Synthesis of [8]Cycloparaphenylene-octacarboxylates via Rh-Catalyzed Stepwise Cross-Alkyne Cyclotrimerization

Article abstract of DOI:10.1021/acs.orglett.7b01231

The synthesis of C₄- and C₂-symmetrical [8]cycloparaphenylene (CPP)-octacarboxylates has been achieved via macrocyclization by the rhodium-catalyzed intermolecular stepwise cross-cyclotrimerization and subsequent reductive aromatization. The C₄-symmetrical octa-tert-butyl [8]CPP-octacarboxylate forms a dimer in which eight ester moieties face each other. The dimers are aligned so as to make a one-dimensional column with a channel structure inside. Both absorption and fluorescence maxima of [8]CPP-octacarboxylates in CHCl₃ were significantly blue-shifted compared to those of [8]CPP due to the presence of eight electron-withdrawing ester moieties.

Full text of DOI:10.1021/acs.orglett.7b01231

Letter
pubs.acs.org/OrgLett
Synthesis of [8]Cycloparaphenylene-octacarboxylates via Rh-
Catalyzed Stepwise Cross-Alkyne Cyclotrimerization
Norihiko Hayase,† Yuta Miyauchi,† Yukimasa Aida,† Haruki Sugiyama,‡ Hidehiro Uekusa,‡ Yu Shibata,†
and Ken Tanaka*,†
‡
†Department of Chemical Science and Engineering and Department of Chemistry, Tokyo Institute of Technology, O-okayama,
Meguro-ku, Tokyo 152-8550, Japan
S
* Supporting Information
ABSTRACT: The synthesis of C4- and C2-symmetrical
[8]cycloparaphenylene (CPP)-octacarboxylates has been
achieved via macrocyclization by the rhodium-catalyzed
intermolecular stepwise cross-cyclotrimerization and subse-
quent reductive aromatization. The C4-symmetrical octa-tert-
butyl [8]CPP-octacarboxylate forms a dimer in which eight
ester moieties face each other. The dimers are aligned so as to
make a one-dimensional column with a channel structure
inside. Both absorption and fluorescence maxima of [8]CPP-
octacarboxylates in CHCl3 were significantly blue-shifted compared to those of [8]CPP due to the presence of eight electron-
withdrawing ester moieties.
Scheme 1
ycloparaphenylenes (CPPs) have attracted considerable
Cattention because of their fascinating structures, unique
properties, and potential applications in materials science.1 One
of the most interesting property of CPPs is the ring-size effect
in frontier molecular orbitals. Decreasing the number of
benzene rings decreases the HOMO−LUMO gap. This feature
is in sharp contrast with linear p-phenylene oligomers, in which
increasing the number of benzene rings decreases the HOMO−
LUMO gap. Following the first synthesis of [9]-, [12]-, and
[18]CPPs by Jasti and Bertozzi in 20082 and Itami in 2009,3
highly strained [5]−[8]CPPs have been successfully synthe-
sized.4 For the application of CPPs in materials science, many
efforts have been made to the synthesis of functionalized CPPs.
Thus, various symmetrically heteroatom-substituted CPPs have
been synthesized by Wang,5 Wegner,6 and Yamago.7 However,
available functional groups were limited to less polar ones such
as alkoxy groups. Recently, our research group reported the
synthesis of a symmetrically multifunctionalized CPP, C3-
symmetrical hexa-tert-butyl [12]CPP-hexacarboxylate 1, via
macrocyclization by the rhodium-catalyzed intermolecular
cross-cyclotrimerization8,9 of a diyne, possessing two benzene
units, with di-tert-butyl acetylenedicarboxylate and subsequent
reductive aromatization (Scheme 1).10,11 After this report,
Wang reported the synthesis of a more strained C3-symmetrical
hexamethyl [9]CPP-hexacarboxylate, via macrocyclization by
the nickel-mediated homocoupling and subsequent oxidative
aromatization.12
(Scheme 2).13 In this paper, we disclose the synthesis of highly
strained C4- and C2-symmetrical [8]CPP-octacarboxylates via
macrocyclization by the rhodium-catalyzed intermolecular
stepwise cross-cyclotrimerization and subsequent reductive
aromatization.
