Synthesis of [2]rotaxanes by the catalytic reactions of a macrocyclic copper complex

Article abstract of DOI:10.1021/ol062247s

(Chemical Equation Presented) We synthesized [2]rotaxanes by the reactions catalyzed by a macrocyclic Cu(I)-henanthroline complex. The catalytic site was located inside the ring component so that the rotaxane could be selectively formed. A C-S bond-formin

Full text of DOI:10.1021/ol062247s

ORGANIC
LETTERS
2006
Vol. 8, No. 22
5133-5136
Synthesis of [2]Rotaxanes by the
Catalytic Reactions of a Macrocyclic
Copper Complex
Shinichi Saito,* Eiko Takahashi, and Kazuko Nakazono
Department of Chemistry, Faculty of Science, Tokyo UniVersity of Science,
Kagurazaka, Shinjuku, Tokyo, Japan 162-8601
ssaito@rs.kagu.tus.ac.jp
Received September 11, 2006
ABSTRACT
We synthesized [2]rotaxanes by the reactions catalyzed by a macrocyclic Cu(I)
−phenanthroline complex. The catalytic site was located inside
the ring component so that the rotaxane could be selectively formed. A C
utilized for the efficient synthesis of a new series of [2]rotaxanes.
−S bond-forming reaction and oxidative dimerization of alkyne was
The rotaxanes are an important class of interlocked com-
pounds, and various synthetic methods have been developed.
Among them, the template method has been widely utilized.
Interactions such as metal-ligand bonds, hydrogen bonds,
and ionic interactions and hydrophobic interactions have been
extensively utilized for this synthetic method.1 These transient
bonds were used to keep the precursors of the components
in the desired position so that the rotaxanes could be isolated
in good yields by the end-capping reactions. A large number
of rotaxanes have been synthesized by this method.
formation of the rotaxanes (Scheme 1). For example, Vo¨gtle
et al. achieved the synthesis of rotaxanes by the anion
template method.2 In these reactions, the anion that was used
for the nucleophilic reaction was “trapped” inside the
macrolactam. Subsequent reaction with various electrophiles
resulted in the formation of the corresponding rotaxanes in
good yields. A further extension of this type of synthesis is
the application of a catalytic reaction. Leigh and co-workers
Recently, a new strategy has been developed for the
synthesis of rotaxanes. Thus, the localization of the site of
the reaction inside the ring component leads to the efficient
Scheme 1. “Trapping” Synthesis of [2]Rotaxanes
(1) Reviews: (a) Schill, G. Catenanes, Rotaxanes, and Knots; Academic
Press: New York, 1971. (b) Molecular Catenanes, Rotaxanes and Knots;
Dietrich-Buchecker, C. O., Sauvage, J. P., Eds.; Wiley-VCH: New York,
1999. (c) Sauvage, J. P. Acc. Chem. Res. 1990, 23, 319-327. (d) Hoss, R.;
Vo¨gtle, F. Angew. Chem., Int. Ed. Engl. 1994, 33, 375-384. (e) Amabilino,
D. B.; Stoddart, J. F. Chem. ReV. 1995, 95, 2725-2828. (f) Ja¨ger, R.; Vo¨gtle,
F. Angew. Chem., Int. Ed. Engl. 1997, 36, 930-944. (g) Nepogodiev, S.
A.; Stoddart, J. F. Chem. ReV. 1998, 98, 1959-1976. (h) Sauvage, J. P.
Acc. Chem. Res. 1998, 31, 611-619. (i) Raymo, F. M.; Stoddart, J. F. Chem.
ReV. 1999, 99, 1643-1663.
10.1021/ol062247s CCC: $33.50
© 2006 American Chemical Society
Published on Web 10/04/2006

