A new approach for the design of novel hexa-host molecules

Article abstract of DOI:10.1016/S0040-4039(01)00950-9

A synthesis of novel hexa-host molecules 1 and 2 by a Pd/Cu-catalyzed cross coupling reaction of the hexakis(4-iodophenoxymethyl)benzene 9 with the corresponding acetylenes 11 or 12 is described.

Full text of DOI:10.1016/S0040-4039(01)00950-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5123–5126
A new approach for the design of novel hexa-host molecules
Ahmed H. M. Elwahy*
Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt
Received 20 March 2001; revised 23 May 2001; accepted 1 June 2001
Abstract—A synthesis of novel hexa-host molecules 1 and 2 by a Pd/Cu-catalyzed cross coupling reaction of the hexakis(4-
iodophenoxymethyl)benzene 9 with the corresponding acetylenes 11 or 12 is described. © 2001 Published by Elsevier Science Ltd.
During recent decades organic hosts that form inclusion
compounds have attracted a great deal of interest.1,2
These compounds have been studied as models for the
processes of molecular recognition via intermolecular
interactions as well as for their abilities to store or
separate guest molecules.3,4 Certain structural features
present in host compounds can maximize opportunities
for inclusion complex formation. These features
include, in addition to the shape of the host molecules,
the presence of a rotational axis of symmetry.5 A wide
range of inclusion behavior has been established for
molecules of the hexa-host type. Suitably hexa-substi-
tuted benzene derivatives as hosts and complex forming
ligands with a great underlying potential have received
considerable attention in recent years.5,6
pared in 80% yield by reacting the potassium salt of
4-hydroxybenzaldehyde
4
with
hexakis(bromo-
methyl)benzene 38 in refluxing DMF for 30 minutes.
Unfortunately, attempted conversion of the aldehyde 5
into the corresponding alkyne 6 by a sequence of
reactions starting from a Wittig-type condensation of
5
with the ylide derived from dibromomethyl-
triphenylphosphonium bromide in THF containing t-
BuOK were unsuccessful. This may be attributed to the
inherent insolubility of the aldehyde in the reaction
mixture.
In the second strategy (Scheme 2) we attempted to
prepare 6 by utilizing the elegant synthetic approach
demonstrated by Hagihara9 to mono- and diethynylare-
nes and the modified synthetic approach by Vollhardt
and others10 to poly(ethynyl)arenes. In these synthetic
approaches, aryl halides and trimethylsilylacetylene
(TMSA) are coupled in the presence of catalytic cop-
per(I) iodide–dichlorobis(triphenylphosphine) palladiu-
m(II) with secondary or tertiary amines as solvent and
base. For this, hexakis(4-iodophenoxymethyl)benzene 9
was prepared and coupled with (TMSA) at 100°C in a
triethylamine–piperidine mixture. Unfortunately, under
these conditions we could not isolate a pure sample of
the corresponding hexakis(4-trimethylsilylethynylphen-
oxymethyl)benzene 11. The reaction instead gave a
mixture of products that were not easily handled and
have not been characterized as yet. Compound 9 was
obtained in 77% yield by sixfold substitution of 3 with
six equivalents of the potassium salt of 8 in refluxing
DMF for 30 minutes. We could also prepare hexakis-
(phenoxymethyl)benzene 10 by reacting 3 with potas-
sium phenoxide in refluxing DMF in a moderate yield
(70%) and short time (30 min) after modification of the
literature procedure.11 It is noteworthy to mention that
inclusion behavior has been established for 8 and other
related compounds.6,11,12
In connection with current interest in the design of
multimolecular host systems, we report herein our
efforts to generate novel sixfold branched phenyl-
acetylenes 1 and 2, which are linked to the core via
phenoxymethylene spacers.
Two strategies have been attempted for the synthesis of
the target molecules 1 and 2. In the first strategy
(Scheme 1) we studied the synthesis of hexakis(4-
ethynylphenoxymethyl)benzene 6 from the correspond-
ing aldehyde 5 via a modified Corey–Fuchs reaction.7
Compound 6 should then undergo a Pd/Cu-catalyzed
cross coupling reaction with the appropriate aryl
halides to give compounds 1 and 2. For this purpose,
hexakis(4-formylphenoxymethyl)benzene
5 was pre-
Keywords: ethynylbenzenes; Pd/Cu-cross coupling reaction;
poly(phenylethynylphenoxymethyl)benzenes.
* Corresponding author. E-mail: aelwahy@chem-sci.cairo.eun.eg
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00950-9

