Thiazolium-tethering rotaxane-catalyzed asymmetric benzoin condensation: Unique asymmetric field constructed by the cooperation of rotaxane components

Article abstract of DOI:10.1080/10426501003773589

Asymmetric benzoin condensation of aromatic aldehydes with two kinds of optically active rotaxanes possessing thiazolium salt moieties was studied. A binaphthyl group as the chiral auxiliary was introduced in either the wheel or the axle component of the rotaxanes. Rate of the catalytic benzoin condensation of benzaldehyde with a rotaxane catalyst without the binaphthyl moiety was compared with its axle component to understand the effect of wheel component. Among several solvents used, methanol was the best solvent, which showed the highest yield (98%) of benzoin in the presence of 5 mol% of either the rotaxane and the axle catalysts. The benzoin condensations of aromatic aldehydes catalyzed by the chiral rotaxanes were studied in detail and found to give optically active benzoins with 0-32% e.e. in 5-92% yield depending on the structure of the rotaxane and the reaction conditions employed. From the results, two intrarotaxane chirality transfers are confirmed: (i) through-space chirality transfer from wheel to axle and (ii) through-bond chirality transfer controlled with an achiral wheel. Because these asymmetric reaction fields are specific to the rotaxane structure, the importance and possibility of the rotaxane field as a particular reaction field are demonstrated. Copyright Taylor & Francis Group.

Full text of DOI:10.1080/10426501003773589

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Phosphorus, Sulfur, and Silicon and the
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Thiazolium-Tethering Rotaxane-
Catalyzed Asymmetric Benzoin
Condensation: Unique Asymmetric Field
Constructed by the Cooperation of
Rotaxane Components
Yuya Tachibana a , Nobuhiro Kihara b , Kazuko Nakazono a &
Toshikazu Takata a
a Department of Organic and Polymeric Materials , Tokyo Institute of
Technology , Tokyo, Japan
b Department of Chemistry, Faculty of Science , Kanagawa
University , Hiratsuka, Japan
Published online: 27 May 2010.
To cite this article: Yuya Tachibana , Nobuhiro Kihara , Kazuko Nakazono & Toshikazu Takata (2010)
Thiazolium-Tethering Rotaxane-Catalyzed Asymmetric Benzoin Condensation: Unique Asymmetric
Field Constructed by the Cooperation of Rotaxane Components, Phosphorus, Sulfur, and Silicon and
the Related Elements, 185:5-6, 1182-1205, DOI: 10.1080/10426501003773589
To link to this article: http://dx.doi.org/10.1080/10426501003773589
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Phosphorus, Sulfur, and Silicon, 185:1182–1205, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003773589
THIAZOLIUM-TETHERING ROTAXANE-CATALYZED
ASYMMETRIC BENZOIN CONDENSATION: UNIQUE
ASYMMETRIC FIELD CONSTRUCTED BY THE
COOPERATION OF ROTAXANE COMPONENTS
Yuya Tachibana,1 Nobuhiro Kihara,2 Kazuko Nakazono,1
and Toshikazu Takata1
1Department of Organic and Polymeric Materials, Tokyo Institute of Technology,
Tokyo, Japan
2Department of Chemistry, Faculty of Science, Kanagawa University,
Hiratsuka, Japan
Asymmetric benzoin condensation of aromatic aldehydes with two kinds of optically active
rotaxanes possessing thiazolium salt moieties was studied. A binaphthyl group as the chiral
auxiliary was introduced in either the wheel or the axle component of the rotaxanes. Rate
of the catalytic benzoin condensation of benzaldehyde with a rotaxane catalyst without the
binaphthyl moiety was compared with its axle component to understand the effect of wheel
component. Among several solvents used, methanol was the best solvent, which showed the
highest yield (98%) of benzoin in the presence of 5 mol% of either the rotaxane and the
axle catalysts. The benzoin condensations of aromatic aldehydes catalyzed by the chiral
rotaxanes were studied in detail and found to give optically active benzoins with 0–32%
e.e. in 5–92% yield depending on the structure of the rotaxane and the reaction conditions
employed. From the results, two intrarotaxane chirality transfers are confirmed: (i) through-
space chirality transfer from wheel to axle and (ii) through-bond chirality transfer controlled
with an achiral wheel. Because these asymmetric reaction fields are specific to the rotaxane
structure, the importance and possibility of the “rotaxane field” as a particular reaction field
are demonstrated.
Keywords Asymmetric benzoin condensation; binaphthyl; rotaxane
INTRODUCTION
Rotaxane is a unique molecular system possessing spatially independent components
of a wheel and axle, which can act cooperatively because they are connected by interlock-
ing, so-called “mechanical bonding.” Therefore, rotaxane skeleton has been utilized as a
key structure of a variety of supramolecular systems such as molecular switches, molecular
Received 10 January 2009; accepted 2 February 2009.
Dedicated to Professor Naomichi Furukawa on the occasion of his 70th birthday.
N.K. is thankful for the Grant-in-Aid for Encouragement of Young Scientists (11750750) from the Ministry
of Education, Science, Sports, and Culture. He is also grateful for the grants from The Association for the Progress
of New Chemistry, The Japan Securities Scholarship Foundation, the Iketani Science and Technology Foundation,
and the Yazaki Memorial Foundation for Science and Technology.
Address correspondence to Toshikazu Takata, Department of Organic and Polymeric Materials, Tokyo
Institute of Technology, Ookayama, Meguro-ku, Tokyo 152-8552, Japan. E-mail: ttakata@polymer.titech.ac.jp
1182

THIAZOLIUM-TETHERING
1183
machines, and so on.1 We have also reported various rotaxane-based supramolecular sys-
tems2 including through-space photoinduced electron transfer system for the artificial pho-
tosynthetic system,3 molecular switch, and molecular motor. Furthermore, we have found
the unusual stabilization of a functional group placed on the axle component by the pres-
ence of the wheel component.4 Thus the rotaxane system can provide a quite fascinating
scaffold for the construction of functionalized supramolecular systems such as catalysts
utilizing the unique characteristics of the “rotaxane field.” We envisioned the significance
of a novel asymmetric field constructed by the cooperation of rotaxane components, which
prompted us to consider the benzoin condensation from the reaction mechanism involving
controllable reactive intermediate as suggested by Breslow.5 We have recently succeeded
in developing the first rotaxane catalysts for the asymmetric benzoin condensation.6 This
article describes the synthesis and characteristics of the chiral rotaxane catalysts in detail.
RESULTS AND DISCUSSION
Design of Rotaxane Catalyst for Benzoin Condensation
Breslow’s mechanism (Scheme 1) reveals that the stereoselectivity of product ben-
zoin in typical benzoin condensation is determined at the step of the addition of second
Scheme 1 Catalytic cycle of benzoin condensation.

1184
Y. TACHIBANA ET AL.
benzaldehyde to the catalyst–substrate adduct, so-called Breslow intermediate.5 Namely,
the stereochemistry of both the initial benzaldehyde adduct, thiazolinilydene benzyl al-
cohol, and the attack of second benzaldehyde at re or si face of the adduct undoubtedly
determines the stereochemistry of the benzoin. Therefore, the substituents of the thiazolium
moiety would control the direction of the second addition to benzaldehyde.
Many asymmetric catalysts such as thiamine 1 for the benzoin condensation have
appeared so far, as shown in Figure 1. The first research on the asymmetric benzoin conden-
sation was presented by Sheehan and Hunnemann in 1966 employing the chiral thiazolium
salt (+)-2 as the catalyst precursor,7 although the observed enantiomeric excess of the
benzoin was as low as 2%. Using modified thiazolium salts such as 3, Sheehan and Hara
could obtain the benzoin with 52% e.e. and 6% chemical yield.8 Since these reports, various
chiral thiazolium salts have been synthesized as the catalysts for the asymmetric benzoin
condensation, although the enantioselectivity was not as high (1–57%).9 Thiazolium salt 3
seems to be the best catalyst among those reported so far, which gave satisfactory enan-
tioselectivity (47–57% ee) and chemical yield (20–30%).10 A new type of thiazolium salt
catalysts having C2-symmetry was also studied (Figure 1, 4).11 On the other hand, rather
high enantioselectivity (86% ee) was achieved with triazolium salts12–14 such as 512 and 613
due to the advantageous introduction of two N-substituents around the reaction center. This
might suggest that the enantioselectivity can be enhanced by the groups spatially arranged
around the reaction center, in addition to the N-substituent, in the rotaxane catalyst system
in which components are combined through space.
Prior to the design of asymmetric rotaxane catalysts, the effect of the presence of the
wheel component on the reaction rate was studied, because the reaction might be severely
Figure 1 Chiral thiazolium and triazolium salts for the enantioselective benzoin condensation.

