A high-yield, one-step synthesis of o-phenylene ethynylene cyclic trimer via precipitation-driven alkyne metathesis

Article abstract of DOI:10.1021/jo0517803

A shape-persistent, conjugated o-phenylene ethynylene cyclic trimer was prepared in one step from tetrasubstituted benzene monomer 4 in 86% isolated yield through precipitation-driven alkyne metathesis. The template-free, selective generation of the molec

Full text of DOI:10.1021/jo0517803

of the carbon-carbon triple bonds is about 1.2 Å, which
provides a suitable geometry for π-alkylene/transition-
metal bonding interactions.2c The metal can be either in
or out of the plane of the macrocycle. The interesting
structural and conducting properties of the transition-
metal complexes derived from 1 have been extensively
explored.2b-d
A High-Yield, One-Step Synthesis of
o-Phenylene Ethynylene Cyclic Trimer via
Precipitation-Driven Alkyne Metathesis
Wei Zhang, Scott M. Brombosz,† Jose L. Mendoza,‡ and
Jeffrey S. Moore*
Roger Adams Laboratory, Departments of Chemistry and
Materials Science & Engineering, University of Illinois at
Urbana-Champaign, Urbana, Illinois 61801
jsmoore@uiuc.edu
Received August 23, 2005
Although there have been a series of phenylene
ethynylene trimeric macrocycles reported to date, their
preparation is mainly restricted to cross-coupling ap-
proaches, and usually only low yields are obtained.3,4 The
primary disadvantage of the coupling approach is that
the product distribution is kinetically determined. Since
these irreversible reactions do not have the ability to
correct undesired bond formations, oligomer growth that
overshoots the length of target macrocycles cannot con-
tribute to the yield of the desired product.
On the other hand, given the successful examples of
dynamic covalent chemistry in organic synthesis,5 we
envisioned a one-step approach to arylene ethynylene
macrocycles from monomers could be accomplished via
reversible alkyne metathesis. By utilizing molybdenum
catalyst that is both functional group tolerant and active
near room temperature,6 we have accomplished one-step,
gram-scale synthesis of hexameric phenylene ethynylene
macrocycles.7 Macrocycle formation is a thermodynami-
cally favored process under equilibrium control.8
A shape-persistent, conjugated o-phenylene ethynylene cyclic
trimer was prepared in one step from tetrasubstituted
benzene monomer 4 in 86% isolated yield through precipita-
tion-driven alkyne metathesis. The template-free, selective
generation of the molecular triangle 5 is a thermodynami-
cally favored process and under equilibrium control. A novel
tetrameric macrocycle 7 was generated via scrambling
metathesis between tricycle 5 and hexacycle 6 using this
dynamic covalent chemistry.
There has been growing interest in shape-persistent,
arylene ethynylene macrocycles as building blocks for
molecular materials and supramolecular chemistry.1
These macrocycles have rigid, noncollapsible hydrocarbon
backbones and are able to organize in solution, the
molten phase, and solid state (noncovalent nanotubes,
discotic liquid crystals, guest-host complexes, etc.).
Among these structures, the conjugated cyclic trimer
comprising three o-phenylene ethynylene units (1) has
