Full text of DOI:10.1021/ja412671k

Article
pubs.acs.org/JACS
Axle Length Does Not Affect Switching Dynamics in Degenerate
Molecular Shuttles with Rigid Spacers
Philip G. Young, Keiji Hirose,* and Yoshito Tobe
Division of Frontier Materials Science, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka
560-8531, Japan
S
* Supporting Information
ABSTRACT: For a series of [2]rotaxane molecular shuttles
possessing linear rigid rod-like axles of varying lengths between
degenerate recognition sites, the activation barrier for shuttling
motion was clearly shown to be constant. Moreover, dynamic
NMR studies have revealed that both the entropic and
enthalpic contributions to the shuttling motion remain
constant regardless of the actual length of the rigid rod-like
axles employed herein.
involved with the evaluation of entropic contributions to the
switching rates both experimentally and computationally.7
In order to gain an enhanced understanding of the impact
axle length has on the activation barrier to ring shuttling, to
increase our ability to rationally design molecular shuttles,
kinetic studies using suitable model rotaxanes are indispensable.
The rotaxanes we chose to investigate incorporate oligo-
(phenylene) spacers that separate two secondary ammonium
binding stations (Figure 1, type 1n, n = 1−4). Two large
INTRODUCTION
■
The potential of mechanically interlocked molecules to
function as nanoscale devices has driven their rapid develop-
ment in recent years.1 These devices exploit the unique relative
motions of molecular components in response to physical or
chemical stimuli.2 [2]Rotaxanes are composed of a linear
molecular axle interpenetrated with a macrocyclic ring.3 Bulky
stoppers, placed at each end of the axle, ensure the macrocyclic
ring remains interlocked, or mechanically bound. Due to their
potential use as molecular switches, much attention has been
devoted to [2]rotaxanes that possess two recognition sites,
between which the interlocked macrocyclic ring can shuttle.4 In
such molecular shuttles, the control of ring shuttling along the
axle component is of crucial importance, as this kinetic
parameter, sometimes referred to as switching rate, may
directly determine their effectiveness in a device setting.1b,5 It
follows that an increased understanding of shuttling motion is
an indispensable requirement for the rational design of
nanoscale devices.
Figure 1. General structures of the [2]rotaxanes investigated.
Although there have been numerous reports on the general
effects of the structural features of rotaxanes on ring shuttling,
there are relatively few that offer detailed kinetic analyses.6
Moreover, there is a distinct absence of research that deals
specifically with elucidating the effect of axle length on ring
shuttling. Rotaxanes with increasing numbers of flexible axle
components, such as poly(ethylene glycol) (PEG) units or
straight aliphatic carbon chains, unfortunately have inherent
drawbacks as model rotaxanes that render the detailed
evaluation of kinetic factors difficult. In such systems, effects
arising from conformational isomerism, including loss of
conformational freedom during ring shuttling, back-folding,6d,j
harpooning,6a or Coulombic repulsion between components,2a
can highly complicate ring shuttling. Additional practical
complications, such as small spectral changes, spectral complex-
ity,6i or poor solubility,6b add to the abundance of difficulties
stoppers, based on 1,3-bis(triisopropylsilyl)benzene, are located
at either end of the axle, and an interpenetrated dibenzo-24-
crown-8 ether (DB24C8) is able to shuttle between the two
charged stations.
Prominent features of rotaxanes 1n are the rigid rod-like
structures they are expected to sustain, a direct consequence of
their aromatic backbones. Thus, by incorporating an increasing
number of phenylene spacers in the axle, we are able to
systematically extend the distance between the two ammonium
stations from 6.9 (n = 1) to 19.6 Å (n = 4).8 As a result of their
rigid linear nature, effects arising from conformational isomer-
ism of the axle can be ruled out in 1n, thus allowing us to gain
Received: December 13, 2013
Published: May 9, 2014
© 2014 American Chemical Society
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a
Scheme 1. Synthesis of the Rigid Rod-Like [2]Rotaxanes Studied
a
See Supporting Information for experimental details of 2a−2d. Reagents and conditions: (i) Boc2O (1 equiv), 4-dimethylaminopyridine, CH2Cl2,
rt; (ii) lithium aluminum hydride, THF, 0 °C to rt; (iii) NH4PF6, acetone, H2O; (iv) DB24C8, CH2Cl2, −20 °C; (v) 7, n-Bu3P, CH2Cl2, −20 °C to
rt; (vi) trifluoroacetic acid, CH2Cl2, then saturated aqueous NH4PF6.
unbiased knowledge of how length influences the activation
barrier for ring shuttling. In addition, on the basis of our
previous work with structurally related rotaxanes,9 rotaxanes of
type 1n are expected to provide clear spectral changes suitable
for reliable evaluation of kinetic parameters.
