Synthesis of [ n ]rotaxanes by template-directed clipping: The role of the dialkylammonium recognition sites

Article abstract of DOI:10.1021/ol100256w

Linear and rectangular [n]rotaxanes were synthesized by template-directed clipping of heterocrown ether components onto the dumbbell-shaped molecules containing different dialkylammonium recognition sites. The effect of the structure of the dialkylammoniu

Full text of DOI:10.1021/ol100256w

ORGANIC
LETTERS
2010
Vol. 12, No. 8
1712-1715
Synthesis of [n]Rotaxanes by
Template-Directed Clipping: The Role of
the Dialkylammonium Recognition Sites
Jun Yin, Suvankar Dasgupta, and Jishan Wu*
Department of Chemistry, National UniVersity of Singapore, 3 Science DriVe 3,
Singapore, 117543
chmwuj@nus.edu.sg
Received February 1, 2010
ABSTRACT
Linear and rectangular [n]rotaxanes were synthesized by template-directed clipping of heterocrown ether components onto the dumbbell-
shaped molecules containing different dialkylammonium recognition sites. The effect of the structure of the dialkylammonium sites on the
clipping efficiency was investigated, and selective clipping led to formation of a rectangular [4]rotaxane.
Interlocked molecules based on rotaxanes, catenanes, mo-
lecular knots, and molecular necklaces1 have been widely
developed due to their potential application in molecular-
scale functional devices.2 For example, rotaxanes have been
used as molecular switches within nanoelectronics,3 artificial
muscles,4 macroscopic liquid transport,5 and mesoporous
silica-mounted nanovalves.6 Therefore, there have been a
large number of rotaxanes synthesized by diversified ap-
proaches such as clipping, slipping, capping, active templates,
and others.7 In the clipping approach, a dumbbell-shaped
component recognizes and binds the macrocyclic precursors
and simultaneously templates the formation of the macro-
cycles around recognition sites. For example, Stoddart’s
group8 reported efficient synthesis of [n]rotaxanes by clipping
two components of a 24-crown-8 heterocrown ether, the 2,6-
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Ratner, M., Eds.; New York Academy of Sciences: New York, 1998. (b)
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J.; Raymo, F. M.; Stoddart, J. F.; Heath, J. R. Science 2000, 289, 1172–
1175. (c) Yu, H.; Luo, Y.; Beverly, K.; Stoddart, J. F.; Tseng, H.-R.; Heath,
J. R. Angew. Chem., Int. Ed. 2003, 42, 5706–5711. (d) Choi, J. W.; Flood,
A. H.; Steuerman, D. W.; Nygaard, S.; Braunschweig, A. B.; Moonen,
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J. O.; Xu, K.; Stoddart, J. F.; Heath, J. R. Chem.sEur. J. 2006, 12, 261–
279. (e) Green, J. E.; Choi, J. W.; Boukai, A.; Bunimovich, Y.; Johnston-
Halperin, E.; Delonno, E.; Luo, Y.; Sheriff, B. A.; Xu, K.; Shin, Y. S.;
Tseng, H.-R.; Stoddart, J. F.; Heath, J. R. Nature 2007, 445, 414–417.
(2) (a) Sauvage, J. P., Dietrich-Buchecker, C., Eds. Molecular Catenanes,
Rotaxanes and Knots: A Journey through the World of Molecular Topology;
Wiley VCH: Weinheim, 1999. (b) Pease, A. R.; Jeppesen, J. O.; Stoddart,
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10.1021/ol100256w  2010 American Chemical Society
Published on Web 03/15/2010

pyridinedicarboxaldehyde 4 and the tetraethylene glycol
bis(2-aminophenyl)ether 5 (Figure 1), onto dumbbell-shaped
Scheme 1
Figure 1
molecules containing dialkylammonium sites, and a similar
method was also adopted by other groups.9
In all these cases, the recognition sites have a common
dibenzylammonium moiety (i.e., in 1). However, no one has
studied the effect of different dialkylammonium structures,
e.g., a benzyl-aliphatic alkylammonium (2) or an arylben-
zylammonium (3), on the efficiency of the clipping reaction.
