Preparation of a rigid macrocycle with two exotopic phenanthroline binding sites

Article abstract of DOI:10.1055/s-1999-2714

The preparation of the first rigid macrocyclic bisphenan-throline with exotopic binding sites is described using a series of Sonogashira coupling reactions.

Full text of DOI:10.1055/s-1999-2714

750
LETTER
Preparation of a Rigid Macrocycle with Two Exotopic Phenanthroline Binding
Sites
Michael Schmittel,* Horst Ammon
Institut für Organische Chemie der Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany
New address: FB 8 (Chemie - Biologie), Organische Chemie I, Universität GH Siegen, Adolf Reichwein Str., D-57068 Siegen, Germany
Fax: + 49 271 740 3270, E-mail: schmittel@chemie.uni-siegen.de
Received 1 March 1999
alternative reaction sequence that provided high yields in
Abstract: The preparation of the first rigid macrocyclic bisphenan-
a reproducible manner.
throline with exotopic binding sites is described using a series of
Sonogashira coupling reactions.
Key words: phenanthroline, bisphenanthroline, macrocyclization,
Sonogashira coupling
Over the last years macrocyclic phenanthrolines1 with en-
dotopic coordination sites have attracted a lot of attention
due to their key role in the formation of catenanes,2 rotax-
anes,3 concave reagents4 and molecular knots.5 More re-
cently, a vivid interest has emerged to prepare
macrocyclic systems with exotopic binding sites, because
such systems (phenanthrolines6 A or bipyridines B7) offer
a huge potential for the preparation of novel metallosu-
pramolecular structures.
Our current research aims at using ligands A in combina-
tion with linear bisphenanthrolines and Cu+ to prepare re-
Scheme 1 Preparation of supramolecular bisheteroleptic phenanthro-
dox active molecular box structures (such as F see
Scheme 1). However, when we reacted C with D8 follow-
ing our concept6b of preparing bisheteroleptic copper(I)
phenanthroline complexes, the [1+1] adduct E was ob-
tained exclusively. This finding emphasizes the need of
available rigid macrocycles in order to realize box struc-
tures of type F.
line complexes.
We started from p-bromoaniline (5), which was first di-
azotized in sulfuric acid and then converted to 6 (73%) by
addition of a KI-solution. After a Sonogashira coupling
with trimethylsilylacetylene replacing selectively the io-
dine in 6 at room temperature, 7 could be isolated in a
yield of 98%. Subsequently, at higher temperature and
longer reaction time the bromine atom in 7 was substitut-
ed by triisopropylsilylacetylene to furnish 8 in 98%. After
selective removal of the TMS protecting group the mono-
protected spacer unit 9 was afforded in a yield of 89%.
To prepare a rigid macrocyclic bisphenanthroline of type
A we started from our highly soluble phenanthroline
building block 1,9 which we wanted to combine with the
linear spacer 2 and the connecting unit 3 using a series of
Sonogashira couplings to assemble our target macrocycle
4 following the Moore protocol.10
In practice, spacer 2 had to be protected in order to avoid
problems during the coupling with 1. Recently, the
TIPS protected diethynylbenzene 9 was described by
Dixneuf,11 but in our hands his procedure proved to be
very tricky and capricious. Hence, we constructed 9 in an
The preparation of connecting unit 3 posed no problems.
According to a method of Kajigaeshi12 phenol 10 (Scheme
4) was converted to the diiodo compound 11 in 87% using
[PhCH2NMe3]+[ICl2]-. Diiodide 3 was then obtained after
Synlett 1999, No. 6, 750–752 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Preparation of a Rigid Macrocycle with Two Exotopic Phenanthroline Binding Sites
751
reacting 11 with methyl iodide in the presence of
K2CO3.13
Scheme 4
Scheme 2
Scheme 5
As expected, the macrocyclization proved to be tricky.
Best yields were obtained for the final step when the
cyclization to 4 was carried out by adding a solution of 13
and 14 dropwise (32 h) to a highly diluted solution of
Pd(PPh3)4 in benzene at reflux. Rewardingly, a pale yel-
low analytically pure solid (16%), which could unambi-
guously be identified by its characteristic NMR14 and
APCI15 data as the desired macrocycle 4, precipitated after
several hours from a solution of the crude product in chlo-
roform. Originally, the tiny brittle needles obtained by
precipitation from chloroform could not be dissolved in
any usual solvent, even at elevated temperature, but upon
protonation one readily obtained a solution of 4∑2H+ in
chloroform or dichloromethane. Deprotonation of 4∑2H+
