Highly efficient synthesis of [3]rotaxane assisted by preorganisation of pseudorotaxane using bis(crown ether)s

Article abstract of DOI:10.1080/10610278.2010.514611

The tether-assisted synthesis of [3]rotaxane by olefin metathesis has been studied in detail. Bis(crown ether)s, in which two crown ethers are connected by a linker, were threaded onto ammonium salts bearing a terminal olefin to form pseudorotaxanes. The pseudorotaxanes were converted into tethered rotaxanes in the presence of Grubbs catalyst, followed by removal of the linkers to produce [3]rotaxanes in excellent yields. Preorganisation of the two reactive ends has led to a great improvement in the yield of [3]rotaxanes. The ring strain of the tethered rotaxanes and the flexibility of the pseudorotaxanes were responsible for the formation of the tethered rotaxanes.

Full text of DOI:10.1080/10610278.2010.514611

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Supramolecular Chemistry
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Highly efficient synthesis of [3]rotaxane assisted by
preorganisation of pseudorotaxane using bis(crown
ether)s
Hajime Iwamoto a , Yukimi Yawata b , Yoshimasa Fukazawa b & Takeharu Haino b
a Department of Chemistry , Graduate School of Science and Technology, Niigata University ,
Niigata, Japan
b Department of Chemistry , Graduate School of Science, Hiroshima University , Higashi-
Hiroshima, Japan
Published online: 15 Nov 2010.
To cite this article: Hajime Iwamoto , Yukimi Yawata , Yoshimasa Fukazawa & Takeharu Haino (2010) Highly efficient
synthesis of [3]rotaxane assisted by preorganisation of pseudorotaxane using bis(crown ether)s, Supramolecular Chemistry,
22:11-12, 815-826, DOI: 10.1080/10610278.2010.514611
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Supramolecular Chemistry
Vol. 22, Nos. 11–12, November–December 2010, 815–826
Highly efficient synthesis of [3]rotaxane assisted by preorganisation of pseudorotaxane using
bis(crown ether)s†
Hajime Iwamotoa*, Yukimi Yawatab, Yoshimasa Fukazawab and Takeharu Hainob*
aDepartment of Chemistry, Graduate School of Science and Technology, Niigata University, Niigata, Japan; bDepartment of Chemistry,
Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Japan
(Received 31 May 2010; final version received 22 July 2010)
The tether-assisted synthesis of [3]rotaxane by olefin metathesis has been studied in detail. Bis(crown ether)s, in which two
crown ethers are connected by a linker, were threaded onto ammonium salts bearing a terminal olefin to form
pseudorotaxanes. The pseudorotaxanes were converted into tethered rotaxanes in the presence of Grubbs catalyst, followed
by removal of the linkers to produce [3]rotaxanes in excellent yields. Preorganisation of the two reactive ends has led to a
great improvement in the yield of [3]rotaxanes. The ring strain of the tethered rotaxanes and the flexibility of the
pseudorotaxanes were responsible for the formation of the tethered rotaxanes.
Keywords: [3]rotaxane; preorganisation; bis(crown ether); olefin metathesis
Introduction
of rotaxane (5). These recent developments in the
synthesis of rotaxanes have allowed the fabrication of
molecular machines, molecular muscles, nanoelectrome-
chanical systems and nanovehicles (6).
Rotaxanes, consisting of dumbbell-shaped molecules that
are threaded through one or more macrocycles, are an
attractive research field within supramolecular chemistry
(1). Their unique molecular architectures have attracted
great interest and imply potential applications in new
materials and nanoscale molecular devices. Therefore, the
synthesis of these molecules has been intensively studied.
Initially, the synthesis of the interlocked rotaxane
structures was accomplished using a statistical threading
approach, in which the statistical probability of threading a
linear molecule through the annulus of a macrocycle to
form an interpenetrated rotaxane was very low (2).
To overcome the low yields obtained by this technique, a
variety of methodologies were developed. The application
of templation strategies has led to a great improvement in
the yields of the rotaxane synthesis. Templation based on
supramolecular concept was achieved using hydrogen
bonding, donor–acceptor interactions and metal com-
plexation, leading to effective assembly of the cyclic
components and the linear backbone (3). A variety of
reactions, including copper(I)-catalysed alkyne–azide 1,3-
dipolar cycloaddition, oxidative coupling of alkynes and
imine formation, have been explored for successful
formation of covalent bonds to prevent the dethreading
of macrocycles from the linear backbone (4). Other
possible strategies, such as clipping, capping, slipping and
entering, were developed for the high-yield assembly
The concept of preorganisation proposed by Cram (7)
has played an important role in supramolecular chemistry
and host–guest chemistry. Based on this concept, a variety
of macrocyclic receptors, including crown ethers, cryp-
tands, cyclophanes, calixarenes and spherands, were
designed and synthesised to investigate their complexation
properties (8). Preorganised host molecules decrease the
loss of conformational entropy upon binding with matching
guest species. Because of this minimisation of entropy loss,
preorganised hosts show strong binding abilities. This
concept is also applicable to organic synthesis. Metastable
prereactive intermediates or complexes were formed in
chemical reactions (9). Such preorganisation steps control
reactivity and selectivity of chemical transformations.
Olefin metathesis has become a tool for synthetic
organic and polymer chemists (10). Due to functional
group tolerant catalysts for new CZC bond formation,
olefin metathesis promoted by Grubbs catalyst was also
applied to synthesise topological molecules, rotaxanes
(11) and catenanes (12). We previously reported that the
olefin metathesis reaction provided a powerful tool to
prepare [3]catenane (13). In the course of this study, the
metathesis reaction has been applied to the synthesis of
rotaxane (14). Inspired by the concept of preorganisation,
*Corresponding authors. Email: iwamoto@chem.sc.niigata-u.ac.jp; haino@sci.hiroshima-u.ac.jp
†Dedicated to the memory of Prof. Dmitry M. Rudkevich.
ISSN 1061-0278 print/ISSN 1029-0478 online
q 2010 Taylor & Francis
DOI: 10.1080/10610278.2010.514611
http://www.informaworld.com

816
H. Iwamoto et al.
we describe here a full account of tether-assisted synthetic
methodology of [3]rotaxane via olefin metathesis.
The synthesis of ammonium salts 2a–c is illustrated in
Scheme 3. Condensation of amines 5a–c (15) with 3,5-di-
tert-butyl-benzoic acid gives the corresponding amide,
which was reduced with LiAlH4 to give secondary amines
6a–c. Treatment with hydrochloric acid, followed by
anion exchange from chloride to hexafluorophosphate,
gave 2a–c.
The synthesis of bis(crown ether)s 4a–c is shown in
Scheme 4. Esterification of crown ether derivative 7 (16)
with 1,4-butanediol, 1,6-hexanediol and 1,8-octanediol
gave bis(crown ether)s 4a–c.
To study the binding behaviour of crown 1 and
ammonium salt 2b, a standard titration experiment was
carried out using 1H NMR spectroscopy at room
temperature in dichloromethane-d2 (Figure 1). Simple
mixing of the compounds yielded well-resolved signals
resulting from the free and bound states, the equilibrium of
which was in slow exchange on the NMR timescale.
Methylene protons Hd and He adjacent to the ammonium
moiety shifted downfield, whereas upfield shifts placed
allylic proton Hc and methyl proton Hf within the shielding
region of the two aromatic rings connected to the crown
ring. The protons of crown 1 showed characteristic
changes upon the addition of 2b. The oxymethylene
protons appeared in the region of 3.7–4.2 ppm in the
absence of the ammonium salt. Upon the addition of 2b,
they became well resolved in the region of 3.3–4.3 ppm.
Results and discussion
One of the most straightforward [3]rotaxane synthetic
methods is the coupling of two [2]pseudorotaxanes, which
consist of a half dumbbell-shaped component threaded
through a macrocyclic wheel. Half dumbbell-shaped
ammonium salt 2 bearing a terminal C ¼ C double bond
threads through the cavity of crown ether 1 to give
pseudorotaxane 1 z 2, which can be directly subjected to
the metathesis reaction to produce 1 z 3 z 1 (Scheme 1). This
reaction process is sterically and entropically unfavour-
able. The encounter between the two macrocycles might
create a serious steric interaction; one or both of the
macrocycles can slip away from the half dumbbell-shaped
molecule to form [2]rotaxane 1 z 3 and/or the simple
dumbbell-shaped molecule 3, reducing the yield of
[3]rotaxane. When two half dumbbell-shaped components
thread into bis-macrocycle 4, in which the two macro-
cycles are covalently connected with each other with a
suitable linkage, the subsequent coupling reaction should
proceed easily because the two terminal olefins are already
preorganised to react with each other to give the tethered
rotaxane 3 z 4 (Scheme 2). The removal of the linkage can
give rise to [3]rotaxane 1 z 3 z 1.
Scheme 1. Synthesis of [3]rotaxane by olefin metathesis using crown ether.