Herein, dumbbell-shaped molecules 3, 7, and 10 with
different ammonium structures were prepared, and their
clipping was investigated in detail. Synthesis of some new
supramolecular architectures by selective clipping was also
exploited.
reversible dynamic imine, which was reduced by NaBH4 in
the solution of THF and MeOH to give the kinetically stable
amine (C-NH). Protonation of the free amine with excess of
TFA and subsequent counterion exchange with saturated
NH4PF6 solution afforded the unsymmetrical dialkylammo-
niums 7 in 85% yield for three steps. The compound 10 with
dibenzylammonium and unsymmetrical benzyl-aliphatic alky-
lammonium units was synthesized through a similar method.
The diester 810 with Boc-protected alkyldiamines was
reduced by LiAlH4, and the obtained alcohol was oxidized
by pyridinium chlorochromate (PCC) to give the desired
dialdehyde 9, which was then treated with 3,5-dimethoxy-
benzylamine to afford the desired imine. After reduction with
NaBH4, the Boc protective groups were deprotected with
excess TFA, and the as-formed amines were simultaneously
protonated. Subsequent counterion exchange with saturated
NH4PF6 afforded 10 in 75% yield for three steps. Similarly,
compound 3 was prepared in 92% yield by condensation of
4-tert-butylaniline and 3,5-dimethoxybenzaldehyde followed
by reduction, protonation, and counterion exchange.
Scheme 1 outlines the synthesis of dumbbell-shaped
ammoniums 7 and 10. Condensation of 1,6-hexanediamine
with 3,5-dimethoxybenzaldehyde gave the corresponding
(4) (a) Jime´nez-Molero, M. C.; Dietrich-Buchecker, C.; Sauvage, J.-P.;
De Cian, A. Angew. Chem., Int. Ed. 2000, 39, 1295–1298. (b) Collin, J.-
P.; Dietrich-Buchecker, C.; Gavin˜a, P.; Jimenez-Molero, M. C.; Sauvage,
J.-P. Acc. Chem. Res. 2001, 34, 477–487. (c) Huang, T. J.; Brough, B.;
Ho, C.-M.; Liu, Y.; Flood, A. H.; Bonvallet, P. A.; Tseng, H.-R.; Stoddart,
J. F.; Baller, M.; Magonov, S. Appl. Phys. Lett. 2004, 85, 5391–5393. (d)
Liu, Y.; Flood, A. H.; Bonvallet, P. A.; Vignon, S. A.; Northrop, B. H.;
Tseng, H.-R.; Jeppesen, J. O.; Huang, T. J.; Brough, B.; Baller, M.;
Magonov, S.; Solares, S. D.; Goddard, W. A.; Ho, C.-M.; Stoddart, J. F.
J. Am. Chem. Soc. 2005, 127, 9745–9759. (e) Wu, J.; Leung, K. C. F.;
Ben´ıtez, D.; Han, J. Y.; Cantrill, S. J.; Fang, L.; Stoddart, J. F. Angew.
Chem., Int. Ed. 2008, 47, 7470–7474.
(5) Berna´, J.; Leigh, D. A.; Lubomska, M.; Mendoza, S. M.; Pe´rez,
E. M.; Rudolf, P.; Teobaldi, G.; Zerbetto, F. Nat. Mater. 2005, 4, 704–
710.
The clipping reaction was first tested for 3 by mixing
together equimolar amounts of 3-5 in CD3CN, and the
clipping process was followed by 1H NMR spectroscopy.
