue de la Houssiniere, BP32229, F-44322 Nantes, France
§Institut Organische Chemie, Justus-Liebig Universitat, Heinrich-Buff-Ring 62, D-35392 Giessen, Germany
̈
S
* Supporting Information
ABSTRACT: A new modular approach to the smallest substituted
cycloparaphenylenes (CPPs) is presented. This versatile method
permits access to substituted CPPs, choosing the substituent at a late
stage of the synthesis. Variously substituted [8]CPPs have been
synthesized, and their properties analyzed. The structural character-
istics of substituted CPPs are close to those of unsubstituted CPPs.
However, their optoelectronic behavior differs remarkably due to the
larger torsion angle between the phenyl units.
trained aromatic macrocycles have attracted the attention
1
Sof chemists for over 80 years.
Recently, interest in
cycloparaphenylenes (CPP) has increased dramatically, as they
can be viewed as the shortest fragment of an armchair carbon
nanotube (CNT). The development of an efficient entry into
these compounds might allow the controlled preparation of
CNTs from a CPP precursor.2 Since the first synthesis of CPP
in 2008,3 several syntheses of various CPPs were proposed.4
Interest for such molecules is not limited to the potential for
CNT growth. Indeed, this class of molecules also finds
applications for complexation5 and possesses appealing
characteristics itself. Their properties have been both
theoretically and experimentally investigated.3,4k,5b,6 In order
to gain deeper insight into this class of strained molecules, it
would be of great interest to study the effect of substituents on
the properties of CPPs. Up to now very few substituted CPPs
Figure 1. Strategy toward the synthesis of substituted CPPs.
have been synthesized.7 Therefore, we aim to provide a highly
modular synthesis of substituted CPPs, allowing access to CPPs
with different functional groups for further chemistry. Besides
new host−guest possibilities, substituted CPPs could find
applications in nanoporous materials with a defined pore size,
and also as chemosensors.8
Structure 2 (Scheme 1) was synthesized according to
literature procedures.4f,o Building block 4 was obtained by
protecting dialkyne 3 with (3-cyanopropyl)dimethylsilyl
(CPDMS). This protecting group was chosen to facilitate the
separation of the non-, mono-, and diprotected products
obtained by this statistical reaction.12 The two building blocks 2
and 4 were subsequently assembled via Sonogashira reaction
producing differently substituted diynes 5 again in statistical
yields. Deprotection of 5a−c using TBAF furnished the key
intermediates 6a−c in moderate to good yields. Performing the
reaction with K2CO3 in MeOH/THF led to partial degradation.
With TBAF the reaction proceeded extremely fast. The
Initially, our strategy relied on a [2 + 2 + 2] cycloaddition
reaction. The strain required should have been compensated by
the aromaticity gained.9 But unexpectedly, no attempt in this
direction was successful. Therefore, a modified approach has
been applied (Figure 1) still relying on a [2 + 2 + 2]
cycloaddition reaction, as it allows introduction of substituents
in a late stage of the synthesis. A building block containing
methoxymethyl (MOM) protected cyclohexanediol units,
suggested by Vogtle10 and later by Hopf and Sankararaman11
̈
and recently applied by Itami,4f,i,j,o provided the required
curvature.
Received: January 20, 2014
Published: March 5, 2014
© 2014 American Chemical Society
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Scheme 1. Synthesis of the Macrocyclic Precursor
reaction required careful monitoring in order to be stopped
before degradation occurred. This improved method was also
amenable to a larger scale (12 mmol). With monomer
fragments 6a−c available, macrocycles 7a−c were prepared
by dimerization via Sonogashira coupling. Treatment of 6a−c
with Pd(PPh3)4 and copper iodide in THF (38 mM) in the
presence of diisopropylamine generated the desired macro-
cycles 7a−c in yields between 4 and 11%. Suspension in the
ethylacetate/hexane mixture and filtration gave the pure
product after an initial purification by column chromatography
on silica. Halving the mixture concentration did not change the
resultant yield. However, doubling the concentration dropped
the yield to 2%. A single crystal was obtained and measured by
X-ray spectroscopy. The solid state structure showed a unique
rectangular shaped macrocycle shown in Figure 2a.
Table 1. [2 + 2 + 2] Cycloaddition
applied with solid alkynes as they are used in excess. For this
intermediate, a solid state structure was also determined
(Figure 2b). The reaction proceeds for a wide range of
precursors, offering a reliable method of functionalization for
this type of molecule.
The final step of the synthesis of substituted CPPs involved
deprotection−elimination and aromatization of macrocycle 8.
