End-cap exchange of rotaxane by the Tsuji-Trost allylation reaction

Article abstract of DOI:10.1021/ol047639i

(Chemical Equation Presented) Rotaxanes possessing a cinnamyl ester group at the axle terminal were prepared. The terminal end-cap was modified with a bulky malonate ester in excellent yield by the Tsuji-Trost allylation reaction, which was carried out in the presence of a palladium catalyst.

Full text of DOI:10.1021/ol047639i

ORGANIC
LETTERS
2005
Vol. 7, No. 7
1199-1202
End-Cap Exchange of Rotaxane by the
Tsuji Trost Allylation Reaction
−
Nobuhiro Kihara,*,† Seiko Motoda,† Tsutomu Yokozawa,‡ and
Toshikazu Takata*,†,§
Department of Applied Chemistry, Graduate School of Engineering,
Osaka Prefecture UniVersity, Gakuen-cho, Sakai, Osaka 599-8531, Japan,
Department of Applied Chemistry, Kanagawa UniVersity, 3-27-1 Rokkakubashi,
Kanagawa-ku, Yokohama 221-8686, Japan, and Department of Organic and Polymeric
Materials, Tokyo Institute of Technology, Ookayama, Meguro, Tokyo 152-8552, Japan
kihara@chem.osakafu-u.ac.jp
Received November 16, 2004 (Revised Manuscript Received February 3, 2005)
ABSTRACT
Rotaxanes possessing a cinnamyl ester group at the axle terminal were prepared. The terminal end-cap was modified with a bulky malonate
ester in excellent yield by the Tsuji Trost allylation reaction, which was carried out in the presence of a palladium catalyst.
−
A rotaxane is an interlocked compound comprising a
macrocyclic wheel and a dumbbell-shaped axle as compo-
nents.1 The bulky substituents present at the terminal ends
of the axle prevent the dethreading of the axle from the
wheel. Reactions of rotaxane that involve a modification of
the main skeleton are extremely limited because the bond-
scission may lead to the destruction of the interlocked
structure. The rotaxanes whose end-cap group can be
chemically replaced are considered beneficial because several
types of rotaxanes with desired structures and functional
groups can be prepared from a common intermediary
rotaxane by the same chemical procedure. Stoddart has
reported the successful end-cap exchange of phosphonium
salt-terminated rotaxanes by the Wittig reaction.2 Leigh also
reported the end-cap exchange reaction by the transesteri-
fication reaction.3 However, since these reactions were
carried out under strongly basic conditions, the base-sensitive
functional groups show incompatibility with these reactions.
In the course of our study on the chemical modification of
interlocked compounds,4 palladium-catalyzed coupling reac-
tions have caught our attention.5,6 The palladium-catalyzed
coupling reactions are important from the view of end-cap
(2) (a) Rowan, S. J.; Stoddart, J. F. J. Am. Chem. Soc. 2000, 122, 164.
(b) Rowan, S. J.; Cantrill, S. J.; Stoddart, J. F.; White, A. J. P.; Williams,
D. J. Org. Lett. 2000, 2, 759. (c) Chiu, S. H.; Rowan, S. J.; Cantrill, S. J.;
Ridvan, L.; Ashton, P. R.; Garrell, R. L.; Stoddart, J. F. Tetrahedron 2002,
58, 807. (d) Rowan, S. J.; Stoddart, J. F. Polym. AdV. Technol. 2002, 13,
777.
(3) Hannam, J. S.; Lacy, S. M.; Leigh, D. A.; Saiz, C. G.; Slawin, A.
M. Z.; Stitchell, S. G. Angew. Chem., Int. Ed. 2004, 43, 3260.
(4) (a) Takata, T.; Shoji, J.; Furusho, Y. Chem. Lett. 1997, 881. (b)
Furusho, Y.; Shoji, J.; Watanabe, N.; Kihara, N.; Adachi, T.; Takata, T.
Bull. Chem. Soc. Jpn. 2001, 74, 139. (c) Watanabe, N.; Furusho, Y.; Kihara,
N.; Takata, T.; Kinbara, K.; Saigo, K. Bull. Chem. Soc. Jpn. 2001, 74, 149.