To synthesize more strained and densely substituted CPP-
carboxylates, we attempted the rhodium-catalyzed intermolec-
ular cross-cyclotrimerization of a diyne, possessing no benzene
units, with di-tert-butyl acetylenedicarboxylate, while not
macrocycles but a substituted benzobarrelene was generated
Received: April 24, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01231
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
1
mass spectrometry). The H and 13C NMR spectra revealed
that the structures of these CPPs are highly symmetrical.
A single crystal of [8]CPP-octacarboxylate 7aa, that is
suitable for X-ray crystal structure analysis, was easily grown by
vapor diffusion of n-hexane into a solution of 7aa in EtOAc at
room temperature under air. The crystal structure of 7aa
revealed that 7aa forms a dimer around the inversion center, in
which eight ester moieties face each other (the red and magenta
pair, and green and blue pair in Figure 1bc). In the dimer, the
ester moieties engage with each other using the dispersion force
interaction16 among tert-butyl groups (Figure S1). Diameter of
the ring of 7aa is 9.9−11.2 Å (Figure S2), which is significantly
smaller that that of 1 (16.4 Å).10a Torsion angles of
neighboring phthalate and benzene rings of 7aa were 42.8−
47.9° (Figure S3), which are close to that of 1 (47.6°),10a but
significantly larger than that of neighboring two benzene rings
of nonsubstituted [8]CPP (30.7°).17 The dimers of 7aa are
aligned along the crystallographic b-axis so as to make a column
with a channel structure inside. In the column, there are gaps
between the dimers, in which the ester groups of adjacent
columns and solvent molecules are filled. Thus, the adjacent
columns with concave-convex shape fit together like gears to be
closely packed by dispersion force intermolecular interactions
(Figure 1). As seen in the previous reports, inclusion of
solvents within the ring of CPPs was frequently observ-
ed.4i,6,10,11 Indeed, disordered solvent molecules (EtOAc and n-
hexane) were incorporated within the ring of 7aa, although the
precise assignment of the solvent molecules could not be made.
The UV/vis absorption and fluorescence properties of 7aa,
7ba, and 7bb were compared with those of nonsubstituted
[8]CPP (Table 1 and Figures S4−6).4j Both absorption and
fluorescence maxima of 7aa, 7ba, and 7bb in CHCl3 were
significantly blue-shifted compared to those of [8]CPP due to
the presence of eight electron-withdrawing ester moieties. The
absolute fluorescence quantum yields (ΦF) of 7aa, 7ba, and
7bb were 0.013−0.018, which are lower than that of [8]CPP
(ΦF = 0.1).4h
Scheme 2
In order to avoid the formation of the undesired
benzobarrelene, we designed the stepwise cross-cyclotrimeriza-
tion strategy as shown in Scheme 3. The intermolecular cross-
Scheme 3
To understand the electronic structures of 7aa, a DFT
calculation was performed using Gaussian 09 at the B3LYP/6-
31G(d) level. Figure 2 shows the pictorial representations of six
frontier molecular orbitals (MOs) of 7aa. The HOMO and
LUMO are delocalized over the entire ring, whereas four other
orbitals rather delocalize to two opposite sides.