reported the synthesis of rotaxanes by the Cu(I)-catalyzed
reaction.3 In their study, the catalytic site of the reaction was
located inside the ring, which led to the efficient synthesis
of a rotaxane by the 1,3-cycloaddition of an organic azide
with a terminal alkyne. A substoichiometric amount of Cu
source was sufficient under some reaction conditions since
the Cu source could be transferred among the cyclic
components.
For the synthesis of a stable [2]rotaxane, a precursor with
a large and stable blocking group was required. We chose
the tris(4-biphenyl)methyl group4 as the blocking group and
prepared the precursors which were suitable for the synthesis
of the rotaxanes. The syntheses of an iodoarene (5), thiol
(6), and alkyne (7) are summarized in Scheme 3. Thus,
We have been interested in the possibility of the synthesis
of the rotaxanes by the fixation of the reactive moiety inside
the ring component. Especially, catalytic reactions are very
attractive since a large number of reactions are currently
available. In this paper, we report the synthesis of [2]-
rotaxanes by the catalytic reactions of a macrocyclic Cu-
(I)-phenanthroline complex.
Scheme 3. Synthesis of the Precursors for the Axle
Components
New Cu(I)-phenanthroline complex 2 was prepared in
83% yield by the reaction of macrocyclic phenanthroline 14
with CuI (Scheme 2). Among various Cu-catalyzed reactions,
Scheme 2. Synthesis of Macrocyclic Cu(I)-Phenanthroline
Complex 2
alcohol 37 was brominated and reacted with 4-iodophenol
to yield an iodoarene 5, which would be an adequate
precursor for the C-S bond-forming reaction. Other precur-
sors such as thiol 6 and alkyne 7 were prepared by standard
methods in good yields.
we chose two reactions for the synthesis of [2]rotaxanes.
The C-S bond-forming reaction of alkylthiol with iodoarenes
would proceed in the presence of 2, since it has been recently
shown that the reaction of aryl iodide with thiol proceeded
in the presence of CuI and neocuproine.5 As the second
reaction, the oxidative homocoupling reaction of alkynes
(Glaser coupling, Hay coupling)6 was selected since the
catalytic activity of various Cu complexes has been reported.
We carried out the synthesis of [2]rotaxanes utilizing the
reactions catalyzed by the macrocyclic complex 2. The C-S
bond-forming reaction was examined, and the result is
shown in Scheme 4. The reaction of the iodide 5 with thiol
6 proceeded in the presence of 2 and KOt-Bu as a base, and
rotaxane 8 was isolated in 27% yield. In this reaction it was
necessary to use an excess of 5 as well as 6, and a significant
amount of the cross-coupled product 9 was also isolated.
Since the complete dissociation of Cu species from 2 was
observed when the reaction was completed, the formation
of 9 might be explained by the progress of the reaction that
was catalyzed by the dissociated Cu species.
(2) (a) Hu¨bner, G. M.; Gla¨ser, J.; Seel, C.; Vo¨gtle, F. Angew. Chem.,
Int. Ed. 1999, 38, 383-386. (b) Reuter, C.; Wienand, W.; Hu¨bner, G. M.;
Seel, C.; Vo¨gtle, F. Chem. Eur. J. 1999, 5, 2692-2697. (c) Schmieder, R.;
Hu¨bner, G. M.; Seel, C.; Vo¨gtle, F. Angew. Chem., Int. Ed. 1999, 38, 3528-
3530. (d) Reuter, C.; Vo¨gtle, F. Org. Lett. 2000, 2, 593-595. (e) Hu¨bner,
G. M.; Reuter, C.; Seel, C.; Vo¨gtle, F. Synthesis 2000, 103-108.
(3) Aucagne, V.; Ha¨nni, K. D.; Leigh, D. A.; Lusby, P. J.; Walker, D.
B. J. Am. Chem. Soc. 2006, 128, 2186-2187.
We also examined the oxidative homocoupling of alkyne
7 in the presence of 2. In this reaction, I2 turned out to be a
(4) Saito, S.; Nakazono, K.; Takahashi, E. J. Org. Chem. 2006, 71, 7477-
7480.
(5) Bates, C. G.; Gujadhur, R. K.; Venkataraman, D. Org. Lett. 2002, 4,
2803-2806.
(6) Siemen, P.; Livingston, R. C.; Diedrich, F. Angew. Chem., Int. Ed.
2000, 39, 2632-2657 and references cited therein.
(7) (a) Liu, Q.; Burton, D. J. Tetrahedron Lett. 1997, 38, 4371-4374.
(b) Batsanov, A. S.; Collings, J. C.; Fairlamb, I. J. S.; Holland, J. P.; Howard,
J. A. K.; Lin, Z.; Marder, T. B.; Parsons, A. C.; Ward, R. M.; Zhu, J. J.
Org. Chem. 2005, 70, 703-706.
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Org. Lett., Vol. 8, No. 22, 2006

