4556
J . Org. Chem. 1997, 62, 4556-4557
Sch em e 1a
High -Yield Ma cr ocycliza tion via Gla ser
Cou p lin g of Tem p or a r y Cova len t
Tem p la ted Bisa cetylen es
Sigurd Ho¨ger,* Anne-De´sire´e Meckenstock, and
Heike Pellen
Max-Planck-Institut fu¨r Polymerforschung,
Ackermannweg 10, D-55128 Mainz, Germany
Received February 25, 1997 (Revised Manuscript Received April
8, 1997 )
The synthesis of well-defined, shape-persistent nanom-
eter-scale objects has obtained increasing attention dur-
ing the last several years. Besides one-dimensional
structures, those of higher dimensionality are especially
interesting1 because they can be used as host molecules
if they contain appropriate binding sites.2 Some of the
most established cyclic structures are based on the
phenylacetylene backbone. Two extreme synthetic strat-
egies can be distinguished. Staab and co-workers pre-
pared cyclic hexa-m-phenylacetylene in a one-pot reaction
by a 6-fold Stephens-Castro coupling of 3-iodophenyl-
acetylene in 4.6% yield.3 Despite the low yield for the
cyclization step, this method is impressive because the
starting materials are readily accessible. A completely
different approach was investigated by the group of
Moore.4 They prepared similar and other phenylacet-
ylene macrocycles in good to excellent yields by an
intramolecular coupling of the corresponding R-iodo-ω-
ethynyl precursor; however, the synthesis of the precur-
sors is relatively time consuming. One way to overcome
this dilemma, which also occurs when the Glaser coupling
is used as the bond-forming step,5 has been investigated
by the group of Sanders, using the template directed
synthesis of cyclic porphyrin-acetylene structures; how-
ever, this method is restricted to metal-containing com-
pounds.6 We are interested in shape-persistent macro-
cycles containing both nonpolar and polar side groups in
a switchable arrangement, which have been prepared by
the intermolecular Glaser coupling of two rather large
and rigid bisacetylenes. In order to reduce the number
of synthetic steps, we became interested in using small
and easily preparable starting materials like 6 for the
cyclization step.
a
Key: (a) 3-bromo-1-propanol, K2CO3, DMF, 70 °C (92%); (b)
t-BuMe2SiCl, imidazole, DMF, rt (87%); (c) 3, PdCl2(PPh3)2, CuI,
piperidine, 60 °C (91%); (d) Bu4NF, THF, rt (92%); (e) p-toluic acid
chloride, pyridine, THF, rt (80%); (f) CuCl/CuCl2, pyridine, rt; GPC
diagram of 6 (I) and of the crude product of the cyclization of 6
(II).
Scheme 1 illustrates the synthesis of the protected
amphiphilic bisacetylene 6 and its cyclization. Protection
of the free OH group of 5 as an aryl ester and cyclization
of 6 by a modified Eglington-Glaser coupling using high
dilution conditions gave a mixture of different oligomers,
as determined by gel permeation chromatography (GPC).7
The fact that we were not able to detect residual
1
absorptions for acetylenic protons in the H-NMR spectra
supports the assumption that a mixture of cyclic oligo-
mers and cyclic or noncyclic polymers was formed. The
smallest cyclic product of the reaction, the cyclic trimer,
was only formed in about 20-25% yield and, moreover,
due to their similar physical properties we were not able
to separate the reaction products by recrystallization or
column chromatography.8
* To whom correspondence should be addressed. Fax: Int. + 6131/
379 100. E-mail: hoeger@mpip-mainz.mpg.de.
(1) Selected reviews and some new examples: (a) Tour, J . M. Chem.
Rev. 1996, 96, 537. (b) Bunz, U. H. F. Angew. Chem., Int. Ed. Engl.
1994, 33, 1073. (c) Timmermann, P.; Verboom, W.; van Veggel, F. C.
J . M.; van Hoorn, W. P.; Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl.
1994, 33, 1292. (d) Ho¨ger, S.; Enkelmann, V. Angew. Chem., Int. Ed.
Engl. 1995, 34, 2713.
Our approach now is to circumvent the low yield of the
statistical intermolecular reaction described above and
still retain the advantage of small and easily preparable
bisacetylenes. Therefore, we present here a template-
directed synthesis of shape-persistent macrocycles based
on the phenylacetylene backbone by using the Glaser
coupling as the bond-forming step and a covalent linkage
of the monomers to the template.9 For this purpose, the
(2) Host molecules based on phenylacetylene structures: (a) Mor-
rison, D. L.; Ho¨ger, S. J . Chem. Soc., Chem. Commun. 1996, 2313. (b)
Anderson, H. L.; Sanders, J . K. M. J . Chem. Soc., Chem. Commun.
1989, 1714. (c) Mackeay, L. G.; Anderson, H. L.; Sanders, J . K. M. J .
Chem. Soc., Chem. Commun. 1992, 43. (d) Anderson, S.; Neidlein, U.;
Gramlich, V.; Diederich, F. Angew. Chem., Int. Ed. Engl. 1995, 34,
1596.
(3) Staab, H. A.; Neunhoeffer, K. Synthesis 1974, 424.
(4) Zhang, J .; Pesak, D. J .; Ludwig, J . L.; Moore, J . S. J . Am. Chem.
Soc. 1994, 116, 4227.
(5) (a) de Meijere, A.; Kozhushkov, S.; Haumann, T.; Boese, R.; Puls,
C.; Cooney, M. J .; Scott, L. T. Chem. Eur. J . 1995, 1, 124. (b) Boldi, A.
M.; Diederich, F. Angew. Chem., Int. Ed. Engl. 1994, 33, 486.
(6) For recent articles dealing with template reactions see: (a)
Anderson, S.; Anderson, H. L.; Sanders, J . K. M. Acc. Chem. Res. 1993,
26, 469. (b) Hoss, R.; Vo¨gtle, F. Angew. Chem., Int. Ed. Engl. 1994,
33, 375. (c) Dietrich, B.; Viout, P.; Lehn, J .-M. Macrocyclic Chemistry;
VCH: Weinheim, 1993; Chapter 3.3.
(7) The GPC diagrams were measured in THF, and a UV detector
operating at λ ) 254 nm was used. The molecular weight was obtained
from polystyrene calibration of the GPC columns.
(8) To confirm that it is actually the cyclic trimer, we esterified
compound 9 and compared the GPC diagram with the one obtained
for the cyclization of 6.
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