A facile synthesis of large extraannular-functionalized phenyl-ethynyl macrocycles containing m-terphenyl units

Article abstract of DOI:10.1021/ol026870y

(equation presented) Two large extraannular-functionalized phenyl-ethynyl macrocycles containing m-terphenyl units are described. The synthesis of the m-terphenyl building blocks is based on the transformation of pyrylium salts to arenes.

Full text of DOI:10.1021/ol026870y

ORGANIC
LETTERS
2002
Vol. 4, No. 24
4269-4272
A Facile Synthesis of Large
Extraannular-Functionalized
Phenyl-Ethynyl Macrocycles Containing
m-Terphenyl Units
,†
Sigurd Ho1ger,* Silvia Rosselli, Anne-De´sire´e Ramminger, and Volker Enkelmann
Max Planck Instituite for Polymer Research, Ackermannweg 10,
55128 Mainz, Germany
shoeger@polyibm2.chemie.uni-karlsruhe.de
Received September 9, 2002
ABSTRACT
Two large extraannular-functionalized phenyl-ethynyl macrocycles containing m-terphenyl units are described. The synthesis of the m-terphenyl
building blocks is based on the transformation of pyrylium salts to arenes.
Shape-persistent macrocycles based on the phenylene or
phenylene-ethynylene backbone are fairly rigid structures
having a lumen (interior size) in the range of one to several
nanometers. Although some of the compounds are based on
purely para-substituted aromatics, most macrocycles prepared
to date have a polygonic shape. They contain corner pieces
of ortho- or meta-substituted aromatics that introduce kinks
into the structure, necessary to form the ring.1
terminated phenyl-ethynyl-oligomers, it became apparent that
the synthesis of rings with a large internal void is often highly
time-consuming.2 We therefore searched for a simple syn-
thesis of expanded aromatic structures containing halogens
(bromide or iodide) in an arrangement as it is found in meta-
substituted benzene derivatives so that these structures can
be used as corner pieces of a macrocyclic backbone.
Moreover, the synthesis of these extended building blocks
should allow the introduction of functional groups at various
positions because this allows the preparation of macrocycles
with a predetermined functional group orientation. If a
polygonic macrocycle is based on the phenyl-ethynyl back-
bone that contains meta- and also para-substituted aromatic
During our work on large rigid macrocycles synthesized
by the intermolecular oxidative dimerization of ethynyl-
† New address: Universita¨t Karlsruhe, Polymer-Institut, Hertzstr. 16,
76187 Karlsruhe, Germany.
(1) Reviews about shape-persistent macrocycles: (a) Moore, J. S. Acc.
Chem. Res. 1997, 30, 402. (b) Ho¨ger, S. J. Polym. Sci., Part A 1999, 37,
2685. (c) Haley, M. M.; Pak, J. J.; Brand, S. C. Topic Curr. Chem. 1999,
201, 81. (d) Grave, C.; Schlu¨ter, A. D. Eur. J. Org. Chem. 2002, 3075.
(2) Ho¨ger, S.; Meckenstock, A.-D.; Mu¨ller, S. Chem. Eur. J. 1998, 4,
2421.
10.1021/ol026870y CCC: $22.00 © 2002 American Chemical Society
Published on Web 11/02/2002

