Locking the Dynamic Axial Chirality of Biphenyl Crown Ethers through Threading

Article abstract of DOI:10.1002/asia.202001046

This paper describes the syntheses of [2]rotaxanes comprising 23- and 26-membered biphenyl crown ethers as the macrocyclic components and secondary ammonium ions as the dumbbell-shaped components, and the locking of the dynamic axial chirality of the biph

Full text of DOI:10.1002/asia.202001046

CHEMISTRY
AN ASIAN JOURNAL
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Accepted Article
Title: Locking the dynamic axial chirality of biphenyl crown ethers
through threading
Authors: Tomoya Kimura, Shinobu Miyagawa, Hikaru Takaya, Masaya
Naito, and Yuji Tokunaga
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10.1002/asia.202001046
Chemistry - An Asian Journal
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Locking the dynamic axial chirality of biphenyl crown ethers
through threading
Tomoya Kimura,[a] Shinobu Miyagawa,[a] Hikaru Takaya,[b, c] Masaya Naito,[a] Yuji Tokunaga*[a]
Dedication
[a]
T. Kimura, Dr. S. Miyagawa, Dr. M. Naito, Prof. Dr. Y. Tokunaga
Department of Materials Science and Engineering, Faculty of Engineering, University of Fukui, Bunkyo, Fukui 910-8507 (Japan)
E-mail: tokunaga@u-fukui.ac.jp
[b]
[c]
Prof. Dr. H. Takaya
International Research Center for Elements Science, Institute for Chemical Research, Kyoto University, Uji 611-0011 (Japan)
Prof. Dr. H. Takaya
Institute for Molecular Science, National Institute of Natural Science, Nishigo-Naka, Myodaiji, Okazaki 444-8585 (Japan)
Supporting information for this article is given via a link at the end of the document.
Abstract: This paper describes the syntheses of [2]rotaxanes
comprising 23- and 26-membered biphenyl crown ethers as the
macrocyclic components and secondary ammonium ions as the
dumbbell-shaped components and the locking of the dynamic axial
chirality of the biphenyl moieties in these structures. Chiral high-
performance liquid chromatography (HPLC) revealed that our
[2]rotaxane featuring the 26-membered crown ether racemized at
room temperature, but the racemization of the [2]rotaxane featuring
the 23-membered crown ether did not proceed at room temperature
over a period of three days. After separation of the enantiomers of
the [2]rotaxane incorporating the 23-membered crown ether through
chiral HPLC, we studied its racemization at elevated temperature.
The rate of stereoinversion in dimethylsulfoxide (a polar solvent) was
faster than that in o-dichlorobenzene (a nonpolar solvent), and
herein we discuss these kinetic parameters.
(HPLC).[10] The Stoddart group[11] observed planar (rotation of a
naphthyl group), axial (rotation of biphenyl and bipyridyl groups),
and helical (twisted conformation of two macrocyclic rings)
chiralities in a single catenane in solution at low temperature;
moreover, they achieved chiral transcription by means of a bias
toward a kind of dynamic chirality in response to a chiral
additive.[12,13]
The absolute locking of (dynamic) chirality resulting from
interlocked structures has also been investigated. For example,
Ogoshi[14] synthesized a catenane and rotaxane featuring a
planar-chiral pillararene macrocycle. Leigh[4a] and Saito[15] found
that changes in the position of the macrocyclic component in
rotaxanes could produce point and planar chiralities,
respectively. Although several examples of the regulation of
rates of dynamic chirality in interlocked structures have been
demonstrated, only Saito[15] has systematically examined the
effects of the steric features of the axle component on the rates
of racemization.
Introduction
In this paper, we report the effects of interlocking on the
racemization of the biphenyl moieties in simple [2]rotaxanes
incorporating 23- and 26-membered biphenyl crown ethers as
the macrocyclic components and ammonium ions as the
dumbbell-shaped components, as well as the effects of solvent
on the rates of racemization (Figure 1).
The stereochemistry of interlocked molecules is a fascinating
topic in the study of supramolecular chemistry.[1] Indeed, chiral
interlocked molecules have been used as asymmetric catalysts[2]
as well as hosts for the recognition of other chiral molecules.[3]
Chirality can be induced through entanglement in such
interlocked molecules as rotaxanes,[4–6] catenanes,[7] and so
on.[8] Fixing the positional relationship between one component
and the others (breaking symmetry) can generate topologically
asymmetric structures without introducing covalent bonds
between the components. For examples of rotaxanes, planar
chiral rotaxane consisting of directional axle and macrocyclic
components, [5] point chiral rotaxane arising from the position of
the macrocyclic component on the axle component,[4] and
helically chiral rotaxane through double threading;[6] such
chirality cannot be racemized without cleavage of covalent or
mechanical bonds.
Dynamic chirality can also be induced through interlocking—
namely, when an interlocked structure restricts an inversion of
conformation. Mitchell and Sauvage[9] reported the enantiomeric
conformers—derived from restricted rotation of the macrocyclic
components—of a catenane in solution at low temperature;
subsequently, they achieved partial separation of its copper
complex through chiral high-performance liquid chromatography
?