A complicated mixture containing the oligomers (Schiff
base) of the condensation product of 4 and 5 was observed
after 1 day, but there was no evidence that a [2]rotaxane
was formed. In contrast, the clipping reaction of diben-
zylammonium type molecules (e.g., 1) under similar
conditions gave the respective rotaxanes in nearly quan-
titative yield.8 We then tested the clipping reaction of 7
(6) (a) Hernandez, R.; Tseng, H.-R.; Wong, J. W.; Stoddart, J. F.; Zink,
J. I. J. Am. Chem. Soc. 2004, 126, 3370–3371. (b) Nguyen, T. D.; Tseng,
H.-R.; Celestre, P. C.; Flood, A. H.; Liu, Y.; Stoddart, J. F.; Zink, J. I.
Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 10029–10034. (c) Nguyen, T. D.;
Liu, Y.; Saha, S.; Leung, K. C. F.; Stoddart, J. F.; Zink, J. I. J. Am. Chem.
Soc. 2007, 129, 626–634. (d) Saha, S.; Leung, K. C. F.; Nguyen, T. D.;
Stoddart, J. F.; Zink, J. I. AdV. Funct. Mater. 2007, 17, 685–693.
(7) Yin, J.; Chi, C.; Wu, J. Chem.sEur. J. 2009, 15, 6050–6057.
(8) (a) Glink, P. T.; Oliva, A. I.; Stoddart, J. F.; White, A. J. P.; Williams,
D. J. Angew. Chem., Int. Ed. 2001, 40, 1870–1875. (b) Horn, M.; Ihringer,
J.; Glink, P. T.; Stoddart, J. F. Chem.sEur. J. 2003, 9, 4046–4054. (c)
Arico´, F.; Chang, T.; Cantrill, S. J.; Khan, S. I.; Stoddart, J. F. Chem.sEur.
J. 2005, 11, 4655–4666. (d) Leung, K. C.-F.; Arico´, F.; Cantrill, S. J.;
Stoddart, J. F. Macromolecules 2007, 40, 3951–3959. (e) Haussmann, P. C.;
Khan, S. I.; Stoddart, J. F. J. Org. Chem. 2007, 72, 6708–6713. (f) Wu, J.;
Leung, K. C.-F.; Stoddart, J. F. Proc. Natl. Acad. Sci. U.S.A. 2007, 104,
17266–17271. (g) Leung, K. C.-F.; Wong, W.-Y.; Arico´, F.; Haussmann,
P. C.; Stoddart, J. F. Org. Biomol. Chem. 2010, 8, 83–89.
1
with 2 equiv each of 4 and 5 in CD3CN. Based on H
NMR spectroscopic analysis, a dynamic8 [3]rotaxane was
formed together with some uncomplexed and partially
complexed dumbbell compounds and imine oligomers. The
mixture was treated with BH3·THF to reduce the dynamic
imine bond into the kinetically stable C-NH bond, and
(9) (a) Yoon, I.; Narita, M.; Goto, M.; Shimizu, T.; Asakawa, M. Org.
Lett. 2006, 8, 2341–2344. (b) Narita, M.; Yoon, I.; Aoyagi, M.; Goto, M.;
Shimizu, T.; Asakawa, M. Eur. J. Inorg. Chem. 2007, 4229–4237. (c) Zhou,
W.; Li, J.; He, X.; Li, C.; Lv, J.; Li, Y.; Wang, S.; Liu, H.; Zhu, D.
Chem.sEur. J. 2008, 14, 754–763. (d) Klivansky, L. M.; Koshkakaryan,
G.; Cao, D.; Liu, Y. Angew. Chem., Int. Ed. 2009, 48, 4185–4189.
(10) Ashton, P. R.; Baldoni, V.; Balzani, V.; Credi, A.; Hoffmann,
H. D. A.; Mart´ınez-D´ıaz, M.-V.; Raymo, F. M.; Stoddart, J. F.; Venturi,
M. Chem.sEur. J. 2001, 7, 3482–3493.
Org. Lett., Vol. 12, No. 8, 2010
1713

then the [3]rotaxane 11 was separated by column chro-
matography in 86% yield. The H NMR spectrum of the
pure [3]rotaxane 11 is shown in Figure 2B, and compared
The above experiments also indicated that efficiency of
the clipping reaction on different types of ammoniums
followed a priority sequence of 1 > 2 > 3, which is similar
to the studies of threading crown ethers onto different
ammonium sites.11 To exploit the possible self-sorting
clipping, the template 10 containing two different types of
ammonium units was submitted for similar clipping reaction.