THIAZOLIUM-TETHERING
1185
disturbed by the presence of the “big” wheel component when the thiazolium salt group
is introduced in the axle component, at which the thiazolium salt group is placed for the
synthetic requirement. For this purpose, two new thiazolium salt catalysts, i.e., achiral
rotaxane catalyst 9 having thiazolium salt moiety at the axle component and non-rotaxane
catalyst 10 (axle catalyst) were prepared to compare their catalytic activity. Scheme 2
illustrates the synthetic routes of these catalysts. The precursor rotaxane 8 was synthesized
Scheme 2 Preparation of rotaxane 9 and non-rotaxane 10 catalysts. (a) DB24C8, 3,5-dimethylbenzoic anhydride,
Bu3P, CH2Cl2, r.t., 81%; (b) 1. Chloroacetic anhydride, Et3N, DMF, 40◦C, 48 h, 76%; 2. thiazole, NaI, r.t., 3
d; 3. Amberlite IRA-400 (Cl-type), 92% (2steps); (c) 1. Chloroacetic anhydride, THF, –40◦C, 16 h, 74%; 2.
3,5-dimethylbenzoic anhydride, Bu3P, CH2Cl2, r.t., 8 h, 84%; 3. thiazole, NaI, r.t., 3 d; 4) Amberlite IRA-400
(Cl-type), 99% (2 steps).
in 81% yield from hydroxy-functionalized sec-ammonium salt 7, dibenzo-24-crown-8-ether
(DB24C8), 3,5-dimethylbenzoic anhydride, and catalyst tributylphosphane, according to
the threading followed by the end-capping method.15 Introduction of thiazolium salt moiety
into the rotaxane axle was carried out at the ammonium nitrogen atom of the rotaxane axle
by N-chloroacetylation16 followed by the substitution with thiazole, because of the easy
modification in addition to the prompt neutralization of the ammonium moiety. The yield
of the chloroacetylation was 76%, while that of the thiazolium introduction was 92%. Final
rotaxane catalyst 9 was obtained in 92% yield by the counter anion exchange with Cl−. By
a similar treatment of the hydroxy-functionalized sec-ammonium hexafluorophosphate 7
with chloroacetic anhydride, 3,5-dimethylbenzoic anhydride for the OH-acylation, thiazole,
and Amberlite IRA-400 (Cl-type), the non-rotaxane catalyst 10 was obtained in 62% overall
yield.
When the benzoin condensation of benzaldehyde (0.40 M) with two catalysts 9 and
10 (10 mol%) was carried out in the presence of triethylamine (20 mol%) in methanol at
50◦C, benzoin was obtained as the product in a high yield (Scheme 3). The reaction rate

1186
Y. TACHIBANA ET AL.
Scheme 3 Benzoin condensation catalyzed by rotaxane 9 and non-rotaxane 10ꢁꢁ.
was evaluated by plotting the yield of benzoin vs. time, as shown in Figure 2, where the
reaction progress was monitored by 1H NMR.
Although the initial rate of the condensation with the non-rotaxane catalyst 10 was
two times larger than that with rotaxane catalyst 9, the yield of benzoin reached ca. 80%
within 3 h in each case. This result suggests that the crown ether wheel certainly controls the
reaction kinetically due probably to the sterically bulky group positioned near the reaction
center, but the degree of the rate degradation is not so serious, indicating the possible
enantioselectivity during the benzoin condensation with chiral rotaxane catalyst.
Enantioselectivity is often affected by not only the sterically asymmetric field, but also
the weak interactions such as π-stacking and hydrogen bonding, especially in supramolec-
ular system. Since the weak interaction is strongly influenced by the property of the reaction
medium solvent such as donor number and solvent polarity, effect of the solvent is one
of the important issues to be settled. Furthermore the solvent-dependency of the rotaxane
structure and the component mobility is also of importance for the catalytic event: The
wheel component, when the axle component is fixed, can take both circum rotation and
translation on the axle by Brownian motion, which is usually favored in a polar solvent. So
we examined the effect of solvent in the benzoin condensation with the rotaxane catalysts
(Table I). Whereas methanol or water is generally used as the solvent, it is known that
deuterated solvents accelerate the reaction by heavy atom effect, as previously reported.17
In fact, deuterated methanol used in the condensations with 9 and 10 resulted in the forma-
tion of higher yield of benzoin (83% vs. 76 or 77%, Table I, entries 1 and 7) than methanol
Figure 2 Plot of the yield of benzoin (%) vs. time (h) for the benzoin condensation with rotaxane 9 and non-
rotaxane (axle) 10. The reaction was carried out with benzaldehyde (0.40 M), Et3N (0.08 M), and thiazolium salt
(0.04 M) at 50◦C in methanol-d4 (0.07 mL). Initial rate of the benzoin condensation and isolated yield after 3 h:
Vint (rotaxane 9) = 9.0 × 10−2/M · min−1, (82%), Vint (non-rotaxane 10) = 4.3 × 10−1/M · min−1, (82%).

THIAZOLIUM-TETHERING
1187
Table I Effect of solvent and concentration on the yield of benzoina
Entry
Cat.
(Mol%)
Solvent
Benzaldehyde/M
Yield/%
1
2
3
4
5
6
7
8
9
9
10
10
5
5
5
CD3OD
CH3OH
CH3OH
DMSO
CH2Cl2
CH3CN
CD3OD
CH3OH
CH3OH
DMSO
CH2Cl2
CH3CN
0.40
0.40
0.80
0.80
0.80
0.80
0.40
0.40
0.80
0.80
0.80
0.80
83
77
98
97
48
55
83
76
98
98
34
51
5
10
10
10
5
5
5
10
11
12
5
aThe reaction was carried out using benzaldehyde, Et3N (20 mol%), and thiazolium catalyst at 50◦C in solvent
(0.70 mL) for 24 h.
(entries 2 and 8). DMSO was a good solvent similar to methanol (entries 4 and 10). Both
dichloromethane and acetonitrile afforded low yield of benzoin independent of the kind of
catalyst used (entries 5, 6, 11, and 12). Thus, methanol or DMSO was concluded to be a
suitable solvent. Since such a polar solvent was chosen as effective solvent, to inhibit the
intermolecular interaction, but intramolecular supramolecular interaction may be still alive
between the rotaxane components, which can cooperatively produce an asymmetric field.
This result seems to indicate that such a rotaxane can possesses a good asymmetric
reaction field with some significant steric effects around the catalytic center.
Meanwhile, the effect of the concentration on the yield of benzoin was consistent with
the reaction mechanism shown in Scheme 1: Higher concentration of the catalyst combined
with lower concentration of the substrate (77% or 76%, entries 2 and 8) gave lower yield
of benzoin than lower concentration of the catalyst combined with higher concentration of
the substrate (98%, Table I, entries 3 and 9) did in either catalyst system.
On the basis of the above results in addition to the previous results, we have designed
two types of chiral rotaxane catalysts having the thiazolium moieties on their axle com-
ponents (13 and 16) for the asymmetric benzoin condensation. C2 chiral binaphthyl group
was chosen as a chiral auxiliary from the viewpoint of its stable chirality and spatially
wider asymmetric field. The binaphthyl group was arranged at the wheel for 13 or axle
component for 16. In the case of the chiral wheel-containing rotaxane 13, free circumrota-
tion and translation of the wheel would construct an effective asymmetric field around the
thiazolium moiety, while the spatially restricted asymmetric field placed near the bulky bi-
naphthyl end-cap would limit the direction of second attack of substrate by the presence of
the DB24C8 wheel capable of undergoing translation on the axle. MM2 calculation results
of the Breslow’s intermediates that are expected to be formed in the benzoin condensation
also suggest the construction of potential asymmetric fields around the reaction centers of
these rotaxane catalysts as shown in Figure 3. For example, the chiral auxiliary binaphthyl
group on the wheel seems to make an asymmetric space near the initial benzaldehyde
adduct of the thiazolium in the stable structure of the Breslow’s intermediate derived from
13.

1188
Y. TACHIBANA ET AL.
Figure 3 MM2 calculated structures of Breslow’s intermediates 13Bi and 16Bi that are expected to be formed
during the benzoin condensation catalyzed by the rotaxane catalysts 13 and 16.
Synthesis of Optically Active Rotaxane Catalysts
Synthetic routes of the optically active rotaxane catalysts are illustrated in Schemes
4 and 5. The chiral wheel of rotaxane 13 was synthesized from (R)-1,1ꢁ-bi(2-naphthol)
according to the typical crown ether synthetic method (Scheme 4). Synthesis of the sec-
ammonium salt axle part having both bulky end and hydroxy group at the termini 11 was
carried out according to our previous report.18 Trimethylene and hexamethylene chains
were used as the spacers of the axle part. A mixture of the wheel component and the sec-
ammonium salt was treated with 3,5-di-tert-butylbenzoic anhydride in the presence of a
catalytic amount of tributylphosphane (10 mol%) at room temperature for 3 h to afford 20%
(n = 1) and 71% (n = 4) yields of ammonium-type rotaxane 12. Chloroacetylation followed
by the reaction with thiazole of 12 resulted in the formation of thiazolium chloride rotaxane
13a and 13b in 52% and 64%, yields, respectively after the counter anion exchange with
chloride ion using an ion exchange column. Low yield of shorter alkyl chain type rotaxane

THIAZOLIUM-TETHERING
1189
Scheme 4 Synthesis of rotaxane 13 having the optically active wheel component and thiazolium salt group on the
axle. (a) 3,5-Di-tert-butylbenzoic anhydride, Bu3P, CH2Cl2, r.t., 3 h, 20% (12a), 71% (12b); (b) 1. Chloroacetic
acid, Et3N, DMF, 50◦C, 24 h, 88% (n = 1), 92% (n = 4); 2. Thiazole, NaI; 3. Amberlite IRA-400 (Cl-type) 52%
(13a, 2 steps), 64% (13b, 2 steps).
12a in the end-capping process is attributed to the steric hindrance of the crown ether wheel,
as reported previously.
The structures of the rotaxane catalysts 13 were confirmed by specific rotation along
with 1H NMR, 13C NMR, IR, and MS spectra in addition to elemental analysis. Figure 4
Scheme 5 Synthesis of rotaxane catalyst 16 having the optically active end-cap and the thiazoium salt on the
axle. (a) 3,5-Dimethylbenzoic anhydride, Ti(i-OPr)4, TfOH, CH2Cl2, r.t., 6h, 75%; (b) 1. Chloroacetic acid, Et3N,
ꢀR
DMF, 40◦C, 24 h, 94%; 2. Thiazole, NaI, 100◦C, 24 h; 3. Amberlite IRA-400 (Cl-type), 50% (2steps); (c) 1.
Chloroacetic anhydride, THF, –40◦C, 15 h, 87%; 2. 3,5-Dimethylbenzoic anhydride, Bu3P, CH2Cl2, r.t., 11 h,
79%; 3. Thiazole, NaI, r.t., 24 h, 99%.