Figure 1. Schematic representation of the concept of locking dynamic axial
chirality in a [2]rotaxane.
Results and Discussion
Synthesis of [2]rotaxanes 6 and 7
Scheme 1 displays our approach for the preparation of the
[2]rotaxanes 6 and 7 possessing 23- and 26-membered biphenyl
crown ether rings, as the macrocyclic components and
secondary ammonium ions as the axle components. Cyclization
of the biphenol 1[13,16] and the ditosylate 2a[17] or the dichloride
1
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2b[18] in the presence of Cs2CO3 gave the 23- and 26-membered
biphenyl crown ethers 3a and 3b, respectively. The reactions of
the crown ethers 3, the formylammonium salt 4,[19] and the
arylamines 5,[20] through thermodynamic covalent chemistry,[21]
followed by sodium borohydride–mediated reduction of the imino
groups, afforded the [2]rotaxanes 6a and 6b, respectively, in
their singly protonated forms. The [2]rotaxanes 6a and 6b were
up to 125 °C led to peak broadening, with the two broad signals
of the protons H4 coalescing, finally these peaks overlapped at
127 °C. The rate of rotation of the biphenyl unit (kc) 366 sec-1
was calculated from Δδ values of the signals at 120 °C (Figure
S1).
We also recorded variable temperature (VT) NMR spectra of
the crown ether 3b possessing a 26-membered ring. The 4H
1
converted to the hydrophilic [2]rotaxanes 7a and 7b, respectively, signals, which appeared in the H NMR spectrum at 3.53–3.60
through selective acylation of their aniline moieties,[22] allowing
separation of their enantiomers through chiral HPLC.
ppm in DMSO-d6 at 25 °C (Figure S2), broadened upon
increasing the temperature. These two sets of signals coalesced
at 110 °C. From the Δδ values at 90 °C, kc of the crown ether 3b
in DMSO-d6 was calculated to be 381 sec-1 at 110 °C.
The mass spectra of the Boc-[2]rotaxanes 7a and 7b featured
peaks at m/z 1252.45 (calcd. 1252.45) and 1512.66 (calcd.
1512.66), respectively, corresponding to the species that had
lost their PF6– anions, confirming their interlocked structures.
1
In the H NMR spectrum (600 MHz, CDCl3) of the [23]crown-
rotaxane 6a (Figure 2b), the signals of the aliphatic protons of
the macrocyclic component appeared at 3.02–4.24 ppm, with
the signals of protons H4 and H5 separated significantly (at 3.98
and 4.20 ppm for H4; at 3.65 and 3.87 ppm for H5). In addition,
the signals of the diastereotopic benzylic protons Ha in the axle
component were split in two (3.73 and 3.94 ppm). In contrast,
the signal of the diastereotopic protons Hd appeared as a singlet
at 4.35 ppm. With the macrocyclic component encircling the
dialkylammonium center, it is likely that only protons Ha would be
influenced by the axially chiral biphenyl unit of the macrocyclic
component. The signals of the [23]crown-Boc-rotaxane 7a were
similar to those of 6a, except for those of the protons Hd, He, and
Hg, neighboring the aniline moieties, which shifted to low-field
(Figure 2c). The signals of the diastereotopic protons Hd
7
6
5
Br
Br
8
4
O
O
O
9
for 3a
O
O
23
O
TsO
O Ts
1
Br
Br
6
O
2a
3
Cs2CO3
OH
OH
2
3a
7
6
5
for 3b
8
4
Br
9
Cl
Cl
O
O
O
O
10
3
1
11
O
O
O
26
Cs2CO3
CsI
1
O
3
2b
O
O
3
Br
1
appeared as a pair of doublets in the H NMR spectrum of 7a.
2
3b
We suspect that N-acylation led to loss of the conformational
flexibility of 7a.
R
1)
5a: R = Me
5b: R = tBu
3,
H2N
R
N
5
H2
CHO
OHC
PF6
2) NaBH4
3) Boc2O,
4a
tBu
tBu
R2
g
f
OH
e
R1
N
d
c
R2
b
a
Br
Br
6a: R1 = H, R2 = Me, [23]crown ether
6b: R1 = H, R2 = tBu, [26]crown ether
7a: R1 = Boc, R2 = Me, [23]crown ether
7b: R1 = Boc, R2 = tBu, [26]crown ether
NH2
PF6
R2
R2
R1
N
Scheme 1. Synthesis of the Boc-[2]rotaxanes 7.
NMR spectral study of the dynamic chirality of the
macrocycles 3 and the Boc-[2]rotaxanes 7
Figure 2. Partial 1H NMR spectra (600 MHz, CDCl3) of (a) the
biphenyl[23]crown ether 3a, (b) the [23]crown-[2]rotaxane 6a, and (c) the
[23]crown-Boc-[2]rotaxane 7a.