Supramolecular Chemistry
817
Scheme 2. Synthesis of [3]rotaxane by olefin metathesis using bis(crown ether)s.
Threading of 2b into 1 reduces the molecular symmetry of
crown ether 1; each methylene proton of 1 becomes
chemically non-equivalent; thus, this spectral change upon
the addition of 1 is evidence of the formation of a guest–
host complex between 1 and 2b. Protons Hd, He and Hf
were integrated in the free and bound states, and the
binding constant (Ka) of the guest–host complex was
determined as 5800 ^ 1200 L mol21 based on their ratio.
The synthesis of [3]rotaxane 1 z 3a–c z 1 was per-
formed without the assistance of tether linkages according
to Scheme 1. A mixture of 50 mmol L21 of crown ether 1
and 50 mmol L21 of ammonium salts 2a–c in CH2Cl2 was
treated with 10 mol% of second-generation Grubbs
catalyst (17). The isolated yields of [3]rotaxane 1 z 3a–
c z 1 and [2]rotaxane 1 z 3a–c are listed in Table 1. In the
reaction condition, 94% of ammonium salt 2 is estimated
to form the guest–host complex based on Ka determined
above. According to their statistical distributions, theor-
etical yields of [3]rotaxanes and [2]rotaxanes are 88 and
11%, respectively (18).1 The metathesis reactions of 2 in
the presence of 1 produced [3]rotaxanes and [2]rotaxanes,
the ratios of which were remarkably less than the
theoretical value of 8.0. During the metathesis reaction,
the two crown ethers come together and probably create a
serious steric interaction that decreases the yield of
[3]rotaxane and increases that of the [2]rotaxane; in fact,
the shorter the ammonium salts 2, the lower the ratio of
chemical yields of [3]rotaxane to [2]rotaxane.
The tether-assisted synthesis of [3]rotaxane 1 z 3a–c z 1
was performed according to Scheme 2. A mixture of
25 mmol L21 of bis(crown ether)s 4a–c and 50 mmol L21
of ammonium salts 2a–c in CH2Cl2 was treated with
10 mol% of second-generation Grubbs catalyst (17) to
create tethered rotaxanes 3a–c z 4a–c.2 After removal of
the linkage by methanolysis, the desired [3]rotaxane
1 z 3a–c z 1 was obtained with [2]rotaxane 1 z 3a–c as a by-
product.3 The metathesis reaction of ammonium salts 2a–
c in the presence of bis(crown ether)s 4a–c dramatically
improved the chemical yields of [3]rotaxane compared to
their control reaction (entries 4, 8 and 12). The reactions of
2a–c in the presence of the shortest 4a (entries 1, 5 and 9)
greatly improved the ratios of the chemical yields of
[3]rotaxane to [2]rotaxane, more so than those of the
control reactions (entries 4, 8 and 12). By contrast, the
ratios in the reaction of 2a–c in the presence of 4c (entries
3, 7 and 11) are close to those of the control reactions. The
metathesis reaction of 2b in the presence of 4b (entry 6),
followed by methanolysis, resulted in the highest yield of
[3]rotaxane 1 z 3b z 1 and diminished the formation of
[2]rotaxane 1 z 3b. Tethering two crown moieties clearly
enhanced the chemical yields of the [3]rotaxanes and
suppressed the side reactions. The tethered bis-crown
structures obviously play a key role in the preorganisation
of reactive pseudorotaxanes 2 z 4 z 2.
Scheme 3. Reagentsandconditions:(a)3,5-di-tert-butylbenzoic
acid, EDCI z HCl (1-ethyl-3-(3-dimethylaminopropyl)-carbodi-
imide hydrochloride), DMAP, CH2Cl2; LiAlH4, THF, reflux and
(b) HCl, MeOH; NH4PF6, acetone.
Scheme 4. Reagents and conditions: (a) diol, EDCI z HCl,
DMAP, CH2Cl2. Diol is 4a for 1,4-butanediol, 4b for 1,6-
hexanediol and 4c for 1,8-octanediol.

818
H. Iwamoto et al.
1
Figure 1. Partial H NMR spectra in CD2Cl2 at 238C of (a) 1, (b) 1 (1.68 £ 1023 mol L21) þ 2b (3.93 £ 1023 mol L21), (c) 2b.
Table 1. Yields of [3]rotaxane 1 z 3a–c z 1 and [2]rotaxane 1 z 3a–c and the ratio of chemical yields of [3]rotaxane to [2]rotaxane.
Tethered
rotaxanes
[3]Rotaxanes
(%)
[2]Rotaxanes
(%)
Entry
Ammonium salts
Crown ethers
Ratio of chemical yields
1
2
3
4
5
6
7
8
9
2a
4a
4b
4c
1
4a
4b
4c
1
4a
4b
4c
1
3a z 4a
3a z 4b
3a z 4c
–
3b z 4a
3b z 4b
3b z 4c
–
3c z 4a
3c z 4b
3c z 4c
–
1 z 3a z 1
1 z 3b z 1
1 z 3c z 1
38
1 z 3a
1 z 3b
1 z 3c
18
30
29
22
9
2.1
0.8
1.1
1.0
8.2
10.5
3.8
1.7
8.6
3.6
5.3
2.8
24
32
21
74
84
61
40
60
47
53
44
2b
2c
8
16
23
7
13
10
16
10
11
12
The intramolecular cyclisation of the reactive pseu-
dorotaxanes 2 z 4 z 2 must compete with side reactions
involving [2]rotaxane formation, intermolecular polym-
erisation, etc. (Figure 2). The rate of cyclisation may be
explained 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 the
formation of small and medium rings, while the ring strain
of large-membered cyclic system is commonly negligible
(18). Although the formation process of the rotaxane is too
complicated to be understood in detail, the entropic
contribution upon the cyclisation may rationalise the
results presented here. The tethered rotaxane forms via
macrocyclisation; thus, the entropic contribution, meaning
the probability of end-to-end encounters, should mainly
drive the reaction pathway. The probability of an end-to-
end encounter generally decreases with increasing
distance between the two reactive ends. Increasing the
length of the linkers connecting the two crown ethers
reduces the probability of the encounter of the two
terminal olefins for the formation of complex 2 z 4 z 2.
The probabilities are also influenced by the flexibility of
the terminal olefin. The more flexible the pseudorotaxane
2 z 4 z 2 becomes, the greater is the entropic cost

Supramolecular Chemistry
819
Figure 2. Schematic representation of the reaction pathway for
the formation of [3]rotaxane and [2]rotaxane.
of complexation. In the series of the reaction of
pseudorotaxane with 2b, in which the [3]rotaxane was
obtained in excellent yield, the most flexible pseudorotax-
ane 2b z 4c z 2b must pay the largest entropic cost during
the cyclisation; thus, the lowest yield of tethered rotaxane
Figure 3. Stereoplot of the calculated structure of tethered
rotaxane 3b z 4b.
Table 2. Calculated steric energy DSEa [kJ/mol] of tethered
rotaxane 3 z 4 upon complexation.
2
3b z 4c can be rationalised by the entropic contribution.
However, 2b z 4a z 2b, having a shorter linker, gave a lower
yield of the [3]rotaxane than 2b z 4b z 2b (entries 5 and 6).
The macrocyclisation process may result in an increase in
the steric energy of 3a z 4b, which may decrease the yield
of the tethered rotaxane. This result suggests that the steric
interaction between the two crown moieties cannot be
negligible; in fact, [3]rotaxane 1 z 3a z 1 was obtained with
monocrown ether 1 in 21% yield (entry 4), which was
lower than the yields of 40 and 44% when 2b and 2c were
reacted with 1 (entries 8 and 12).
To estimate the steric interaction during the cyclisation
of pseudorotaxanes 2 z 4 z 2, molecular mechanics calcu-
lations of tethered rotaxanes 3 z 4 may be informative (19).
Molecular mechanics calculations of tethered rotaxanes
3 z 4 were carried out using MacroModel V9.1. Initial
geometries were generated using the Monte Carlo/low-
mode search mixed method, and the structural optimis-
ations were performed using the OPLS2005 force field
with the GB/SA solvation parameters for chloroform (19).
All of the combinations of 3a–c and 4a–c were
calculated. A characteristic example of the calculated
structures of tethered rotaxane 3b z 4b is shown in Figure 3.
The ammonium salts form the hydrogen bonding
interactions with the crown ethers, and the alkyl chains
connecting the two crown rings adopt the extended zigzag
conformation. The two aromatic rings of each crown
moiety are tilted inward to reduce the unfavourable steric
interactions with the two tert-butyl groups placed at the
aromatic ring of the ammonium salt.
Diammonium salt
Bis(crown ether)
3a
3b
3c
4a
4b
4c
2321.9
2305.5
2306.4
2328.9
2314.5
2310.1
2332.8
2319.1
2322.4
aThe calculated values were obtained by following equation: DSE ¼ SE3 z 4
(SE3 1 SE4).
–
macrocyclic tethered rotaxanes 3 z 4 might govern the
ease of cyclisation. The ring strain energies of 3 z 4 can be
estimated by the steric energy differences (DSE) obtained
from the steric energies of the tethered rotaxane 3 z 4, axle
3 and bis(crown ether)s 4 (Table 2). The DSE gave large
negative values, suggesting that all of the cyclisation
processes are enthalpically favourable. Indeed, all of the
cyclisation reactions of the complexes 2 z 4 z 2 produced the
desired [3]rotaxane in good yields. 3a–c z 4a received the
largest gain in DSE. Increasing the length of the tether
alkyl chains of the bis(crown ether)s 4 reduced the stability
of the tethered rotaxane 3 z 4. These calculation results are
fairly consistent with the fact that the reactions of 4a with
2a–c exhibited better results than the others in terms of
yields of [3]rotaxanes 1 z 3 z 1.
The cyclisation of 2 z 4 z 2 is an intramolecular process
producing [3]rotaxane, whereas the intermolecular metath-
esis of 2 z 4 and 2 gives rise to [2]rotaxanes. The ratio of
[3]rotaxane to [2]rotaxane may indicate the relative rate of
the intra- and intermolecular processes in the cyclisation
reaction of 2 z 4 z 2; thus, the ratios (entries 1–3, 5–7 and
9–11) are greater than the values observed in the
It is well known that the ring strain of cyclised
products is closely associated with the ease of cyclisation
for chain molecules (20); thus, the strain of the