1190
Y. TACHIBANA ET AL.
Figure 4 1H NMR spectra of chiral wheel-type rotaxane 13a (n = 1, upper) and 13b (n = 4, bottom) (500 MHz,
CDCl3, 298 K).
1
shows H NMR spectra of two rotaxane catalysts 13a and 13b. Although both spectra
are considerably too complicated to enable the detailed assignment of all signals, several
characteristic signals confirm the structures of them. Namely, a thiazolium methine proton
signal a appeared around 10 ppm due to its high acidity, while an aromatic proton signal d
of di-tert-butylphenyl ring was at 8.2 ppm. Methylene signal b at the thiazolium linking was
split probably because of the diastereotopic protons Ha and Hb. Chemical shift difference
between two b protons of 13a or 13b would depend on the degree of asymmetry based on the
spatial distance difference from the binaphthyl group: b proton signals of 13a appeared to
have a more pronounced chemical shift difference than those of 13b because the binaphthyl
group on the wheel of 13a comes to the thiazolium group nearer than those of 13b due
to the difference of the methylene spacer length. Other spectroscopic data and elemental
analysis data were clearly consistent with the proposed structure of 13. The optical purity
of 13 should be ca. 98%, since the optical purity of the starting optically active crown ether
was 98% by HPLC determination using a chiral column.
The chiral axle-type rotaxane 16 was synthesized from chiral binaphthyl-
functionalized axle part 14,17 by a procedure similar to that employed for 13 (Scheme 5).
Pseudorotaxane formed in situ from 14 and DB24C8 by the assistance of trifluoromethane-
sulfonic acid, which was subjected to the end-capping reaction with 3,5-dimethylbenzoic
anhydride in the presence of titanium tetraisopropoxide (10 mol%), giving the chiral
axle-type rotaxane catalyst 16 in 75% yield.19 Trifluoromethanesulfonic acid usually works
as a very effective catalyst in the end-capping reaction with acid anhydride for the terminal
OH acylation. However, no catalysis of trifluoromethanesulfonic acid was confirmed in the
preparation of 16, although the reason why it was not effective is unclear at present time.

THIAZOLIUM-TETHERING
1191
The corresponding reference compound 17 without wheel component was also prepared
from 14 by a similar method to that for 16 from 15.
The structures of the rotaxane catalyst 16 and the axle catalyst 17 were similarly
confirmed by 1H NMR, 13C NMR, IR, MS spectra, and specific rotation along with elemental
1
analysis. H NMR spectra of 16 and 17 are shown in Figure 5. Similarly to the case of
the assignment of 13, signals a and d in the down-field area were quite consistent with the
structures of them, although most signals of 17 including a and d were split due to the syn
and anti structures caused by the amide moiety. Since the split signal was not observed with
16, the amide structure would be fixed as syn or anti probably because of the presence of
the crown ether wheel. Diastereotopic protons signals b and c of both catalysts also support
the proposed structures. All signals of 17 other than those of the aromatic region could be
assignable, as shown in the spectrum. Other spectroscopic data and elemental analysis data
were clearly consistent with the proposed structures of 16 and 17. Optical purity of these
catalysts should be ca. 98% for the same reason as 13.
Rotaxane-Catalyzed Benzoin Condensation
The benzoin condensation of benzaldehydes with rotaxane catalyst 13 was carried
out as shown in Scheme 6, and the results are summarized in Table II. The condensation of
benzaldehyde (1.6 M) catalyzed by 13a (0.16 M) in the presence of triethylamine (0.32 M)
in methanol was carried out for 24 h at 0◦C (Table II, entry 1). The product benzoin
was isolated in an excellent yield (90%) by chromatographic purification. Although the
asymmetric yield of 18a (21% e.e.) was not very high (entry 1), the e.e. of 18a increased
Figure 5 1H NMR spectra of chiral axle catalyst 17 (upper) and chiral axle-type rotaxane catalyst 16 (lower)
(500 MHz, CDCl3, 298 K).

1192
Y. TACHIBANA ET AL.
Scheme 6 Benzoin condensation catalyzed by rotaxane 13a and 13b.
up to 32% (entry 2) when decreased concentration (0.016 M) of 13a was used. The e.e.
value of the products as determined by HPLC with a chiral column was independent of
the length of the reaction period (3–24 h). The results suggest the good catalytic activity
of 13a, whereas the dependency of the e.e. value on the catalyst concentration may be
indicative of the presence of two possible catalytic pathways including a stereoselection
via nonsingle molecular catalysis.20 Meanwhile no chiral induction was observed when
separate dumbbell and wheel components were employed as catalyst.
The condensations at certain concentrations (0.004 M catalyst and 0.8 M substrate)
were examined to characterize and compare the rotaxane catalysts 13a and 13b with
different axle lengths. Inspection of the data of Table II (entries 1–10) revealed the through-
space chirality transfer between the wheel and axle components of 13a in terms of the
formation of an optically active product. The data of Table II also show that (i) the length
of the axle component slightly affects the chemical and asymmetric yields (entries 11–19);
(ii) the introduction of substituents (Me and Cl) on benzaldehydes decreases the chemical
Table II Asymmetric benzoin condensation with rotaxane catalyst 13a
Aldehyde
Entry
Cat.
(Mol%)
X
/M
Solvent
Temp./◦C
Yield/%
e.e./%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
13a
10
1
5
5
5
5
5
5
5
5
10
1
5
5
5
5
5
5
H
1.6
1.6
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
1.6
1.6
0.8
0.8
0.8
0.8
0.8
0.8
0.8
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
DMSO
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
DMSO
0
0
30
0
90
14
70
34
17
5
79
16
10
39
91
14
73
34
10
81
28
16
49
21 (R)
32 (R)
16 (R)
23 (R)
27 (R)
21 (R)b
11 (R)
18 (R)
25 (R)
0 (R)
12 (R)
21 (R)
10 (R)
16 (R)
22 (R)
4 (R)
−20
0
0
0
0
0
0
0
30
0
Cl
Me
Furfural
H
13b
−20
0
Cl
Me
Furfural
CH3OH
CH3OH
CH3OH
0
0
0
11 (R)
21 (R)
0 (R)
5
aThe reaction was carried out with benzaldehyde, Et3N (20 mol%), and catalyst in solvent (0.70 mL) for 24 h.
bFor 3 h.

THIAZOLIUM-TETHERING
1193
Table III Asymmetric benzoin condensation with rotaxane catalyst 16 and dumbbell catalyst 17a
Benzaldehyde
Entry
Cat.
(Mol%)
X
/M
Solvent
Temp./◦C
Yield/%
e.e./%
1
2
3
4
5
6
7
8
9
16
5
5
5
5
5
5
5
5
5
5
5
5
H
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
0.8
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
30
0
–20
0
0
0
30
0
–20
0
0
0
82
40
7
21 (S)
32 (S)
16 (S)
18 (S)
13 (S)
6 (S)
1 (S)
2 (S)
3 (S)
1 (S)
Cl
Me
Furfural
H
16
22
19
90
65
56
70
26
59
17
10
11
12
Cl
Me
Furfural
2 (S)
3 (S)
aThe reaction was carried out with aldehyde (0.80 M), Et3N (0.16 M), and thiazolium salt (0.04 M) in solvent
(0.70 mL) for 24 h.
reactivity (entries 8–10, 17–19); (iii) dimethyl sulfoxide as solvent causes an increase in
chemical yield and a decrease in asymmetric yield, although the degree of both yields is
small (entries 7, 16); and (iv) a typical temperature effect characterized by a decrease in
chemical yield and an increase in optical yield occurs as the temperature is lowered (entries
3–5, 13–15).
The molecular model studies of 13 showed that the rotation of the wheel is not free and
that the binaphthyl group tends to access the thiazolium moiety to avoid the steric repulsion
against the terminal bulky 3,5-di-tert-buthylphenyl groups of the axle. The stereoselectivity
confirmed that this condensation might come from the strong influence of the crown wheel
that surrounds the thiazolium moiety.
As mentioned above, a through-space chirality transfer was observed with 13. There-
fore, the rotaxane catalyst 16 having the chiral group at the end of the axle is interesting
enough to evaluate the through-bond chirality transfer and to compare the degree of chi-
rality transfer with that via through-space chirality transfer. The chirality transfer through
the bond was confirmed with 16 under the same conditions (Scheme 7), although the e.e.
values of 18 were a little lower than those of 13 as shown in Table III (entries 1–6). In-
teresting to note is the opposite absolute configuration of the product benzoin, which held
R configuration when 13 was used as the catalyst while S configuration when 16 and 17
Scheme 7 Benzoin condensation catalyzed by rotaxane 16 and non-rotaxane 17.

1194
Y. TACHIBANA ET AL.
were employed, even though the same chiral auxiliary was used. Of course it is reason-
ably understood because the structures of their asymmetric fields are completely different
from each other. The much lower e.e. value of 18 with the wheel-free catalyst 17 (1–3%,
Table III, entries 7–12) clearly reveals the significance of the presence of the wheel com-
ponent in the stereoselection step. The role of the wheel component linked mechanically to
the reaction center can be understood as one of the protections of the less stereoselective
side of the asymmetric field or as one of the enhancements of the influence of the chiral
environment.
Mechanism and Stereochemistry of the Enantioselective Reaction with
the Rotaxane Catalysts
The initial step of the benzoin condensation is the formation of a singlet carbene
by the deprotonation of thiazolium with base, as shown in Scheme 1. Then it reacts with
benzaldehyde to form Breslow’s intermediate (Bi). The second electrophilic addition of
benzaldehyde to this adduct occurs under the direction control by the asymmetric field.
In the case with 13, the (R)-binaphthyl group accelerates the electrophilic addition of re-
face of prochiral benzaldehyde to si-face of 13a·benzaldehyde adduct (13aBi) as shown
in Figure 6, judging from the streochemical results of the present benzoin condensation
giving benzoin with R configuration (Table II). The addition may be assisted by the hydrogen
bonding between OH group of 13aBi and carbonyl group of benzaldehyde, while one of
the naphthalene plane more strongly controls the arrangement of the benzene plane of
benzaldehyde by the π–π interaction between them. The other naphthalene plane may
contribute to rigidify the asymmetric field by overlaying it. When the longer axle rotaxane
catalyst 13b is used, the asymmetric field is not so limited by the more free translation
of the wheel component on the axle bearing the longer spacer. As a result, the degree of
enantioselectivity decreases.
On the other hand, the achiral wheel component of chiral axle-type rotaxane catalyst
16 works as a steric barrier, so that the second addition of benzaldehyde to the adduct occurs
mainly from the side of the binaphthyl group when the mechanism proceeds according to
Figure 7. As a result, the addition favorably occurs between the re-face of adduct 16Bi
and si-face of the second benzaldehyde via the opposite fashion to that of 13, yielding (S)-
benzoin selectively. Because the structures of the intermediate and the transition state are
Figure 6 Mechanism of the benzaldehyde addition to 13a·benzaldehyde adducts (13aBi). MM2 calculated
structure of molecular model of 13a·benzaldehyde adduct generated by MM2 calculation.