attracted great interest.2 Macrocycle 1 and its derivatives
are structural units of graphyne.2a The distance from the
center of the 12-membered dehydroannulene to the center
Recently, Vollhardt et al. synthesized trimeric phe-
nylene ethynylene macrocycles through alkyne metath-
esis catalyzed by Schrock’s catalyst.9 Although the un-
(3) For reviews on synthesis of dehydrobenzoannulenes, see: (a)
Marsden, J. A.; Palmer, G. J.; Haley, M. M. Eur. J. Org. Chem. 2003,
2355-2369. (b) Youngs, W. J.; Tessier, C. A.; Bradshaw, J. D. Chem.
Rev. 1999, 99, 3153-3180. (c) Haley, M. M. Synlett 1998, 557-565
and ref 1f.
(4) For recent examples, see: (a) Li, Y.; Zhang, J.; Wang, W.; Miao,
Q.; She, X.; Pan, X. J. Org. Chem. 2005, 70, 3285-3287. (b) Iyoda, M.;
Sirinintasak, S.; Nishiyama, Y.; Vorasingha, A.; Sultana, F.; Nakao,
K.; Kuwatani, Y.; Matsuyama, H.; Yoshida, M.; Miyake, Y. Synthesis
2004, 1527-1531. (c) Nishinaga, T.; Miyata, Y.; Nodera, N.; Komatsu,
K. Tetrahedron 2004, 60, 3375-3382. (d) Iyoda, M.; Vorasingha, A.;
Kuwatani, Y.; Yoshida, M. Tetrahedron Lett. 1998, 39, 4701-4704. (e)
Solooki, D.; Ferrara, J. D.; Malaba, D.; Bradshaw, J. D.; Tessier, C.
A.; Youngs, W. J. Inorg. Synth. 1997, 31, 122-128.
† Summer intern from Illinois Wesleyan University.
‡ Summer intern from Instituto Tecnologico y de Estudios Superiores
de Monterrey Campus Monterrey.
(1) For reviews, see: (a) Ho¨ger, S. Angew. Chem., Int. Ed. 2005, 44,
3806-3808. (b) Ho¨ger, S. Chem. Eur. J. 2004, 10, 1320-1329. (c) Zhao,
D.; Moore, J. S. Chem. Commun. 2003, 807-818. (d) Yamaguchi, Y.;
Yoshida, Z. Chem. Eur. J. 2003, 9, 5430-5440. (e) Bunz, U. H. F.;
Rubin, Y.; Tobe, Y. Chem. Soc. Rev. 1999, 28, 107-119. (f) Haley, M.
M.; Pak, J. J.; Brand, S. C. Top. Curr. Chem. 1999, 201, 81-130. (g)
Moore, J. S. Acc. Chem. Res. 1997, 30, 402-413. (h) Young, J. K.;
Moore, J. S. In Modern Acetylene Chemistry; Stang, P. J., Diederich,
F., Eds.; VCH: Weinheim, 1995; Chapter 12.
(5) Rowan, S. J.; Cantrill, S. J.; Cousins, G. R. L.; Sanders, J. K.
M.; Stoddart, J. F. Angew. Chem., Int. Ed. 2002, 41, 898-952.
(6) (a) Zhang, W.; Kraft, S.; Moore, J. S. Chem. Commun. 2003, 832-
833. (b) Zhang, W.; Kraft, S.; Moore, J. S. J. Am. Chem. Soc. 2004,
126, 329-335.
(7) Zhang, W.; Moore, J. S. J. Am. Chem. Soc. 2004, 126, 12796.
Bunz previously reported the synthesis of hexameric macrocycles via
alkyne metathesis. Under their conditions, which required high
temperature (150 °C), the desired products were obtained in only 0.5-
6% yields. Ge, P.-H.; Fu, W.; Herrmann, W. A.; Herdtweck, E.;
Campana, C.; Adams, R. D.; Bunz, U. H. F. Angew. Chem., Int. Ed.
2000, 39, 3607-3610.
(2) (a) Eickmeier, C.; Junga, H.; Matzger, A. J.; Scherhag, F.; Shim,
M.; Vollhardt, K. P. C. Angew. Chem., Int. Ed. 1997, 36, 2103-2108.
(b) Ferrara, J. D.; Tessier-Youngs, C.; Youngs, W. J. J. Am. Chem.
Soc. 1985, 107, 6719-6721. (c) Youngs, W. J.; Kinder, J. D.; Bradshaw,
J. D.; Tessier, C. A. Organometallics 1993, 12, 2406-2407. (d) Ferrara,
J. D.; Djebli, A.; Tessier-Youngs, C.; Youngs, W. J. J. Am. Chem. Soc.
1988, 110, 647-649.
(8) Zhang, W.; Moore, J. S. J. Am. Chem. Soc. 2005, 127, 11863-
11870.
10.1021/jo0517803 CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/19/2005
10198
J. Org. Chem. 2005, 70, 10198-10201