furnished a solution of 4 in chloroform, from which the
pale yellow solid precipitated again after 0.5-2 h depend-
Scheme 3
With the necessary building blocks (Scheme 2) at hand we
started to attach the protected spacer unit 9 to the phenan-
throline 1 using a Sonogashira coupling at higher temper-
ature in a yield of 91% (Scheme 5). After removing the
TIPS protecting group with (n-Bu)4NF, the resulting
phenanthroline 13 was reacted with the connecting unit 3
in large excess (10-fold) affording 14 in 84%.
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752
M. Schmittel, H. Ammon
LETTER
(3) a) Zhu, S. S.; Swager, T. M. J. Am. Chem. Soc. 1997, 119,
ing on the concentration of the solution. NMR in-
vestigations during this time displayed sharp resonances
for all protons in the beginning but after a while the 2,9-
and 5,6-proton signals at the phenanthroline core started
to broaden. All other signals remained sharp during ag-
gregation. We interpret the broadening of signals solely at
the phenanthroline cores as an indication that formation of
the aggregate16 almost exclusively involves the bisimine
units (Figure 1).
12568; b) Solladié, N.; Chambron, J.-C.; Dietrich-Buchecker,
C. O.; Sauvage, J.-P. Angew. Chem. 1996, 108, 957; Angew.
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Int. Ed. Engl. 1990, 29, 1154; b) Zhu, S. S.; Caroll, P. J.;
Swager, T. M. J. Am. Chem. Soc. 1996, 118, 8713.
(6) a) Schmittel, M.; Ganz, A. Synlett, 1997, 710; b) Schmittel,
M.; Ganz, A. Chem. Commun. 1997, 999.
(7) a) Kelly, T. R.; Lee, Y.-J.; Mears, R. J. J. Org. Chem. 1997,
62, 2774; b) Kaes, C.; Hosseini, M.; Rickard, C. E. F.;
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Hosseini, M. W.; Cian, A. De; Fischer, J. Tetrahedron Lett.
1997, 38, 3901.
In conclusion, we report the first preparation of a rigid
macrocyclic ring system with exotopic phenanthroline
binding sites. Despite the planar structure macrocycle 4
exhibits sufficient solubility to make it a key building
block for our approach to molecular boxes, such as F
(Scheme 1). We will report the realization of these novel
structures in due course.
(8) Schmittel, M.; Michel, C.; Ganz, A.; Herderich, M. J. Prakt.
Chem. 1999, 341, 228.
(9) Solubility of 1: 1079 mg in 1 ml of chloroform; Schmittel, M.;
Ammon, H. Synlett, 1997, 1096.
(10) a) Zhang, J.; Pesak, D. J.; Ludwick, J. L.; Moore, J. S. J. Am.
Chem. Soc. 1994, 116, 4227; b) Bedard, T. C.; Moore, J. S. J.
Am. Chem. Soc. 1995, 117, 10662; c) Stang, P. J.; Diedrich, F.;
Modern Acetylene Chemistry, VCH Weinheim, 1995.
(11) Lavastre, O.; Ollivier, L.; Dixneuf, P. H. Tetrahedron, 1996,
52, 5495. The conditions of the diazotization step proved to be
very critical since they led to partial deprotection of the
trimethylsilylethynyl group.
Figure 1 Cartoon describing aggregation of the macrocycle 4.
Acknowledgement
(12) Kajigaeshi, S.; Kakinami, T.; Moriwaki, M.; Watanabe, M.;
Fujisaki, S.; Okamoto, T. Chem. Lett. 1988, 795.
Generous financial support from the Deutsche For-
schungsgemeinschaft and the Fonds der Chemischen Industrie is
gratefully acknowledged.
(13) Helgeson, R. C.; Selle, B. J.; Goldberg, I.; Knobler, C. B.;
Cram, D. J. J. Am. Chem. Soc. 1993, 115, 11506.
(14) 1H-NMR (CDCl3/5% TFA, 200 MHz): δ = 0.93 (t, J = 6.9 Hz,
12 H, 6'-H), 1.33-1.64 (m, 24 H, 3'-, 4'-, 5'-H), 1.40 (s, 18 H,
13''-H), 1.80-2.00 (m, 8 H, 2'-H), 3.25 (t, J = 6.0 Hz, 8 H, 1'-
H), 4.30 (s, 6 H, 15''-H), 7.61 (s, 4 H, 10''-H), 7.72 (d, J = 8.6
Hz, 8 H, 5''-H), 7.80 (d, J = 8.6 Hz, 8 H, 4''-H), 8.74 (s, 4 H, 5-
, 6-H), 9.10 (s, 4 H, 2-, 9-H).
References and Notes
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Faraday Trans. 1997, 93, 4145; d) Kern, J.-M.; Sauvage, J.-
P.; Weidmann, J.-L.; Armaroli, N.; Flamigni, L.; Ceroni, P.;
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547, 281; f) Bazzicalupi, C.; Bencini, A.; Fusi, V.; Giorgi, C.;
Paoletti, P.; Valtancoli, B. Inorg. Chem. 1998, 37, 941.
(2) a) Dietrich-Buchecker, C.; Frommberger, B.; Lüer, I.;
Sauvage, J.-P.; Vögtle, F. Angew. Chem. 1993, 105, 1526,
Angew. Chem., Int. Ed. Engl. 1993, 32, 1434; b) Amabilino,
D. B.; Ashton, P. R.; Reder, A. S.; Spencer, N.; Stoddart, J. F.
Angew. Chem. 1994, 106, 450, Angew. Chem., Int. Ed. Engl.
1994, 33, 433.
(15) Mass spectrum (APCI): Found: m/z 1515 =
[12C10913C1H104N4O2]H+
(16) Mitchell, P. R. J. Chem. Soc. Dalton 1980, 1079.
Article Identifier:
1437-2096,E;1999,0,06,0750,0752,ftx,en;G08899ST.pdf
Synlett 1999, No. 6, 750–752 ISSN 0936-5214 © Thieme Stuttgart · New York