820
H. Iwamoto et al.
metathesis reactions of 2 z 1 (entries 4, 8 and 12), perhaps
suggesting that the intramolecular process is more
preferable than the intermolecular processes. 3a–c z 4a
provided DSEs of 2332.8, 2328.9 and 2321.9 kJ/mol,
while the highest DSEs of 2305.5 and 2306.4 kJ/mol
resulted from 3a z 4b–c. On the basis of the large ratio of
[3]rotaxane to [2]rotaxane, the cyclisation reactions of 2a–
c z 4a should be favourable (entries 1–3). The ratios from
the reactions of 2a z 4b–c (entries 2 and 3) are smallest and
close to the control experiment (entry 4), suggesting that
their cyclisation process should be unfavourable and must
compete with other intermolecular processes. The DSEs of
the formation of the tethered rotaxanes 3 z 4 seem to
correlate with the ratios: the longer the tether of 4, the
higher the DSE, and the larger the decrease in the ratio.
In other words, high DSEs should reduce the formation of
the tethered rotaxanes and promote the dethreading
process that increases the formation of [2]rotaxanes.
Formation of the tethered rotaxane can be preferable with
decreasing DSEs, resulting in the increase of the ratio of
[3]rotaxane to [2]rotaxane. The results of the molecular
mechanics calculations may explain the selective for-
mation of [3]rotaxanes in terms of the steric factors upon
macrocyclisation, even though the entropic contribution
upon cyclisation cannot be quantified.
and 175 MHz (13C NMR), respectively. 1H NMR chemical
shifts (d) are given in parts per million using the residual
solvent as an internal standard. 13C NMR chemical shifts
(d) are given in parts per million from internal chloroform-
d (d ¼ 77.0). The mass spectra were recorded with a JEOL
JMS-SX 102A high-resolution double-focusing mass
spectrometer at the Instrument Center for Chemical
Analysis, Hiroshima University, and Thermo Scientific
Exactive. Elemental analyses were performed on a
PerkinElmer 2400 CHN elemental analyser.
All reactions were carried out under an argon
atmosphere unless otherwise noted. THF was freshly
distilled over sodium benzophenone. Dichloromethane
was freshly distilled over CaH2. Column chromatography
was performed using Merck silica gel (70–230 mesh). All
reagents were of commercial grade and were used without
further purification.
3,5-Bis(1,1-dimethylethyl)-N-5-hexen-1-yl-benzamide
The addition of 5-hexen-1-amine (5a) (15) (100 mg,
1.01 mmol) to a solution of 3,5-di-tert-butylbenzoic acid
(230 mg, 0.98 mmol), EDCI z HCl (1-ethyl-3-(3-dimethyl-
aminopropyl)-carbodiimide hydrochloride) (300 mg,
1.56 mmol) and a catalytic amount of DMAP in dry
CH2Cl2 (10 mL) was done at room temperature. After
being refluxed for 5 h, the reaction was quenched with 1 M
HCl and extracted with CHCl3. The organic layer was
washed with saturated NaHCO3 and brine, and was dried
over anhydrous Na2SO4. After removing Na2SO4 by
filtration, the solvent was concentrated in vacuo. The crude
product was purified by column chromatography on silica
gel (20% ethyl acetate in hexane) to give 330 mg of amide
Conclusion
We have demonstrated the synthesis of [3]rotaxane using
bis(crown ether)s under olefin metathesis conditions.
The bis(crown ether)s are threaded by ammonium salts to
form the pseudorotaxanes, in which the two terminal
olefins are preorganised to accommodate the metathesis
reaction. Bis(crown ether)s and ammonium salts thereby
form pseudorotaxanes that show efficient reactivity to
produce the tethered rotaxanes, subsequent tether cleavage
of which affords [3]rotaxane in excellent yield.
The formation of the tethered rotaxanes is influenced not
only by the length of the tether connecting the two crown
ethers but also by the flexibility of the axles. To achieve
rational design of prereactive intermediates towards
[3]rotaxane synthesis, enthalpic and entropic contributions
must be carefully treated. This study does not perfectly
rationalise the yield of [3]rotaxanes, but the molecular
mechanics calculations of the tethered rotaxanes are
informative for estimating their ease of cyclisation.
1
(1.05 mmol, quant.). H NMR (300 MHz, CDCl3) d 7.56
(s, 3H), 6.07 (br, 1H), 5.82 (m, 1H), 5.03 (d, J ¼ 18.0 Hz,
1H), 4.94 (d, J ¼ 12.8 Hz, 1H), 3.46 (m, 2H), 2.12 (m,
2H), 1.66 (m, 2H), 1.51 (m, 2H), 1.13–1.40 (s, 18H); 13
C
NMR (175 MHz, CDCl3) d 168.6, 151.2, 138.5, 134.5,
125.5, 120.9, 114.8, 39.9, 35.0, 33.4, 31.4, 29.2, 26.2;
HRMS (ESI) m/z calcd for C21H34NO 316.2635, found
316.2629 [M þ H]þ.
3,5-Bis(1,1-dimethylethyl)-N-7-octen-1-yl-benzamide
The addition of 7-octen-1-amine (5b) (15) (2.2 g,
17.3 mmol) to a solution of 3,5-di-tert-butylbenzoic acid
(4.2 g, 17.9 mmol), EDCI z HCl (5.4 g, 28.2 mmol) and a
catalytic amount of DMAP in dry CH2Cl2 (180 mL) was
done at room temperature. After being refluxed for 5 h, the
reaction was quenched with 1 M HCl and extracted with
CHCl3. The organic layer was washed with saturated
NaHCO3 and brine, and was dried over anhydrous
Na2SO4. After removing Na2SO4 by filtration, the solvent
was concentrated in vacuo. The crude product was purified
by column chromatography on silica gel (20% ethyl
Experimental section
General procedures
The 1H and 13C NMR spectra at high field were recorded
with JEOL-ECA 600, JEOL-Lambda 500 and Varian-
Mercury 300 NMR spectrometers at 600, 500 and
300 MHz (1H NMR), respectively, and with a JEOL-
ECA 600 and Varian 700 MR NMR spectrometer at 150