(d) Watanabe, N.; Kihara, N.; Takata, T. Org. Lett. 2001, 3, 3519. (e)
Watanabe, N.; Ikari, Y.; Kihara, N.; Takata, T. Macromolecules 2004, 37,
6663.
† Osaka Prefecture University.
‡ Kanagawa University.
§ Tokyo Institute of Technology.
(1) Selected books: (a) In Molecular Catenanes, Rotaxanes and Knots;
Sauvage, J.-P., Dietrich-Buchecker, C., Eds.; Wiley-VCH: Weinheim, 1999.
(b) Raymo, F. M.; Stoddart, J. F. In Templated Organic Synthesis; Diederich,
F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 2000; p 75. (c) Steed, J.
W.; Atwood, J. L. Supramolecular Chemistry; Wiley: Chichester, 2000; p
511.
10.1021/ol047639i CCC: $30.25
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exchange reactions for the following reasons: (i) the course
of the reaction can be controlled by the type of palladium
complex used and (ii) the reaction proceeds under mild
conditions such that high tolerance toward functional groups
is realized. However, a bond scission occurs when a
palladium complex activates a rotaxane, and this may lead
to the destruction of the interlocked structure. This destruc-
tion may be avoided by the use of a bulky palladium complex
as a catalyst. In this paper, we report a highly efficient end-
cap exchange reaction of rotaxanes by the Tsuji-Trost
allylation reaction (Figure 1).
to give the corresponding rotaxane 2a in 93% yield (Scheme
1).8
Scheme 1
The Tsuji-Trost allylation reaction involves the coup-
ling of the allyl ester group with nucleophiles such as the
malonate ester anion. If the malonate ester anion is protona-
ted by the ammonium group present in a rotaxane, the
Tsuji-Trost reaction will not proceed. However, we have
reported that the ammonium group of rotaxanes is barely
acidic due to the strong intramolecular hydrogen-bonding
interaction with the surrounding crown ether.9 Therefore, we
could safely expect that the malonate ester anion maintains
nucleophilicity even in the presence of the ammonium group
of rotaxanes.
Figure 1. Schematic representation of the successful end-cap
exchange reaction of rotaxane. The reactive group (blue square)
must be larger than the cavity of the wheel component even after
its activation to avoid the activation-induced destruction of the
interlocked structure.
A rotaxane system comprising the dibenzo-24-crown-8
(DB24C8) and a secondary ammonium salt (established by
Busch and developed by Stoddart7) was used for the end-
cap exchange reaction in this study. A secondary ammonium
salt bearing a terminal hydroxy group 1a was end-capped
with a bulky acid anhydride 3 in the presence of DB24C8
The Tsuji-Trost allylation reaction of sodium diethyl
allylmalonate (4), bearing an acid-sensitive allyl group and
base-sensitive ester groups, with the cinnamyl ester group
of 2a was investigated in THF using palladium(II) acetate-
dppp as the catalyst system in which dppp was selected as
the bulky ligand. The reaction proceeded unexpectedly
slowly. When the reaction was carried out with 30 mol %
of palladium(II) acetate, 47% of the desired rotaxane 5a was
obtained with a 12% recovery of 2a after 20 h, although
cinnamyl benzoate gave the corresponding allylation product
in 70% yield under the same reaction conditions within 3 h
(5) (a) Tsuji, J. Transition Metal Reagents and Catalysts; Wiley:
Chichester, 2000. (b) Tsuji, J. Palladium Reagents and Catalysts; Wiley:
Chichester, 1995.
(6) Palladium-catalyzed rotaxane synthesis: (a) Stanier, C. A.; O’Connell,
M. J.; Clegg, W.; Anderson, H. L. Chem. Commun. 2001, 493. (b) Stanier,
C. A.; O’Connell, M. J.; Clegg, W.; Anderson, H. L. Chem. Commun. 2001,
787. (c) Michels, J. J.; O’Connell, M. J.; Taylor, P. N.; Wilson, J. S.; Cacialli,
F.; Anderson, H. L. Chem. Eur. J. 2003, 9, 6167. (d) Terao, J.; Tang, A.;
Michels, J. J.; Krivokapic, A.; Anderson, H. L. Chem. Commun. 2004, 56.