RESULTS AND DISCUSSION
■
The synthesis of [2]rotaxanes is outlined in Scheme 1. One of
the amine centers of the key axle intermediates 2a−2d, in
which the central axle aromatic components consist of rigid
rod-like oligo(phenylene) groups of varying lengths (see
Supporting Information for the synthesis), was protected with
a tert-butoxycarbonyl (Boc) group by treatment with 1 equiv of
di-tert-butyl dicarbonate. The presence of a single Boc
protecting group will ensure exclusive formation of desired
[2]rotaxanes, as opposed to [3]rotaxanes, in the later capping
reaction.9c,10 Reduction of the resulting methyl esters 3a−3d
1
Figure 2. Partial H NMR spectra (400 MHz, DMSO-d6, 303 K) of
with lithium aluminum hydride gave diols 4a−4d, which were
(a) 1a, (b) 1b, (c) 1c, and (d) 1d. See Scheme 1 for proton
treated with aqueous ammonium hexafluorophosphate to
assignments.
provide salts 5a−5d. Rotaxane formation was accomplished
by the well-established threading-followed-by-capping protocol
that involves complex formation of each of the hexafluor-
ophosphate salts 5a−5d with DB24C8 at −20 °C to form
pseudorotaxanes 6a−6d, followed by treatment with anhydride
stopper 79e in the presence of n-tributyl phosphine.11 The Boc-
protected [2]rotaxanes 8a−8d were subsequently treated with
trifluoroacetic acid to provide 1a−1d.
DB24C8 ring and dibenzylammonium centers of each axle,
which result in the localization of the macrocycle around one of
the equivalent ammonium centers, thus desymmetrizing the
otherwise C∞h-symmetrical system.10,12 Notably, ring shuttling
remained slow on the NMR time scale in CDCl3,
CDCl2CDCl2, CD3CN, and Tol-d8 up to the temperature
limits of each solvent as revealed by the persistence of two
sharp singlets for Ha and Hb in variable temperature
measurements (Supplementary Figures S48−S51). On the
other hand, coalescence of the complexed and uncomplexed
signals was observed in DMSO-d6 and DMF-d7 within the
temperature limits of these solvents, indicating a significant
difference in shuttling behavior between the former nonpolar
solvents and these two polar solvents. The lower barriers for
the shuttling in DMSO-d6 and DMF-d7 are ascribed to far
better solvating ability of the positively charged ammonium
centers of each rotaxane, making the solvents more effectively
able to compete with the noncovalent interactions with
DB24C8 compared to the nonpolar solvents.13
The 1H NMR spectra of rotaxanes 1a−1d in CDCl3,
CDCl2CDCl2, CD3CN, tolune-d8 (Tol-d8), DMF-d7, and
DMSO-d6 at 303 K revealed slow shuttling of the DB24C8
ring between the ammonium stations on the time scale of the
1
NMR (see Figure 2 for H NMR spectra of 1a−1d in DMSO-
d6). Specifically, all spectra indicated the existence of a
nonsymmetrical system with separate sets of signals observed
for the complexed and uncomplexed sides of each of the
[2]rotaxanes. This slow ring shuttling condition in 1a−1d was
best exemplified by the presence of two sharp singlets in the 1H
NMR spectra appearing at approximately 5.4 and 5.3 ppm that
were assigned to the nonequivalent benzylic protons Ha and
Hb, respectively. The observed slow shuttling can be justified by
the strong noncovalent binding interactions between the
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1
Variable-temperature H NMR investigations were carried
variable temperature 1H NMR experiments were observed
across the series of rotaxanes (see Supplementary Figures S52−
S59 for variable temperature spectra).