Supramolecular Chemistry
821
acetate in hexane) to give 3.9 g of amide (11.4 mmol,
3,5-Bis(1,1-dimethylethyl)-N-7-octen-1-yl-
benzenemethanamine (6b)
66%). 1H NMR (300 MHz, CDCl3) d 7.56 (s, 3H), 6.07 (br,
1H), 5.82 (m, 1H), 5.03 (d, J ¼ 19.8 Hz, 1H), 4.94 (d,
J ¼ 11.3 Hz, 1H), 3.46 (m, 2H), 2.12 (m, 2H), 1.66 (m,
2H), 1.42 (m, 6H), 1.34 (s, 18H); 13C NMR (175 MHz,
CDCl3) d 168.6, 151.2, 139.0, 134.6, 125.4, 120.9, 114.3,
40.1, 35.0, 33.7, 31.4, 31.3, 29.7, 28.8, 26.8; HRMS (ESI)
m/z calcd for C23H38NO 344.2948, found 344.2939
[M þ H]þ.
LiAlH4 (0.5 g, 13.2 mmol) was carefully added to a
solution of 3,5-bis(1,1-dimethylethyl)-N-7-octen-1-yl-
benzamide (3.9 g, 11.4 mmol) in dry THF (100 mL), at
08C. After being refluxed for 3 h, the reaction was
quenched with saturated aqueous Na2SO4, and the
resulting precipitate was filtrated off. The filtrate was
concentrated in vacuo. The crude product was purified by
column chromatography on silica gel (CHCl3) to give 2.6 g
of amine 6b (7.9 mmol, 69%). 1H NMR (300 MHz,
CDCl3) d 7.32 (s, 1H), 7.19 (s, 2H), 5.75 (m, 1H), 4.99 (d,
J ¼ 19.2 Hz, 1H), 4.91 (d, J ¼ 11.1 Hz, 1H), 3.84 (br, 2H),
2.66 (br, 2H), 1.99 (m, 2H), 1.54 (m, 2H), 1.10–1.312 (m,
24H); 13C NMR (175 MHz, CDCl3) d 150.7, 139.4, 139.1,
122.3, 120.9, 114.2, 54.7, 49.6, 34.8, 33.7, 31.5, 29.9, 29.0,
28.8, 27.2; HRMS (ESI) m/z calcd for C23H40N 330.3155,
found 330.3145 [M þ H]þ.
3,5-Bis(1,1-dimethylethyl)-N-9-decen-1-yl-benzamide
The addition of 9-decen-1-amine (5c) (15) (1.8 g,
11.6 mmol) to a solution of 3,5-di-tert-butylbenzoic acid
(2.7 g, 11.5 mmol), EDCI z HCl (3.5 g, 18.3 mmol) and a
catalytic amount of DMAP in dry CH2Cl2 (100 mL) was
done at room temperature. After being refluxed for 5 h, the
reaction was quenched with 1 M HCl and extracted with
CHCl3. The organic layer was washed with saturated
NaHCO3 and brine, and was dried over anhydrous
Na2SO4. After removing Na2SO4 by filtration, the solvent
was concentrated in vacuo. The crude product was purified
by column chromatography on silica gel (20% ethyl
acetate in hexane) to give 3.5 g of amide (9.42 mmol,
81%). 1H NMR (300 MHz, CDCl3) d 7.56 (s, 3H), 6.07 (br,
1H), 5.81 (m, 1H), 4.99 (d, J ¼ 17.3 Hz, 1H), 4.92 (d,
J ¼ 10.2 Hz, 1H), 3.42 (m, 2H), 2.03 (m, 2H), 1.60 (m,
2H), 1.27–1.41 (m, 28H); 13C NMR (175 MHz, CDCl3) d
168.6, 151.2, 139.1, 134.6, 125.4, 120.9, 114.1, 40.1, 35.0,
33.8, 31.4, 29.8, 29.4, 29.3, 29.0, 28.9, 27.0; HRMS (ESI)
m/z calcd for C25H42NO 372.3261, found 372.3252
[M þ H]þ.
3,5-Bis(1,1-dimethylethyl)-N-9-decen-1-yl-
benzenemethanamine (6c)
LiAlH4 (0.37 g, 9.75 mmol) was carefully added to a
solution of 3,5-bis(1,1-dimethylethyl)-N-9-decen-1-yl-
benzamide (3.3 g, 8.88 mmol) in dry THF (90 mL) at
08C. After being refluxed for 3 h, the reaction was
quenched with saturated aqueous Na2SO4, and the
resulting precipitate was filtrated off. The filtrate was
concentrated in vacuo. The crude product was purified by
column chromatography on silica gel (5% methanol in
1
CH2Cl2) to give 3.0 g of amine 6c (8.39 mmol, 94%). H
NMR (300 MHz, CDCl3) d 7.31 (t, J ¼ 1.8 Hz, 1H), 7.15
(s, 2H), 5.81 (m, 1H), 4.98 (d, J ¼ 18.0 Hz, 1H), 4.93 (d,
J ¼ 10.8 Hz, 1H), 3.77 (s, 2H), 2.65 (t, J ¼ 6.8 Hz, 2H),
2.02 (m, 2H), 1.57 (m, 2H), 1.11–1.39 (m, 28H); 13C
NMR (175 MHz, CDCl3) d 150.7, 139.2, 122.3, 121.0,
114.1, 54.6, 49.6, 34.8, 33.8, 31.5, 29.9, 29.5, 29.4, 29.1,
28.9, 27.4; HRMS (ESI) m/z calcd for C25H44N 358.3168,
found 358.3457 [M þ H]þ.
3,5-Bis(1,1-dimethylethyl)-N-5-hexen-1-yl-
benzenemethanamine (6a)
LiAlH4 (0.25 g, 6.59 mmol) was carefully added to a
solution of 3,5-bis(1,1-dimethylethyl)-N-5-hexen-1-yl-
benzamide (1.9 g, 6.02 mmol) in dry THF (60 mL) at
08C. After being refluxed for 3 h, the reaction was
quenched with saturated aqueous Na2SO4, and the
resulting precipitate was filtrated off. The filtrate was
concentrated in vacuo. The crude product was purified
by column chromatography on silica gel (5% methanol
in CHCl3) to give 1.8 g of amine 6a (5.97 mmol, 99%).
1H NMR (300 MHz, CDCl3) d 7.32 (t, J ¼ 1.8 Hz, 1H),
7.15 (d, J ¼ 1.8 Hz, 2H), 5.80 (m, 1H), 4.99 (d,
J ¼ 18.3 Hz, 1H), 4.94 (d, J ¼ 12.0 Hz, 1H), 3.78 (s,
2H), 2.82 (t, J ¼ 7.2 Hz, 2H), 2.69 (m, 2H), 1.48 (m,
2H), 1.41 (m, 2H), 1.33 (s, 18H); 13C NMR (175 MHz,
CDCl3) d 150.7, 139.5, 138.8, 122.3, 120.9, 114.4, 54.7,
49.5, 34.8, 33.6, 31.5, 29.5, 26.7; HRMS (ESI) m/z
calcd for C21H36N 302.2842, found 302.2835
[M þ H]þ.
3,5-Bis(1,1-dimethylethyl)-N-7-octen-1-yl-
benzenemethanammonium hexafluorophosphate (2b)
Concentrated HCl was added dropwise to a solution of
amine 6b (1.9 g, 5.8 mmol) in methanol (25 mL) until the
resulting solution was of pH 2. After being stirred for 2 h,
evaporation of the solvents produced a white solid that was
dissolved in acetone (25 mL). Excess NH4PF6 was added
to the solution. The solvent was removed in vacuo, and the
residue was dissolved by hot water and then cooled to
room temperature. The precipitated white solid was
collected by filtration to give ammonium salt 2b (2.5 g,
92%). 1H NMR (300 MHz, CDCl3) d 7.49 (d, J ¼ 2.4 Hz,
1H), 7.25 (s, 2H), 6.72 (br, 2H), 5.72 (m, 1H), 4.94 (d,
J ¼ 17.1 Hz, 1H), 4.90 (d, J ¼ 10.2 Hz, 1H), 4.24 (s, 2H),