Various conditions were tried to achieve the target compound,
based on the nonmicrowave conditions initially developed by
Itami et al.4m Using sodium bisulfate in DMSO/m-xylene at
130 °C under air, the aromatization reaction produced the
desired CPPs. Differently substituted CPPs were obtained with
this method (Scheme 2). The larger torsion angle (see
discussion below) could account for the low yield in this last
step.
Figure 2. (a) Crystal structure of macrocycle 7a (solvent omitted), (b)
crystal structure of 8b (solvent omitted), (c) crystal structure of 9d
(for a−c ORTEP drawings, hydrogen omitted), and (d) packing
structure of 9d.
We then investigated the [2 + 2 + 2] cycloaddition reaction
on macrocycles 7a−c. The reaction was performed under
microwave irradiation (100 °C, 6 h) with Wilkinson’s catalyst
and an excess of alkyne. The results with various alkynes are
summarized in Table 1. The reaction proceeded in moderate to
very good yields. Purification was done by simple filtration and
washing of the reaction mixture, affording easily the desired
pure product. However, this method of purification cannot be
A suitable single crystal of 9d was obtained by slow
evaporation of a solution in dichloromethane and measured
by X-ray spectroscopy (Figure 2c). In the solid state only the
syn-isomer (R-groups on the same side of the ring) is observed.
1
The H NMR shows for all CPPs prepared sharp lines of only
one species meaning that only one isomer is present as rotation
is too high in energy according to preliminary calculations. The
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respectively. The results show that side-group functionalization
can vary the ring strain within around 11 kcal/mol from the
unsubstituted [8]CPP ring strain (62.9 kcal/mol). This range is
comparable with the change in ring strain from [6]CPP to
[8]CPP.
Scheme 2. Aromatization Reaction
The optical properties (UV−vis absorption and fluores-
cence) of the different substituted CPPs 9 were measured
(Figure 3). The absorbance maxima (λabs) of the substituted
ring has a round shape with a diameter of 10.95 Å (average
calculated between the ipso-bonds and the centers of the phenyl
rings). This value is comparable to the diameter calculated for
[8]CPP.4k Bond lengths are 1.400, 1.379, and 1.489 Å for
CipsoCortho, CorthoCortho, and CipsoCispo bonds respectively,
suggesting benzenoid character, as in the case for unsubstituted
CPPs. In all CPPs phenyl rings are distorted. The angles
between the normal benzene plane and the distorted out-of-
plane atoms (α) respectively the CipsoCispo bond (β) display
the degree of distortion. Those parameters were determined for
a range of calculated CPP structures by Itami et al.6b In the
substituted CPP 9d, α equals 8.5° and β equals 14.4° which are
comparable to the values for [8]CPP (α = 9.3°, β = 13.7°).6b
The torsion angle between the middle unsubstituted ring C
(Figure 2) and the other unsubstituted rings B is 32.8°, which is
close to the value measured for [8]CPP.6b The angle between
the substituted ring A and its adjacent rings B is 53.8°. This
value is larger than that for unsubstituted CPPs. Based on these
results, even less π-conjugation can be expected in substituted
CPPs than the unsubstituted CPPs. Additionally, the packing
arrangement is different from unsubstituted CPPs, where
channels are sometimes observed. Here, pairs of rings arrange
parallel to each other, and these pairs assemble forming a basket
weave motif (Figure 2d).
The crystal structures of these three molecules illustrate the
increasing strain of the molecules toward the end of the
synthesis. The solid state structure of the macrocycle 7a (Figure
2a) shows no deformation of the phenyl rings. However, in
precursor structure 8b (Figure 2b), most of the phenyl rings are
already distorted with α = 3.7°. One ring shows a deviation
from planarity similar to the case of the equivalent CPP. The
torsion angle between most of the phenyl rings is 80.3° which is
far more prominent than that for CPP. This is due to the
remaining flexibility of the molecule.
Previous theoretical studies have calculated the structures
and strain energies of CPPs using density functional theory
(DFT) at the B3LYP/6-31G(d) level of theory. Strain energy
was estimated via a homodesmotic reaction of CPPn and n
biphenyls giving n p-terphenyls.6g However, we adopted a
different approach to calculate the strain energy of 9, which
seems more appropriate to us, due to the fact that only the
strain energy of the two relevant structures, the cyclic and the
infinite linear PP, are calculated. This is achieved by breaking a
bond in the CPP and straightening the fragment. This structure
was placed in a repeating supercell so that the broken bonds
connect to each other across opposite sides of the cell. This
approach avoids any additional energetic terms due to changes
in conjugation that may be present in the hypothetical
homodesmotic reaction approach and is better adapted to
substituted rings. With this method, via DFT optimization (see
Supporting Information for details), the strain energy obtained
was 63.7, 51.1, 73.6, and 62.4 kcal/mol for 9a, 9b, 9c, and 9d
Figure 3. UV−vis absorption (solid lines) and fluorescence spectra
(dashed lines) of substituted CPPs 9a−d. The fluorescence was
normalized to the absorption maximum (measured in chloroform 10−4
M).