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A. H. M. Elwahy / Tetrahedron Letters 42 (2001) 5123–5126
In a search for an expedient pathway to prepare 1 and
2 our attention focused on compound 9 as a precursor
which should then undergo further coupling with the
appropriate ethynylarenes with the Pd/Cu catalytic sys-
tem. Thus, six equivalents of phenylacetylene could be
coupled with 9 at 100°C in the presence of bis-
(triphenylphosphine) palladium chloride and CuI in a
triethylamine–piperidine mixture to give a 75% yield of
1 as pale yellow crystals.
conditions afforded 2 in 70% yield, as orange crystals.
The symmetry of compounds 1 and 2 are manifested
by a single set of signals in the 1H and 13C NMR
spectra.
Physical data for compounds 1, 2, 5, 9 and 1014,15
1: Pale yellow crystals (ethyl acetate/petroleum ether),
mp 276–278°C; MS (ESI) m/z (%) 1316 (100%); 1H
NMR (CDCl3) l 5.23 (s, 12H, OCH2), 6.85–7.51 (m,
54H, ArH); 13C NMR (CDCl3) l 63.79 (OCH2), 88.55,
89.13 (CꢀC), 114.74, 116.52, 123.52, 128.11, 128.40,
131.58, 133.28, 137.90, 158.33.
The same methodology can be extended to the prepara-
tion of 2. Thus, reaction of 9 with 6 equivalents of
1-ethynyl-4-(phenylethynyl)benzene 1213 under similar
Scheme 1.