822
H. Iwamoto et al.
2.95 (m, 2H), 1.98 (m, 2H), 1.73 (m, 2H), 1.24–1.33 (m,
24H); 13C NMR (150 MHz, CDCl3) d 152.5, 138.6, 128.2,
124.1, 114.5, 52.8, 46.9, 34.9, 33.4, 31.3, 28.4, 28.2, 25.9,
25.7; HRMS (FAB, NBA matrix) m/z calcd for C23H40N
330.3151, found 330.3161 [M – PF6]þ; elemental analysis
calcd (%) for C23H40F6NP z acetone: C 58.52, H 8.69, N
2.62. Found: C 58.69, H 9.08, N 2.89.
The crude product was purified by column chromatography
on silica gel (5% MeOH in CHCl3) to give 240 mg of 4a
(0.23 mmol, 92%). 1H NMR (600MHz, CDCl3) d 7.64 (d,
J ¼ 8.9 Hz, 2H), 7.52 (s, 2H), 6.88–6.83 (m, 10H), 4.36
(brs, 4H), 4.30–4.10 (m, 16H), 4.02–3.79 (m, 32H), 1.91
(brs, 4H); 13C NMR (150MHz, CDCl3) d 166.2, 152.9,
148.8, 148.2, 123.8, 122.9, 121.4, 114.3, 114.0, 112.0, 71.4,
71.3, 71.2, 69.9, 69.7, 69.6, 69.5, 69.4, 69.3, 69.2, 25.6;
HRMS (FAB, NBA matrix) m/z calcd for C54H71O20
1039.4539, found 1039.4515 [M þ H]þ; element analysis
calcd (%) for C54H70O20 z H2O: C 61.35, H 6.86. Found: C
61.30, H 6.65.
3,5-Bis(1,1-dimethylethyl)-N-5-hexen-1-yl-
benzenemethanammonium hexafluorophosphate (2a)
Following the procedure for preparation of 2b, 1.8 g of 2a
(4.02 mmol, 93%) was obtained from 6a (1.3 g,
4.31 mmol). 1H NMR (300 MHz, CDCl3) d 7.51 (t,
J ¼ 1.8 Hz, 1H), 7.24 (d, J ¼ 1.8 Hz, 2H), 6.49 (br, 2H),
5.70 (m, 1H), 4.95 (d, J ¼ 17.4 Hz, 1H), 4.93 (d,
J ¼ 9.8 Hz, 1H), 4.23 (s, 2H), 2.99 (t, J ¼ 7.8 Hz, 2H),
1.86 (m, 2H), 1.72 (m, 2H), 1.47 (m, 2H), 1.32 (s, 18H);
13C NMR (150 MHz, CDCl3) d 152.7, 137.2, 128.1, 124.3,
124.0, 115.6, 53.0, 46.9, 34.9, 32.7, 31.2, 25.1, 25.1;
HRMS (FAB, NBA matrix) m/z calcd for C21H36N
302.2842, found 302.2873 [M – PF6]þ; elemental analysis
calcd (%) for C21H36F6NP z acetone: C 56.37, H 8.11, N
3.13. Found: C 56.73, H 8.31, N 2.97.
Synthesis of bis(crown ether) 4b
Following the procedure for preparation of 4a, 7 (250 mg,
0.41 mmol), EDCI z HCl (240 mg, 0.90 mmol), 1,6-hex-
anediol (22 mg, 0.19 mmol) and a catalytic amount of
DMAP were reacted in dry CH2Cl2 (2 mL). Purification by
column chromatography (SiO2) with 19:1 CHCl3/MeOH
gave 170 mg of 4b (0.16 mmol, 86%). 1H NMR (600 MHz,
CDCl3) d 7.63 (d, J ¼ 8.3 Hz, 2H), 7.52 (s, 2H), 6.99–6.82
(m, 10H), 4.29 (t, J ¼ 3.4 Hz, 4H), 4.26–4.10 (m, 16H),
4.07–3.69 (m, 32H), 1.90–1.75 (m, 4H), 1.61–1.45 (m,
4H); 13C NMR (150 MHz, CDCl3) d 166.3, 152.8, 148.9,
148.2, 123.8, 123.1, 121.4, 114.4, 114.0, 112.0, 71.5, 71.4,
71.3, 69.9, 69.8, 69.6, 69.5, 69.4, 69.3, 69.2, 28.7, 25.8;
HRMS (FAB, NBA matrix) m/z calcd for C56H75O20
1067.4852, found 1067.4861 [M þ H]þ; elemental anal-
ysis calcd (%) for C56H74O20 z H2O: C 61.98, H 7.06.
Found: C 61.83, H 7.03.
3,5-Bis(1,1-dimethylethyl)-N-9-decen-1-yl-
benzenemethanammonium hexafluorophosphate (2c)
Following the procedure for preparation of 2b, 3.8 g of 2c
(7.55 mmol, .99%) was obtained from 6c (2.7 g,
7.55 mmol). 1H NMR (300 MHz, CDCl3) d 7.50 (t,
J ¼ 1.5 Hz, 1H), 7.24 (d, J ¼ 1.5 Hz, 2H), 6.60 (br, 2H),
5.78 (m, 1H), 4.96 (d, J ¼ 17.8 Hz, 1H), 4.91 (d,
J ¼ 11.6 Hz, 1H), 4.25 (s, 2H), 2.97 (m, 2H), 2.00 (t,
J ¼ 7.2 Hz, 2H), 1.70 (m, 2H), 1.24–1.35 (m, 28H); 13C
NMR (150 MHz, CDCl3) d 152.6, 139.0, 128.2, 124.2,
124.1, 114.2, 52.9, 47.1, 43.9, 34.9, 33.7, 31.3, 29.0, 28.8,
28.8, 26.0, 25.7; HRMS (FAB, NBA matrix) m/z calcd for
C25H44N 358.3468, found 358.3502 [M – PF6]þ;
elemental analysis calcd (%) for C25H44F6NP z acetone:
C 59.88, H 8.97, N 2.49. Found: C 59.42, H 9.41, N 2.71.
Synthesis of bis(crown ether) 4c
Following the procedure for preparation of 4a, 7 (350 mg,
0.71 mmol), EDCI z HCl (335 mg, 1.75 mmol), 1,8-octane-
diol (51 mg, 0.35 mmol) and a catalytic amount of DMAP
were reacted in dry CH2Cl2 (2 mL). Purification by column
chromatography (SiO2) with 19:1 CHCl3/MeOH gave
320 mg of 4c (0.29 mmol, 84%). 1H NMR (600 MHz,
CDCl3) d 7.64 (d, J ¼ 8.2 Hz, 2H), 7.52 (s, 2H), 6.94–6.80
(m, 10H), 4.27 (t, J ¼ 6.6 Hz, 4H), 4.24–4.10 (m, 16H),
4.00–3.77 (m, 32H), 1.80–1.71 (m, 4H), 1.49–1.35 (m,
8H); 13C NMR (150 MHz, CDCl3) d 166.4, 152.8, 148.9,
148.2, 123.8, 123.2, 121.4, 114.4, 114.0, 112.0, 71.4, 71.3,
71.2, 69.9, 69.8, 69.6, 69.5, 69.4, 69.3, 69.2, 29.2, 28.7,
25.9; HRMS (FAB, NBA matrix) m/z calcd for C58H79O20
1095.5165, found 1095.5165 [M þ H]þ; elemental anal-
ysis calcd (%) for C58H78O20 z H2O: C 62.58, H 7.24.
Found: C 62.22, H 7.24.
Synthesis of bis(crown ether) 4a
The addition of 1,4-butanediol (22 mg, 0.24mmol) to a
solution of 6,7,9,10,12,13,20,21,23,24,26,27-dodecahydro-
dibenz[b,n][1,4,7,10,13,16,19,22]octaoxacyclotetracosin-2-
carboxylic acid (7) (250 mg, 0.51 mmol), EDCI z HCl
(240mg, 1.25mmol) and a catalytic amount of DMAP in
dry CH2Cl2 (2 mL) was done at room temperature. After
stirring for 5 h, the reaction mixture was poured into
ice-cooled 1 M HCl and extracted with CHCl3. The organic
layer was washed with saturated NaHCO3 and brine, and
was dried over anhydrous Na2SO4. After removing Na2SO4
by filtration, the solvent was concentrated in vacuo.
General procedure for synthesis of [3]rotaxane 1 z 3 z 1
A solution of ammonium salt 2 (0.1 mmol) and bis(crown
ether) 4 (0.05 mmol) in dry CH2Cl2 (2 mL) was stirred for

