Novel π-expanded radialene macrocycles with inner cavity

Article abstract of DOI:10.1021/ol048146g

(Chemical Equation Presented) Polyenyne macrocycles with π-extended [9]- and [12]radialene frameworks have been synthesized. These radialenes exhibit restricted rotation of the aromatic rings, and the D₃- and D ₄-symmetric structures

Full text of DOI:10.1021/ol048146g

ORGANIC
LETTERS
2004
Vol. 6, No. 25
4667-4670
Novel
π-Expanded Radialene
Macrocycles with Inner Cavity
Masahiko Iyoda,*,† Yoshiyuki Kuwatani,† Sachiko Yamagata,† Nobuko Nakamura,†
Mie Todaka,† and Gaku Yamamoto‡
Department of Chemistry, Graduate School of Science, Tokyo Metropolitan UniVersity,
Hachioji, Tokyo 192-0397, Japan, and Department of Chemistry, School of Science,
Kitasato UniVersity, Sagamihara, Kanagawa 228-8555, Japan
iyoda-masahiko@c.metro-u.ac.jp
Received September 14, 2004
ABSTRACT
Polyenyne macrocycles with
π-extended [9]- and [12]radialene frameworks have been synthesized. These radialenes exhibit restricted rotation
of the aromatic rings, and the D3- and D4-symmetric structures in solutions have been determined by dynamic NMR. The macrocyclic radialenes
bear small to medium inner cavities, and the small cavity of the
π
-extended [9]radialene can incorporate a silver cation.
Polyenyne macrocycles have attracted considerable attention
because of their π-conjugation, all-carbon networks, forma-
tion of unusual metal complexes, self-association, and
inclusion properties.1,2 Among them, cylindrical π-systems
with a shape-persistent macrocyclic structure3 can be re-
garded as π-cavitands and are expected to show unique
structures, host/guest interactions, and interesting electronic
properties.4 Although these molecules do not exhibit perfect
cyclic conjugation, fully unsaturated macrocycles form a
π-cavity with a concave-convex nature. We report here the
synthesis of π-extended [9]- and [12]radialenes starting from
the [3]dendralene precursor, together with their unique
structural properties.
between the neighboring exocyclic methylene groups may
destabilize the large-numbered radialenes. One possible
(2) For recent examples, see: (a) Mitzel, F.; Boudon, C.; Gisselbrecht,
J.-P.; Seiler, P.; Gross, M.; Diederich, F. Chem. Commun. 2003, 1634. (b)
Tobe, Y.; Ohki, I.; Sonoda, M.; Niino, H.; Sato, T.; Wakabayashi, T. J.
Am. Chem. Soc. 2003, 125, 5614. (c) Heuft, M. A.; Collins, S. K. Fallis, A.
G. Org. Lett. 2003, 5, 1911. (d) Campbell, K.; Kuehl, C. R.; Ferguson, M.
J.; Stang, P. J.; Tykwinski, R. R. J. Am. Chem. Soc. 2002, 124, 7266.
(3) For reviews, see: (a) Scott, L. T. Angew. Chem., Int. Ed. 2003, 42,
4133. (b) Zhao, D.; Moore, J. S. Chem. Commun. 2003, 807. (c) Yamaguchi,
Y.; Yoshida, Z. Chem. Eur. J. 2003, 9, 5430. (d) Ho¨ger, S. Chem. Eur. J.
2004, 10, 1320.
(4) For recent examples, see: (a) Kawase, T.; Tanaka, K.; Shiono, N.;
Seirai, Y.; Oda, M. Angew. Chem., Int. Ed. 2004, 43, 1722. (b) Kuwatani,
Y.; Igarashi, J.; Iyoda, M. Tetrahedron Lett. 2004, 45, 359. (c) Srinivasan,
M.; Sankararaman, S.; Hopf, H.; Varghese, B. Eur. J. Org. Chem. 2003,
660. (d) Kawase, T.; Tanaka, K.; Seirai, Y.; Shiono, N.; Oda, M. Angew.
Chem., Int. Ed. 2003, 42, 5597.
Although [3]- to [6]radialenes have been synthesized and
fully characterized,5,6 larger [7]- and [8]radialenes were
previously unknown, mainly because the steric repulsion
(5) For a review, see: Hopf, H. Angew. Chem., Int. Ed. Engl. 1992, 31,
931.
(6) For recent examples, see: (a) Eisler, S.; Tykwinski, R. R. Angew.
Chem., Int. Ed. 1999, 38, 1940. (b) Nielsen, M. B.; Schreiber, M.; Baek,
Y. G.; Seiler, P.; Lecomte, S.; Boudon, C.; Tykwinski, R. R.; Gisselbrecht,
J.-P.; Gramlich, V.; Skinner, P. J.; Bosshard, C.; Gu¨nter, P.; Goss, M.;
Diederich, F. Chem. Eur. J. 2001, 7, 3263. (c) Ho¨pfner, T.; Jones, P. G.;
Ahrens, B.; Dix, I.; Ernst, L.; Hopf, H. Eur. J. Org. Chem. 2003, 2596. (d)
Tobe, Y.; Umeda, R.; Iwasa, N.; Sonoda, M. Chem. Eur. J. 2003, 9, 5549.
(e) Kuwatani, Y.; Yamamoto, G.; Iyoda, M. Org. Lett. 2003, 5, 3371.
† Tokyo Metropolitan University.
‡ Kitasato Universiry.
(1) For reviews, see: (a) Marsden, J. A.; Palmer, G. J.; Haley, M. M.
Eur. J. Org. Chem. 2003, 2355. (b) Hopf, H. In Modern Arene Chemistry;
Astruc, D., Ed.; Wiley-VCH: Weinheim, 2002; pp 169-195. (c) Wan, W.
B.; Brand, S. C.; Pak, J. J.; Haley, M. M. Chem. Eur. J. 2000, 6, 2044. (d)
Bunz, U. H. F.; Rubin, Y.; Tobe, Y. Chem. Soc. ReV. 1999, 28, 107.
10.1021/ol048146g CCC: $27.50
© 2004 American Chemical Society
Published on Web 11/12/2004