A complicated mixture containing various dynamic [n]ro-
taxanes with the crown ether rings randomly located at
different ammonium sites were formed when the ratio of
compounds 4, 5, and 10 was 2:2:1, suggesting that there was
no obvious selectivity between the two types of ammonium
sites. Addition of an additional 2 equiv each of compounds
4 and 5 led to the formation of a dynamic [5]rotaxane
together with some uncomplexed and partially complexed
dumbbell molecules and imine olgiomers. Again, the pure
kinetically stable [5]rotaxane 12 was separated after reduction
of the as-formed dynamic rotaxanes. Compared with the 1H
NMR spectrum of 10 (Figure 2C), the resonances of two
1
+
ammoniums (-NH2 ) displayed similar downfield shifts in
the pure [5]rotaxane 12 (Figure 2D). In addition, the other
resonances such as Ha′, Hb′, Hc′, Hi′, Hj′, and Hk′ of 10 showed
similar upfield shifts. Furthermore, the four crown ether rings
have two different chemical environments (RA and RB) and
as results, some resonances for the protons on crown ethers
(e.g., H3) can be easily distinguished. The structures of the
[5]rotaxane 12 were also confirmed by ESI mass spectrom-
etry (Figure 3B). So, although there was less selectivity on
the clipping reaction, the dumbbell 10 containing different
dialkylammonium sites still could be used to construct a
complex hetero[5]rotaxane 12 in which four same macro-
cylces encircle onto two different types of recognition sites.
Figure 2.
1H NMR spectra (500 MHz in CD3CN at rt) of 7 (A);
[3]rotaxane 11 (B); 10 (C); and [5]rotaxane 12 (D). (Resonance
protons are labeled in Scheme 1.)
with the spectrum of template 7 (Figure 2A), the resonance
of the protons on the stopper units (Ha, Hb and Hc) showed
+
an obvious upfield shift while the ammonium (-NH2
)
displayed a downfield shift. In addition, the resonances
for the central alkyl chain (He, Hf, and Hg) also shifted
upfield due to the shielding effect of the encircling crown
ethers. The structure of 11 was further proved by the ESI
mass spectrometry (Figure 3A).
To further exploit the possibility of using these building
blocks to build up new supramolecular architectures, the
component 4 was replaced by tetraaldehyde 6.8c The clipping
reaction by using compounds 5-7 with the molar ratio of
2:1:1 was conducted. Due to the very poor solubility of 6,
the mixture became nearly clear only after stirring for 15
days at room temperature. A rectangular dynamic [4]rotaxane
was formed as proved by the 1H NMR spectroscopy (Figure
4A) which was in agreement with Stoddart’s study by using
dibenzylammonium sites.8c A characteristic resonance peak
(H3) at 8.31 ppm assigned to imine protons was observed.
+
Compared with 7, the resonances of ammoniums (-NH2 )
in the dynamic [4]rotaxane displayed an obvious downfield
shift. Some resonances assigned to the uncomplexed 5 and
7 were also observed because even after a long time stirring,
there was still some insoluble 6 in the solution. After
reduction by BH3·THF, the pure kinetically stable, rectangular
[4]rotaxane 13 was separated in 67% yield. The well-resolved
1H NMR spectrum of 13 clearly proved its structure (Figure
4B). The ammonium resonances in 13 underwent an upfield
shift along with disappearance of imine protons (H3).
Moreover, the resonance peaks of stopper units (Hb and Hc)
displayed crossed upfield and downfield shift. The structure
Figure 3. ESI mass spectra of [3]rotaxane 11 (A); [5]rotaxane 12
(B); [4]rotaxane 13 (C); and the dynamic [4]rotaxane 14 (D).
(11) (a) Zhang, C.; Li, S.; Zhang, J.; Zhu, K.; Li, N.; Huang, F. Org.