(7) (a) Kolchinski, A. G.; Busch, D. H.; Alcock, N. W. J. Chem. Soc.,
Chem. Commun. 1995, 1289. (b) Ashton, P. R.; Glink, P. T.; Stoddart, J.
F.; Tasker, P. A.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 1996, 2,
729. (c) Amabilino, D. B.; Stoddart, J. F. Chem. ReV. 1995, 95, 2725. (d)
Hubin, T. J.; Busch, D. H. Coord. Chem. ReV. 2000, 200-205, 5. (e) Takata,
T.; Kihara, N. ReV. Heteroat. Chem. 2000, 22, 197. (f) Kihara, N.; Takata,
T. J. Synth. Org. Chem. Jpn. 2001, 59, 206.
(8) (a) Kawasaki, H.; Kihara, N.; Takata, T. Chem. Lett. 1999, 1015.
(b) Kihara, N.; Shin, J.-I.; Ohga, Y.; Takata, T. Chem. Lett. 2001, 592. (c)
Kihara, N.; Nakakoji, N.; Takata, T. Chem. Lett. 2002, 924. (d) Watanabe,
N.; Yagi, T.; Kihara, N.; Takata, T. Chem. Commun. 2002, 2720.
(9) Kihara, N.; Tachibana, Y.; Kawasaki, H.; Takata, T. Chem. Lett. 2000,
506.
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Org. Lett., Vol. 7, No. 7, 2005

with complete conversion. The reactivity of the cinnamyl
group in 2a was greatly suppressed (Scheme 2).
2c proceeded smoothly to afford the desired rotaxanes 5b
and 5c in good yields. The results are summarized in Table
1. The yield of 5 increases with a decrease in the amount of
Scheme 2
Table 1. Allylation of 4 with Rotaxanes 2b and 2c Catalyzed
by Palladium Complexesa
rotaxane
Pd catalyst (mol %)
dppp/mol %
yield/%
2b
2b
2b
2c
2c
2c
Pd(OAc)2 (20)
Pd(OAc)2 (10)
Pd(OAc)2 (5)
Pd(OAc)2 (20)
Pd(OAc)2 (10)
Pd2(dba)3 (5)
30
15
10
30
15
15
79
85
96
83
86
51
a Reactions were carried out with 3 equiv of 4 in THF at rt for 20 h.
Yields were determined by isolation.
the catalyst. When 5 mol % of palladium(II) acetate was
used as the catalyst, 5b was obtained in 96% yield.11 The
fact that 5 was obtained in excellent yields indicates that
the ammonium group in rotaxane did not prevent the Tsuji-
Trost allylation reaction. Even though the reaction proceeded
slowly, Pd2(dba)3 can also be used as a catalyst.
It should be noted that the direct preparation of 5 from
any ester of 1, DB24C8, and 4 by the Tsuji-Trost allylation
end-capping reaction is impossible. Unlike the ammonium
group present in a rotaxane, the ammonium group in the
crown ether complex is easily neutralized by 4 that leads to
a loss in the intermolecular interactions, because the com-
plexation of the crown ether is under equilibrium.
Next, we investigated the effect of acylative neutralization
of 2b on the end-cap exchange reaction. For this experiment,
rotaxane 6b was prepared in a manner similar to that
described above and was subjected to the Tsuji-Trost
allylation reaction. Rotaxane 7 was obtained in 76% yield
by a successful end-cap exchange reaction (Scheme 4). Since
There are two possible reasons for the decrease in
reactivity. One of them is the deactivation of the catalyst by
the action of the ammonium group and the other is that the
cinnamyl ester group is protected by the bulky DB24C8
wheel. To demonstrate the effect of the ammonium group,
rotaxane 6a was prepared by the acylative neutralization of
2a,9 and the Tsuji-Trost allylation reaction was investigated
using 6a. When the reaction was carried out under the above-
mentioned conditions, no reaction occurred, and 6a was
recovered quantitatively. This clearly indicates that the
DB24C8 component disturbed the allylation reaction due to
steric hindrance.10 Since the DB24C8 component cannot
thread over the acetamide group, DB24C8 was present
around the cinnamyl group in 6a.