approach to large-numbered radialenes is π-extension of exo-
methylene groups by insertion of double or triple bonds.6
However, no π-extended large-numbered radialene has been
synthesized, mainly due to synthetic reasons, i.e., the lack
of suitable dendralene precursors. We recently reported the
synthesis of hexaaryl[3]radialenes (aryl ) phenyl or p-
chlorophenyl) starting from dibromohexaaryl[3]dendralenes.7,8
On the basis of these results, we designed the synthesis of
π-extended large-numbered radialenes with an inner cavity.
The Sonogashira reaction of dibromo[3]dendralene 18 with
trimethylsilylacetylene (TMSA) produced the bis(tri-
methylsilylethynyl)[3]dendralene 2 (55%), together with the
[3]radialene 3 (12%). Since the two bromine atoms in 1 are
located close to each other (Br‚‚‚Br: 3.95 Å), the formation
of 3 took place simultaneously. Deprotection of 2 with KOH
in methanol-THF afforded bis(ethynyl)[3]dendralene 4 in
77% yield (Scheme 1). The dendralene 4 in solution
Figure 1. ORTEP view of the bis(ethynyl)[3]dendralene 4. The
twist angles (deg) of the aryl rings a, b, c, a′, b′, and c′ from the
CdC planes are 46.8(6), 65.0(6), 48.1(7), 49.8(6), 41.1(7), and
49.0(7). See the Supporting Information for bond lengths and angles
of 4.
Scheme 1. Synthesis of Bis(ethynyl)[3]dendralenes 2, 4, and 5
among 4-chlorophenyl groups, the molecule is significantly
distorted and adopts a twisted chiral conformation with
approximate C2 symmetry. The planes of the two outer CdC
bonds are twisted by 60.6 and 49.3° from the plane of the
inner CdC bond, and thus, the two ethynyl groups are
oriented with a dihedral angle of 96° and the intramolecular
distances between the acetylene carbons are 3.50 and 4.82
Å for C(8)‚‚‚C(10) and C(7)‚‚‚C(9), respectively. The aryl
rings are twisted from the attaching CdC planes by 41.1-
65.0° (average: 50.0°) and the rings a and b are stacked
face-to-face with a distance of 3.20 Å.
1
The H NMR spectrum of 4 is highly dependent on
temperature as shown in Figure 2. The signals ascribed to
the c rings are almost temperature independent and appear
as a single sharp AB quartet (AA′BB′, strictly), indicating
that the rotation of these rings is fast on the NMR time scale
throughout the temperature range examined. The signals due
to the b rings are sharp at high temperatures but significantly
broadened at -50 °C although no splitting was observed at
low temperatures. The signals due to the a rings are
broadened and buried under the baseline at 10 °C and appear
as four separate signals at -50 °C, indicating the retarded
rotation of the aryl groups [o-H: δ 7.44 and 5.37 (9 in Figure
2c); m-H: δ 7.33 and 6.74 (b in Figure 2c)]. Quantitative
saturation transfer experiments gave ∆Gq ) 12.4 kcal mol-1
at 200 K for the ring a rotation.10
gradually decomposed at room temperature on standing under
air for a long time. However, 4 in the crystalline state is
very stable and can be stored at room temperature without
decomposition.
The molecular structure of 4 obtained by X-ray crystal-
lography is shown in Figure 1.9 Due to the steric repulsion
(7) For dendralenes, see: (a) Hopf, H. Angew. Chem., Int. Ed. Engl.
1984, 23, 948. (b) Norinder, V. J. THEOCHEM 1987, 150, 85. (c) Cadogan,
J. I. G.; Cradock, S.; Gillam, S.; Gosney, I. J. Chem. Soc., Chem. Commun.
1991, 114. (d) Fielder, S.; Rowan, D. D.; Sherburn, M. S. Angew. Chem.,
Int. Ed. 2000, 39, 4331. (e) Hopf, H. Angew. Chem., Int. Ed. 2001, 40,
705.
(8) Iyoda, M.; Nakamura, N.; Todaka, M.; Ohtsu, S.; Hara, K.; Kuwatani,
Y.; Yoshida, M.; Matsuyama, H.; Sugita, M.; Tachibana, H.; Inoue, H.
Tetrahedron Lett. 2000, 41, 7059.
(9) Crystallographic data for 4: C46H26Cl6, MW ) 791.41, triclinic, space
group P-1 (No. 2), a ) 11.766(2) Å, b ) 16.768(3) Å, c ) 10.475(1) Å,
R ) 91.42(1)°, â ) 93.51(1)°, γ ) 109.86(1)°, V ) 1937.7(5) Å3, Z ) 2,
Dc ) 1.356 g/cm3, F(000) ) 808, µ(Mo KR) ) 4.75 cm-1, R ) 0.071, Rw
) 0.129, GOF ) 1.949. All measurements were performed on a Rigaku
AFC7R diffractometer with graphite monochromated Mo KR (λ ) 0.710 69
Å) radiation at 23 °C. Among a total of 9375 reflections measured, 8893
were unique and the observed (I > 3.00σ(I)) 3986 reflections were used
for the refinement. The crystal structure was solved by a direct method
and refined by the full-matrix least-squares method.
Judging from the chiral nature of 4 (Figure 1), it is
reasonable to assume that 4 adopts a chiral conformation in
solution and that enantiomerization takes place. The observed
barrier to ring a rotation, ∆Gq ) 12.2 kcal mol-1, affords
the lower limit of the enantiomerization barrier, but the exact
value cannot be elucidated. Thus, we studied the dendralene
5 carrying 1-hydroxy-1-methylethyl groups as a chirality
(10) (a) Sandstro¨m, J. Dynamic NMR Spectroscopy; Academic Press:
London, 1982; Chapter 4. (b) Yamamoto, G. Bull. Chem. Soc. Jpn. 1992,
65, 1967.
4668
Org. Lett., Vol. 6, No. 25, 2004