A comparison of the energy diagram of nonsubstituted
[8]CPP to that of 7aa is shown in Figure 3. In 7aa, the orbitals
of HOMO−1 and HOMO−2 as well as those of LUMO+1 and
LUMO+2 are pseudo-degenerated. This feature is similar to
[8]CPP.4k On the other hand, in comparison with [8]CPP,
energy levels of HOMO, HOMO−1, and HOMO−2 of 7aa
decrease significantly (0.26−0.45 eV), but that of LUMO is
almost unchanged, and those of LUMO+1 and LUMO+2
decrease slightly (0.24−0.33 eV) presumably due to the
presence of eight electron-withdrawing ester moieties, which
results in decreasing electron density to decrease the HOMO
and LUMO energies and enlarging torsion angles of
neighboring benzene rings to decrease the HOMO energy
and increase the LUMO energy.17 Thus, increasing the
HOMO/LUMO gap (3.86 eV for 7aa vs 3.41 eV for
[8]CPP) corresponds to the blue-shifted absorption maximum
(301 nm for 7aa vs 340 nm for [8]CPP, Table 1).
cyclotrimerization of diyne 2,14 in which one terminal position
is protected with the triisopropylsilyl group, and di-tert-butyl
acetylenedicarboxylate (3a) in the presence of the cationic
rhodium(I)/H8−BINAP catalyst proceeded at room temper-
ature to give protected diyne 4a. Deprotection with TBAF
(tetrabutylammonium fluoride) afforded terminal diyne 5a.
The second intermolecular cross-cyclotrimerization of 5a and
3a afforded [8]CPP precursor 6aa. The subsequent reductive
aromatization of 6aa with lithium naphthalenide15 afforded C4-
symmetrical octa-tert-butyl [8]CPP-octacarboxylate 7aa. In a
similar way, C4-symmetrical octamethyl [8]CPP-octacarbox-
ylate 7bb was also synthesized by using dimethyl acetylenedi-
carboxylate (3b) instead of 3a, although the overall yield of 7bb
was very low. Importantly, C2-symmetrical tetra-tert-butyl and
tetramethyl [8]CPP-octacarboxylate 7ba could be synthesized
by using 3b in the first rhodium-catalyzed cross-cyclotrimeriza-
tion and 3a in the second rhodium-catalyzed cross-cyclo-
trimerization. Compounds 7aa, 7ba, and 7bb were identified by
1H and 13C NMR spectroscopy and HRMS (high-resolution
In summary, we disclosed the synthesis of C4- and C2-
symmetrical [8]CPP-octacarboxylates via macrocyclization by
the rhodium-catalyzed intermolecular stepwise cross-cyclo-
B
DOI: 10.1021/acs.orglett.7b01231
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Comparison of Photophysical Properties of
[8]CPP-Octacarboxylates 7aa, 7ba, 7bb, and [8]CPP
a
UV
absorption
fluorescence λmax (nm)
ϕF (excitation
CPP
7aa
λmax (nm)
(excitation wavelength (nm)) wavelength (nm))
301
300
287
403 (301)
406 (300)
406 (287)
0.014 (280)
0.013 (300)
0.018 (300)
7ba
7bb
[8]
b
b
c
340
533
0.1
CPP
a
Measured in CHCl3 at 25 °C unless otherwise indicated. At 1.0 ×
b
c
10−5 M. Data of ref 4j. Data of ref 4h.
Figure 2. Pictorial representation of six frontier molecular orbitals of
7aa, calculated at the B3LYP/6-31G(d) level of theory.
Figure 3. Energy diagrams for MOs of nonsubstituted [8]CPP (left)
and 7aa (right). Two-way arrows represent HOMO−LUMO gaps.
channel filled with solvent molecules. Both absorption and
fluorescence maxima of [8]CPP-octacarboxylates in CHCl3
were significantly blue-shifted compared to those of [8]CPP
due to the presence of eight electron-withdrawing ester
moieties. Future works will focus on further synthesis and
utilization of a variety of symmetrically multifunctionalized
cycloparaphenylenes.