out in DMSO-d6 and DMF-d7 to elucidate the kinetic
parameters of the ring shuttling in rotaxanes 1a−1d. The
rates of ring shuttling (k [s−1]) were derived from 1H NMR line
shape analyses (LSA)14 of the Ha and Hb resonances at
increasing temperatures (Supporting Information). As a
representative example, shown in Figure 3a and b are
1
Based on the rates of ring shuttling derived from H NMR
LSA, the free energies of activation (ΔG⧧) for ring shuttling
were calculated for 1a−1d in DMSO-d6 and DMF-d7 using the
Eyring equation (Supplementary Figures S52−S59). Selected
kinetic data for rotaxanes 1a−1d in DMSO-d6, DMF-d7 are
summarized in Table 1, respectively. The ΔG⧧ values are higher
in DMF-d7 relative to DMSO-d6 at identical temperatures,
which is presumably due to the differences in the abilities of the
solvents to solvate the charged ammonium docking stations.
Considering the relative Gutmann donor numbers (DN) of
each solvent, where the DN for DMSO and DMF are 29.8 and
26.6,15 respectively, then it becomes clear that ring shuttling is
less impeded in solvents that are better able to donate their
electrons into noncovalent bonds. Surprisingly, at each given
temperature the data show that the activation barriers for ring
shuttling are similar for each rotaxane, irrespective of the length
of the axle. For instance, at 303 K in DMSO-d6 the ΔG⧧ value
for rotaxane 1a, which contains just one phenylene group
between the ammonium stations, is the same as that for 1d,
which contains four phenylene groups between the ammonium
stations (cf. 16.0 kcal mol−1). Such assessments of ΔG⧧ can
also be carried out at higher temperatures in both DMSO-d6
and DMF-d7, where the ΔG⧧ values show very slight variation.
These observations indicate that increasing axle length has no
significant impact on the activation barrier of ring shuttling.
In order to gain a deeper understanding of ring shuttling, the
kinetic parameters were examined (Table 2). In both DMSO-d6
Table 2. Summary of Kinetic Properties for 1a−1d in
DMSO-d6 and DMF-d7
Figure 3. Experimentally determined, simulated variable-temperature
1H NMR (400 MHz) spectra of Ha and Hb of rotaxane 1c in (a)
DMSO-d6 and (b) DMF-d7. For each temperature the calculated rate
constants (k) are shown.
DMSO-d6
DMF-d7
ΔH⧧
ΔS⧧
ΔH⧧
ΔS⧧
(kcal mol−1
)
(cal K−1 mol−1
)
(kcal mol−1
)
(cal K−1 mol−1
)
1
experimental, simulated variable-temperature H NMR spectral
1a
1b
1c
1d
6.4 0.2
6.4 0.1
6.7 0.1
6.4 0.2
−32.5 0.6
−31.3 0.4
−31.1 0.3
−31.8 0.5
5.6 0.2
6.5 0.3
6.1 0.2
6.2 0.2
−35.6 0.6
−33.5 0.6
−34.9 0.7
−34.9 0.5
data of protons Ha and Hb of rotaxane 1c in DMSO-d6 and
DMF-d7, respectively. In DMSO-d6 protons Ha and Hb initially
appeared as two sharp singlets at 303 K, with LSA revealing an
exchange rate (i.e., shuttling rate [k]) of 18 s−1 (Figure 3a). An
increase in temperature was accompanied by a gradual
broadening of Ha and Hb and a concomitant increase in
shuttling rate as indicated by LSA. At 363 K, coalescence of Ha
and Hb was observed, which was followed by further sharpening
of the newly formed singlet at even higher temperatures. Taken
together, these observations indicated a state of slow (k = 18
s−1 at 303 K) to fast ring shuttling (k = 427 s−1 at 413 K) on
the NMR time scale. In contrast to the observations in DMSO-
d6, in DMF-d7 Ha, and Hb of 1c remained as two sharp singlets
up to 358 K (k = 30 s−1); coalescence of the signals was not
observed until 403 K (k = 101 s−1, Figure 3b), indicating a
substantial difference in shuttling behavior. Similar trends in the
and DMF-d7 the ΔH⧧ parameters for ring shuttling across the
series of rotaxanes are on average 6.3 kcal mol−1, regardless of
composition of the axle, with a maximum variation of 1.1 kcal
mol−1. These findings suggest that the length of the rigid axles
has no significant impact on the activation enthalpy. The
seemingly static nature of ΔH⧧ is proposed to be a
consequence of the mutual shuttling mechanism that takes
place in each rotaxane. That is, for each rotaxane the
fundamental requirement of ring shuttling takes place by the
breakage of hydrogen bonds between a DB24C8 ring and a
dibenzylammonium station by solvent coordination. The extent
Table 1. Kinetic Data for Ring Shuttling in DMSO-d6 and DMF-d7 for Rotaxanes 1a−1d Derived from Dynamic NMR Studies