substituted cyclic product 1 can be obtained in 54% yield
at 80 °C, methoxy substituted analogue 2 was only
obtained in 28% yield even after 140 h, with 20% catalyst
loading. To further improve the synthesis of trimeric
phenylene ethynylene macrocycles and also to explore the
scope of our newly developed synthetic protocol, we now
report the efficient, one-step preparation of an alkoxy
subsituted o-phenylene ethynylene cyclic trimer using the
precipitation-driven alkyne metathesis.7 Under equilib-
rium control, the thermodynamically favored cyclic trimer
5 was obtained in high yield.
FIGURE 1. GPC trace of purified cyclic trimer 5 (THF, 25
°C).
The reversibility of macrocycle 5 formation was dem-
onstrated by a scrambling experiment, in which a 1:2
mixture of two different phenylene ethynylene macro-
cycles (5 and 613) was subjected to metathesis (eq 1). The
reaction was conducted in CCl4 at 30 °C for 22 h followed
by FD-MS analysis (Figure 2). A tetrameric macrocycle,
presumably structure 7 (m/z ) 1200) having two o-
disubstituted units from 5 (m/z ) 900) and two m-
disubstituted units from 6 (m/z ) 1800) was observed,
demonstrating the reversibility of macrocycle formation.
This template-free,14,15 selective generation of trian-
gular cycle 5 via precipitation-driven alkyne metathesis
is thus confirmed to be a thermodynamically controlled
process.8 The initial growth of the oligomers is driven by
the poor solubility of the diarylacetylene byproduct. Once
the chains are sufficiently long, the oligomers can trans-
form into corresponding cyclic oligomers (n g 3) through
intramolecular metathesis with nearly complete removal
of end groups. At this point, open-chain and macrocyclic
intermediates can equilibrate leading predominantly to
the thermodynamically more stable trimeric macrocycles.
Sonogashira cross-coupling10 of 1,2-diethynyl-4,5-di-
hexyloxybenzene (3)11 and 4-benzoyl-4′-bromobiphenyl
gave the desired tetrasubstituted benzene monomer 4
(Scheme 1). The metathesis reaction of 4 was performed
in CCl4 catalyzed by a molybdenum alkylidyne catalyst6
(10 mol % loading) generated in situ from the corre-
sponding molybdenum triamide and p-nitrophenol. The
reaction mixture was stirred for 22 h at 30 °C, during
which time the precipitation of the byproduct diary-
lacetylene drove the reaction to completion. After removal
of the precipitate, the filtrate was concentrated and the
macrocyclic product was purified by column chromatog-
raphy, affording triangular cycle 5 as a yellow solid with
86% isolated yield.
The obtained cyclic trimer 5 was fully characterized
1
by H NMR, 13C NMR, FAB-MS, GPC, and elemental
analysis, which unambiguously demonstrate the desired
1
cyclic trimer. The H NMR spectrum of 5 revealed the
In conclusion, the cyclic trimer 5 has been successfully
synthesized by using precipitation-drivien alkyne me-
tathesis. The selective generation of cyclic trimer is a
thermodynamically favored process and under equilib-
rium control. The successful synthesis of 5 as well as
generation of a tetracycle via scrambling metathesis of
tricycle 5 and hexacycle 6 further demonstrates the
general scope of the one-step protocol for arylene ethyn-
ylene macrocycle preparation and the importance of
dynamic covalent chemistry in constructing thermo-
dynamically favored molecular architectures in high
yields.
presence of only one type of aromatic proton (δ 6.72) and
the 13C NMR spectrum showed a unique signal core-
sponding to the acetylene carbon (δ 91.8), which are
consistent with D3h symmetry for the trianular structure.
FAB mass spectrometry showed the molecular ion at m/z
) 900.6269 (calcd 900.6268), supporting the structure of
cyclic trimer 5. GPC trace of macrocycle 5 (Figure 1)
showed the monodisperse product distribution (PD )
1.00) and a Mn of 1090, further supporting the generation
of the target structure. Finally, the elemental analysis
result is also consistent with the expected composition
of 5.12
SCHEME 1. Synthesis of o-Phenylene Ethynylene Cyclic Trimer 5
J. Org. Chem, Vol. 70, No. 24, 2005 10199