Figure 1. Packing structure of 7aa determined by X-ray crystallo-
graphic analysis: (a) viewed along the columnar direction; (b) viewed
along the row direction (b) in (a). (c) Viewed along the row direction
(c) in (a).
trimerization and subsequent reductive aromatization. C4-
symmetrical octa-tert-butyl [8]CPP-octacarboxylate forms a
dimer in which eight ester moieties face each other. The dimers
are aligned so as to make a column with one-dimensional
C
DOI: 10.1021/acs.orglett.7b01231
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(5) Huang, C.; Huang, Y.; Akhmedov, N. G.; Popp, B. V.; Petersen, J.
L.; Wang, K. K. Org. Lett. 2014, 16, 2672.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b01231.
■
S
(6) Tran-Van, A.-F.; Huxol, E.; Basler, J. M.; Neuburger, M.; Adjizian,
J.-J.; Ewels, C. P.; Wegner, H. A. Org. Lett. 2014, 16, 1594.
(7) (a) Kuroda, Y.; Sakamoto, Y.; Suzuki, T.; Kayahara, E.; Yamago,
S. J. Org. Chem. 2016, 81, 3356. (b) Kayahara, E.; Zhai, X.; Yamago, S.
Can. J. Chem. 2017, 95, 351.
(8) (a) Tanaka, K.; Shirasaka, K. Org. Lett. 2003, 5, 4697. (b) Tanaka,
K.; Toyoda, K.; Wada, A.; Shirasaka, K.; Hirano, M. Chem. - Eur. J.
2005, 11, 1145.
Experimental procedures and compound characterization
data (PDF)
X-ray crystallographic file for (CIF)
(9) For reviews, see: (a) Tanaka, K. Synlett 2007, 2007, 1977.
(b) Shibata, Y.; Tanaka, K. Synthesis 2012, 44, 323. (c) Transition-
Metal-Mediated Aromatic Ring Construction; Tanaka, K., Ed.; Wiley:
Hoboken, 2013; Chapter 4, p 127.
(10) (a) Miyauchi, Y.; Johmoto, K.; Yasuda, N.; Uekusa, H.; Fujii, S.;
Kiguchi, M.; Ito, H.; Itami, K.; Tanaka, K. Chem. - Eur. J. 2015, 21,
18900. (b) Nishigaki, S.; Miyauchi, Y.; Noguchi, K.; Ito, H.; Itami, K.;
Shibata, Y.; Tanaka, K. Eur. J. Org. Chem. 2016, 2016, 4668.
(11) Our research group recently reported the synthesis of
alternating donor-acceptor cycloparaphenylenes via the rhodium-
catalyzed intermolecular cross-cyclotrimerization. See: Nishigaki, S.;
Fukui, M.; Kawauchi, S.; Sugiyama, H.; Uekusa, H.; Shibata, Y.;
Tanaka, K. Chem. - Eur. J. 2017, 23, x.
(12) Li, S.; Huang, C.; Thakellapalli, H.; Farajidizaji, B.; Popp, B. V.;
Petersen, J. L.; Wang, K. K. Org. Lett. 2016, 18, 2268.
(13) Miyauchi, Y.; Shibata, Y.; Tanaka, K. Chem. Lett. 2016, 45, 86.
(14) Sankararaman, S.; Srinivasan, M. Org. Biomol. Chem. 2003, 1,
2388.
(15) The use of sodium naphthalenide instead of lithium
naphthalenide lowered the yield of 7aa. For the optimization of the
reductive aromatization step, see the Supporting Information.
(16) For a review, see: Wagner, J. P.; Schreiner, P. R. Angew. Chem.,
Int. Ed. 2015, 54, 12274.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: ktanaka@apc.titech.ac.jp.
ORCID
Ken Tanaka: 0000-0003-0534-7559
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported partly by ACT-C (No.
JPMJCR1122YR) from the Japan Science and Technology
Agency (Japan) and Grants-in-Aid for Scientific Research (Nos.