DMSO-d6
(kcal mol−1
DMF-d7
ΔG⧧
(kcal mol−1
)
ΔG⧧
)
ΔG⧧
(kcal mol−1
)
ΔG⧧
(kcal mol−1
)
ΔG⧧
393 K
(kcal mol−1
)
303 K
353 K
393 K
353 K
1a
1b
1c
1d
16.0
15.8
16.0
16.0
17.8
17.4
17.6
17.6
19.1
18.7
18.8
18.9
18.2
18.3
18.4
18.5
19.6
19.7
19.8
19.9
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of these hydrogen bond interactions, as well as ion-dipole
interactions and π−π interactions between DB24C8 and each
axle in transition states, are thought to be the essentially the
same across this series of rotaxanes. Indeed, the average ΔH⧧
value of 6.3 kcal mol−1 is consistent with the breakage of
moderate [N+−H···O] hydrogen -bonding interactions, with
any minor π−π interactions between the ring and axle.16
Though the ring shuttling from one station to the other
involves bypassing a different number of phenylene spacers,
taking into account that there are no significant changes in
steric barriers associated with the number of spacer units
present, it is reasonable that there is no significant variation in
ΔH⧧.
between a succinamide station and a reduced naphthalimide
group along flexible carbon chains of varying lengths decreases
with increasing axle length.19 This behavior was originally
described by a biased random walk model; however, the origin
of the bias was not identified, and the general validity of this
model has recently been questioned by new findings.6a An
alternative “harpooning” mechanism is proposed to take place
in which the macrocyclic ring is simultaneously bound to both
stations of the rotaxane, a situation made possible by the
flexible carbon linkers present. Brouwer and co-workers’
proposed harpooning mechanism is compatible with the length
dependence originally reported since the formation of the
transition state structure is less probable as the length of the
spacer is increased. Importantly, as the rotaxanes presented
herein are composed of rigid rod-like axles, harpooning can be
excluded, and the lack of length dependence on shuttling
dynamics can be explained. On the basis of the experimental
data obtained, it can be proposed that the overriding rate-
determining factor is the strong interaction of the DB24C8 ring
with the ammonium stations. In addition to this, a significant
amount of energy is required for recomplexation since this
would involve the displacement of strongly bound solvent
molecules. The amount of free energy required for decom-
plexation and complexation of the DB24C8 ring with the
ammonium stations is greatest among the free energy barriers
associated with the shuttling of the ring along the axle within
the length examined in this work. In such a situation the ring
most probably moves back and forth along the axle several
times before rebinding with equal probability to either of the
ammonium ions.
Considering the consistency of the ΔG⧧ values observed for
1a−1d (Table 1) and the similarity of the activation enthalpies
(Table 2), the activation entropies (ΔS⧧) were not expected to
play an important role in the determination of ΔG⧧. Indeed
Table 2 shows that there is only a slight variation in the ΔS⧧
values across this series of rotaxanes in each solvent. In both
DMSO-d6 and DMF-d7 average values of ΔS⧧ for this series of
rotaxanes were found to be −31.7 and −34.7 cal K−1 mol−1
(with maximum variations of 1.4 and 2.1 cal K−1 mol−1),
respectively. It is clear from the large negative values of ΔS⧧
that ring shuttling involves a great deal of ordering. Indeed, we
expect there to be a large entropic effect on ring shuttling based
on the breakage and restoration of ion pairs as the ring shuttles
between each positively charged center.6h,17 Specifically,
extensive reordering of the solvent molecules is likely to
occur as a result of the hexafluorophosphate counterions
becoming essentially “naked” as one dissociates completely
from an ammonium center.17d Furthermore, studies by
Stoddart and co-workers suggest that the overall rigidity of a
rotaxane is increased as a DB24C8 ring slips over a p-
phenylene group.6h
CONCLUSIONS
■
The detailed analyses of ring shuttling in a family of degenerate
molecular shuttles presented herein suggest that axle length has
no significant impact on the activation barrier for ring shuttling.
