Tether-assisted synthesis of [3]rotaxane by olefin metathesis

Article abstract of DOI:10.1246/cl.2010.24

The tether-assisted synthesis of [3]rotaxane by olefin metathesis is described. The bis(crown ether)s, in which two crown ethers are connected by a linker, were converted to tethered rotaxanes, followed by removal of the linkers to produce [3]rotaxane. The biscrown structures promoted the formation of the tethered rotaxane, resulting in a notable improvement in the yield of the [3]rotaxane.

Full text of DOI:10.1246/cl.2010.24

doi:10.1246/cl.2010.24
24
Published on the web December 5, 2009
Tether-assisted Synthesis of [3]Rotaxane by Olefin Metathesis
Hajime Iwamoto,*1 Yukimi Yawata,2 Yoshimasa Fukazawa,2 and Takeharu Haino2
1Department of Chemistry, Graduate School of Science and Technology, Niigata University,
2-8050 Ikarashi, Nishi-ku, Niigata 950-2181
2Department of Chemistry, Graduate School of Science, Hiroshima University,
1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526
(Received October 1, 2009; CL-090887; E-mail: iwamoto@chem.sc.niigata-u.ac.jp)
to produce 1¢5¢1. However, this reaction process is sterically
The tether-assisted synthesis of [3]rotaxane by olefin
and entropically unfavorable. The encounter between the two
macrocycles might create a serious steric interaction; one or both
of the macrocycles can slip away from axle precursor 3 to form
the simple axle and/or [2]rotaxane, reducing the production of
[3]rotaxane.
The concept of preorganization is widely accepted in
organic chemistry.7 The covalent connection of two macrocycles
with suitable linkages results in the formation of biscrown
structures. When axle precursors 3 thread into biscrown
structures, the terminal olefins are already preorganized for the
next reaction. The final ester hydrolysis can give rise to the
desired [3]rotaxane (Figure 1).
The synthesis of [3]rotaxane 1¢5¢1 was performed by using
the bis(crown ether)s 2a-2c and the axle precursor 3 under
the following conditions:8 A mixture of 25 mM of 2a-2c and
50 mM of 3 in CH2Cl2 was treated with 10 mol % of 2nd
generation Grubbs catalyst9 at 50 °C in a sealed tube followed by
methanolysis of tethered rotaxanes 4a-4c10 gave rise to the
desired [3]rotaxane 1¢5¢1 with [2]rotaxane 1¢5 as by-product.11
These compounds were purified by column chromatography and
GPC. The isolated yields of [3]rotaxane 1¢5¢1 and [2]rotaxane
1¢5 are listed in Table 1. The metathesis reaction of axle
precusor 3 in the presence of monocrown 112 afforded the
desired [3]rotaxane 1¢5¢1 in 40% yield and [2]rotaxane 1¢5 in
23% yield. In contrast, for the metathesis reactions of 3 in the
presence of 2a-2c, the subsequent methanolysis resulted in
a great improvement in the production of [3]rotaxane 1¢5¢1,
metathesis is described. The bis(crown ether)s, in which two
crown ethers are connected by a linker, were converted to
tethered rotaxanes, followed by removal of the linkers to
produce [3]rotaxane. The biscrown structures promoted the
formation of the tethered rotaxane, resulting in a notable
improvement in the yield of the [3]rotaxane.
Topologically complex molecules, such as [n]rotaxanes and
[n]catenanes, have received great interest in the field of
supramolecular chemistry due to their unique molecular archi-
tectures, which suggest potential applications in molecular
machines and switches.1 The synthesis of their mechanically
interlocked structures is enormously challenging. Many stra-
tegies have been developed, including clipping, capping,
slipping, and entering.2 A number of interesting rotaxane-based
architectures have been reported.3
Olefin metathesis, which is commonly used in the synthesis
of a number of organic molecules, has also been applied to the
synthesis of topologically complex molecules, including rotax-
anes4 and catenanes,5 showing remarkable efficiency in produc-
ing these products. In our previous work,6 we demonstrated that
the olefin metathesis reaction provides a powerful tool to prepare
[3]catenanes. Based on that work, the metathesis reaction can be
extended to the synthesis of [3]rotaxane 1¢5¢1 (Figure 1). The
most straightforward synthetic method is to use pseudorotaxane
1¢3, which can be directly subjected to the metathesis reaction
tBu
tBu
−
tBu
2PF6
O
O
O
O
−
2PF6
−
2PF6
O
O
tBu
tBu
O
O
tBu
O
O
O
O
O
O
O
O
O
N+
O
O
O
O
O
O
O
O
H2
H2N+
H2N+
O
O
O
O
O
O
O
O
(CH2)n
O
O
O
O
OMe
OMe
Olefin
O
O
(CH2
)
6
(CH2
)
(CH2
O
)
6
6
metathesis
Solvolysis
O
O
O
O
O
O
O
O
(CH2)n
O
(CH2)n
O
(CH2
)
(CH2
)
6
6
(CH2
O
)
O
6
O
O
O
O
O
O
O
O
O
O
O
O
O
+NH2
+NH2
O
O
O
O
+NH2
O
2a: n = 4
2b: n = 6
2c: n = 8
O
O
O
O
O
O
O
O
tBu
tBu
tBu
tBu
tBu
tBu
tBu
4a: n = 4
4b: n = 6
4c: n = 8
tBu
•
•
1 5 1
•
•
3 2a 3: n = 4
•
•
3 2b 3: n = 6
H2N+
(CH2
•
•
3 2c 3: n = 8
O
O
−
O
O
PF6
O
O
)
6
3
O
O
O
OMe
1
Figure 1. Schematic representation of [3]rotaxane synthesis by olefin metathesis using bis(crown ether)s.
Chem. Lett. 2010, 39, 24-25
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