15H03775 and 26102004) from the Ministry of Education,
Culture, Sports, Science and Technology (Japan). We thank
Prof. Keisuke Suzuki and Prof. Ken Ohmori (Tokyo Institute of
Technology) for collecting the 13C NMR spectrum of 7bb,
Prof. Takashi Ishizone (Tokyo Institute of Technology) for his
valuable advice for the preparation of sodium and lithium
naphthalenides, and Mr. Shuhei Nishigaki (Tokyo Institute of
Technology) for his assistance for the analysis of the packing
structures of the octa-tert-butyl [8]CPP-octacarboxylate. We
also thank Takasago International Corp. for the gift of H8−
BINAP and Umicore for generous support in supplying the
rhodium complex.
(17) Segawa, Y.; Fukazawa, A.; Matsuura, S.; Omachi, H.; Yamaguchi,
S.; Irle, S.; Itami, K. Org. Biomol. Chem. 2012, 10, 5979.
REFERENCES
■
(1) For recent reviews of CPPs, see: (a) Segawa, Y.; Yagi, A.; Matsui,
K.; Itami, K. Angew. Chem., Int. Ed. 2016, 55, 5136. (b) Darzi, E. R.;
Jasti, R. Chem. Soc. Rev. 2015, 44, 6401. (c) Lewis, S. E. Chem. Soc. Rev.
2015, 44, 2221. (d) Yamago, S.; Kayahara, E.; Iwamoto, T. Chem. Rec.
2014, 14, 84. (e) Tran-Van, A.-F.; Wegner, H. A. Beilstein J.
Nanotechnol. 2014, 5, 1320. (f) Omachi, H.; Segawa, Y.; Itami, K.
Acc. Chem. Res. 2012, 45, 1378. (g) Sisto, T. J.; Jasti, R. Synlett 2012,
23, 483. (h) Itami, K. Pure Appl. Chem. 2012, 84, 907. (i) Bunz, U. H.
F.; Menning, S.; Martín, N. Angew. Chem., Int. Ed. 2012, 51, 7094.
(2) Jasti, R.; Bhattacharjee, J.; Neaton, J. B.; Bertozzi, C. R. J. Am.
Chem. Soc. 2008, 130, 17646.
(3) Takaba, H.; Omachi, H.; Yamamoto, Y.; Bouffard, J.; Itami, K.
Angew. Chem., Int. Ed. 2009, 48, 6112.
(4) For [5]CPP, see: (a) Evans, P. J.; Darzi, E. R.; Jasti, R. Nat. Chem.
2014, 6, 404. (b) Kayahara, E.; Patel, V. K.; Yamago, S. J. Am. Chem.
Soc. 2014, 136, 2284. (c) Patel, V. K.; Kayahara, E.; Yamago, S. Chem. -
Eur. J. 2015, 21, 5742. For [6]CPP, see: (d) Xia, J.; Jasti, R. Angew.
Chem., Int. Ed. 2012, 51, 2474. (e) Kayahara, E.; Iwamoto, T.; Suzuki,
T.; Yamago, S. Chem. Lett. 2013, 42, 621. (f) Kayahara, E.; Patel, V. K.;
Xia, J.; Jasti, R.; Yamago, S. Synlett 2015, 26, 1615. For [7]CPP, see:
(g) Sisto, T. J.; Jasti, R. Synlett 2012, 23, 483. (h) Darzi, E. R.; Sisto, T.
J.; Jasti, R. J. Org. Chem. 2012, 77, 6624. (i) Sibbel, F.; Matsui, K.;
Segawa, Y.; Studer, A.; Itami, K. Chem. Commun. 2014, 50, 954. See
also ref 4c. For [8]CPP, see: (j) Yamago, S.; Watanabe, Y.; Iwamoto,
T. Angew. Chem., Int. Ed. 2010, 49, 757. (k) Iwamoto, T.; Watanabe,
Y.; Sakamoto, Y.; Suzuki, T.; Yamago, S. J. Am. Chem. Soc. 2011, 133,
8354. See also ref 4c, e, h,i.
D
DOI: 10.1021/acs.orglett.7b01231
Org. Lett. XXXX, XXX, XXX−XXX