Scheme 2. Synthesis of the Extended Radialenes 6-9
afforded the corresponding cyclic trimer 7 in 23% yield,
together with a small amount of the cyclic dimer 6. The
trimer 7 was isolated as yellow fine crystals and characterized
by spectroscopic analysis, whereas 6 was only detected by
TOF-MS.
1
Figure 2. Temperature-dependent H NMR spectra (500 MHz)
of 4 at (a) 100 °C in C2D2Cl4, (b) 10 °C in C2D2Cl4, and (c) -50
°C in CD2Cl2. See the Supporting Information for further details.
probe, this was similarly prepared from 1 (Scheme 1). The
gem-dimethyl groups are diastereotopic at room temperature,
and the two singlets at δ 1.41 and 1.38 (CDCl3) coalesced
into a single peak at 43 °C. Total line shape analysis afforded
∆Gq ) 17.1 kcal mol-1 at 300 K for the enantiomerization.
Meanwhile, saturation transfer experiments for the ring a
signals of 5 gave ∆Gq ) 13.5 kcal mol-1 at 250 K for the
ring a rotation (Figure 3).
The Sonogashira reaction of 4 with p-diiodobenzene was
carried out using Pd(PPh3)4 and CuI in triethylamine-
benzene at 60 °C for 20 h. Although the reaction produced
a complex mixture of cyclic and acyclic oligomers, the cyclic
trimer 8 (27%) and the cyclic tetramer 9 (11%) were isolated
by gel-permeation liquid chromatography (GPLC), followed
by column chromatography on alumina. The trimer and
tetramer 8 and 9 were obtained as yellow prisms and the
structures were fully characterized.
1
The H and 13C NMR spectra of the cyclic trimer 7 are
rather simple, reflecting its highly symmetric structure with
D3 symmetry on the NMR time scale, where the three
dendralene moieties have the same sense of chirality.
Semiempirical MO calculations (AM1) support the structure
with a 3-fold axis as the most stable conformation (see the
Abstract graphic), and the C2 conformer, in which one of
the dedralene unit has the opposite sense of chirality, is 6.5
kcal mol-1 less stable than the one at the global minimum.
The rotation of rings b and c is fast and that of the a rings
is slow on the NMR time scale at 30 °C in CD2Cl2, and
∆Gq ) 15.5 kcal mol-1 at 300 K was obtained for the rotation
of the a rings, which is higher than in 4 and 5. No
information is available for the enantiomerization in 7, but
an energy barrier significantly higher than 15.5 kcal mol-1
is expected, judging from the data for 5. The AM1 calcula-
tions suggest that 7 has an inner cavity of 2.6 Å, by
considering the van der Waals radii. Interestingly, 7 forms
a silver complex on mixing with an excess amount of
Ag(OCOCF3) or AgClO4.12 The complex formation was
Figure 3. Conformational mobility of 5 and activation energies
for the two restricted movements in 5.
As shown in Figure 1, the conformation of 4 is favorable
for intermolecular coupling reactions because the two ethynyl
groups are located in the same direction. Thus, homocoupling
of the acetylene units in 4 and Sonogashira coupling of 4
with p-diiodobenzene would form the corresponding cyclic
oligomers (Scheme 2). Reaction of 4 with Cu(OAc)2‚2H2O
in pyridine-methanol under Eglinton-Glaser conditions11
(11) Behr, O. M.; Eglington, G.; Galbraith, A. R.; Raphael, R. A. J.
Chem. Soc. 1960, 3614.
Org. Lett., Vol. 6, No. 25, 2004
4669