structures, only the latter can rotate freely. Their orientation
can be influenced by an external parameter, while the
orientation of the functional groups at the corner pieces is
given by the actual structure of these building blocks.3
Here we report a new approach toward functionalized 4,4′′-
diiodo-m-terphenylenes and their use in the synthesis of
shape-persistent macrocycles.4,5 The key step in our reaction
sequence is the transformation of a 2,4,6-triarylpyrylium salt
to the corresponding arene by the reaction with sodium
phenylacetate as described by Zimmermann and Fischer
(Scheme 1).6
Scheme 2a
Scheme 1. Arenes from Pyrylium Salts
Pyrylium salts containing a variety of functional groups
are easily available in large quantities. Their synthesis and
subsequent transformation to arenes tolerate bromo and iodo
groups, thus avoiding protective group transformation (e.g.,
TMS to I7 or N3Et2 to I8) prior to the macrocycle synthesis.9
In addition, Ar′ and Ar′′′ may contain functional groups. This
strategy therefore allows the synthesis of macrocycles with
intraannular as well as extraannular functional groups. The
synthesis of these structures is of increasing interest because
intraannular-functionalized macrocycles can act as host
molecules for appropriate guest molecules.10 Extraannular-
functionalized macrocycles have shown to be versatile
building blocks for new materials showing interesting
aggregation phenomena.11
a Reaction conditions: (a) BF3‚Et2O (48%); (b) Ac2O, AgBF4
(20%); (c) BBr3 (98%); (d) K2CO3 (78%).
Scheme 2 shows the synthesis of a building block for the
preparation of extraannular-functionalized macrocycles. Con-
densation of 1 equiv of 4-methoxy-benzaldehyde (1) with 2
equiv of 4-iodo-acetophenone (2) in the presence of BF3‚
Et2O at 100 °C for 2 h gave 3 in 48% yield.
(3) (a) Okuyama, K.; Hasegawa, T.; Ito, M.; Mikami, N. J. Phys. Chem.
1984, 88, 1711. (b) Ho¨ger, S.; Enkelmann, V. Angew. Chem., Int. Ed. Engl.
1995, 34, 2713. (c) Morrison, D. L.; Ho¨ger, S. J. Chem. Soc., Chem.
Commun. 1996, 2313. (d) Ho¨ger, S.; Enkelmann, V.; Bonrad, K.; Tschierske,
C. Angew. Chem., Int. Ed. 2000, 39, 2268. (e) Ho¨ger, S.; Morrison, D. L.;
Enkelmann, V. J. Am. Chem. Soc. 2002, 124, 6734.
(4) Efficient and simple routes to m-terphenyls were reported by Hart et
al.: (a) Du, C.-J. F.; Hart, H.; Ng, K.-K. D. J. Org. Chem. 1986, 51, 3162.
(b) Saednya, A.; Hart, H. Synthesis 1996, 1455. However, that approach
has limitations with respect to 4,4′′-dihalogenated compounds.
(5) For an oligo(het)arylene building block in macrocycle synthesis, see,
for example: Manickam, G.; Schlu¨ter, A. D. Eur. J. Org. Chem. 2000,
3475.
(6) Zimmermann, T.; Fischer, G. W. J. Prakt. Chem. 1987, 329, 975.
See also: Dimroth, K.; Neubauer, G. Chem. Ber. 1959, 92, 2042.
(7) Manickam, G.; Schlu¨ter, A. D. Eur. J. Org. Chem. 2000, 3475.
(8) Moore, J. S.; Weinstein, E. J.; Wu, Z. Tetrahedron Lett. 1991, 32,
2465.
(9) Balaban, A. T.; Dinculescu, A.; Dorofeenko, G. N.; Fischer, G. W.
Koblik, A. V.; Mezheritskii, V. V.; Schroth, W. AdV. Heterocycl. Chem.,
Supp. 2; Academic Press: New York, 1982.
Compound 3 was refluxed in acetic anhydride with 4 for
1.5 h, and 5 was isolated after chromatographic purification
in 9-17% yield. This yield is remarkably low and to some
extent due to the formation of the side product 6. The
nucleophilic substitution of the methoxy group by iodide is
a result of the activating para-positioned electron-withdraw-
ing pyrylium ring. Reacting 3 and 4 in the presence of 1
equiv of AgBF4 (as an iodide scavenger) increased the yield
up to 20%.12 Nevertheless, the preparation of several grams
of 5 can be performed without difficulties due to the simple
preparation of 3. Treatment of 5 with BBr3 afforded 7 (98%),
which was alkylated with 3-bromopropyl benzoate (8) to give
9 (78%) (Scheme 2).
Recrystallization of the phenyl-substituted 4,4′′-diiodo-m-
phenylene 5 from acetic acid gave crystals suitable for X-ray
(10) For the concept of intraannular functional groups, see, for ex-
ample: (a) Vo¨gtle, F.; Neumann, P. Tetrahedron 1970, 26, 5299. (b) Weber,
E.; Vo¨gtle, F. Chem. Ber. 1976, 109, 1803.
(11) (a) Rosselli, S.; Ramminger, A.-D.; Wagner, T.; Silier, B.; Wiegand,
S.; Ha¨ussler, W.; Lieser, G.; Scheumann, V.; Ho¨ger, S. Angew. Chem., Int.
Ed. 2001, 40, 3138. (b) Ho¨ger, S.; Bonrad, K.; Rosselli, S.; Ramminger,
A.-D.; Wagner, T.; Silier, B.; Wiegand, S.; Ha¨ussler, W.; Lieser, G.;
Scheumann, V. Makromol. Symp. 2002, 177, 185. (c) Ho¨ger, S. Bonrad,
K.; Mourran, A.; Beginn, U.; Mo¨ller, M. J. Am. Chem. Soc. 2001, 123,
5651.
(12) The use of an excess of AgBF4 led to an undefined product mixture.
(13) 5‚AcOH: C32H24I2O‚AcOH, monoclinic, P21/a, colorless, a )
18.581(1) Å, b ) 7.4812(7) Å, c ) 22.069(1) Å, â ) 96.821(3) °, Z ) 4,
Dx ) 1.610 g/cm, T ) 195 K, 4568 reflections measured, 3525 unique
reflections, 1843 observed reflections. Refinement on F with anisotropic
C, O, and N; H with fixed isotropic temperature factors in the riding mode;
R ) 0.0569, Rw ) 0.0527, GOF ) 0.857.
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Org. Lett., Vol. 4, No. 24, 2002