THIAZOLIUM-TETHERING
1195
Figure 7 Mechanism of the benzaldehyde addition to 16·benzaldehyde adducts (16Bi). MM2-calculated structure
of molecular model of 16·benzaldehyde adducts generated by MM2 calculation.
flexible in solution state enough to permit the amide bond rotation and the circumrotation
and translation of the wheel component, the benzoin obtained with 16 has an asymmetric
yield lower than that with 13. However, the introduction of wheel component to make the
rotaxane structure was very effective, and the present results emphasized the importance of
the cooperation of the component in the rotaxane catalyst system.
In summary, the first rotaxane catalysis was demonstrated in this work. The results
obtained here would help to clarify the fundamental features of the rotaxane structure
capable of constructing a unique reaction field as exemplified in the asymmetric benzoin
condensation. Study on a more precise design for the asymmetric rotaxane catalyst with
higher chemical and asymmetric yields based on the guiding principle obtained here is
underway.
EXPERIMENTAL
Methods and Materials
1H and 13C NMR spectra were recorded on JEOL GSX500 (500 MHz) and JEOL
GX270 (270 MHz) spectrometers using tetramethylsilane as an internal standard. IR spectra
were recorded on a Jasco FT/IR-460plus spectrometer. FAB-MS analyses were made on a
Finnigan MAT TSQ-70 instrument. Melting points were measured on a Yanako MP-3 instru-
ment. Optical rotations were measured on a Jasco DIP-1000 instrument. Preparative GPC
was carried out using JAI LC-908 equipped with JAIGEL-1C and JAIGEL-2C columns.
Enantiomeric excess (e.e.) was measured on a Jasco Gulliver system equipped with Dai-
cel Chiralpak AD-H column. Acetonitrile, N,N-dimethylformamide, triethylamine, and all
aldehydes were used after distillation over calcium hydride. Methanol was distilled over
magnesium before use. Dichloromethane was treated with phosphorous pentoxide before
distillation over calcium hydride. Other chemicals were reagent grade and used without
further purification.
General Procedure for Benzoin Condensation21
To a solution of triethylamine and an aldehyde, a chiral thiazolium salt was added
under an argon atmosphere. The reaction mixture was allowed to stand at mentioned
temperature. After 24 h, the reaction mixture was evaporated to give the crude solid, which

1196
Y. TACHIBANA ET AL.
was purified by silica gel column chromatography (eluent: dichloromethane). The product
was identified as benzoin by 1H NMR spectra.
Preparation of Achiral Rotaxane Catalyst 9
Rotaxane 8 was chloroacetylated by according to the literature.16
The N-chloroacetylated rotaxane (240 mg, 0.25 mmol) was dissolved in thiazole
(3.0 g, 35 mmol). Then sodium iodide (38 mg, 0.25 mmol) was added to the solution, and
it was stirred for 3 days. After that, it was poured into 1 M HCl (300 mL) with vigorous
stirring, and the formed precipitate was combined by filtration. The precipitate was dissolved
in methanol and passed through anion exchange column (Amberlite IRA-400 treated with
hydrochloric acid followed by water, eluent: methanol). Thiazolium salt–thethered rotaxane
9 was obtained as white solid in 92% yield (230 mg, 0.23 mmol).
mp 209–210◦C (dec.). 1H NMR (500 MHz, CDCl3) δ 11.20 and 10.96 (two s, 1H),
ppm. 13C NMR (125.7 MHz, CDCl3) δ 166.43, 164.03, 161.41, 148.31, 148.01, 138.57,
138.00, 137.95, 137.77, 137.52, 136.59, 136.05, 134.23, 133.80, 130.49, 128.94, 128.53,
127.98, 127.65, 127.15, 126.48, 125.59, 124.62, 124.02, 120.66, 120.37, 111.51, 111.44,
69.75, 69.52, 69.45, 69.27, 67.97, 66.47, 55.69, 49.79, 49.64, 21.40, 21.33, 20.99, 20.86
ppm. IR (KBr) 2920 (νC H, as), 2883 (νC H, s), 1702 (νC O, ester), 1658 (νC O, amide),
1253 (νC
CO, as), 1125 (νC
CO, s) cm−1. FAB-MS (matrix: m-NBA) m/z 961.1 [M-
O
O
Cl−]+.
Preparation of Achiral Non-Rotaxane Catalyst 10
N-Chloroacetylation of amino alcohol. Amino alcohol (that is, the precursor
of 7) was previously synthesized according to the literature as the starting material. To a
solution of amino alcohol (811 mg, 3.18 mmol) in THF (20 mL), a solution of chloroacetic
anhydride (544 mg, 3.18 mmol) in THF (10 mL) was added at –40◦C. After stirring for
16 h, the reaction mixture was washed with 5% NaOH aq. and brine. Then the organic layer
was dried with magnesium sulfate, filtered, and concentrated. The residue was purified by
silica gel column chromatography (CHCl3, Rf = 0.14). N-Chloroacetylamide alcohol was
obtained as colorless oil in 75% (493 mg, 2.36 mmol) yield.
1H NMR (270 MHz, CDCl3) δ 7.40–7.15 (m, 4H), 6.95, 6.92 (d, J = 6.5 Hz, 1H),
6.82 and 6.74 (two s, 2H), 4.72–4.43 (m, 6H), 4.13 (s, 2H), 2.31 and 2.29 (d, 6H), 1.72
(br, 1H) ppm. 13C NMR (67.5 MHz, CDCl3) δ 166.95, 166.84, 140.86, 140.45, 138.31,
137.78, 135.67, 135.06, 134.99, 134.18, 129.18, 129.12, 128.90, 127.81, 127.15, 126.83,
126.12, 125.59, 125.51, 123.90, 123.76, 123.68, 77.24, 77.16, 64.12, 64.03, 63.95, 49.97,
49.87, 49.77, 48.39, 48.31, 41.25, 41.18, 41.11, 21.03 ppm. IR (neat) 3409 (νO H), 2918
(νC H, as), 2858 (νC H, s), 1650 (νC O) cm−1
.
O-Acylation of N-chloroacetylamide alcohol. To a solution of the obtained
N-chloroacetylamide alcohol (330 mg, 0.99 mmol) and 3,5-dimethylbenzoic anhydride
(300 mg, 1.06 mmol) in dichloromethane (10 mL), tributylphosphane (25 µL, 0.10 mmol)
was added at room temperature. After 8 h, the mixture was washed with 5% Na2CO3 aq,
dried with sodium sulfate, and concentrated. The crude product was purified by silica gel
column chromatography (CHCl3, Rf = 0.57). N-chloroacetylamide ester was obtained as
colorless oil in 84% (387 mg, 0.84 mmol) yield.
1H NMR (270 MHz, CDCl3) δ 7.68 (s, 2H), 7.47–7.40 (m, 2H), 7.26–7.17 (m, 3H),
6.94 and 6.91 (twos, 1H), 6.82 and 6.74 (two s, 2H), 5.35 and 5.33 (d, 2H), 4.63–4.45