25
Table 1. Yields of [3]rotaxane 1¢5¢1 and [2]rotaxane 1¢5
grateful to the Izumi Science and Technology Foundation, the
Electric Technology Research Foundation of Chugoku, the
Kinki-chiho Hatsumei Center, the JGC-S Scholarship Founda-
tion, and the Uchida Energy Science Promotion Foundation for
financial support.
2a
2b
2c
1
[3]rotaxane 1¢5¢1
[2]rotaxane 1¢5
74%
9%
84%
8%
61%
16%
40%
23%
References and Notes
1
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Figure 2. Stereoplot of the calculated structure for tethered rotaxane 4b.
while the formation of [2]rotaxane diminished. It is particularly
striking that an 84% yield of 1¢5¢1 was achieved when bis-
crowns 2b and 3 were subjected to the reactions. The tethered
biscrown structures obviously play a key role in the preorgani-
zation of reactive intermediates 3¢2a-2c¢3.
3
4
The rate of cyclization may be interpreted in terms of the
activation energy and the probability of end-to-end encounters.
The activation energy is thought to reflect the strain energy of
ring formation.13 The probability of an end-to-end encounter
generally decreases with increasing distance between the two
reactive ends. The length of the linkers connecting the two
crown ethers should affect the probabilities of the two terminal
olefins of the complex coming close together. The more flexible
the intermediate 3¢2¢3 becomes, the greater the entropic cost
that must be paid. The most flexible intermediate, 3¢2c¢3, must
pay the largest entropic cost during cyclization; thus, its reaction
showed the lowest yield of 1¢5¢1. In contrast, 3¢2a¢3, with
a shorter linker, gave a lower yield of the tethered rotaxane
than 3¢2b¢3. Since the axle formed by coupling the two axle
precursors is too long to fit nicely within the linked bis(crown
ether), the cyclization process may result in an increase in the
steric energy of 4a. This may decrease the yield of the tethered
rotaxane. A molecular modeling study of the tethered rotaxane
supports this idea. In the calculated structure, the interaction
between the crown ether and the ammonium salt works well, and
alkyl chain of 4b adopts an extended trans zigzag conformation
without strain (Figure 2). This result indicates that the olefin
metathesis reaction of pseudorotaxane 3¢2b¢3 proceeds more
smoothly to produce tethered rotaxane 4b than the reaction using
3¢2a¢3 or 3¢2c¢3.
5
6
7
a) D. J. Cram, Angew. Chem., Int. Ed. Engl. 1988, 27, 1009. b) N. Ghalit,
D. T. S. Rijkers, J. Kemmink, C. Versluis, R. M. J. Liskamp, Chem.
Commun. 2005, 192.
8
General procedure for synthesis of [3]rotaxane: A solution of ammonium
salt 3 (0.1 mmol), bis(crown ether) 2a-2c (0.05 mmol) in dry CH2Cl2
(2 mL) was stirred for 30 min in a sealed tube. To the solution, 2nd
generation Grubbs catalyst was added. After being stirred for 5 h at 50 °C,
the reaction mixture was passed through silica gel pad (10% methanol in
CHCl3). Removal of the solvent, a brownish solid was obtained. The
solid was treated with KOMe in dry methanol at 50 °C for 12 h. The
reaction mixture was quenched with saturated aqueous NH4Cl, and
extracted with CHCl3. The organic layer was dried over anhydrous
Na2SO4. After removing Na2SO4 by filtration, the solvent was concen-
trated in vacuo. The crude product was purified by GPC (CHCl3) to give
[3]rotaxane 1¢5¢1 and [2]rotaxane. Supporting Information is available
electronically on the CSJ-Journal Web site, http://www.csj.jp/journals/
chem-lett/index.html.
In conclusion, we examined the synthesis of [3]rotaxane
using bis(crown ether)s under olefin metathesis conditions. The
bis(crown ether)s formed tethered rotaxanes, and subsequent
cleavage of the linker gave [3]rotaxane in excellent yield. This
method should also be applicable to the synthesis of heteromeric
[3]rotaxane derivatives.
9
T. M. Trnka, R. H. Grubbs, Acc. Chem. Res. 2001, 34, 18.
10 Isolated yields of tethered rotaxane 4a-4c are 54%, 61%, and 47% yields,
respectively (see the SI).
11 There is no evidence in terms of the olefin geometry formed by
metathesis reaction.
¹1
12 An association constant of 5800 « 1200 M
was determined by
1H NMR titration in CD2Cl2 for the crown ether 1 and the axle precursor
3 (see the SI).
This work was supported by Grant-in-Aids for Scientific
Research for Young Scientists (B) (No. 19750035) from the
Japan Society for the Promotion of Science (JSPS). We are
13 a) S. Usui, T. Haino, T. Hayashibara, Y. Hirai, Y. Fukazawa, M. Kodama,
Chem. Lett. 1992, 527. b) T. Takahashi, H. Yamada, T. Haino, Y. Kido, Y.
Fukazawa, Tetrahedron Lett. 1992, 33, 7561.
Chem. Lett. 2010, 39, 24-25
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/