determined by 1H NMR (Supporting Information) and
MALDI TOF-MS (Figure 4) spectra, the latter showing a
molecular ion corresponding to 7‚Ag+ at m/z 2474.8, together
with a molecular ion of 7 at m/z 2368.2.
Figure 5. Inner cavities and AM1-calculated structures of 8 and
9.
Figure 4. Formation of the silver complex 7‚Ag+.
ing either an extension of π-conjugation or an increase of
planarity in 7-9 (see the Supporting Information). Although
7 possesses a smaller π-conjugated system than 8 and 9, 7
shows a longer absorption maximum than 8 and 9. Since
the B3LYP/6-31G* calculations of the core radialene frame-
works in 7-9 exhibit similar structural parameters (bond
distances, NAO charges, etc.) except for the ethynylene
bridges, all expanded radialenes can be regarded as a similar
cross-conjugated system. Thus, the longer absorption maxi-
mum in 7 may be attributable to its larger effective
conjugation.
The cyclic trimer and tetramer 8 and 9 expanded by 1,4-
phenylene-ethynylene bridges show D3- and D4-symmetric
1H and 13C NMR signals at room temperature, although the
1H NMR spectra of 8 and 9 exhibit temperature dependence.
AM1 calculations suggest that 8 and 9 adopt conformations
with the highest symmetry. The activation energy for the
rotation of the central benzene ring in 8 is ∆Gq ) 15.1 kcal
mol-1 (quantitative saturation transfer experiments in CDCl3
at -5 °C), which is slightly smaller than that of 7. However,
the activation energy for the rotation of the ring in 9 could
not be determined by 1H NMR, because 9 was decomposed
at higher temperatures. As shown in Figure 5, AM1 calcula-
tions show the unique structures of 8 and 9 with inner
cavities. Thus, 8 and 9 have larger inner cavities than 7, and
hence 8 and 9 formed no silver complexes on mixing with
Ag(OCOCF3).
Acknowledgment. This work has been supported in part
by CREST of JST (Japan Science and Technology Corp.).
We thank Dr. Yoshihiro Miyake, Dr. Masato Yoshida, and
Prof. Masahiko Hada, Tokyo Metropolitan University, for
helpful discussions.
UV-vis spectra of the expanded radialenes 7-9 exhibited
longer wavelength absorptions than [3]dendralene 4, reflect-
Supporting Information Available: Spectroscopic data
of 2, 4, 5, 7, 7‚Ag+, 8, and 9 and X-ray data of 4. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(12) (a) Yoshida, T.; Kuwatani, Y.; Hara, K.; Yoshida, M.; Matsuyama,
H.; Iyoda, M.; Nagase, S. Tetrahedron Lett. 2001, 42, 53. (b) Iyoda, M.;
Horino, T.; Takahashi, F.; Hasegawa, M.; Yoshida, M.; Kuwatani, Y.
Tetrahedron Lett. 2001, 42, 6833.
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