THIAZOLIUM-TETHERING
1197
(m, 4H), 4.14 (s, 2H), 2.35 (s, 6H), 2.30 and 2.29 (two s, 6H) ppm. 13C NMR (67.5 MHz,
CDCl3) δ 166.68, 166.52, 165.98, 138.19, 137.67, 137.48, 136.27, 135.78, 135.62, 135.50,
135.18, 134.20, 129.51, 129.10, 129.03, 128.85, 128.77, 128.35, 128.04, 127.94, 126.91,
126.29, 125.59, 125.55, 123.79, 123.70, 77.23, 77.16, 65.76, 65.66, 65.60, 50.15, 49.69,
48.36, 41.28, 41.21, 41.14, 20.96, 20.79 ppm. IR (neat) 2918 (νC H, as), 2860 (νC H, s),
1716 (νC O ester), 1658 (νC O amide) cm−1
.
The addition of thiazole to N-chloroacetylamide ester. To a solution of
N-chloroacetylamide ester (360 mg, 0.78 mmol) in thiazole (1.5 mL, 21 mmol), sodium
iodide (234 mg, 1.56 mmol) was added at room temperature. After 24 h, the solution
was poured into a 1 M HCl (300 mL) with vigorous stirring. The formed precipitate was
combined by filtration. The crude product was dissolved in methanol and passed through
anion exchange column (Amberlite IRA-400 treated with hydrochloric acid followed by
water, eluent: methanol). Thiazolium salt 10 was obtained as white solid. Yield 99% (446
g, 0.77 mmol).
mp 144–145◦C. 1H NMR (500 MHz, DMSO-d6) δ 10.38 (s, 1H), 8.62–8.61 (m, 1H),
8.35–8.33 (m, 1H), 7.59 (d, J = 7.5 Hz, 2H), 7.43–7.29 (m, 3H), 7.29 (d, J = 7.5 Hz,
2H), 6.94–6.83 (m, 3H), 5.98 and 5.95 (two s, 2H), 5.35 and 5.31 (two s, 2H), 4.61–4.40
(m, 4H), 2.31–2.22 (m, 12H) ppm. 13C NMR (125.7 MHz, DMSO-d6) δ 165.55, 164.97,
164.85, 161.76, 138.53, 137.90, 137.71, 137.29, 136.36, 1354.94, 135.63, 135.51, 135.44,
135.03, 134.66, 134.63, 129.36, 129.00, 128.58, 128.33, 128.07, 127.85, 127.56, 126.67,
125.44, 125.03, 65.77, 65.70, 55.12, 49.63, 49.17, 48.28, 20.93, 20.72 ppm. IR (KBr) 1717
(νC O, ester), 1659 (νC O, amide), 1210 (νC
CO, as) cm−1. FAB-MS (matrix: m-NBA) m/z
O
513.1 [M Cl−]+.
Preparation of Chiral-Wheel–Type Rotaxane 13a and 13b
Binaphthyl-benzo-26-crown ether: Diol precursor. To a solution of tert-
BuOK (10.3 g, 87.2 mmol) in THF (40 mL), catechol (3.89 g, 35.0 mmol) in THF
(40 mL) was added, then the mixture was refluxed for 3 h. Additionally, a solution of
2-[2-(2chloroethoxy)ethoxy]-ethanol (15.1 g, 87.5 mmol) in THF (20 mL) was added and
refluxed for a further 40 h. After cooled to ambient temperature, to the reaction mixture was
added 5% Na2CO3 aq., and it was extracted with chloroform. The combined organic layer
was washed with brine, dried with magnesium sulfate, and concentrated in vacuo. The ob-
tained crude product was purified by silica gel column chromatography (EtOAc:methanol =
9:1; Rf = 0.23). Diol precursor with catechol and oxymethylene groups was obtained in
57% (7.41 g, 19.8 mmol) yield as a colorless oil.
1H NMR (270 MHz, CDCl3) δ 6.90 (s, 4H), 4.16–4.11 (m, 4H), 3.87–3.83 (m, 4H),
3.74–3.63 (m, 8H), 3.59–3.54 (m, 4H), 3.49 (s, 4H) ppm. 13C NMR (67.5 MHz, CDCl3) δ
148.5, 121.2, 114.6, 72.3, 70.4, 70.0, 69.4, 68.6, 61.2 ppm. IR (KBr) 3400 (νO H), 2924
(νC H, as), 2875 (νC H, s), 1255 (ν
C, as), 1126, (ν
C, as), 1058 (νC
C, s) cm−1
.
C
O
C
O
O
Ditosylation. To a solution of diol derivative (7.24 g, 19.3 mmol) in cold pyridine
(40 mL), a solution of p-toluenesulfonyl chloride (11.0 g, 57.9 mmol) in cold pyridine
(40 mL) was added dropwise at 0◦C. After addition, the mixture was stirred for 24 h at
0◦C. The reaction mixture was poured into 6 M HCl (200 mL), and it was extracted with
ethylacetate. The combined organic layer was washed with 5% Na2CO3 aq followed by
brine. And then it was dried with MgSO4, and the solvent was removed by rotary evaporator.
The crude product was purified by silica gel column chromatography (EtOAc:hexane =

1198
Y. TACHIBANA ET AL.
1:1; Rf = 0.21). Ditosylate was obtained in 47% yield (6.14 g, 8.99 mmol) as a colorless
oil.
1H NMR (270 MHz, CDCl3) δ 7.65 (d, J = 8.2 Hz, 4H), 7.19 (d, J = 8.2 Hz, 4H),
6.78 (s, 4H), 4.04–3.98 (m, 8H), 3.70–3.66 (m, 4H), 3.57–3.51 (m, 8H), 3.49–3.44 (m, 4H),
2.28 (s, 6H) ppm. 13C NMR (67.5 MHz, CDCl3) δ 148.4, 144.3, 132.4, 129.8, 129.4, 127.8,
127.4, 121.1, 114.5, 70.3, 69.3, 69.0, 68.5, 68.2, 21.2 ppm. IR (KBr) 2927 (νC H, as), 2872
(νC H, s), 1354 (νS( O), as), 1176 (νS( O), s) cm−1
.
Cyclization of ditosylate with (R)-binaphthol. To a suspension of (R)-(+)-
binaphthol (441 mg, 1.54 mmol) and cesium carbonate (5.02 g, 15.4 mmol) in THF (40 mL),
a solution of ditosylate (1.05 g, 1.54 mmol) in THF (40 mL) was added, and the mixture
was refluxed for 24 h. After it was cooled to ambient temperature, 5% Na2CO3 was added,
and it was extracted with ethylacetate. The combined organic layer was washed with brine,
dried with MgSO4, and then the solvent was removed under the reduced pressure. The
resulting residue was purified by silica gel column chromatography (EtOAc:hexane = 3:1;
Rf 0.42). Binaphthyl-benzo-26-crown ether was obtained in 69% yield (663 mg, 1.06 mmol)
as colorless oil.
1H NMR (270 MHz, CDCl3) δ 7.83 (dd, J = 1.3, 8.9 Hz, 2H), 7.77 (d, J = 8.2 Hz,
2H), 7.41 (dd, J = 1.6, 8.9 Hz, 2H), 7.28–7.10 (m, 6H), 6.86 (br, 4H), 4.16–3.93 (m,
8H), 3.77 (s, 4H), 3.58–3.24 (m, 12H) ppm. 13C NMR (67.5 MHz, CDCl3) δ 154.0, 148.6,
133.7, 129.1, 129.0, 127.5, 125.9, 125.1, 123.3, 121.1, 120.3, 115.9, 114.0, 70.6, 70.5, 69.7,
69.6, 69.4, 68.9 ppm. IR (KBr) 2924 (νC H, as), 2871 (νC H, s), 1256 (νC
C, as), 1127
O
(νC
C, s) cm−1. FAB-MS (matrix: m-NBA) m/z 624.3 [M−]+. Anal. calcd for C38H40O8:
O
C 73.06; H 6.45. found: C 72.94; H 6.44.
Preparation of (R)-Chiral-Wheel-Rotaxane (12)
To a solution of ammonium salt 11 (0.70 mmol) and chiral crown ether (0.70 mmol) in
CH2Cl2 (1.4 mL), 3,5-di-tert-butylbenzoic anhydride (0.84 mmol) and tributylphosphane
(0.07 mmol) were added. After the reaction mixture was allowed to stand at room temper-
ature for 6 h, the mixture was washed with 1 M hydrochloric acid, 5% sodium carbonate,
and brine, then dried with MgSO4, and evaporated in vacuo to give a crude product, which
was purified by preparative HPLC (eluent: chloroform).
12a: White solid. Yield 20%, mp 96◦C. 1H NMR (500 MHz, CDCl3) 7.87 (d, J = 2.0
Hz, 2H), 7.84 (d, J = 8.5 Hz, 2H), 7.81–7.78 (m, 2H), 7.69 (s, 1H), 7.55 (d, J = 8.5 Hz, 1H),
7.37–7.33 (m, 3H), 7.26–7.13 (m, 4H), 7.09 (br, 2H), 7.04 (s, 2H), 6.94 (d, J = 8.5 Hz, 1H),
6.86–6.81 (m, 3H), 6.76–6.74 (m, 1H), 4.32–4.10 (m, 7H), 4.04–4.00 (m, 2H), 3.77–3.67
(m, 3H), 3.63–3.49 (m, 5H), 3.39–3.17 (m, 10H), 3.03–2.93 (m, 3H), 2.00–1.85 (m, 2H),
1.37 (s, 18H), 1.17 (s, 18H) ppm. 13C NMR (125 MHz, CDCl3) δ 166.83, 154.48, 154.15,
151.15, 146.66, 146.33, 133.59, 133.55, 130.85, 130.00, 129.94, 129.77, 129.66, 129.16,
127.97, 127.31, 126.51, 126.47, 125.08, 124.94, 124.41, 124.22, 124.09, 123.63, 123.34,
121.85, 121.77, 120.97, 118.12, 116.65, 112.42, 112.20, 71.23, 71.00, 70.82, 70.71, 70.47,
70.07, 69.69, 69.37, 68.28, 67.71, 61.44, 52.96, 45.96, 35.01, 34.76, 31.46, 31.33, 26.11
ppm. IR (KBr): 2962 (νC H), 1717 (νC O, ester), 1240 (νC
CO, as), 1129 (νC
CO, s), 843
O
O
(νP F, as ), 557 (νP F, s ) cm−1. FAB-MS (m-NBA): m/z 1118.4, calcd for [M-PF6]+: 1118.7.
[α]D 105.4◦ (c = 0.100, CH2Cl2). Anal, calcd for C71H92F6NO10P·H2O: C, 66.49; H,
27
7.39; N, 1.09. found: C, 66.33; H, 7.41; N, 1.24.
12b: White solid. Yield 71%, mp 86–88◦C. 1H NMR (500 MHz, CDCl3) δ 8.00 (d,
J = 9.0 Hz, 1H), 7.91–7.85 (m, 5H), 7.65 (s, 1H), 7.57 (d, J = 9.5 Hz, 1H), 7.39–7.34 (m,

