A set of homologous hetarylenediyne macrocycles by oxidative acetylene-acetylene coupling

Article abstract of DOI:10.1021/ol800316b

(Chemical Equation Presented) The synthesis of a set of bipyridine-containing macrocycles by oxidative acetylene-acetylene dimerization is described. The cycles are separated by preparative GPC, and the smallest homologue is analyzed by single-crystal X-ray diffraction, which shows a layered structure with channels that are partially filled with parts of the flexible chains of adjacent macrocycles. The cyclic trimer has a D_3h symmetry and is a possible candidate for the formation of metal organic supramolecular assemblies on surfaces.

Full text of DOI:10.1021/ol800316b

ORGANIC
LETTERS
2008
Vol. 10, No. 11
2091-2093
A Set of Homologous Hetarylenediyne
Macrocycles by Oxidative
Acetylene-Acetylene Coupling
Dorina M. Opris,† Alexander Ossenbach,§ Dieter Lentz,‡ and A. Dieter Schlu¨ter*,§
Institut fu¨r Chemie and Biochemie, Freie UniVersita¨t Berlin, Takustrasse 3,
D-14195 Berlin, Germany, Institut fu¨r Chemie and Biochemie, Freie UniVersita¨t
Berlin, Fabeckstrasse 34-36, D-14195 Berlin, Germany, and Institute of Polymers,
Department of Materials, ETH Zu¨rich, Wolfgang-Pauli Strasse 10,
8093 Zu¨rich, HCI J 541, Switzerland
schlueter@mat.ethz.ch
Received February 12, 2008
ABSTRACT
The synthesis of a set of bipyridine-containing macrocycles by oxidative acetylene-acetylene dimerization is described. The cycles are separated
by preparative GPC, and the smallest homologue is analyzed by single-crystal X-ray diffraction, which shows a layered structure with channels
that are partially filled with parts of the flexible chains of adjacent macrocycles. The cyclic trimer has a D3h symmetry and is a possible
candidate for the formation of metal organic supramolecular assemblies on surfaces.
Shape-persistent macrocycles are presently an intensely
researched target in both organic and materials chemistry.1
The interest is spurred by fascinating potential properties/
applications that include host-guest interactions,2 organiza-
tion into and transport through porous materials,3 and 2D
pattern formation on surfaces.2c,4 They may also serve as
constituents for the construction of novel 3D structures.5 A
number of synthetic routes have been developed, and cycles
with diameters of up to several nanometers were obtained.6
The oxidative acetylene dimerization has often been used in
ring closure reactions7 as well as for the preparation of open
chain linear oligomers.8 Homo- and heteroaromatic macro-
cycles with different sizes and substitution patterns have been
† Freie Universita¨t Berlin, Takustrasse 3.
‡ Freie Universita¨t Berlin, Fabeckstrasse 34-36.
§ ETH Zu¨rich.
(1) For reviews, see:(a) Grave, C.; Schlu¨ter, A. D. Eur. J. Org. Chem.
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Zhang, W.; Moore, J. S. Angew. Chem., Int. Ed. 2006, 45, 4416–4439. (d)
Hisaki, I.; Sonoda, M.; Tobe, Y. Eur. J. Org. Chem. 2006, 833–847.
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Chem., Int. Ed. 2005, 44, 4178–4182. (b) Dali-Youcef, R.; Baxter, P. N. W.
J. Org. Chem. 2005, 13, 4935–4953. (c) Furukawa, S.; Tahara, K.; De
Schryver, F. S.; v. d. Auweraer, M.; Tobe, Y.; De Feyter, S. Angew. Chem.,
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J. Org. Chem. 2008, 73, 1745–1751.
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1999, 40, 8347–8350. (c) Rucareanu, S.; Mongin, O.; Schuwey, A.; Hoyler,
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10.1021/ol800316b CCC: $40.75
Published on Web 05/08/2008
2008 American Chemical Society