FIGURE 2. FD-MS of crude product from scrambling metathesis of macrocycle 5 and 6.
chromatography (n-hexane/CH2Cl2, 3/2, v/v) to give macrocycle
5 as a yellow solid (28.9 mg, 86%): mp 125-126 °C; 1H NMR
(CDCl3, 400 MHz) δ 6.72 (s, 6H), 3.95 (t, J ) 7.6 Hz, 12H), 1.80
(m, 12H), 1.30-1.50 (m, 36H), 0.90 (t, J ) 6.4 Hz, 18H); 13C
NMR (CDCl3, 100 MHz) δ 149.0, 119.6, 115.5, 91.8, 68.9, 31.5,
29.0, 25.6, 22.5, 14.0; MS (FAB) m/z 900.7 (66), 816.6 (15), 731.5
(7), 307.1 (20), 154.1 (100); HR-MS (C60H84O6) calcd 900.6268,
found 900.6269; TLC Rf ) 0.34 (n-hexane/CH2Cl2, 1/1, v/v); GPC
(9) Miljaniæ, O. Sˇ.; Vollhardt, K. P. C.; Whitener, G. D. Synlett 2003,
29-34.
(10) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 4467-4470. (b) Sonogashira, K.; Yatake, T.; Tohda, Y.; Taka-
hashi, S.; Hagihara, N. J. Chem. Soc., Chem. Commun. 1977, 291-
292. (c) Sonogashira, K. In Handbook of Organopalladium Chemistry
for Organic Synthesis; Negishi, E., Ed.; Wiley-Interscience: New York,
2002; pp 493-529.
(11) (a) Zhou, Q.; Carroll, P. J.; Swager, T. M. J. Org. Chem. 1994,
59, 1294-1301. (b) Bowles, D. M.; Palmer, G. J.; Landis, C. A.; Scott,
J. L.; Anthony, J. E. Tetrahedron 2001, 57, 3753-3760.
(12) See the Experimental Section for detailed characterization data.
(13) Macrocycle 6 was synthesized from the corresponding m-
dialkoxybenzene monomer via precipitation-driven alkyne metathesis
(see the Supporting Information for details). On MALDI-MS of the
metathesis product, only hexameric (m/z ) 1800) and pentameric (m/z
) 1500) macrocycles were observed. Such a macrocycle mixture was
subjected to the subsequent scrambling metathesis experiment without
further separation.
(14) Ho¨ger applied a template-cyclization to synthesize phenylene
ethynylene macrocycles in excellent yields. However, the covalently
attached templates require the introduction of specific functional
groups into the cyclization precursors, and extra synthetic steps are
needed for attachment and cleavage. See: (a) Ho¨ger, S. J. Polym. Sci.
Part A: Polym. Chem. 1999, 37, 2685-2698. (b) Ho¨ger, S.; Mecken-
stock, A. D. Chem. Eur. J. 1999, 5, 1686-1691. (c) Ho¨ger, S.;
Enkelmann, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 2713-2716.
(15) Sanders utilized noncovalent template approach in synthesis
of large shape-persistent rings. Cyclic porphyrin oligomers were
obtained in 50-70% yield. (a) Anderson, H. L.; Sanders, J. K. M.
Angew. Chem., Int. Ed. Engl. 1990, 29, 1400-1403. (b) McCallien, D.
W. J.; Sanders, J. K. M. J. Am. Chem. Soc. 1995, 117, 6611-6612.
Experimental Section
Macrocycle (5). In an argon-filled glovebox, a solution of
molybdenum triamide6 (7.5 mg, 0.011 mmol) and p-nitrophenol
(4.7 mg, 0.034 mmol) in CCl4 (1.0 mL) was added to a solution
of monomer 4 (94.3 mg, 0.11 mmol) in CCl4 (2.1 mL). The flask
was sealed and removed from the glovebox. The resulting
mixture was stirred for 22 h at 30 °C. After removal of the
precipitate by vacuum filtration, the filtrate was concentrated
in vacuo and the macrocyclic product was purified by column
10200 J. Org. Chem., Vol. 70, No. 24, 2005

1090 (Mn), 1.00 (Mw/Mn). Anal. Calcd for C60H54O4 (900.6): C,
79.96; H, 9.39. Found: C, 79.87; H, 9.44.
Materials Research Laboratory at the University of
Illinois at Urbana-Champaign.
Supporting Information Available: Characterization
data for compound 3, 4, and precursors to 6; experimental
details. This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. This material is based upon
work supported by the National Science Foundation
under Grant No. 0345254 and the U.S. Department of
Energy, Division of Materials Sciences, under Award
No. DEFG02-91ER45439, through the Frederick Seitz
JO0517803
J. Org. Chem, Vol. 70, No. 24, 2005 10201