THIAZOLIUM-TETHERING
1199
3H), 7.26–7.15 (m, 7H), 6.99 (br, 2H), 6.88–6.85 (m, 4H), 4.26–4.14 (m, 8H), 4.10–4.05
(m, 1H), 4.02–3.99 (m, 1H), 3.93–3.90 (m, 1H), 3.77–3.74(m, 1H), 3.67–3.30 (m, 14H),
3.23–3.10 (m, 3H), 2.95–2.91 (m, 1H), 2.82 (br, 1H), 2.57 (br, 1H), 1.58–1.52 (m, 2H),
1.36 (s, 18H), 1.20 (s, 18H), 1.16–1.07 (m, 2H), 1.01–0.96 (m, 2H) ppm. 13 C NMR (125
MHz, CDCl3) δ 167.07, 154.77, 154.29, 151.15, 150.92, 146.82, 146.58, 133.62, 133.49,
130.93, 129.97, 129.90, 129.87, 129.79, 129.67, 128.02, 127.92, 126.96, 126.53, 126.47,
124.99, 124.97, 124.37, 124.30, 123.54, 123.29, 121.85, 121.77, 121.66, 121.18, 118.19,
116.98, 112.45, 112.38, 71.53, 70.95, 70.82, 70.76, 70.567, 70.33, 70.16, 69.62, 69.16,
68.26, 68.11, 64.40, 53.00, 48.83, 34.94, 34.78, 31.39, 31.32, 28.44, 26.13, 25.99, 25.33
ppm. IR (KBr): 2961 (νC H), 1714 (νC O, ester), 1246 (νC
CO, as), 1129 (νC
CO, s), 844
O
O
(νP F, as ), 558 (νP F, s ) cm−1. FAB-MS (m-NBA): m/z 1160.7, calcd for [M-PF6]+: 1160.7.
[α]D27 98.0◦ (c = 0.100, CH2Cl2) Anal, calcd for C74H98F6NO10P·H2O: C, 67.10; H, 7.61;
N, 1.06. found: C, 67.47; H, 7.75; N, 1.20.
N-Chloroacetylation of Rotaxane 12
A solution of 12 (0.131 mmol), chloroacetic anhydride (1.31 mmol), and triethy-
lamine (0.66 mmol) in N,N-dimethylformamide (2.0 mL) was stirred at 50◦C for 24 h.
After addition of aqueous 5% sodium carbonate solution, the mixture was extracted with
ethyl acetate. The organic layer was washed with a mixture of 5% sodium carbonate solu-
tion and methanol (v/v = 1/1), 2 M hydrochloric acid, and brine, then dried over anhydrous
magnesium sulfate, and evaporated in vacuo to give a crude product, which was purified
by preparative HPLC (eluent: chloroform).
N-Chloroacetylated chiral-wheel-type rotaxane 12a White solid. Yield 88%, mp
115–117◦C. 1H NMR (500 MHz, CDCl3) δ 7.99 (d, J = 9.0 Hz, 1H), 7.88 (d, J = 8.0 Hz,
1H), 7.83 (d, J = 1.5 Hz, 2H), 7.67 (s, 1H), 7.50 (d, J = 8.5 Hz, 1H), 7.44 (d, J = 8.0
Hz, 1H), 7.33–7.30 (m, 1H), 7.24–7.15 (m, 7H), 7.07 (s, 1H), 6.85- 6.77 (m, 4H), 6.30 (s,
2H), 4.75 (d, J = 16.5 Hz, 1H), 4.62–4.57 (m, 1H), 4.36–4.29 (m, 4H), 4.20–4.15 (m, 2H),
4.10–4.02 (m, 3H), 3.95–3.92 (m, 2H), 3.84–3.80 (m, 1H), 3.72–3.60 (m, 4H), 3.54–3.22
(m, 9H), 3.10–3.03 (m, 2H), 2.98–2.95 (m, 1H), 2.88–2.84 (m, 1H), 2.67–2.64 (m, 1H),
2.38–2.28 (m, 1H), 2.13–2.04 (m, 1H), 1.32 (s, 18H), 1.11 (s, 18H) ppm. 13C NMR (125
MHz, CDCl3) δ 167.27, 167.19, 154.56, 154.45, 150.65, 150.05, 148.31, 148.16, 136.33,
133.76, 133.60, 130.43, 129.41, 129.16, 129.14, 128.20, 127.63, 126.52, 125.89, 125.62,
125.34, 124.98, 123.63, 123.46, 123.63, 123.46, 123.39, 121.13, 121.00, 120.85, 120.04,
119.82, 119.30, 117.58, 115.29, 112.89, 112.40, 71.44, 71.15, 70.91, 70.58, 70.47, 70.18,
69.89, 68.79, 68.72, 68.64, 63.44, 47.99, 43.88, 42.35, 34.97, 34.63, 31.48, 27.00 ppm.
IR (KBr): 2962 (νC H), 1710 (νC O, ester), 1656 (νC O, amide), 1248 (νC
CO, as), 1118
O
(νC
CO, s) cm−1. FAB-MS (m-NBA): m/z 1193.7, calcd for [M]+: 1193.6. [α]D27 192.2◦
(c =O0.100, CH2Cl2). Anal. Calcd for C73H92ClNO11·H2O: C, 72.28; H, 7.81; N, 1.15.
found: C, 72.26; H, 7.52; N, 1.24.
12b: White solid. Yield 92%, mp 83–84◦C. 1H NMR (500 MHz, CDCl3) δ 7.94 (d,
J = 9.0 Hz, 1H), 7.90 (d, J = 2.0 Hz, 2H), 7.86–7.82 (m, 2H), 7.72 (d, J = 8.0 Hz, 1H),
7.65–7.64 (m, 1H), 7.47–7.42 (m, 2H), 7.33–7.30 (m, 1H), 7.26–7.16 (m, 6H), 7.13 (s, 1H),
6.83–6.67 (m, 5H), 6.50 (s, 2H), 4.59 (d, J = 16.0 Hz, 1H), 4.34–4.30 (m, 1H), 4.20–4.03
(m, 8H), 3.98 (d, J = 13.0 Hz, 1H), 3.93–3.89 (m, 1H), 3.83–3.69 (m, 4H), 3.61 (d, J = 16.0
Hz, 1H), 3.59–3.55 (m, 2H), 3.49–3.34 (m, 5H), 3.26–3.19 (m, 4H), 3.12–3.09 (m, 1H),
3.00–2.92 (m, 2H), 2.84–2.81 (m, 1H), 1.58–1.50 (m, 2H), 1.37 (s, 18H), 1.17 (s, 18H),
1.13–0.89 (m, 4H) ppm. 13C NMR (125 MHz, CDCl3) δ 167.21, 166.86, 154.58, 154.43,

1200
Y. TACHIBANA ET AL.
150.77, 150.15, 148.31, 148.23, 136.7, 133.64, 133.61, 130.19, 129.56, 129.43, 129.28,
129.24, 128.16, 127.72, 126.69, 125.92, 125.79, 125.31, 125.08, 123.59, 123.52, 120.89,
120.84, 120.43, 120.39, 120.16, 119.63, 116.50, 115.58, 112.87, 112.63, 71.07, 70.79,
70.75, 70.62, 70.52, 70.42, 70.31, 70.18, 70.04, 69.24, 68.66, 68.43, 65.70, 48.05, 48.00,
42.18, 35.00, 34.70, 31.53, 31.48, 29.09, 28.34, 25.79, 25.55 ppm. IR (KBr): 2962 (νC H),
1713 (νC O, ester), 1654 (νC O, amide), 1245 (νC
CO, as), 1123 (νC
CO, s) cm−1. FAB-MS
O
O
(m-NBA): m/z 1235.6, Calcd for [M]+: 1235.7. [α]D27 191.8◦ (c = 0.100, CH2Cl2). Anal.
Calcd for C76H98ClNO11·H2O: C, 72.73; H, 8.03; N, 1.12. found: C, 72.71; H, 7.72; N,
1.20.
(R)-Chiral Axle Rotaxane Thiazolium Salt 13
A mixture of N-chloroacetylated rotaxane (140 mg, 0.117 mmol), sodium iodide
(175 mg, 1.17 mmol), and thiazole (0.70 mL, 9.8 mmol) was allowed to stand at 80◦C
for 24 h. The resulting mixture was poured into 1 M HCl (100 mL). The precipitate was
collected by filtration. The crude product was dissolved in methanol and passed through
anion exchange column (Amberlite IRA-400 treated by hydrochloric acid followed by
water, eluent: methanol). The crude product was further purified by preparative HPLC
(eluent: chloroform).
1
13a: White solid. Yield 52%, mp 176–177◦C. H NMR (500 MHz, CDCl3) δ 9.95
(br, 1H), 8.30 (s, 1H), 7.95 (d, J = 9.5 Hz, 1H), 7.89–7.85 (m, 3H), 7.72 (s, 1H), 7.51 (d,
J = 8.0 Hz, 1H), 7.38–7.13 (m, 10H), 6.91–6.83 (m, 3H), 6.66 (d, J = 8.0 Hz, 1H), 6.22
(s, 2H), 5.96- 5.93 (m, 1H), 4.75–4.61 (m, 3H), 4.47–4.43 (m, 1H), 4.25–4.20 (m, 2H),
4.08–4.02 (m, 4H), 3.92–3.6 (m, 8H), 3.57–3.02 (m, 10H), 2.30–2.84 (m, 1H), 2.64–2.60
(m, 1H), 2.33–2.18 (m, 4H), 1.38 (s, 18H), 1.15 (s, 18H) ppm. 13C NMR (125 MHz, CDCl3)
δ 167.31, 163.44, 161.71, 154.50, 154.24, 150.89, 150.30, 148.34, 147.73, 136.31, 135.45,
133.65, 133.50, 129.97, 129.47, 129.36, 129.32, 128.96, 128.16, 127.67, 127.17, 126.95,
126.17, 125.89, 125.22, 124.93, 123.75, 123.63, 123.50, 122.01, 121.75, 121.05, 120.31,
119.84, 119.06, 117.27, 114.72, 112.80, 71.38, 70.65, 70.62, 70.47, 70.39, 70.18, 70.07,
69.89, 68.60, 68.22, 63.00, 54.88, 49.02, 43.62, 34.97, 34.60, 31.44, 31.42, 26.52 ppm.
IR (KBr): 2961 (νC H), 1710 (νC O, ester), 1662 (νC O, amide), 1247 (νC
CO, as), 1119
O
(νC
CO, s) cm−1. FAB-MS (matrix: m-NBA) m/z 1243.6, calcd for [M-Cl−]+: 1243.7.
O
[α]D 245.6◦ (c 0.100, CH2Cl2). Anal, calcd for C76H95ClN2O11S·5H2O: C, 66.62; H,
29
7.72; N, 2.04; S, 2.34. found: C, 66.88; H, 7.36; N, 2.18; S, 2.26.
13b was similarly prepared using N-chloroacetylated rotaxane 12b (600 mg,
0.485 mmol). The reaction was carried out at room temperature for 24 h.
1
13b: White solid. Yield 64%, mp 142–143◦C. H NMR (500 MHz, CDCl3) δ 9.88
(br, 1H), 8.19 (s, 1H), 7.91–7.90 (m, 4H), 7.86 (d, J = 8.0 Hz, 1H), 7.78 (d, J = 8.5 Hz,
1H), 7.66 (s, 1H), 7.50 (d, J = 9.0 Hz, 1H), 7.36–7.15 (m, 9H), 6.87–6.85 (m, 3H), 6.69
(d, J = 7.5 Hz, 1H), 6.37 (s, 2H), 5.77 (d, J = 17.5 Hz, 1H), 4.83 (d, J = 16.5 Hz, 1H),
4.50–4.21 (m, 2H), 4.27–4.07 (m, 5H), 4.01–3.92 (m, 3H), 3.84–3.69 (m, 4H), 3.62–3.46
(m, 7H), 3.33–3.20 (m, 4H), 3.13–3.12 (m, 2H), 2.97–2.93.(m, 1H), 2.69- 2.65 (m, 1H),
2.39 (br, 3H), 1.66–1.60 (m, 4H), 1.36 (s, 18H), 1.26–1.23 (m, 2H), 1.18 (s, 18H) ppm.
13C NMR (125 MHz, CDCl3) δ 167.20, 163.27, 161.24, 154.48, 154.26, 150.88, 150.21,
148.23, 147.96, 136.38, 35.85, 133.46, 133.39, 129.81, 129.51, 129.49, 129.43, 129.03,
128.05, 127.68, 126.91, 126.53, 126.24, 126.03, 125.18, 124.96, 123.81, 123.78, 123.46,
121.78, 121.43, 120.43, 120.29, 120.20, 119.25, 116.04, 115.22, 113.95, 112.78, 70.99,
70.82, 70.52, 70.51, 70.47, 70.38, 70.31, 70.13, 69.45, 68.79, 68.62, 65.07, 55.16, 49.05,