Supramolecular Chemistry
823
30 min in a sealed tube. Second-generation Grubbs
catalyst was added to the solution. After being stirred for
5 h at 508C, the reaction mixture was passed through a
silica gel pad (10% methanol in CHCl3). The solvent was
removed, and a brownish solid was obtained.
(m, 10H), 3.31–4.00 (m, 19H), 3.02–3.30 (br, 4H), 1.56–
2.08 (m, 4H), 1.31 (m, 4H), 1.30 (brs, 18H), 1.19 (brs, 18H),
1.08 (m, 4H); HRMS (ESI) m/z calcd for C66H102N2O10
541.3762, found 541.3773 [M – 2PF6]2þ/2.
The solid was treated with KOMe in dry methanol at
508C for 12 h. The reaction 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 concentrated in
vacuo. The crude product was purified by GPC (CHCl3) to
give [3]rotaxane 1 z 3 z 1 and [2]rotaxane 1 z 3.
[3]Rotaxane 1 z 3c z 1
1H NMR (600 MHz, CDCl3) d 7.65 (d, J ¼ 8.2 Hz, 2H),
7.52 (s, 2H), 7.32 (s, 2H), 7.25 (s, 4H), 7.16 (br, 4H), 6.94
(d, J ¼ 8.9 Hz, 2H), 6.89 (brs, 8H), 5.32 (m, 2H), 4.61 (m,
4H), 4.01–4.33 (m, 16H), 3.38–3.97 (m, 38H), 3.18 (brs,
4H), 1.85 (m, 4H), 1.36 (brs, 4H), 1.18 (s, 36H), 1.05–1.32
(m, 8H), 0.99 (brs, 12H); 13C NMR (150 MHz, CDCl3) d
166.3, 151.5, 151.3, 149.6, 147.2, 131.5, 124.2, 123.9,
123.6, 123.1, 121.8, 113.3, 112.6, 112.5, 111.8, 70.6, 70.5,
70.4, 70.0, 69.8, 68.4, 68.3, 68.2, 68.1, 52.7, 51.9, 49.0,
34.7, 32.3, 31.2, 29.4, 29.0, 28.8, 28.6, 26.3, 26.1; HRMS
(ESI) m/z calcd for C100H152N2O20 850.5464, found
850.5478 [M – 2PF6]2þ/2.
[3]Rotaxane 1 z 3b z 1
1H NMR (600 MHz, CDCl3) d 7.65 (brs, 2H), 7.52 (s, 2H),
7.32 (s, 2H), 7.28 (s, 4H), 7.18 (br, 4H), 6.95 (brs, 2H),
6.89 (brs, 8H), 5.19 (m, 2H), 4.62 (m, 4H), 4.01–4.32 (m,
16H), 3.36–3.97 (m, 38H), 3.20 (brs, 4H), 1.74 (m, 4H),
1.22–1.46 (m, 8H), 1.18 (s, 36H), 0.89–1.09 (m, 8H); 13
C
NMR (150 MHz, CDCl3) d 166.3, 151.5, 151.2, 147.0,
131.4, 124.1, 123.8, 123.1, 121.7, 113.2, 112.5, 111.7,
70.5, 70.45, 70.4, 69.9, 69.7, 68.3, 68.2, 68.1, 52.6, 51.9,
48.9, 34.6, 32.1, 31.8, 31.2, 28.9, 28.5, 28.2, 26.2, 26.1,
25.7; HRMS (ESI) m/z calcd for C96H144N2O20 822.5155,
found 822.5132 [M – 2PF6]2þ/2.
[2]Rotaxane 1 z 3c
1H NMR (600 MHz, CDCl3) d 7.65 (br, 1H), 7.52 (br, 1H),
7.38 (br, 2H), 7.34 (br, 4H), 7.16 (br, 4H), 6.83–7.10 (br,
5H), 5.32 (m, 2H), 4.61 (m, 2H), 4.01–4.33 (m, 10H),
3.38–3.97 (m, 19H), 2.97–3.37 (br, 4H), 1.70–2.16 (m,
4H), 1.27 (brs, 18H), 1.19 (brs, 18H), 0.80–1.67 (br, 24H);
13C NMR (150 MHz, CDCl3) d 166.3, 151.7, 151.5, 147.1,
141.5, 131.4, 124.3, 123.9, 123.3, 123.2, 121.9, 113.3,
112.6, 111.8, 70.6, 70.5, 70.0, 69.9, 68.5, 68.4, 68.2, 52.7,
52.0, 49.0, 34.8, 34.7, 32.4, 31.3, 31.2, 29.6, 29.3, 28.9,
28.8, 26.3, 25.9; HRMS (ESI) m/z calcd for C74H118N2O10
597.4388, found 597.4365 [M – 2PF6]2þ/2.
[2]Rotaxane 1 z 3b
1H NMR (600 MHz, CDCl3) d 7.66 (d, J ¼ 6.9 Hz, 1H),
7.53 (s, 1H), 7.40 (m, 2H), 7.34 (br, 2H), 7.17 (br, 4H),
6.82–6.98 (br, 5H), 5.25 (m, 2H), 4.61 (m, 2H), 4.00–4.33
(m, 10H), 3.34–3.95 (m, 19H), 2.92–3.25 (br, 4H), 1.56–
2.07 (m, 8H), 1.29 (brs, 18H), 1.19 (brs, 18H), 0.77–1.45
(m, 12H); 13C NMR (150 MHz, CDCl3) d 166.5, 151.9,
151.6, 151.4, 147.2, 141.6, 131.5, 124.5, 124.4, 124.3,
123.3, 121.9, 113.4, 112.7, 111.9, 70.7, 70.6, 70.0, 69.9,
68.5, 68.4, 68.2, 52.8, 52.1, 49.1, 34.9, 34.8, 31.3, 29.7,
26.2; HRMS (ESI) m/z calcd for C70H110N2O10 569.4075,
found 569.4061 [M – 2PF6]2þ/2.
General procedure for synthesis of tethered rotaxane 3b z 4
A solution of ammonium salt 2b (0.1 mmol) and bis(crown
ether) 4 (0.05 mmol) in dry CH2Cl2 (2 mL) was stirred for
30 min in a sealed tube. Second-generation Grubbs
catalyst was added to the solution. After being stirred for
5 h at 508C, the reaction mixture was passed through a
silica gel pad (10% methanol in CHCl3). The solvent was
removed, and the residue was purified by GPC (CHCl3) to
give tethered rotaxane 3b z 4.
[3]Rotaxane 1 z 3a z 1
1H NMR (600 MHz, CDCl3) d 7.63 (d, J ¼ 8.2 Hz, 2H),
7.49 (s, 2H), 7.28 (s, 2H), 7.23 (s, 4H), 7.18 (br, 4H), 6.92
(d, J ¼ 8.9 Hz, 2H), 6.86 (s, 8H), 4.97 (m, 2H), 4.60 (m,
4H), 4.00–4.41 (m, 16H), 3.36–4.00 (m, 38H), 3.19 (brs,
4H), 1.69 (m, 4H), 1.38 (m, 4H), 1.16 (s, 36H), 1.07 (m,
4H); HRMS (ESI) m/z calcd for C92H136N2O20 794.4838,
found 794.4816 [M – 2PF6]2þ/2.
Tethered rotaxane 3b z 4a
1H NMR (600 MHz, CDCl3) d 7.73–7.67 (m, 2H), 7.60–
7.55 (m, 2H), 7.41 (br s, 2H), 7.38 (br s, 4H), 7.20–7.08
(br, 4H), 7.06–7.01 (m, 2H), 6.91 (br s, 8H), 5.12–4.98
(m, 2H), 4.61 (br s, 4H), 4.50–4.27 (m, 8H), 4.26–4.02
(m, 12H), 3.94–3.68 (m, 16H), 3.61 (br s, 8H), 3.43–3.23
(m, 8H), 3.12–2.98 (m, 4H), 1.91 (br s, 4H), 1.67–1.46
(m, 4H), 1.26 (br s, 40H), 0.90–0.71 (m, 12H); 13C NMR
(150 MHz, CDCl3) d 165.9, 151.5, 151.4, 147.5, 147.1,
131,7, 129.9, 124.55, 124.47, 124.2, 123.5, 123.3, 121.9,
[2]Rotaxane 1 z 3a
1H NMR (600 MHz, CDCl3) d 7.64 (d, J ¼ 8.2 Hz, 1H),
7.54 (s, 1H), 7.43 (m, 2H), 7.34 (br, 4H), 7.18 (br, 4H),
6.72–7.05 (m, 5H), 5.32 (m, 2H), 4.61 (brs, 2H), 4.00–4.42