Table 2. Photo-optical Properties of Substituted CPPs
λabs (nm) λem (nm) quantum yield fluorescence lifetime (ns)
9a
9b
9c
9d
306
301
312
312
465
451
465
453
0.24
0.06
0.36
0.46
3.5
3.3
3.7
4.3
CPPs lie between 301 and 312 nm (Table 2). These occur at
shorter wavelengths than those for the corresponding
unsubstituted [8]CPP (340 nm), which can be rationalized
by the larger torsion angle compared to that for unsubstituted
CPPs. Extinction coefficients are also considerably smaller than
that for [8]CPP.4k The emission maxima (λem) were observed
between 451 and 465 nm (Table 2). These values are again
smaller than that for the unsubstituted [8]CPP (540 nm).6b
The absolute fluorescence quantum yields were measured in
chloroform using a calibrated integrating sphere. These yields
are smaller than those measured for [9]CPP using the same
method,6b indicating an influence of the substitution on the
photoluminescence pathways. With these values our CPPs fit
perfectly into the expected range. They match the trend among
CPPs synthesized to date, namely the larger the diameter and
the larger the distortion due to substitution, the lower the
emission wavelength.4k,6b
In conclusion, using a [2 + 2 + 2] cycloaddition reaction as
the key step allowed us to synthesize the smallest substituted
CPPs in a highly modular way. The advantage of this strategy is
that the substitution can be chosen at a late stage of the
synthesis. Differently substituted CPPs were thus synthesized.
Structural properties of the substituted CPPs are similar to
those of unsubstituted CPPs, with small variations in optical
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Letter
Lett. 2010, 12, 2262. (h) Bachrach, S. M.; Stuck, D. J. Org. Chem. 2010,
̈
properties. Future work will examine the special properties of
substituted CPPs, the synthetic strategy toward longer
fragments of carbon nanotubes, and applications in nanoporous
materials.
75, 6595. (i) Wong, B. M. J. Phys. Chem. C 2009, 113, 21921.
(7) (a) Yagi, A.; Segawa, Y.; Itami, K. J. Am. Chem. Soc. 2012, 134,
2962. (b) Sisto, T. J.; Tian, X.; Jasti, R. J. Org. Chem. 2012, 77, 5857.
(c) Nishiuchi, T.; Feng, X.; Enkelmann, V.; Wagner, M.; Mullen, K.
̈
Chem.Eur. J. 2012, 18, 16621.
ASSOCIATED CONTENT
* Supporting Information
■
(8) (a) O’Mahony, A. M.; Wang, J. Analytical Methods 2013, 5, 4296.
S
(b) Miles, B. N.; Ivanov, A. P.; Wilson, K. A.; Dog
Edel, J. B. Chem. Soc. Rev. 2013, 42, 15.
̆
Synthesis and characterization of all new compounds; crystallo-
graphic data of 7a, 8b, and 9d; details of theoretical modeling.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(9) Bharat; Bhola, R.; Bally, T.; Valente, A.; Cyran
Dobrzycki, Ł.; Spain, S. M.; Rempała, P.; Chin, M. R.; King, B. T.
́
Angew. Chem., Int. Ed. 2010, 49, 399.
(10) Friederich, R.; Nieger, M.; Vogtle, F. Chem. Ber. 1993, 126,
̈
1723.
AUTHOR INFORMATION
Corresponding Author
(11) Srinivasan, M.; Sankararaman, S.; Hopf, H.; Varghese, B. Eur. J.
Org. Chem. 2003, 2003, 660.
■
(12) Hoger, S.; Bonrad, K. J. Org. Chem. 2000, 65, 2243.
̈
*E-mail: Hermann.A.Wegner@org.Chemie.uni-giessen.de.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was financially supported by the University of Basel,
■
Staatssekreteriat fur Bildung und Forschung SBF, COST
̈
MP0901 NanoTP, and French ANR-2010-BLAN-0819-04
“SPRINT”.
REFERENCES
(1) Tahara, K.; Tobe, Y. Chem. Rev. 2006, 106, 5274.