THIAZOLIUM-TETHERING
1201
47.53, 34.93, 34.60, 31.43, 31.40, 29.41, 27.69, 25.95, 25.89 ppm. IR (KBr): 2961 (νC H),
1714 (νC O, ester), 1658 (νC O, amide), 1245 (νC
CO, as), 1124 (νC
CO, s) cm−1. FAB-MS
O
O
(m-NBA): m/z 1285.7, calcd for [M-Cl−]+: 1285.7. [α]D29 230.0◦ (c 0.100, CH2Cl2). Anal,
calcd for C79H101ClN2O11S·4H2O: C, 68.05; H, 7.88; N, 2.01; S, 2.30. found: C, 68.17; H,
7.56; N, 2.14; S, 2.20.
Preparation of (R)-Aminoalcohol 14
Protection of (R)-binaphthol with MOM group. To a suspension of NaH
(9.0 g, 230 mmol) in THF-DMF (2:1, 600 mL), a solution of (R)-(+)-binaphthol (30 g,
105 mmol) in THF (240 mL) was added dropwise at 0◦C under an atmosphere of Ar gas.
After 6 h stirring at 0◦C, chloromethoxymethyl ether (29 mL, 580 mmol) was added to the
mixture and stirred another 6 h at 0◦C. Then the reaction was quenched with water, and it
was extracted with dichloromethane. The combined organic layer was dried with Na2SO4,
and the solvent was removed under reduced pressure. The obtained residue was purified by
reprecipitation from CH2Cl2-MeOH. After filtration, a protected binaphthol was obtained
as colorless needles in 73% (29 g, 77 mmol) yield.
1
mp 104–105◦C. H NMR (270 MHz, CDCl3) δ 7.95 (d, J = 9.2 Hz, 2H), 7.87 (d,
J = 8.1 Hz, 2H), 7.57 (d, J = 8.9 Hz, 2H), 7.37–7.31 (m, 2H), 7.25–7.13 (m, 4H), 5.09 (d,
J = 6.8 Hz, 2H), 4.97 (d, J = 6.8 Hz, 2H), 3.14 (s, 6H) ppm. IR (KBr) 2952 (νC H, as),
2900 (νC H, s), 1241 (νC
C, as), 1147 (νC
C, s) cm−1
.
O
O
(R)-3-Formyl-2, 2ꢀ-dimethyloxymethyl-1,1ꢀ-binaphthyl (formylation). To
a solution of the protected binaphthol (6.00 g, 16.0 mmol) in THF (50 mL), n-BuLi in
hexane (6.20 mL, 16.1 mmol) was added dropwise at 0◦C, and it was kept 0◦C for 3 h
with stirring. After addition of DMF (1.86 mL, 24.0 mmol), it was stirred for 1 h at 0◦C.
The reaction mixture was washed with sat. NH3 aq, 5% Na2CO3 aq and brine, then dried
with Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column
chromatography (EtOAc:hexane = 1:5; Rf 0.30). The product was obtained as a colorless
needle in 84% yield (5.42 g, 1.35 mmol).
mp 126–127◦C. 1H NMR (270 MHz, CDCl3) δ 10.59 (s, 1H), 8.56 (s, 1H), 7.99 (t,
J = 8.4, 2H), 7.86 (d, J = 7.8, 1H), 7.60 (d, J = 8.9, 1H), 7.45–7.14 (m, 6H), 5.14–5.02
(m, 2H), 4.76–4.68 (m, 2H), 3.14 (s, 3H), 2.98 (s, 3H) ppm. 13C NMR (67.5 MHz, CDCl3)
δ 190.78, 153.60, 152.59, 136.78, 133.54, 130.87, 130.09, 129.97, 129.46, 128.89, 128.80,
127.85, 126.73, 126.65, 125.78, 125.69, 124.98, 124.10, 119.27, 116.16, 100.00, 97.74,
57.04, 56.98, 55.92, 55.86 ppm. IR (KBr) 2950 (νC H, as), 2892 (νC H, s), 1690 (νC
)
O
cm−1
.
(R)-3-Formyl-2,2ꢀ-dihydroxy-1,1ꢀ-binaphthyl (deprotection). The formy-
lated binaphthyl (5.39 g, 13.4 mmol) was dissolved in chloroform (100 mL). Then 12 M
HCl (30 mL) and isopropanol (120 mL) were added the solution, and the mixture was
stirred for 38 h at room temperature. After the reaction mixture was washed with water and
brine, it was dried with Na2SO4, filtered, and concentrated. The obtained crude product
was used in the next reaction without further purification. Yellowish solid; 95% (3.98 g,
12.7 mmol).
mp 212–213◦C. 1H NMR (270 MHz, CDCl3) δ 10.58 (s, 1H), 10.11 (s, 1H), 8.31 (s,
1H), 7.98–7.84 (m, 3H), 7.43- 7.19 (m, 6H), 7.08 (2H, dd, J = 8.3, 0.7), 5.06 (s, 1H) ppm.
13C NMR (67.5 MHz, CDCl3) δ 196.31, 154.19, 151.34, 138.96, 138.89, 137.56, 133.28,