In the 1H NMR spectrum (20 °C, 600 MHz, CDCl3) of the 23-
membered macrocycle 3a (Figure 2a), the pairs of signals of the
aliphatic protons were partially separated (e.g., the signals of the
H4 protons appeared at 4.03–4.07 and 4.08–4.12 ppm).
Because the rate of rotation of the biphenyl moiety was slow on
the NMR spectroscopic time scale, the geminal protons become
chemically nonequivalent. Heating a solution of 3a in DMSO-d6
To evaluate the rotation of the biphenyl moiety in 7a, we
heated its solution in DMSO-d6 and recorded 1H NMR spectra
(Figure S3). We observed chemically nonequivalent signals,
2
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10.1002/asia.202001046
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1
racemized species, respectively. The plot of the concentrations
of the non-racemized products provided a first-order curve. We
obtained the racemization rate constant k from the slope of the
straight line of the plot of ln[(peak area of enantiomers)/(all
area)] with respect to time (t); we calculated a half-life (τ) of 0.54
h (Figure 4).
suggesting slow rotation of the biphenyl moiety, in the H NMR
spectra recorded at temperatures of up to 125 °C. Thus, the
rotation of the biphenyl moiety in 7a was inhibited by the
presence of the axle component, with the signals of the
[23]crown ether broadening only at temperatures above 100 °C
(Figure S1).
We also subjected the [2]rotaxane 7b, incorporating the
[26]crown ether, to VT NMR spectroscopy (Figures 3 and S4). In
the spectra of 7b, the signals of the aliphatic protons became
broad at temperatures above 100 °C, but coalescence of these
signals did not occur at temperatures below 125 °C, consistent
with the inhibiting effect of the threading of the axle-shaped
component [recalling that the signals of the [26]crown ether 3b
coalesced at 125 °C (Figure S2)].
Figure 4. First-order plot for the racemization of the [26]crown-Boc-[2]rotaxane
7b under HPLC conditions.
Synthesis of urea-rotaxane 8
Because we could not examine the racemization of the
[23]crown-Boc-rotaxane 7a as a result of its low stability, we
synthesized the stable urea-rotaxane 8 from the ammonium salt
4b and the [23]crown ether 3a (Scheme 2). After treatment of 4b
with DMAP in the presence of 3a in dichloroethane and CH3CN
(thereby deprotonating the anilinium moiety of 4b and forming
the pseudorotaxane), we obtained the rotaxane 8 through urea
formation. The mass spectrum of 8 featured a signal at m/z
– +
1110.32, corresponding to the species [8 – PF6 ] (calcd. m/z
1110.32). In the 1H NMR spectrum of 8 (600 MHz, CD3CN;
Figure 5), the signals of the protons H4 (4.05 and 4.30 ppm) and
H5 (3.69 and 3.89 ppm) of the macrocyclic component were
widely separated as pairs, with the signals of the diastereotopic
protons Ha appearing as sets near 3.7 and 3.9 ppm, similar to
the spectral features of the [23]crown-rotaxane 6a.
Figure 3. Partial 1H NMR spectra (600 MHz, CDCl3) of (a) the
biphenyl[26]crown ether 3b, (b) the [26]crown-[2]rotaxane 6b, and (c) the
[26]crown-Boc-[2]rotaxane 7b.
Chiral HPLC separation of the enantiomers of the
N
[2]rotaxanes 7
H2
DMAP
We separated the enantiomers of the [23]crown-Boc-rotaxane
7a through chiral HPLC using CHIRALPAK IA-3 as the
stationary phase (Figure S10). Two peaks of equal area
appeared in the HPLC chromatogram of 7a. After separation of
these enantiomers, we prepared their solutions in several
solvents and monitored them through chiral HPLC at room
temperature. The enantiomeric excess in each solution did not
change after three days at room temperature. We then heated
the solutions of chiral 7a at 60–90 °C to monitor the
racemization process. Because the heating resulted in
decomposition of 7a, we could not estimate the exact rate of
racemization.
The enantiomers of the [26]crown-Boc-rotaxane 7b were
partially separated using the same chiral stationary phase
(Figure S11). The chromatograms of 7b revealed evidence for
interconversion of the enantiomers during HPLC analysis.[23]
Namely, the two usual peaks and a plateau peak were present
in the chromatograms; the ratio of the peak areas was
dependent on the retention time, and changed with respect to
the flow rate. We roughly integrated the three peaks, assigning
the two peaks and the plateau to the non-racemized and
OCN
NH2
2HPF6
H2N
PF6
4b
[23]crown ether 3a
e
d
HN
O
f
HN
c
b
a
Br
Br
6
7
8
O
NH2
O
O
O
9
O
O
1
O
4
5
3
2
O
HN
HN
8
Scheme 2. Synthesis of the [23]crown-urea-[2]rotaxane 8.