Scheme 4. Synthesis of a [2]Rotaxane by the Cu-Catalyzed C-S Bond-Forming Reaction
good oxidant,7 and we were pleased to find that the rotaxane
10 was isolated in 72% yield (Scheme 5). It is note-
worthy that only a small excess of 7 was required for this
reaction. The dissociation of the Cu species from 2 was much
slower in this reaction, and it was necessary to add KCN to
the reaction mixture to remove the Cu species completely
from the phenanthroline complex. The observed higher
yield of the rotaxane 10 might be explained in part by the
Scheme 5. Synthesis of a [2]Rotaxane by Cu-Catalyzed Oxidative Coupling of 7
Org. Lett., Vol. 8, No. 22, 2006
5135

shown in Figure 1.10 The observed shifts of the signals are
in accordance with other structurally similar rotaxanes.4 For
example, the signals of the resorcinol moiety of 1 appeared
at δ 6.55 and 6.51 ppm, while those of 10 appeared at δ
6.61 and 6.45 ppm. The upfield shifts of some signals were
also observed. Furthermore, the observed mass spectra of 8
and 10 are strong supporting evidence for the formation of
the rotaxanes.
In summary, we succeeded in the synthesis of [2]rotaxanes
by the reactions catalyzed by a macrocyclic Cu(I)-phenan-
throline complex. The catalytic site was located inside the
ring component so that the rotaxane could be efficiently
formed. Only a small excess of a precursor was required for
the synthesis of a rotaxane in a good yield. The study
provided a new and efficient method for the synthesis of a
new series of [2]rotaxanes. Application of this reaction to
the preparation of rotaxanes as well as other supramolecules
will be reported in due course.
Acknowledgment. We thank the Yamada Science Foun-
dation for financial support.
Supporting Information Available: Detailed experi-
mental procedures and spectral data of 2 and 4-11. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Figure 1. 1H NMR spectra of 1, 10, and 11
OL062247S
higher stability of 2 under the reaction condition shown in
Scheme 5.
(9) Selected data for compound 10: 1H NMR (300 MHz, CDCl3) δ 8.39
(d, J ) 8.7 Hz, 4H), 8.20 (d, J ) 8.7 Hz, 2H), 8.01 (d, J ) 8.7 Hz, 2H),
7.69 (s, 2H), 7.56 (d, J ) 8.4 Hz, 12H), 7.49 (d, J ) 8.4 Hz, 12H), 7.41-
7.27 (m, 34H), 7.11 (t, J ) 8.1 Hz, 1H), 6.98 (d, J ) 8.7 Hz, 4H), 6.72 (d,
J ) 8.7 Hz, 4H), 6.61 (s, 1H), 6.45 (d, J ) 8.4 Hz, 2H), 3.93 (t, J ) 6.3
Hz, 4H), 3.90 (t, J ) 7.2 Hz, 4H), 3.78 (t, J ) 6.5 Hz, 4H), 2.63-2.51 (m,
4H), 1.85-1.69 (m, 8H), 1.67-1.54 (m, 4H), 1.54-1.39 (m, 8H), 1.39-
1.23 (m, 8H), 1.21-1.04 (m, 4H). Anal. Calcd for C144H128N2O6: C, 87.24;
H, 6.51; N, 1.41. Found: C, 87.43; H, 6.56; N, 1.21. HR FAB-MS (M +
H) calcd for C144H129N2O6 1981.9852, found 1981.9851.
The structures of the rotaxanes 88 and 109 were fully
1
characterized. The H NMR spectra of 1, 10, and 11 were
(8) Selected data for compound 8: 1H NMR (300 MHz, CDCl3) δ 8.36
(d, J ) 8.7 Hz, 4H), 8.16 (d, J ) 8.4 Hz, 2H), 7.97 (d, J ) 8.4 Hz, 2H),
7.68 (s, 2H), 7.54-7.24 (m, 56H), 7.08 (t, J ) 8.4 Hz, 1H), 6.92 (d, J )
8.7 Hz, 4H), 6.84 (d, J ) 8.4 Hz, 2H), 6.49 (s, 1H), 6.43 (d, J ) 8.4 Hz,
2H), 3.85-3.74 (m, 10H), 2.74 (t, J ) 7.5 Hz, 2H), 2.61-2.41 (m, 4H),
1.83-1.35 (m, 18H), 1.35-1.00 (m, 14H); HR FAB-MS (M + H) calcd
for C134H125N2O5 1873.9314, found 1873.9309.
(10) See the Supporting Information for the comparison of the 1 H NMR
spectra of 1, 8, and 9.
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Org. Lett., Vol. 8, No. 22, 2006