A. H. M. Elwahy / Tetrahedron Letters 42 (2001) 5123–5126
5125
Scheme 2.
1
2: Orange crystals (DMF), mp 238–240°C; H NMR
(DMSO) l 5.39 (s, 12H, OCH2), 6.9–7.54 (m, 78H,
ArH); 13C NMR (DMSO) l 63.96 (OCH2), 87.23,
88.34, 90.56, 90.58 (CꢀC), 114.49, 114.84, 121.66,
122.45, 127.82, 127.95, 130.66, 130.72, 132.15, 136.92,
158.20.
Springer-Verlag: Berlin, 1988 and 1989; Vols. 140 and
149.
3. Toda, F.; Tanaka, K.; Ueda, H. Tetrahedron Lett. 1983,
22, 4669.
4. Bourne, S. A.; Nash, K. L. G.; Toda, F. J. Chem. Soc.,
Perkin. Trans. 2 1996, 2145.
5. For general discussions concerning inclusion host design,
see: (a) MacNicol, D. D.; Downing, G. A. In Comprehen-
sive Supramolecular Chemistry; MacNicol, D. D.; Toda,
F.; Bishop, R., Eds.; Elsevier Science: Oxford, 1996; Vol.
6, p. 421; (b) Weber, E. In Comprehensive Supramolecular
Chemistry; MacNicol, D. D.; Toda, F.; Bishop, R., Eds.;
Elsevier Science: Oxford, 1996; Vol. 6, p. 535; (c) Toda,
F. In Inclusion Compounds; Atwood, J. L.; Davies, J. E.
D.; MacNicol, D. D., Eds.; Oxford University Press:
Oxford, 1991; Vol. 4, p. 126.
6. For selected recent examples, see: (a) Caira, M. R.;
Coetzce, A.; Koch, K. R.; Nassimbeni, L. R.; Toda, F. J.
Chem. Soc., Perkin Trans. 2 1996, 569; (b) Yang, C.;
Chen, X.-M.; Lu, X.-Q.; Zhou, Q.-H.; Yang, Y. S. Chem.
Commun. 1997, 2041; (c) Hartshorn, C. M.; Stell, P. J.
Angew. Chem., Int. Ed. Engl. 1996, 35, 2655; (d) Marx,
H.-W.; Moulines, F.; Wagner, T.; Astruc, D. Angew.
Chem., Int. Ed. Engl. 1996, 35, 1701.
5: Colorless crystals (acetic acid), mp 224–225°C; MS
1
(ESI) m/z (%) 905 [M++Na, 100%]; H NMR (CDCl3)
l 5.45 (s, 12H, OCH2), 7.08 (d, J=8.7 Hz, 12H, ArH),
7.74 (d, J=8.7 Hz, 12H, ArH), 9.79 (s, 6H, CHO).
9: Colorless crystals (DMF/ethanol), mp 275–277°C; 1H
NMR (DMSO) l 5.34 (s, 12H, OCH2), 6.74 (d, J=8.8
Hz, 12H, ArH), 7.53 (d, J=8.8 Hz, 12H, ArH); 13C
NMR (DMSO) l 64.9 (OCH2), 83.74 (ꢁC-I), 118.24,
137.85, 138.34, 158.78.
10: Colorless crystals (toluene), mp 225–227°C (lit.11
228–229°C); MS (FD): m/z (%) 715 [M+, 100%]; 1H
NMR (DMSO) l 5.19 (s, 12H, OCH2), 6.86–7.27 (m,
30H, ArH); 13C NMR (DMSO) l 63.83 (OCH2), 114.97,
121.58, 129.76, 138.18, 158.73.
7. (a) Corey, E. J.; Fuchs, D. L. Tetrahedron Lett. 1972,
3769–3772; (b) Michel, D.; Gennet, D.; Rassat, A. Tetra-
hedron Lett. 1999, 40, 8575.
Acknowledgements
8. Hexakis(bromomethyl)benzene
3
was obtained by
The author thanks Professor Klaus Hafner, University
of Darmstadt for his continuous help and support.
exhaustive bromomethylation of commercially available
1,3,5-trimethylbenzene followed by bromination follow-
ing a literature procedure: Zavada, J.; Pankova, M.;
Holy, P.; Tichy, M. Synthesis 1994, 1132.
References
9. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetra-
hedron Lett. 1975, 4467–4470; (b) Tohda, Y.; Sono-
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1986, 108, 3150; (b) Weber, E.; Hecker, M.; Koepp, E.;
Orlia, W.; Czugler, M.; Csoregh, I. J. Chem. Soc., Perkin
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2. Molecular Inclusion and Molecular Recognition-Clathrate
I and II. Topics in Current Chemistry; Weber, E., Ed.;

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A. H. M. Elwahy / Tetrahedron Letters 42 (2001) 5123–5126
11. Hardy, A. D. U.; MacNicol, D. D.; Wilson, D. R. J. Chem.
Soc., Perkin Trans. 2 1979, 1011. Compound 8 was
alternatively obtained by cyclotrimerization of butynedi-
oldiphenylether, Rosenthal, U.; Schulz, W. J. Prakt. Chem.
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trimethylsilyl derivative followed by deprotection upon
treatment with aqueous NaOH in THF following the
literature procedure: Lavastre, O.; Cabioch, S.; Dixneuf,
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14. The new compounds described gave correct elemental
analyses.
12. Hardy, A. D. U.; MacNicol, D. D.; Swanson, S.; Wilson,
D. J. Chem. Soc., Perkin Trans. 2 1980, 999.
15. NMR spectra were recorded with a Bruker NMR spec-
trometer WM 300 in CDCl3 or DMSO with tetra-
methylsilane as internal standard. Mass spectra (MS) were
obtained with a Varian 311A instrument.
13. Compound 12 was obtained by Pd/Cu-catalyzed carbon–
carbon coupling of the trimethylsilylethynyl para-iodoben-
zene and phenylacetylene to give the corresponding
.