3
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agreement. From a comparison of the two solvents, we
concluded that the racemization in DMSO was enthalpically
favorable, but entropically disfavored. In the transition state, the
biphenyl moiety ought to be flat, with the resulting narrow cavity
of the crown ether potentially weakening (breaking) the
hydrogen bond(s) (Figure 7). Therefore, upon proceeding to the
transition state, energy would be needed to weaken (break) the
hydrogen bonds in o-dichlorobenzene, the nonpolar solvent (i.e.,
an enthalpic cost). In contrast, because the hydrogen bond–
acceptor DMSO can weaken (break) hydrogen bonds, the
transition state for racemization in DMSO would be enthalpically
favorable, but the complexation of the [2]rotaxane with DMSO
would be associated with an entropic cost. Other possibility of
the solvent effect is ion pairing. The neighboring counter anion
–
(PF6 ) could sterically inhibit the rotation of biphenyl unit in the
rotaxane because of tight ion-pairing in nonpolar o-
dichlorobenzene. Overall, the DMSO-assisted transition state
would decrease the free energy of activation (ΔG‡).
Table 1. Kinetic parameters of the racemizations of the crown ethers 3 and the
[2]rotaxanes 7a and 8.
ΔH ‡
ΔS‡
ΔG‡
half-life h
substrate
solvent
kJ/mol
J/mol K
kJ/mol
temperature
3a
[23]crown
5.3x10-7 [a]
(127 °C)
DMSO-d6
ND
ND
ND
ND
ND
ND
ND
ND
ND
3b
[26]crown
5.0x10-7 [a]
(110 °C)
DMSO-d6
Figure 5. Partial 1H NMR spectra (600 MHz, CD3CN) of (a) the axle-shaped
molecule 9, (b) the [23]crown-urea-[2]rotaxane 8, and (c) the
biphenyl[23]crown ether 3a.
7b
8
Mixed
solvent[b]
0.54[c]
(RT)
DMSO[d]
DMSO[e]
C6H4Cl2
87.1
87.3
92.2
–94.6
–94.0
–88.6
115.3
115.3
118.6
14
(83 °C)
18
(81 °C)
43
HPLC analysis of the chiral urea-rotaxane 8
The chiral-HPLC chromatogram of the rotaxane 8 featured two
peaks of equal area (Figure S12), as expected for a 1:1 mixture
of its two enantiomers. After separation through CHIRALPAK IB
(first fraction: 86% ee; second fraction: 94% ee), we examined
the kinetics of the racemization of the urea-rotaxane 8 in DMSO
and o-dichlorobenzene as solvents.
(80 °C)
[a] Determined by VT NMR analysis. [b] Trifluoroacetic acid/diethylamine
/hexane/CHCl3, 1:1:500:500. [c] Determined by retention-time-dependent
HPLC analysis. [d] First fraction of the enantiomer was used for the
racemization. [e] Second fraction of the enantiomer was used for the
racemization.
(a)
(b)
S
O
O
O
O
O
H
O
O
H
H
O
O
O
O
O
O
N
H
O
N
O
Figure 6. Eyring plots for the racemization of the [23]crown-urea-[2]rotaxane 8.
Blue: 8 (first fraction) in DMSO; red: 8 (second fraction) in DMSO; green: 8
(first fraction) in o-dichlorobenzene.
Figure 7. Proposed transition states for the racemizations of the [23]crown-
urea-[2]rotaxane 8 in (a) DMSO and (b) o-dichlorobenzene.
We prepared solutions of the enantiomers of 8 in these two
solvents, heated them at 61–102 °C, and monitored their
racemization using chiral HPLC. We observed first-order
racemization in each solvent (Figure S13 for DMSO; Figure S14
for o-dichlorobenzene), with the racemization in DMSO
proceeding approximately twice as fast as that in o-
dichlorobenzene near 80 °C. Eyring plots of the data for the
racemization of 8 yielded straight lines (Figure 6); Table 1 lists
the corresponding kinetic parameters. The data for the
racemizations of both enantiomers in DMSO were good in
Summary
We have synthesized [2]rotaxanes comprising 23- and 26-
membered biphenyl crown ethers as macrocyclic components
and secondary ammonium ions as dumbbell-shaped
components and investigated the effects of interlocking on the
dynamic axial chirality of their biphenyl moieties. VT NMR
4
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3.58 (m, 4H), 3.64–3.76 (m, 8H), 3.81–3.88 (m, 4H), 3.99–4.05 (m, 2H),
4.07–4.18 (m, 6H), 6.81 (d, J = 8.6 Hz, 2H), 6.88–6.94 (m, 4H), 7.28 (d, J
= 2.4 Hz, 2H), 7.34 (dd, J = 8.6 and 2.4 Hz, 2H). 13C NMR (125 MHz,
CDCl3): δ 68.6, 69.0, 69.6, 69.7, 70.8, 112.5, 114.0, 114.2, 121.4, 129.2,
spectra of the [23]- and [26]crown ethers 3 and the [23]- and
[26]crown-Boc-[2]rotaxanes 7 revealed inhibition of racemization
of the biphenyl moieties in the [2]rotaxanes, a direct result of the
interlocking. The racemization of the [26]crown-Boc-[2]rotaxane
7b proceeded at room temperature, with retention-time-
dependent HPLC analysis revealing a half-life (τ) of 0.54 h under
the HPLC conditions. In contrast, both enantiomers of the
[2]rotaxanes 7a and 8, incorporating the 23-membered biphenyl
crown ether as the macrocyclic component, could be isolated
using chiral HPLC. Because no racemization of the [23]crown-
[2]rotaxanes occurred at room temperature, we concluded that
the size of the crown ether ring affected the dynamics of
racemization of the biphenyl (axially chiral) unit. Racemization of
the [2]rotaxane 8 in DMSO and o-dichlorobenzene occurred at
high temperature, with DMSO enhancing the rate of
racemization. The chiral HPLC monitoring provided the kinetic
parameters for the racemization processes, which were
enthalpically and entropically favorable in polar DMSO and
nonpolar o-dichlorobenzene, respectively
131.4, 133.4, 148.9, 155.6 (one
aliphatic carbon signal
overlapping/missing). HRMS (FAB) calcd. for C30H35Br2O8+ [M + H]+: m/z
681.0693, found: 681.0713. IR (CHCl3, max, cm–1): 3011, 2930, 2874,
1595, 1506, 1485, 1452, 1255, 1128, 1059, 908, 843.