Scheme 3a
a Reaction conditions: (a) Pd2(dba)3, CuI, PPh3 (83%); (b) Pd2(dba)3, CuI, PPh3 (92%); (c) Bu4NF, THF (78%); (d) Bu4NF, THF (91%);
(e) CuCl, CuCl2, pyridine (53%); (f) CuCl, CuCl2, pyridine (20%); (g) KOH, LiOH (87%); (h) KOH, LiOH (91%).
analysis (Figure 1). Due to steric reasons, the methyl- and
the iodo-substituted aromatic rings cannot be in plane with
the central aromatic ring but adopt a propeller-like conforma-
tion. The crystals include one molecule of acetic acid per
asymmetric unit, which forms hydrogen-bonded dimers in
the crystal.13
stituents. Palladium-catalyzed coupling with 10 or 11 in the
presence of CuI and PPh3 provided the two-half rings in their
TIPS-protected forms (12 and 13) in about 80-90% yield.
Subsequent deprotection of 12 and 13 using tetrabutylam-
monium fluoride in THF gave bisacetylenes 14 and 15,
respectively (80-90% yield) (Scheme 3). The cyclization
of 14 and 15 under pseudo high-dilution conditions was
carried out by adding a solution of the bisacetylenes in
Compound 9 is a suitable precursor for the formation of
shape-persistent macrocycles containing extraannular sub-
Org. Lett., Vol. 4, No. 24, 2002
4271

be easily purified by column chromatography and 44 was
isolated in 53% yield. The crude cyclization product of 15
contains about 65% 17 but its purification was not possible
by column chromatography. Pure 17 was obtained by
recrystallization from 1,2-dichloroethene in only 20%.
Deprotection of the macrocycles 15 and 17 was performed
using a mixture of NaOH/LiOH in THF/water. After reflux-
ing overnight, complete deprotection was achieved as
confirmed by TLC, NMR spectra, and mass spectra. Both
macrocycles were obtained in about 90% yield.
In conclusion, we have for the first time shown that 2,6-
(4,4′′-diiodo)-diphenyl pyryliums salts are valuable precur-
sors for diiodo-m-terphenyl units. As shown here, function-
alized pyrylium salts led to diiodo compounds that were used
to prepare extraannular-functionalized shape-persistent mac-
rocycles. The possibility of performing the pyrylium salt to
arene transformation also with functionalized phenyl acetic
acids allows the easy synthesis of large intraannular-
functionalyzed macrocycles.14
Figure 1. Crystal structure of 5‚AcOH.
Supporting Information Available: Detailed experi-
mental procedures and characterization of all compounds in
the text and X-ray data of 5‚HOAc. This material is available
free of charge via the Internet at http://pubs.acs.org.
pyridine in 96 h to a slurry of CuCl/CuCl2 in the same solvent
at 55 °C. The cyclization reaction is a statistical reaction, so
the cyclic dimers 16 and 17 are formed along with cyclic
trimers, oligomers, and polymers. According to the data of
the gel permeation chromatography (GPC), the crude cy-
clization product of 14 contains 16 in about 80%. It could
OL026870Y
(14) Ho¨ger, S. Unpublished results.
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Org. Lett., Vol. 4, No. 24, 2002