Lett. 2007, 9, 5553–5556. (b) Zhang, C.; Zhu, K.; Li, S.; Zhang, J.; Wang,
F.; Liu, M.; Li, N.; Huang, F. Tetrahedron Lett. 2008, 49, 6917–6920.
1714
Org. Lett., Vol. 12, No. 8, 2010

from 7 (Figure 4A), indicating that the clipping reaction
selectively took place at the dibenzylammonium sites!
Compared with 10, the upfield shift of the resonances (Hb′
and Hc′) on the stopper units further confirmed that the
clipping reaction only happened at the dibenzyl ammonium
1
1
sites. A detailed 2D H-1H COSY and H-1H NOSEY
NMR spectroscopic analysis is given in the Supporting
Information. ESI mass spectrometry also supported the
existence of the dynamic rectangular [4]rotaxane 14, and a
-
single peak at m/z ) 840.8 for [M - 4PF6 - 4HPF6]4+
was observed (Figure 3D). Again, due to the poor solubility
of 6, some resonances for uncomplexed 5 and 10 were found
(Figure 4C). These results also indicated an amplified region-
selectivity in a rectangle-shaped macrocycle under a ther-
modynamic control. When additional amounts of 5 and 6
were added with the molar ratio of 5/6/10 ) 4:2:1, no
1
obvious changes were observed in the H NMR spectrum
of the mixture after stirring for 18 days except that the
relative intensity of the uncomplexed component increased
(Figure 4D), which indicated that such clipping reaction only
selectively took place at the -NH2+ sites close to the stopper
units. The further clipping reaction on the central ammonium
sites was forbidden likely due to steric hindrance when the
crown ether components enter the middle of the as-formed
rectangular macrocycle as well as the poor solubility of 6.
The dynamic rotaxane was also reduced by BH3·THF,
however, the poor solubility of the product limited the
separation of the kinetically stable [4]rotaxane in pure form.
1
Figure 4. Partial H NMR spectra (500 MHz in CD3CN at rt) of
the rectangular dynamic [4]rotaxane based on 7 (A); the kinetically
stable [4]rotaxane 13 (B); the dynamic [4]rotaxane 14 when the
ratio of 5/6/10 ) 2:1:1 (C); and the dynamic [4]rotaxane 14 when
the ratio of 5/6/10 ) 4:2:1 (D). (NC indicates noncomplexed
components.)
In conclusion, a detailed study on the clipping reaction
based on different dialkylammonium templates was reported,
and these new building blocks have been used for efficient
synthesis of several linear and rectangular [n]rotaxanes. In
particular, a regioselective formation of a rectangular [4]ro-
taxane 14 was observed for the first time. Our studies also
indicated possible self-sorting clipping of different macro-
cycles onto different (but similar) recognition sites to form
well-defined heterorotaxanes in the future.
of [4]rotaxane 13 was further confirmed by ESI mass
spectrometry (Figure 3C).
Subsequently, we studied the clipping reaction by mixing
10 together with 2 equiv of 5 and 1 equiv of 6 in CD3CN.
Surprisingly, a regioselective clipping reaction was observed,
and a rectangular dynamic [4]rotaxane 14 in which the crown
ether macrocycles selectively encircled onto the dibenzy-
lammonium sites was formed. As shown in Figure 4C, a
characteristic resonance peak (H3) for imine bonds at 8.51
ppm was observed. Moreover, a more downfield shifted peak
at 10.21 ppm for the complexed -NH2+ close to the stopper
units was clearly observed; however, the other ammoniums
Acknowledgment. This work was financially supported
by an AcRF Tier 1 FRC grant (R-143-000-328-133) and a
NUS Young Investigator Award (R-143-000-356-101).
Supporting Information Available: Details on the syn-
thesis and characterization of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
+
(-NH2 ) close to the hexyl unit did not display any obvious
resonance at about 9.00 ppm like the dynamic [4]rotaxane
OL100256W
Org. Lett., Vol. 12, No. 8, 2010
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