[23]Crown-[2]rotaxane 6a
A solution of the crown ether 3a (1.04 g, 1.76 mmol) and the ammonium
salt 4a (0.773 g, 1.94 mmol) in 1,2-dichloroethane (8 mL) and CH3CN (6
mL) was heated at 50 °C for 55 h. 3,5-Dimethylaniline (5a; 1.38 mL, 10.2
mmol) was added and then the mixture was heated at 50 °C for 63 h.
After cooling to room temperature, the mixture was diluted with EtOH (3
mL). NaBH4 (0.338 g, 8.93 mmol) was added at 0 °C and then the
mixture was stirred overnight at 60 °C. The excess NaBH4 was quenched
with 10% HCl aq. and then the mixture was neutralized with sat. NaHCO3
aq. After evaporation of the organic solvent, the aqueous phase was
extracted with CH2Cl2. The organic phase was washed sequentially with
5% HPF6 aq., water, and sat. NaCl aq., dried (Na2SO4), and
concentrated. The residue was purified through column chromatography
(SiO2; CH2Cl2/acetone, 20:1) to give a white solid (1.03 g, 49%). 1H NMR
(600 MHz, CD3CN): δ 2.11 (s, 12H), 2.89–2.94 (m, 2H), 2.98–3.02 (m,
2H), 3.04–3.11 (m, 4H), 3.15–3.20 (m, 2H), 3.30–3.35 (m, 2H), 3.36–3.42
(m, 2H), 3.45–3.50 (m, 2H), 3.61–3.65 (m, 2H), 3.69–3.76 (m, 2H), 3.79–
3.85 (m, 2H), 3.88–3.95 (m, 2H), 3.97–4.02 (m, 2H), 4.18–4.24 (m, 2H),
4.25–4.30 (m, 4H), 4.80–4.91 (m, 2H), 6.21 (br s, 4H), 6.25 (br s, 2H),
6.74 (d, J = 8.9 Hz, 2H), 7.04–7.08 (m, 4H), 7.16 (dd, J = 8.9 and 2.9 Hz,
2H), 7.27–7.40 (m, 6H), 7.45 (d, J = 2.9 Hz, 2H). 13C NMR (125 MHz,
CD3CN): δ 21.6, 47.6, 52.3, 69.5, 71.3, 71.5, 71.8, 111.9, 113.4, 115.8,
Experimental Section
Materials and General Methods
119.8, 128.3, 128.6, 130.7, 131.0, 132.8, 135.7, 139.4, 143.0, 149.4,
+
155.6. HRMS (MALDI) calcd. for C56H68Br2N3O7 [M
–
PF6]+: m/z
The biphenyl 1,[13] the ditosylate 2a,[17b] the ammonium salt 4a,[19b] and
3,5-di-tert-butylaniline 5b[20] were prepared according to previously
reported procedures. The dichloride 2b[18] was prepared using the
method described in the Supporting Information. DMF and
dichloroethane were dried over 4-Å molecular sieves. Other solvents and
commercially available chemicals were used as received. 1H and 13C
NMR spectra were recorded using ECX-500II and ECA-600II
spectrometers, with tetramethylsilane (TMS) as the internal standard.
Mass spectra were recorded using JEOL JMS-700T (FAB) and Bruker
Daltonics autoflex (MALDI) spectrometers. Infrared spectra were
recorded using a Shimadzu FTIR-8600PC spectrometer. HPLC was
1052.3419; found: 1052.3351. IR (CHCl3, max, cm–1): 3449, 3040, 2912,
2873, 1602, 1513, 1478, 1452, 1353, 1226, 1100, 1080, 960, 848, 558.