824
H. Iwamoto et al.
113.3, 112.9, 112.1, 70.6, 70.5, 70.0, 69.8, 69.6, 68.7, 68.6,
68.3, 64.9, 64.8, 64.6, 52.7, 49.1, 34.8, 32.03, 31.99, 31.7,
31.35, 31.28, 31.23, 29.0, 28.9, 28.12, 28.08, 26.3, 26.2,
26.0, 25.6; HRMS (ESI) m/z calcd for C98H146N2O20
835.5235, found 835.5203 [M – 2PF6]2þ/2.
program package. Ten thousand initial geometries were
generated by a low-mode and Monte Carlo mixed search
option, and the given geometries were optimised by a
conjugate gradient energy minimisation using the
OPLS2005 force field with the GB/SA solvation
parameters for CHCl3.
Tethered rotaxane 3b z 4b
1H NMR (600 MHz, CDCl3) d 7.73–7.67 (m, 2H), 7.60–
7.53 (m, 2H), 7.41 (br s, 2H), 7.38 (br s, 4H), 7.20–7.11
(br, 4H), 7.05–6.99 (m, 2H), 6.91 (br s, 8H), 5.20–5.02
(m, 2H), 4.62 (br s, 4H), 4.50–4.05 (m, 20H), 3.96–3.70
(m, 16H), 3.62 (br s, 8H), 3.46–3.28 (m, 8H), 3.12–2.99
(m, 4H), 1.77 (br s, 4H), 1.70–1.46 (m, 8H), 1.26 (br s,
40H), 0.90–0.72 (m, 12H); 13C NMR (150 MHz, CDCl3) d
166.0, 152.9, 151.6, 151.3, 148.9, 147.2, 131.6, 124.2,
124.0, 123.5, 123.2, 121.8, 121.5, 114.1, 113.2, 112.6,
71.3, 70.7, 70.1, 69.9, 69.6, 69.4, 69.2, 68.5, 68.2, 64.9,
64.7, 52.8, 49.2, 34.7, 31.9, 31.3, 28.7, 26.4, 26.2, 25.7;
HRMS (ESI) m/z calcd for C100H150N2O20 849.5364,
found 849.5383 [M – 2PF6]2þ/2.
Acknowledgements
This work was supported by Grant-in-Aid for Scientific Research
for Young Scientists (B) (No. 19750035) from the Japan Society
for the Promotion of Science (JSPS). We are grateful to the
Izumi Science and Technology Foundation, the Electric
Technology Research Foundation of Chugoku, the Kinki-chiho
Hatsumei Center, the JGC-S Scholarship Foundation and the
Uchida Energy Science Promotion Foundation for financial
support.
Notes
1. [3]Rotaxane 1 z 3b z 1 is formed by the homo coupling
reaction of complexed form 1 z 2b; thus, on probability
theory and statistics, the theoretical yield (88%) of
[3]rotaxane 1 z 3b z 1 can be estimated from the square of
the statistical distributions (94%) of complexed form 1 z 2b.
[2]Rotaxane 1 z 3b is formed by the coupling reaction
between complexed form 1 z 2b and uncomplexed form 2b;
thus, the theoretical yield (11%) of [2]rotaxane 1 z 3b can be
estimated from twice as much as the product of the statistical
distributions (94%) of complexed form 1 z 2b and those (6%)
of uncomplexed form 2b.
2. Isolated yields of tethered rotaxane 3b z 4a-c are 54%, 61%,
and 47%, respectively. The yield of the tethered rotaxanes
3b z 4a-c might be reduced during the purification process.
3. The olefin geometries of the [3]- and [2]rotaxanes,
newly formed through olefin metathesis reaction, were not
determined.
Tethered rotaxane 3b z 4c
1H NMR (600 MHz, CDCl3) d 7.72–7.65 (m, 2H), 7.58–
7.53 (m, 2H), 7.41 (br s, 2H), 7.38 (br s, 4H), 7.21–7.10
(br, 4H), 7.04–7.00 (m, 2H), 6.91 (br s, 8H), 5.20–4.98
(m, 2H), 4.62 (br s, 4H), 4.48–4.04 (m, 20H), 3.95–3.70
(m, 16H), 3.61 (br s, 8H), 3.40–3.28 (m, 8H), 3.10–2.98
(m, 4H), 1.74 (br s, 4H), 1.74–1.52 (m, 4H), 1.46–1.33
(m, 8H), 1.26 (br s, 36H), 0.98–0.74 (m, 12H); 13C NMR
(150 MHz, CDCl3) d 165.9, 151.4, 149.7, 147.4, 147.1,
135.9, 131.7, 129.9, 129.5, 124.4, 124.3, 124.2, 123.7,
123.3, 121.9, 113.3, 113.0, 112.9, 112.1, 70.59, 70.51,
70.46, 70.0, 69.8, 69.6, 68.7, 68.6, 68.3, 64.9, 64.9, 52.7,
49.1, 34.8, 32.2, 31.9, 31.4, 31.3, 29.1, 29.0, 28.93, 28.85,
28.7, 28.5, 28.2, 26.3, 26.2, 26.11, 26.07, 25.9, 25.8, 25.7;
HRMS (ESI) m/z calcd for C102H154N2O20 863.5548,
found 863.5526 [M – 2PF6]2þ/2.
References
(1) (a) Amabilino, D.B.; Stoddart, J.F. Chem. Rev. 1995, 95,
2725–2828. (b) Pease, A.R.; Jeppesen, J.O.; Stoddart, J.F.;
Luo, Y.; Collier, C.P.; Heath, J.R. Acc. Chem. Res. 2001,
34, 433–444.
(2) Harrison, T.; Harrison, S. J. Am. Chem. Soc. 1967, 89,
5723–5724.
(3) (a) Iijima, T.; Vignon, S.A.; Tseng, H.-R.; Jarrosson, T.;
Sanders, J.K.M.; Marchioni, F.; Venturi, M.; Apostoli, E.;
Balzani, V.; Stoddart, J.F. Chem. Eur. J. 2004, 10,
6375–6392. (b) Chambron, J.-C.; Heitz, V.; Sauvage, J.-P.
J. Am. Chem. Soc. 1993, 115, 12378–12384. (c) Anelli,
P.L.; Ashton, P.R.; Ballardini, R.; Balzani, V.; Delgado, M.;
Gandolfi, M.T.; Goodnow, T.T.; Kaifer, A.E.; Philp, D.;
Pietraszkiewicz, M.; Prodi, L.; Reddington, M.V.;
Slawin, A.M.Z.; Spencer, N.; Stoddart, J.F.; Vincent, C.;
Williams, D.J. J. Am. Chem. Soc. 1992, 114, 193–218.
(d) Anelli, P.L.; Spencer, N.; Stoddart, J.F. J. Am. Chem.
Soc. 1991, 113, 5131–5133. (e) Ballardini, R.; Balzani, V.;
Dehaen, W.; Dell’Erba, A.E.; Raymo, F.M.; Stoddart, J.F.;
Venturi, M. Eur. J. Org. Chem. 2000, 65, 591–602.
(f) Johnston, A.G.; Leigh, D.A.; Murphy, A.; Smart, J.P.;
Deegan, M.D. J. Am. Chem. Soc. 1996, 118, 10662–10663.
(g) Leigh, D.A.; Murphy, A.; Smart, J.P.; Slawin, A.M.Z.
Angew. Chem. Int. Ed. Engl. 1997, 36, 728–732.
Determination of the association constant
Determination of the association constant for crown ether
1 and axle precursor 2b was carried out using a 1H NMR
titration technique in dichloromethane-d2. The complex of
1 with 2b at 258C was in slow exchange on the NMR
timescale and displayed well-resolved signals for the free
and bound forms. The relative intensities of the protons of
free and bound 2b, along with the known concentrations of
1 and 2b, were used to determine an association constant
(Ka) at 258C, 5800 ^ 1200.
Molecular modelling
Molecular mechanics calculations on the tethered
rotaxanes were performed with the MacroModel V9.1