(2) Omachi, H.; Nakayama, T.; Takahashi, E.; Segawa, Y.; Itami, K.
Nat. Chem. 2013, 5, 572.
■
(3) Jasti, R.; Bhattacharjee, J.; Neaton, J. B.; Bertozzi, C. R. J. Am.
Chem. Soc. 2008, 130, 17646.
(4) (a) Xia, J.; Jasti, R. Angew. Chem., Int. Ed. 2012, 51, 2474. (b) Xia,
J.; Bacon, J. W.; Jasti, R. Chem. Sci. 2012, 3, 3018. (c) Sisto, T. J.; Jasti,
R. Synlett 2012, 23, 483. (d) Omachi, H.; Segawa, Y.; Itami, K. Acc.
Chem. Res. 2012, 45, 1378. (e) Kayahara, E.; Sakamoto, Y.; Suzuki, T.;
Yamago, S. Org. Lett. 2012, 14, 3284. (f) Ishii, Y.; Nakanishi, Y.;
Omachi, H.; Matsuura, S.; Matsui, K.; Shinohara, H.; Segawa, Y.; Itami,
K. Chem. Sci. 2012, 3, 2340. (g) Darzi, E. R.; Sisto, T. J.; Jasti, R. J. Org.
Chem. 2012, 77, 6624. (h) Sisto, T. J.; Golder, M. R.; Hirst, E. S.; Jasti,
̌
R. J. Am. Chem. Soc. 2011, 133, 15800. (i) Segawa, Y.; Senel, P.;
Matsuura, S.; Omachi, H.; Itami, K. Chem. Lett. 2011, 40, 423.
̌
(j) Segawa, Y.; Miyamoto, S.; Omachi, H.; Matsuura, S.; Senel, P.;
Sasamori, T.; Tokitoh, N.; Itami, K. Angew. Chem., Int. Ed. 2011, 50,
3244. (k) Iwamoto, T.; Watanabe, Y.; Sakamoto, Y.; Suzuki, T.;
Yamago, S. J. Am. Chem. Soc. 2011, 133, 8354. (l) Yamago, S.;
Watanabe, Y.; Iwamoto, T. Angew. Chem., Int. Ed. 2010, 49, 757.
(m) Omachi, H.; Matsuura, S.; Segawa, Y.; Itami, K. Angew. Chem., Int.
Ed. 2010, 49, 10202. (n) Jasti, R.; Bertozzi, C. R. Chem. Phys. Lett.
2010, 494, 1. (o) Takaba, H.; Omachi, H.; Yamamoto, Y.; Bouffard, J.;
Itami, K. Angew. Chem., Int. Ed. 2009, 48, 6112. (p) Evans, P. E.; Darzi,
E. R.; Jasti, R. Nat. Chem., in press. (q) Kayahara, E.; Patel, V. K.;
Yamago, S. J. Am. Chem. Soc. 2014, 136, 2284.
(5) (a) Zabula, A. V.; Filatov, A. S.; Xia, J.; Jasti, R.; Petrukhina, M. A.
Angew. Chem., Int. Ed. 2013, 52, 5033. (b) Fomine, S.; Zolotukhin, M.;
Guadarrama, P. J. Mol. Model. 2012, 18, 4025. (c) Iwamoto, T.;
Watanabe, Y.; Sadahiro, T.; Haino, T.; Yamago, S. Angew. Chem., Int.
Ed. 2011, 50, 8342.
(6) (a) Camacho, C.; Niehaus, T. A.; Itami, K.; Irle, S. Chem. Sci.
2013, 4, 187. (b) Segawa, Y.; Fukazawa, A.; Matsuura, S.; Omachi, H.;
Yamaguchi, S.; Irle, S.; Itami, K. Org. Biomol. Chem. 2012, 10, 5979.
(c) Nishihara, T.; Segawa, Y.; Itami, K.; Kanemitsu, Y. J. Phys. Chem.
Lett. 2012, 3, 3125. (d) Li, H.-B.; Page, A. J.; Irle, S.; Morokuma, K.
ChemPhysChem 2012, 13, 1479. (e) Fujitsuka, M.; Cho, D. W.;
Iwamoto, T.; Yamago, S.; Majima, T. Phys. Chem. Chem. Phys. 2012,
14, 14585. (f) Sundholm, D.; Taubert, S.; Pichierri, F. Phys. Chem.
Chem. Phys. 2010, 12, 2751. (g) Segawa, Y.; Omachi, H.; Itami, K. Org.
1597
dx.doi.org/10.1021/ol500194s | Org. Lett. 2014, 16, 1594−1597