[26]Crown-[2]rotaxane 6b
A suspension of the crown ether 1b (0.363 g, 0.530 mmol) and the
ammonium salt 4a (0.194 g, 0.490 mmol) in CHCl3 (10 mL) and CH3CN
(5 mL) was stirred for 13 h at room temperature. After evaporation of the
solvent, CHCl3 (8 mL) and 3,5-di-tert-buthylaniline (5; 509 mg, 2.48
mmol) were added and then the mixture was stirred overnight at 40 °C.
After cooling, the mixture was diluted with EtOH (4 mL). NaBH4 (133 mg,
3.52 mmol) was added at 0 °C and then the mixture was stirred overnight
at room temperature. The excess NaBH4 was quenched with 10% HCl aq.
and then the mixture was neutralized with sat. NaHCO3 aq. After
evaporation of the organic solvent, the aqueous phase was extracted
with CH2Cl2. The organic phase was washed sequentially with 5% HPF6
aq., water, and sat. NaCl aq., dried (Na2SO4), and concentrated. The
residue was purified through column chromatography (SiO2; toluene/THF,
7:1) to give a colorless oil (266 mg, 37%). 1H NMR (600 MHz, CDCl3): δ
1.27 (s, 36H), 3.24–3.45 (m, 6H), 3.46–3.59 (m, 6H), 3.65–3.78 (m, 6H),
3.86–4.12 (m, 10H), 4.25 (s, 4H), 6.50 (d, J = 1.6 Hz, 4H), 6.59 (d, J =
8.9 Hz, 2H), 6.60–6.64 (m, 2H), 6.80 (t, J = 1.6 Hz, 4H), 6.86–6.90 (m,
2H), 7.01–7.04 (m, 4H), 7.16–7.21 (m, 6H), 7.41 (d, J = 2.8 Hz, 2H),
7.36–7.48 (m, 2H). 13C NMR (125 MHz, CDCl3): δ 31.5, 34.8, 47.8, 52.0,
68.1, 69.3, 69.4, 70.3, 70.5, 71.1, 107.5, 112.2, 112.4, 113.3, 115.0,
121.6, 127.6, 127.8, 129.3, 129.4, 131.9, 134.7, 141.7, 146.7, 147.3,
performed using
a Shimadzu LC-20AT apparatus, an SDD-M20A
detector, and DAICEL CHIRALPAK IA3 (0.46  25 cm for analysis), IB3
(0.46  25 cm for analysis), IA (1.0  25 cm for isolation of enantiomers),
and IB (1.0  25 cm for isolation of enantiomers) chiral columns. All
reactions were performed under a positive atmosphere of dry N2. All
solvents were removed through rotary evaporation under reduced
pressure. Silica gel column chromatography was performed using Kanto
Chemical silica gel 60N. Thin-layer chromatography was performed using
Merck Kieselgel 60PF254
.
[23]Crown ether 3a
A suspension of the biphenol 1 (1.05 g, 3.05 mmol), the ditosylate 2a
(1.99 g, 3.39 mmol), and Cs2CO3 (4.20 g, 12.9 mmol) in dry DMF (200
mL) was stirred for 72 h at 110 °C. After evaporation of the solvent, the
residue was treated with dil. HCl aq. and extracted with AcOEt. The
combined organic phase was washed with water and dried (MgSO4).
After evaporation of the solvent, the residue was purified through column
chromatography (SiO2; CH2Cl2/toluene/AcOEt, 1:1:1) to afford a white
solid (0.87 g, 48%). 1H NMR (600 MHz, CDCl3): δ 3.51–3.67 (m, 16H),
3.70–3.77 (m, 4H), 4.03–4.07 (m, 2H), 4.08–4.12 (m, 2H), 6.85 (d, J =
8.9 Hz, 2H), 7.31 (d, J = 2.7 Hz, 4H), 7.39 (dd, J = 8.9 and 2.7 Hz, 4H).
13C NMR (150 MHz, CDCl3): δ 68.8, 69.8, 70.5, 70.7, 70.9, 112.6, 114.0,
+
151.7, 154.6. HRMS (MALDI) calcd. for C74H96Br2N3O8 [M – PF6]+: m/z
1312.5559; found: 1312.5531. IR (CHCl3, max, cm–1): 3447, 3414, 2966,
2904, 2870, 1599, 1505, 1452, 1363, 1247, 1129, 1102, 1063, 956, 879,
558.