Supramolecular Chemistry
825
(h) Gatti, F.G.; Leigh, D.A.; Nepogodiev, S.A.;
Slawin, A.M.Z.; Teat, S.J.; Wong, J.K.Y. J. Am. Chem.
Chem. Soc. 1988, 110, 571–577. (g) Auffinger, P.; Wipff,
G. J. Am. Chem. Soc. 1991, 113, 5976–5988. (h) Ungaro,
R.; Pochini, A. Front. Supramol. Org. Chem. Photochem.
1991, 57–81. (i) Carcanague, D.R.; Knobler, C.B.;
Diederich, F.; J. Am. Chem. Soc. 1992, 114, 1515–1517.
(j) Helgeson, R.C.; Selle, B.J.; Goldberg, I.; Knobler, C.B.;
Cram, D.J. J. Am. Chem. Soc. 1993, 115, 11506–11511.
(k) Judice, J.K.; Keipert, S.J.; Knobler, C.B.; Cram, D.J.
J. Chem. Soc. Chem. Commun. 1993, 1325–1327.
(l) Casnati, A.; Pochini, A.; Ungaro, R.; Ugozzoli, F.;
Arnaud, F.; Fanni, S.; Schwing, M.-J.; Egberink, R.J.M.;
de Jong, F.; Reinhoudt, D.N. J. Am. Chem. Soc. 1995, 117,
2767–2777. (m) Maverick, E.; Cram, D.J. Compr.
Supramol. Chem. 1996, 1, 213–243. (n) Neri, P.; Consoli,
G.M.L.; Cunsolo, F.; Geraci, C.; Piattelli, M. New J. Chem.
1996, 20, 433–446. (o) Yuan, Y.; Gao, G.; Jiang, Z.-L.; You,
J.-S.; Zhou, Z.-Y.; Yuan, D.-Q.; Xie, R.-G. Tetrahedron
2002, 58, 8993–8999. (p) Rajakumar, P.; Srisailas, M.
Tetrahedron Lett. 2003, 44, 2885–2887.
´
Soc. 2001, 123, 5983–5989. (i) Bissell, A.; Cordova, E.;
Kaifer, A.E.; Stoddart, J.F. Nature 1994, 369, 133–137.
(j) Favin˜a, P.; Sauvage, J.-P. Tetrahedron Lett. 1997, 38,
3521–3524. (k) Collin, J.-P.; Favin˜a, P.; Sauvage, J.-P.
New J. Chem. 1997, 21, 525–528. (l) Armaroli, N.;
Balzani, V.; Collin, J.-P.; Favin˜a, P.; Sauvage, J.-P.;
Ventura, B. J. Am. Chem. Soc. 1999, 121, 4397–4408.
(4) (a) Sasabe, H.; Kihara, N.; Furusho, Y.; Mizuno, K.;
Ogawa, A.; Takata, T. Org. Lett. 2004, 6, 3957–3960.
(b) Aucagne, V.; Haenni, K.D.; Leigh, D.A.; Lusby, P.J.;
Walker, D.B. J. Am. Chem. Soc. 2006, 128, 2186–2187.
(c) Dichtel, W.R.; Miljanic, O.S.; Spruell, J.M.;
Heath, J.R.; Stoddart, J.F. J. Am. Chem. Soc. 2006, 128,
10388–10390. (d) Hutin, M.; Schalley, C.A.; Bernardi-
nelli, G.; Nitschke, J.R. Chem. Eur. J. 2006, 12,
4069–4076. (e) Mobian, P.; Collin, J.-P.; Sauvage, J.-P.
Tetrahedron Lett. 2006, 47, 4907–4909. (f) Aucagne, V.;
Berna, J.; Crowley, J.D.; Goldup, S.M.; Haenni, K.D.;
Leigh, D.A.; Lusby, P.J.; Ronaldson, V.E.; Slawin, A.M.Z.;
Viterisi, A.; Walker, D.B. J. Am. Chem. Soc. 2007, 129,
11950–11963. (g) Meyer, C.D.; Joiner, C.S.; Stoddart, J.F.
Chem. Soc. Rev. 2007, 36, 1705–1723. (h) Durot, S.;
Mobian, P.; Collin, J.-P.; Sauvage, J.-P. Tetrahedron 2008,
64, 8496–8503. (i) Prikhod’ko, A.I.; Durola, F.; Sauvage,
J.-P. J. Am. Chem. Soc. 2008, 130, 448–449.
(9) (a) Kim, H.-J.; Kim, H.; Alhakimi, G.; Jeong, E.J.;
Thavarajah, N.; Studnicki, L.; Koprianiuk, A.; Lough, A.J.;
Suh, J.; Chin, J. J. Am. Chem. Soc. 2005, 127,
16370–16371. (b) Ghalit, N.; Rijikers, D.T.S.;
Kemmink, J.; Versluis, C.; Liskamp, R.M.J. Chem.
Commun. 2005, 192–194. (c) Hou, H.; Leung, K.C.F.;
Lanari, D.; Nelson, A.; Stoddart, J.F.; Grubbs, R.H. J. Am.
Chem. Soc. 2006, 128, 15358–15359. (d) Murase, T.;
Horiuchi, S.; Fujita, M. J. Am. Chem. Soc. 2010, 132,
2866–2867.
(10) (a) Grubbs, R.H.; Chang, S. Tetrahedron 1998, 54,
4413–4450. (b) Grubbs, R.H. Tetrahedron 2004, 60,
7117–7140. (c) Grubbs, R.H. Angew. Chem. Int. Ed.
2006, 45, 3760–3765. (d) Vougioukalakis, G.C.;
Grubbs R.H. Chem. Rev. 2010, 110, 1746–1787.
(11) (a) Wisner, J.A.; Beer, P.D.; Drew, M.G.B.;
Sambrook, M.R. J. Am. Chem. Soc. 2002, 124,
12469–12476. (b) Coumans, R.G.E.; Elemans, J.A.A.W.;
Thordarson, P.; Nolte, R.J.M.; Rowan, A.E. Angew. Chem.
Int. Ed. 2003, 42, 650–654. (c) Hannam, J.S.; Kidd, T.J.;
Leigh, D.A.; Wilson, A.J. Org. Lett. 2003, 5, 1907–1910.
(d) Vignon, S.A.; Jarrosson, T.; Iijima, T.; Tseng, H.-R.;
Sanders, J.K.M.; Stoddart, J.F. J. Am. Chem. Soc. 2004,
126, 9884–9885.
(12) (a) Mohr, B.; Weck, M.; Sauvage, J.-P.; Grubbs, R.H.
Angew. Chem. Int. Ed. Engl. 1997, 36, 1308–1310.
(b) Kidd, T.J.; Leigh, D.A.; Wilson, A.J. J. Am. Chem.
Soc. 1999, 121, 1599–1600. (c) Weck, M.; Mohr, B.;
Sauvage, J.-P.; Grubbs, R.H. J. Org. Chem. 1999, 64,
5463–5471. (d) Raehm, L.; Hamilton, D.G.; Sanders,
J.K.M. Synlett 2002, 1743–1764. (e) Vysotsky, M.O.;
Bolte, M.; Thondorf, I.; Boehmer, V. Chem. Eur. J. 2003,
9, 3375–3382. (f) Guidry, E.N.; Cantrill, S.J.;
Stoddart, J.F.; Grubbs, R.H. Org. Lett. 2005, 7,
2129–2132.
(5) (a) Kolchinski, A.G.; Roesner, R.A.; Busch, D.H.;
Alcock, N.W. Chem. Commun. 1998, 1437–1438.
(b) Raymo, F.M.; Houk, K.N.; Stoddart, J.F. J. Am. Chem.
Soc. 1998, 120, 9318–9322. (c) Cantrill, S.J.; Rowan, S.J.;
Stoddart, J.F. Org. Lett. 1999, 1, 1363–1366. (d) Heim, C.;
¨
Affeld, A.; Nieger, M.; Vogtle, F. Helv. Chim. Acta 1999,
82, 746–759. (e) Rowan, S.J.; Stoddart, J.F. Org. Lett.
1999, 1, 1913–1916. (f) Baer, A.J.; Macartney, D.H. Inorg.
Chem. 2000, 39, 1410–1417. (g) Chichak, K.; Walsh, M.C.;
Branda, N.R. Chem. Commun. 2000, 847–848. (h) Furusho,
Y.; Hasegawa, T.; Tsuboi, A.; Kihara, N.; Takata, T. Chem.
Lett. 2000, 29, 18–19. (i) Chang, S.-Y.; Choi, J.; Jeong, K.-
S. Chem. Eur. J. 2001, 7, 2687–2697. (j) Glink, P.T.;
Oliva, A.I.; Stoddart, J.F.; White, A.J.P.; Williams, D.J.
Angew. Chem. Int. Ed. 2001, 40, 1870–1875. (k) Gunter,
M.J.; Bampos, N.; Johnstone, K.D.; Sanders, J.K.M. New
J. Chem. 2001, 25, 166–173. (l) Hunter, C.A.; Low,
C.M.R.; Packer, M.J.; Spey, S.E.; Vinter, J.G.; Vysotsky,
M.O.; Zonta, C. Angew. Chem. Int. Ed. 2001, 40,
2678–2682.
(6) Balzani, V.; Venturi, M.; Credi, A. Molecular Devices and
Machines-Concepts and Perspectives for the Nanoworld;
Wiley-VCH: Weinheim, 2008.
(7) (a) Cram, D.J. Chem. Tech. 1987, 17, 120–125.
(b) Cram, D.J. Angew. Chem. Int. Ed. Engl. 1988, 27,
1009–1020.
(8) (a) Cram, D.J.; Lein, G.M.; Kaneda, T.; Helgeson, R.C.;
Knobler, C.B.; Maverick, E.; Trueblood, K.N. J. Am. Chem.
Soc. 1981, 103, 6228–6232. (b) Cram, D.J.; Kaneda, T.;
Helgeson, R.C.; Brown, S.B.; Knobler, C.B.; Maverick, E.;
Trueblood, K.N. J. Am. Chem. Soc. 1985, 107, 3645–3657.
(c) Reinhoudt, D.N.; Dijkstra, P.J.; In’t Veld, P.J.A.;
Bugge, K.E.; Harkema, S.; Ungaro, R.; Ghidini, E. J. Am.
Chem. Soc. 1987, 109, 4761–4762. (d) Grootenhuis, P.D. J.;
van Eerden, J.; Dijkstra, P.J.; Harkema, S.; Reinhoudt, D.N.
J. Am. Chem. Sci. 1987, 109, 8044–8051. (e) Feinfoudt,
D.N.; Dijkstra, P.J. Pure Appl. Chem. 1988, 60, 477–482.
(f) Cram, D.J.; Carmack, R.A.; Helgeson, R.C. J. Am.
(13) Iwamoto, H.; Itoh, K.; Nagamiya, H.; Fukazawa, Y.
Tetrahedron Lett. 2003, 44, 5773–5776.
(14) Iwamoto, H.; Yawata, Y.; Fukazawa, Y.; Haino, T.
Chem. Lett. 2010, 39, 24–25.
(15) (a) Baeck, M.; Johansson, P.-O.; Waangsell, F.;
Thorstensson, F.; Kvarnstroem, I.; Ayesa, S.; Waehling,
H.; Pelcman, M.; Jansson, K.; Lindstroem, S.; Wallberg,
H.; Classon, B.; Rydergaard, C.; Vrang, L.; Hamelink, E.;
Hallberg, A.; Rosenquist, A.; Samuelsson, B. Bioorg. Med.
Chem. 2007, 15, 7184–7202. (b) Hu, X.; Nguyen, K.T.;
Jiang, V.C.; Lofland, D.; Moser, H.E.; Pei, D. J. Med. Chem.

826
H. Iwamoto et al.
Kido, Y.; Fukazawa, Y. Tetrahedron Lett. 1992, 33,
7561–7564.
2004, 47, 4941–4949. (c) Hattori, K.; Sajiki, H.; Hirota, K.
Tetrahedron 2000, 56, 8433–8441.
(19) (a) Mohamadi, F.; Richards, N.G.J.; Guida, W.C.;
Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.;
Hendrickson, T.; Still, W.C. J. Comput. Chem. 1990, 11,
440–467. (b) Reddy, M.R.; Erion, M.D.; Agarwal, A.;
Viswanadhan, V.N.; McDonald, D.Q.; Still, W.C. J. Comput.
Chem. 1998, 19, 769–780.
(16) Yamaguchi, N.; Hamilton, L.M.; Gibson, H.W.
Angew. Chem. Int. Ed. 1998, 37, 3275–3279.
(17) Trnka, T.M.; Grubbs, R.H. Acc. Chem. Res. 2001, 34,
18–29.
(18) (a) Usui, S.; Haino, T.; Hayashibara, T.; Hirai, Y.;
Fukazawa, Y.; Kodama, M. Chem. Lett. 1992, 21,
527–530. (b) Takahashi, T.; Yamada, H.; Haino, T.;
(20) Casadei, M.A.; Galli, C.; Mandolini, L.J. J. Org. Chem.
1981, 46, 3127–3128.