1202
Y. TACHIBANA ET AL.
131.06, 130.32, 129.91, 129.16, 128.21, 127.68, 126.60, 124.95, 124.81, 124.32, 123.40,
122.05, 117.66, 115.05, 113.13 ppm. IR (KBr) 3468 (νO H), 1652 (νC O) cm−1
.
(R)-3-Formyl-2,2ꢀ-dimethoxy-1,1ꢀ-binaphthyl (methylation). A suspension
of formylated binaphthol (2.18 g, 6.93 mmol) and potassium carbonate (3.87 g, 28.0 mmol)
in iodomethane/DMF (1/1, 60 mL) was refluxed for 12 h. After it was cooled to room
temperature, it was diluted with water and extracted with chloroform. The combined organic
layer was washed with 1 M HCl and brine, dried with MgSO4, filtered, and concentrated
in vacuo. The residue was purified by silica gel column chromatography (EtOAc:hexane =
1:10; Rf 0.20). The desired compound was obtained as yellowish solid in 95% (1.94 g,
12.7 mmol) yield.
mp 126–127◦C. 1H NMR (270 MHz, CDCl3) δ 10.48 (s, 1H), 8.47 (s, 1H), 7.94 (t,
J = 7.6, 2H), 7.80 (d, J = 7.6, 1H), 7.39 (d, J = 9.2, 1H), 7.35–7.02 (m, 6H), 3.71 (s,
3H), 3.41 (s, 3H) ppm. 13C NMR (67.5 MHz, CDCl3) δ 190.61, 156.41, 154.77, 137.12,
133.71, 130.98, 130.18, 130.09, 129.82, 128.88, 128.34, 127.95, 126.79, 126.03, 125.54,
125.52, 124.70, 123.67, 117.68, 113.26, 62.47, 56.47 ppm. IR (KBr) 2931 (νC H, as), 2837
(νC H, s), 1696 (νC O) cm−1
.
(R)-Aminoalcohol 14 (reduction). A solution of binaphthyl aldehyde (1.94 g,
5.67 mmol) and 2-amino-1-ethanol (328 mg, 5.67 mmol) in toluene was refluxed for 24 h
with Dean–Stark trap. After the solvent was removed under reduced pressure, a yellowish
oil was obtained. Then the oil was dissolved in methanol (20 mL), and sodium borohydride
(1.50 g, 40.0 mmol) was added to it. The mixture was stirred for 24 h, and 6 M HCl was added
to stop the generation of hydrogen gas. Then 5% NaOH aq. was added to make it basic,
and it was extracted with chloroform. The combined organic layer was washed with brine,
dried with MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica
gel column chromatography (EtOAc:methanol = 9:1; Rf 0.17). The desired aminoalcohol
14 was obtained as yellowish solid in 86% (1.90 g, 4.90 mmol) yield.
mp 68–71◦C. 1H NMR (270 MHz, CDCl3) δ 7.97 (d, J = 8.6, 1H), 7.84 (d, J = 12.2,
2H), 7.82 (d, J = 14.9, 1H), 7.08 (d, J = 8.9, 1H), 7.35–7.08 (m, 6H), 4.05 (s, 2H), 3.73 (s,
3H), 3.69 (t, J = 4.9, 2H), 3.35 (s, 2H), 3.32 (s, 2H), 2.85 (t, J = 5.0, 2H) ppm. 13C NMR
(67.5 MHz, CDCl3) δ 154.83, 154.63, 133.74, 133.41, 131.83, 130.36, 129.71, 128.83,
127.76, 127.59, 126.53, 125.80, 125.12, 124.96, 124.65, 124.36, 123.49, 118.88, 113.35
60.55, 56.42, 50.43, 49.25 ppm. IR (KBr) 3316 (νO H), 2935 (νC H, as), 2837 (νC
)
H, s
cm−1
.
Preparation of (R)-Chiral-Axle-Type Rotaxane 15
To a mixture of (R)-aminoalcohol 14 (327 mg, 0.84 mmol), DB24C8 (397 mg,
0.89 mmol), and titanium isopropoxide (2.5 µL, 8.4 mmol), dichloromethane (1.2 mL) and
triflic acid (112 µL, 1.27 mmol) were added at 0◦C under an argon atmosphere. The mixture
was stirred at 0◦C for 30 min. 3,5-Dimethylbenzoic anhydride (298 mg, 1.06 mmol) was
then added to the solution. After the reaction was carried out at room temperature for 6 h,
the reaction mixture was washed with 5% sodium carbonate solution, 1 M hydrochloric
acid, and brine, then dried over anhydrous magnesium sulfate, and evaporated in vacuo
to give a crude product, which was purified by silica gel column chromatography (eluent:
chloroform:methanol = 100:1) to give 702 mg (75%) of 15 as a white solid.
mp 96–98◦C. 1H NMR (500 MHz, CDCl3) δ 8.03 (d, J = 9.5 Hz, 1H), 7.88 (s, 1H),
7.85 (d, J = 8.0 Hz, 1H), 7.73 (br, 2H), 7.64 (s, 2H), 7.53 (d, J = 8.5 Hz, 1H), 7.47 (dd,
J = 1.8, 9.3 Hz, 1H), 7.33–7.27 (m, 2H), 7.19–7.02 (m, 5H), 6.85 (br, 8H), 4.74 (br, 2H),

THIAZOLIUM-TETHERING
1203
4.65–4.59 (m, 2H), 4.20–4.05 (m, 10H), 3.82 (br, 8H), 3.75 (s, 3H), 3.70–3.64 (m, 8H),
3.21 (s, 3H), 2.17 (s, 6H) ppm. 13C NMR (125 MHz, CDCl3) δ 165.88, 154.43, 153.46,
147.01, 137.55, 134.67, 134.19, 133.20, 130.35, 130.01, 129.25, 128.51, 127.69, 127.66,
126.96, 126.81, 126.06, 124.89, 124.66, 124.32, 123.78, 123.62, 123.25, 121.32, 121.29,
120.61 (q, JC-F = 320 Hz), 117.51, 112.95, 112.32, 112.30, 77.20, 70.53, 70.48, 69.93,
69.88, 67.89, 67.82, 60.46, 60.07, 55.96, 48.87, 47.92, 20.64 ppm. IR (KBr): 2930 (νC H),
1720 (νC O ester), 1266 (νS O, as), 1031 (νS O, s), 637 (νS O) cm−1. FAB-MS (m-NBA): m/z
968.5, calcd for [M-CF3SO3−]+: 968.5. [α]D26 38.0◦ (c = 0.100, CH2Cl2). Anal, calcd for
C59H66F3NO15S·H2O: C, 62.37; H, 6.03; N, 1.23. found: C, 62.27; H, 6.09; N, 1.36.
(R)-N-Chloroacetyl Rotaxane (N-Chloroacetylation of 15)
A solution of 15 (1.16 g, 1.04 mmol), chloroacetic anhydride (1.77 g, 10.4 mmol),
and triethylamine (724 µL, 5.19 mmol) in N,N-dimethylformamide (15 mL) was stirred
at 40◦C for 24 h. After addition of 5% aqueous sodium carbonate solution, the reaction
mixture was extracted with chloroform. The organic layer was washed with a mixture
of 5% aqueous sodium carbonate solution and methanol (v/v = 1/1), 2 M hydrochloric
acid, and brine, then dried over anhydrous magnesium sulfate, and evaporated in vacuo
to give a crude product, which was purified by silica gel column chromatography (eluent:
chloroform) to give 1.02 g (94%) of N-chloroacetylated rotaxane as a white solid.
mp 214–215◦C. 1H NMR (500 MHz, CDCl3) δ 8.06 (s, 2H), 7.97 (d, J = 9.5 Hz, 1H),
7.84 (d, J = 8.0 Hz, 1H), 7.43–7.40 (m, 2H), 7.29–7.25 (m, 2H), 7.13–7.07 (m, 5H), 6.97
(d, J = 8.0 Hz, 1H), 6.85–6.69 (m, 8H), 5.25–5.20 (m, 1H), 5.13–5.07 (m, 1H), 4.66–4.52
(m, 2H), 4.47–4.34 (m, 2H), 4.26–4.22 (m, 3H), 4.11–4.08 (m, 3H), 3.96–3.78 (m, 8H),
3.71 (s, 3H), 3.68–3.64 (m, 2H), 3.55–3.39 (m, 10H), 3.16 (s, 3H), 2.27 (s, 6H) ppm.
13C NMR (125 MHz, CDCl3) δ 167.54, 166.48, 154.70, 154.43, 148.23, 148.11, 137.35,
133.99, 133.56, 132.77, 131.10, 130.67, 130.40, 129.37, 128.93, 128.78, 128.04, 127.68,
125.85, 125.37, 124.99, 124.54, 124.50, 124.02, 123.61, 123.28, 120.57, 120.50, 119.65,
113.40, 112.56, 111.86, 71.26, 71.19, 70.30, 70.26, 68.06, 68.05, 62.30, 60.05, 56.22, 45.70,
44.35, 42.66, 21.14 ppm. IR (KBr): 2918 (νC H), 1709 (νC O, ester), 1658 (νC O, amide), 1248
(νC
CO, as), 1126 (νC
CO, s) cm−1. FAB-MS (m-NBA): m/z 1043.4, calcd for [M]+:
O
1043.4. [α]D26 42.4◦ (c =O0.100, CH2Cl2). Anal. Calcd for C60H66ClNO13·H2O: C, 67.82;
H, 6.45; N, 1.32. found: C, 68.06; H, 6.63; N, 1.47.
(R)-Chiral Thiazolium Rotaxane (16)
A mixture of N-chloroacetylated rotaxane (486 mg, 0.48 mmol), sodium iodide
(672 mg, 4.48 mmol), and thiazole (1.0 mL, 14 mmol) was allowed to stand at 80◦C for
48 h. The resulting mixture was poured into 1 M HCl (100 mL). The precipitate was
collected by filtration. The crude products were dissolved in methanol, and the solution
was passed through anion exchange column (Amberlite IRA-400 treated by hydrochloric
acid followed by methanol, eluent: methanol). The crude product was further purified by
silica gel column chromatography (eluent: chloroform:methanol = 10:1) to give 281 mg
(56%) of 16 as white solid.
1
mp 172◦C. (dec.) H NMR (500 MHz, CDCl3) δ 10.75 (br, 1H), 8.17 (br, 1H),
7.98–7.96 (m, 2H), 7.92 (s, 2H), 7.84 (d, J = 8.5 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.41 (d,
J = 9.0 Hz, 1H), 7.30–7.26 (m, 2H), 7.22 (s, 1H), 7.13–6.98 (m, 5H), 6.82 (br, 6H), 6.76 (br,
2H), 6.16 (d, J = 16.0 Hz, 1H), 5.92 (d, J = 16.0 Hz, 1H), 5.32–5.26 (m, 1H), 5.17–5.11 (m,

1204
Y. TACHIBANA ET AL.
1H), 4.68 (s, 2H), 4.47–4.35 (m, 2H), 4.26–4.23 (m, 2H), 4.13–4.03 (m, 6H), 3.95–3.89 (m,
4H), 3.68 (s, 3H), 3.65–3.50 (m, 12H), 3.12 (s, 3H), 2.27 (s, 6H) ppm. 13C NMR (125 MHz,
CDCl3) δ 166.60, 163.98, 162.03, 154.64, 154.21, 148.21, 137.50, 133.88, 133.83, 132.89,
130.56, 130.32, 129.85, 129.55, 128.90, 128.57, 127.74, 125.99, 125.40, 125.30, 125.17,
124.66, 124.39, 124.26, 124.11, 123.34, 121.26, 121.14, 119.20, 113.42, 113.39, 112.92,
71.32, 71.24, 70.41, 68.86, 68.73, 61.86, 60.00, 56.25, 55.64, 45.80, 45.10, 21.13 ppm.
IR (KBr): 2919 (νC H), 1709 (νC O, ester), 1664 (νC O, amide), 1248 (νC
CO, as), 1125
O
(νC
CO, s) cm−1. FAB-MS (matrix: m-NBA) m/z 1093.1, calcd for [M-Cl−]+: 1093.5.
O
[α]D29 25.4◦ (c = 0.100, CH 2Cl2). Anal. Calcd for C63H69ClN2O13S·4H2O: C, 62.96; H,
6.46; N, 2.33; S, 2.67. found: C, 62.61; H, 6.24; N, 2.48; S, 2.65.
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