[23]Crown-Boc-[2]rotaxane 7a
A solution of the [2]rotaxane 6a (0.304 g, 0.250 mmol), Boc2O (700 μL,
3.00 mmol), and 2,6-di-tert-butylphenol (0.147 g, 0.750 mmol) in THF (10
mL) was heated at 80 °C overnight. After evaporation of the solvent, the
residue was purified through column chromatography (SiO2;
CH2Cl2/AcOEt, 10:1) to give a white solid (0.306 g, 87%). 1H NMR (600
MHz, CDCl3): δ 1.44 (s, 18H), 2.25 (s, 12H), 2.96–3.22 (m, 10H), 3.37–
3.44 (m, 4H), 3.50–3.57 (m, 2H), 3.65–3.77 (m, 4H), 3.85–4.02 (m, 6H),
4.18–4.24 (m, 2H), 4.82 (d, J = 15.8 Hz, 2H), 4.88 (d, J = 15.8 Hz, 2H),
6.64 (d, J = 7.9 Hz, 2H), 6.77 (br s, 2H), 6.81 (br s, 4H), 6.97–7.02 (m,
4H), 7.13 (dd, J = 7.9 and 1.6 Hz, 2H), 7.21–7.26 (m, 4H), 7.31–7.43 (m,
4H). 13C NMR (150 MHz, CDCl3): δ 21.3, 28.3, 51.4, 53.1, 68.5, 70.46,
70.50, 70.7, 70.9, 80.6, 113.3, 114.4, 123.9, 127.5, 127.6, 129.57,
129.64, 132.0, 134.9, 138.1, 140.2, 142.2, 154.1, 154.8. HRMS (MALDI)
calcd. for C66H84Br2N3O11+ [M – PF6]+: m/z 1252.4467; found: 1252.4462.
IR (CHCl3, max, cm–1): 3040, 3009, 2914, 2875, 1687, 1684, 1598, 1478,
129.2, 131.5, 133.6, 155.7 (one
aliphatic carbon signal
overlapping/missing). HRMS (FAB) calcd. for C24H31Br2O7+ [M + H]+: m/z
589.0431, found: 589.0427. IR (CHCl3, max, cm–1): 3009, 2925, 2872,
1496, 1485, 1452, 1290, 1271, 1246, 1129, 907. Mp: 68–73 °C (iPr2O).
[26]Crown ether 3b
A suspension of the biphenol 1 (2.50 g, 7.27 mmol), the dichloride 2b
(3.29 g, 8.00 mmol), Cs2CO3 (9.57 g, 29.4 mmol), and CsI (0.38 g, 1.5
mmol) in dry DMF (250 mL) was stirred for 72 h at 110 °C. After
evaporation of the solvent, the residue was treated with dil. HCl aq. and
extracted with AcOEt. The organic phase was washed with water and
dried (MgSO4). After evaporation of the solvent, the residue was purified
through column chromatography (SiO2; CH2Cl2/toluene/AcOEt, 2:1:1) to
afford a colorless oil (1.06 g, 21%). 1H NMR (600 MHz, CDCl3): δ 3.54–
5
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1454, 1393, 1368, 1249, 1237, 1212, 1162, 1148, 1099, 1080, 960, 849,
558.
Ñiguez, M. Alajarin, J. Berna, Org. Lett. 2019, 21, 5192–5196; f) A. W.
Heard, S. M. Goldup, Chem 2020, 6, 994–1006.
[3]
For selected examples on chiral recognition of rotaxanes, see: a) N.
Kameta, Y. Nagawa, M. Karikomi, K. Hiratani, Chem. Commun. 2006,
3714–3716; b) E. A. Neal, S. M. Goldup, Chem. Commun. 2014, 50,
5128−5142; c) J. Y. C. Lim, I. Marques, V. Felix, P. D. Beer, J. Am.
Chem. Soc. 2017, 139, 12228–12239; d) J. Y. C. Lim, I. Marques, V.
Felix, P. D. Beer, Angew. Chem. Int. Ed. 2018, 57, 584–588; e) S.
Corra, C. de Vet, J. Groppi, M. L. Rosa, S. Silvi, M. Baroncini, A. Credi,
J. Am. Chem. Soc. 2019, 141, 9129–9133.
[26]Crown-Boc-[2]rotaxane 7b
As described above, the Boc-[2]rotaxane 7b (white powder, 58.3 mg,
89%) was synthesized from the [2]rotaxane 6b (51.3 mg, 35.1 µmol),
Boc2O (95.0 µL, 414 µmol), and 2,6-di-tert-butylphenol (21.2 mg, 105.
µmol) in THF (3 mL), with purification through column chromatography
(SiO2; AcOEt). 1H NMR (600 MHz, CDCl3): δ 1.28 (s, 36H), 1.42 (s, 18H),
3.22–3.44 (m, 6H), 3.45–3.58 (m, 6H), 3.65–3.79 (m, 6H), 3.85–4.11 (m,
10H), 4.71 (d, J = 15.8 Hz, 2H), 4.76 (d, J = 15.8 Hz, 2H), 6.54–6.61 (m,
4H), 6.76–6.80 (m, 2H), 6.94–7.02 (m, 8H), 7.05–7.10 (m, 4H), 7.17 (dd,
J = 8.6 and 2.6 Hz, 2H), 7.21 (t, J = 1.7 Hz, 2H), 7.31–7.43 (m, 2H), 7.41
(d, J = 2.6 Hz, 2H). 13C NMR (150 MHz, CDCl3): δ 28.4, 31.4, 34.8, 52.0,
53.7, 68.0, 69.2, 69.4, 70.3, 70.5, 71.0, 80.3, 112.1, 113.2, 115.1, 119.7,
120.4, 121.7, 127.5, 127.6, 129.26, 129.31, 131.9, 134.7, 140.6, 142.3,
[4]
For selected examples of point chiral rotaxanes, see: a) M. Alvarez-
Pérez, S. M. Goldup, D. A. Leigh, A. M. Z. Slawin, J. Am. Chem. Soc.