prepared using this reaction. We are presently looking for
shape-persistent compounds with D3h symmetry as constitu-
ents for the synthesis of two-dimensional networks,9 and our
attention was drawn to the cyclic trimer [7]2. This cycle has
three bipyridine (bipy) units with a 120° angle between their
main axes and could thus be ideally suited for obtaining
extended structures through square planar metal complex-
ation. We describe herein the synthesis of bipy 6, which is
related to earlier studies on bipy building blocks from this
group and the oligomerization of 6 to a series of macrocycles
[7]n as well as some open-chain zigzag products. The
structure of [7]1 was elucidated by single crystal X-ray
diffraction.
Scheme 2.
Macrocyclization of 6a
aYields for n ) 1, 2, 3, 4: 5%, 12%, 9%, 5%, respectively.
The synthetic sequence to macrocycles [7]n is outlined in
Schemes 1 and 2. The symmetrically substituted bipy 3 was
This compound was easily purified by column chroma-
tography through silica gel and obtained as analytically pure
material on a 3 g scale. The cyclization of 6 was performed
on a 150 mg scale by oxidative acetylene-acetylene dimer-
ization14 using two different reaction conditions (Scheme 2).
The first synthesis was done in a degassed pyridine solution
of Cu2(OAc)4 to which a solution of 6 in pyridine was added
slowly over 5 h followed by stirring at room temperature
for 14 d. In the second, a pyridine solution of 6 was added
over a period of 92 h to a solution of a large amount of
CuCl and CuCl2 in the same solvent followed by stirring
for an additional 2 d at room temperature. To isolate the
oligomer mixture the Cu salts had to be removed, parts of
which were complexed to the bipy units. The decomplex-
ation/removal was done with a solution of KCN in water.
The emulsion that formed led to considerable losses of
organic material (approximately 35%). The raw product was
analyzed by analytical GPC (Waters 150-c Alc using Waters
Styragel HR columns, Waters 410 RI and 484 UV-vis
detectors, THF, PS standards), which showed three sharp
peaks and a broad one (Figure 1). The corresponding
products were separated by preparative GPC, which afforded
them in almost pure form so that an additional column
chromatographic step was sufficient to obtain reasonably pure
(by NMR spectroscopy) compounds. Their structures were
established as [7]1 (cyclic dimer, 8 mg, 5%), [7]2 (cyclic
trimer, 10 mg, 12%), and [7]3 (cyclic tetramer, 14 mg, 9%)
Scheme 1. Synthesis of Macromonomer 6
prepared using a Suzuki-Miyaura cross-coupling reaction
between 5,5′-dibromo-2,2′-bipyridine10 (1) and the silylated
benzene derivative 211 in almost quantitative yield. Both silyl
groups of 3 were then exchanged to iodo using ICl to give
the diiodide 4 nearly quantitatively.12 Compound 4 was
prepared on a 10 g scale. Sonogashira reaction of 4 with
trimethylsilyl acetylene (TMSA) gave 513 whose hydrolytic
treatment with NaOH furnished 6 with its two unprotected
acetylene functions required for oligomerization.
1
on the basis of mass spectrometric and H and 13C NMR
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489.
spectroscopic studies. In a repetition of this experiment also
the cylic pentamer [7]4 could be isolated (7 mg, 5%). Both
reactions gave practically the same yields. Additionally some
higher molecular weight, linear material was found. Figure
1 contains the molecular ion peaks of the cycles’ MALDI-
TOF mass spectra.
The products [7]3 and [7]4 can in principle consist of
monocycles or catenanes (cycles [7]3 and [7]4 have the same
mass as the catenanes from two [7]1 and [7]1/[7]2, respec-
tively). It was difficult to differentiate between these two
options by NMR or MS measurements. For simplicity we
assume that both products are regular cycles. This is
(8) (a) Martin, E. R.; Ma¨der, T.; Diederich, F. Angew. Chem., Int. Ed.
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1
supported by the H and 13C NMR spectra of [7]4, which
give just one set of signals each, which would not to be
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Org. Lett., Vol. 10, No. 11, 2008

representation. All ring atoms and the acetylenic carbon
atoms exhibit normal thermal displacement parameters; those
of the side chains differ drastically and reflect the differences
in packing. The side chain attached to O1 fills the hole left
in the center of another macrocycle and has very large
thermal displacement parameters. The one at O2 shows
normal thermal displacement parameters. The distance
between opposite triple bonds within the cavity amounts to
approximately 15.6 Å, and N1 and N1′ are about 8.0 Å apart
from each other. The cycle is almost planar, with the
bipyridine units are turned out of the plane with torsional
angles of 35° (Figure 2). The cycles form a layer structure
that gives rise to columns with channels (Figures 3). The
Figure 1. (A) GPC curves of purified [7]1 (Aa), [7]2 (Ab), [7]3
(Ac), and the raw oligomerization mixture (Ad). (B) MALDI-TOF
mass spectra of macrocycles [7]1 (Ba), [7]2 (Bb), and [7]3 in a
dithranol matrix (Bc) and [7]4 (Bd, repetition experiment) in a
DCTB matrix. Only the enlarged parts of the isotopically resolved
[M + H]+ signals are shown. The signals at higher masses
correspond to the Na+ and K+ adducts, respectively.
expected for a compound consisting of intertwined [7]1 and
[7]2. Unfortunately single crystals suitable for X-ray diffrac-
tion analysis could not be grown.
Figure 3. ORTEP plot of six molecules of [7]1 showing the stacking
of the aromatic rings.
The unresolved part of the GPC elution curve was assigned
to open chain oligomers with an average molar mass of Mpeak
) 10 600 g/mol based on polystyrene calibration.
Crystals of macrocycle [7]1 were grown by slow diffusion
of methanol into a solution of this cycle into chloroform. Its
molecular structure is depicted in Figure 2 as an ORTEP
distance between two cycles in the column is approximately
8.4 Å. Interestingly and in contrast to another bipyridine-
containing macrocycle published by this group,15 the X-ray
analysis of [7]1 does not reveal any solvent molecules in the
crystal structure.
Acknowledgment. The work was supported by the Deut-
sche Forschungsgemeinschaft (Sfb 448, TP A1). We would
like to thank Dr. Oliver Henze for his kind help with some
synthetic steps. The mass spectra were taken by Dr. Peter
Franke, FU Berlin.
Supporting Information Available: Detailed descriptions
of experimental procedures, characterization of compounds,
spectra, and Crystallographic Information File (cif) of
compound [7]1. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL800316B
(15) (a) Henze, O.; Lentz, D.; Schlu¨ter, A. D. Chem. Eur. J. 2000, 6,
2362–2367. (b) Henze, O.; Lentz, D.; Scha¨fer, A.; Franke, P.; Schlu¨ter,
A. D. Chem. Eur. J. 2002, 8, 357–365. (c) Grave, C.; Lentz, D.; Scha¨fer,
A.; Samori, P.; Rabe, J. P.; Franke, P.; Schlu¨ter, A. D. J. Am. Chem. Soc.
2003, 125, 6907–6918.
Figure 2. ORTEP plot of macrocycle [7]1, viewed perpendicular
to the macrocycle, 50% probability ellipsoids.
Org. Lett., Vol. 10, No. 11, 2008
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