To avoid the retardation of the reaction by the wheel
component, rotaxanes 2b and 2c with longer axles were
prepared from 1b and 1c in 72% and 64% yields, respectively
(Scheme 3). The Tsuji-Trost allylation reactions of 2b and
Scheme 4
Scheme 3
2b afforded 5b in 85% yield under the same reaction
conditions, the reactivity of 6b was slightly lower than that
of 2b. It is obvious that the DB24C8 component acted as a
sterically protective group10 in the allylation of 6b, although
(10) Parham, A. H.; Windisch, B.; Vo¨gtle, F. Eur. J. Org. Chem. 1999,
1233, 3.
Org. Lett., Vol. 7, No. 7, 2005
1201

the steric effect of the DB24C8 component was smaller in
6b than in 6a due to the longer axle of 6b.
In conclusion, we have demonstrated that the Tsuji-Trost
allylation reaction is one of the most effective methods to
carry out the end-cap exchange without triggering the
destruction of the rotaxane structure. Since several palladium
complex-catalyzed coupling reactions are known, it is
possible to design various types of end-cap exchange
reactions for rotaxanes. Based on the high functional group
tolerance of palladium complex-catalyzed reactions, rotax-
anes with a wide variety of functional groups can be
synthesized. Further, the bulky palladium complex itself can
act as the effective end-cap of rotaxanes.
The mechanism of the end-cap exchange reaction is
illustrated in Scheme 5. Palladium(0) species produced from
Scheme 5
Acknowledgment. We acknowledge financial support
from the Ministry of Education, Culture, Sports, Science and
Technology (Grant-in-Aid for Scientific Research (C)) and
Yazaki Memorial Foundation for Science and Technology.
Supporting Information Available: Experimental pro-
cedure and spectroscopic data. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL047639I
(11) Typical Procedure. To a dispersion of sodium hydride (7.8 mg,
0.33 mmol) in THF (0.5 mL) was added diethyl allylmalonate (66 µL, 0.33
mmol), and the mixture was stirred until the solution became transparent.
Rotaxane 2b (128 mg, 0.109 mmol), dppp (4.6 mg, 11.2 µmol), and
palladium acetate (1.3 mg, 5.8 µmol) were added under an argon atmosphere,
and the reaction mixture was allowed to stand at room temperature for 20
h. After water was added, the product was extracted with chloroform. The
organic layer was dried over magnesium sulfate, the solvent was evaporated
in vacuo, and the product was purified by preparative GPC (chloroform) to
obtain 129 mg (96%) of 5b as a pale yellow viscous oil: 1H NMR (CDCl3,
270 MHz) δ 7.55 (br, 2H, NH2), 7.38-7.10 (m, 7H, Ar-H and NH2), 6.90
(s, 8H, Ar-H in crown), 6.78 (d, J ) 8.5 Hz, 2H, Ar-H), 6.37 (d, J )
15.8 Hz, 1H, Ar-CHdC), 5.92-5.80 (m, 1H, CdCH-C), 5.79-5.62 (m,
1H, CHdC), 5.18-5.09 (m, 2H, CdCH2), 4.64-4.60 (m, 2H, Ar-CH2-
N), 4.46-4.07 (m, 12H, O-CH2), 3.85-3.68 (m, 10H, O-CH2), 3.65-
3.55 (m, 4H, O-CH2), 3.42-3.34 (m, 4H, O-CH2), 3.22-3.09 (m, 2H,
N-CH2), 2.77 (d, J ) 7.3 Hz, 2H, CdC-CH2), 2.68 (d, J ) 7.2 Hz, 2H,
CdC-CH2), 1.53-0.95 (m, 32H, CH2 and CH3) ppm.
palladium(II) acetate is coordinated by the bulky dppp ligand.
The oxidative addition of the Pd(0)-dppp complex to the
cinnamyl group affords the allylpalladium(II) complex. The
dissociation of the carboxylate ligand is possible while the
rotaxane structure being retained, since the allylpalladium
group acts as a sterically bulky end-cap. When sodium
diethyl allylmalonate attacks the allylpalladium species, it
yields the allylation product along with the regeneration of
the palladium(0)-dppp complex. Since the attack of the
nucleophile and the release of the palladium moiety occur
simultaneously, the end-cap exchange proceeds without the
destruction of the rotaxane structure.
1202
Org. Lett., Vol. 7, No. 7, 2005