2008, 130, 1836–1838; b) Y. Cakmak, S. Erbas-Cakmak, D. A. Leigh, J.
Am. Chem. Soc. 2016, 138, 1749–1751.
+
146.5, 151.0, 154.5, 154.9. HRMS (MALDI) calcd. for C84H112Br2N3O12
[5]
[6]
First example of planar chiral rotaxane, see: C. Yamamoto, Y. Okamoto,
T. Schmidt, R. Jäger, F. Vögtle, J. Am. Chem. Soc. 1997, 119, 10547–
10548.
[M – PF6]+: m/z 1512.6607; found: 1512.6627. IR (CHCl3, max, cm–1):
2966, 2934, 2904, 2870, 1685, 1598, 1505, 1478, 1452, 1366, 1325,
1248, 1211, 1151, 1129, 957, 848, 558.
Example of helically chiral rotaxane, see: T. Tsukamoto, R. Sasahara,
A. Muranaka, Y. Miura, Y. Suzuki, M. Kimura, S. Miyagawa, T.
Kawasaki, N. Kobayashi, M. Uchiyama, Y. Tokunaga, Org. Lett. 2018,
20, 4745–4748.
[23]Crown-urea-[2]rotaxane 8
A suspension of the [23]crown ether 3a (230 mg, 0.390 mmol), the bis-
ammonium salt 4b (205 mg, 0.400 mmol), and DMAP (49.1 mg, 0.400
mmol) in 1,2-dichloroethane (1.6 mL) and CH3CN (1.6 mL) was heated at
50 °C for 42 h. After cooling to room temperature, 3,5-dimethylphenyl
isocyanate (220 µL, 1.55 mmol) was added and then the mixture was
stirred for 20 h. After evaporation of the solvent, the residue was
dissolved in CH2Cl2 (100 mL). This solution was washed sequentially with
1 M HCl aq., 5% HPF6 aq., and water, dried (Na2SO4), and concentrated.
The residue was purified through column chromatography (SiO2;
toluene/CH2Cl2/AcOEt, 2:1:1) to give a solid (150 mg, 30%). 1H NMR
(600 MHz, CD3CN): δ 2.26 (s, 12H), 3.06–3.12 (m, 2H), 3.15–3.25 (m,
6H), 3.31–3.36 (m, 2H), 3.43–3.59 (m, 8H), 3.67–3.72 (m, 4H), 3.86–3.93
(m, 4H), 4.02–4.07 (m, 2H), 4.27–4.33 (m, 2H), 6.70 (br s, 2H), 6.88 (d, J
= 8.9 Hz, 2H), 7.06–7.11 (m, 8H), 7.20 (br s, 2H), 7.31 (dd, J = 8.9 and
2.5 Hz, 2H), 7.33–7.43 (m, 2H), 7.40 (br s, 2H), 7.42–7.46 (m, 4H), 7.49
(d, J = 2.5 Hz, 2H). 13C NMR (150 MHz, CD3CN): δ 21.5. 52.1, 69.6,
71.40, 71.43, 71.5, 71.7, 72.0, 113.4, 115.9, 117.8, 119.1, 125.4, 126.0,
128.6, 131.7, 132.8, 135.7, 139.6, 140.1, 141.6, 153.4, 155.7. HRMS
[7]
[8]
Selective example and review of chiral catenanes, see: a) C. P.
McArdle, S. Van, M. C. Jennings, R. J. Puddephatt, J. Am. Chem.
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Inomata, T. Sawada, M. Fujita, Chem 2020, 6, 294–303.
(MALDI) calcd. for C56H66Br2N5O9 [M – PF6]+: m/z 1110.3222; found:
1110.3246. IR (KBr, max, cm–1): 3415, 3071, 2914, 2873, 1708, 1672,
+
1601, 1541, 1452, 1313, 1216, 1098, 1080, 960, 846, 558.
[9]
D. K. Mitchell, J.-P. Sauvage, Angew. Chem. Int. Ed. 1988, 27, 930–
931.
Acknowledgements
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FT-ICR-MS analysis was supported by the JURC at ICR, Kyoto
University.
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Keywords: Rotaxane • biphenyl • axial chirality • racemization •
hydrogen bond
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[2]rotaxanes.
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6
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Entry for the Table of Contents
Insert graphic for Table of Contents here.
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[2]Rotaxanes comprising biphenyl crown ethers as the macrocyclic components and secondary ammonium ions as the dumbbell-
shaped components were synthesized. The interlocked structures inhibited racemization of the axially chiral biphenyl moieties, and
the degree of locking of the dynamic axial chirality in these [2]rotaxanes dependant on ring size of the macrocycles and solvent.
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