On the basis of the similarities of activation enthalpy for 1a−
1d, the number of rigid spacer units bears no consequence on
steric barriers for ring shuttling. In addition, the activation
entropy showed little variation. It follows that fine-tuning of
molecular shuttles may be possible by consideration of the
degrees of flexibility present in an axle component. For
example, one can imagine that incorporating a long rigid axle in
a molecular device will serve as a physical barrier, with defined
length, however, such a barrier will not influence the switching
rate. These findings strengthen our fundamental understanding
of molecular shuttles and will no doubt be of great use to the
creators of new functional devices.
Although activation entropy is influenced by many factors,18
the nonvariation of the activation of entropy in this series of
rotaxanes suggests that each rotaxane endures a similar extent
of conformational loss in the transition state. Evidently, the
actual lengths of the rigid linear rod-like spacer units employed
herein have no direct effect on the activation entropy for
shuttling, so the system can be described by the steady-state
approximation. As previously mentioned, the larger activation
barriers in DMF-d7 relative to those in DMSO-d6 are due to the
differences in their abilities to solvate the two charged stations.
It is clear that these solvent effects manifest themselves in the
ΔS⧧ parameters, being on average more negative in DMF-d7
than in DMSO-d6. This can be explained by considering a larger
penalty will be paid for decomplexation of the DB24C8 ring
from a charged center of a rotaxane in DMF-d7 relative to
DMSO-d6. That is, based on their respective dielectric
constants, DMF-d7 molecules will become more ordered in
the transition state relative to DMSO-d6 molecules. We believe
the ordering of these highly polar solvents around the charged
ammonium stations in the transition states, as well as the effect
of breaking and restoring of ion pairs, gives rise to the large
negative values of ΔS⧧ for 1a−1d.
EXPERIMENTAL SECTION
■
General Methods. Melting points were measured with a hot-stage
apparatus equipped with a thermometer. 1H nuclear magnetic
resonance (NMR) spectra were recorded at 303 K using a Bruker
AVANCEIII-400 at a frequency of 400 MHz or a JEOL JNM-ECS400
at a frequency of 400 MHz and are reported as parts per million
(ppm) downfield shift from tetramethylsilane (δH 0.00) or
deuterochloroform (CDCl3, δH 7.26 ppm) as internal references,
unless otherwise stated. The data are reported as chemical shift (δ),
multiplicity (br = broad, s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet), coupling constant (J, Hz), relative integral. 13C
nuclear magnetic resonance spectra were recorded at 303 K using a
Bruker AVANCEIII-400 at a frequency of 100 MHz or a JEOL JNM-
ECS400 at a frequency of 100 MHz and are reported as parts per
million (ppm) downfield shift from deuterochloroform (δC 77.16
ppm) or tetramethylsilane (δC 0.00) as internal references, unless
Given the similarities in kinetic parameters across this series
of rotaxanes, it is clear that axle length does not significantly
influence the rate of ring shuttling. It is worth noting that the
lack of spacer length dependence on switching dynamics with
our rigid rod-like rotaxanes significantly contrasts that of
rotaxanes reported by others. In particular, Brouwer and co-
workers have found that the movement of a tetralactam ring
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otherwise stated. The substitution of carbon signals was determined on
the basis of distortionless enhancement by polarization transfer
(DEPT) 135° experiments. IR spectra were recorded as a KBr disk or
a neat film using a JASCO FT/IR-4200 spectrometer. Low resolution
mass spectral analyses (fast atom bombardment [FAB] and electron
impact [EI]) were performed by means of a JEOL JMS-700V
spectrometer. Low resolution mass spectral analyses (laser desorption
[LD]) mass measurements were performed by means of a Shimadzu/
Kratos AXIMA-CFR spectrometer. High resolution electrospray
ionization spectra were recorded on a JEOL JMS-700V spectrometer.
Elemental analyses were carried out by using a Perkin-Elmer 2400II
analyzer. Analytical thin layer chromatography (TLC) was performed
using precoated silica gel plates (Merck Kieselgel 60 F254).
Preparative column chromatography was carried out using Fuji Silysia
BW-300 silica gel (SiO2; 0.038−0.075 mm) with the indicated
solvents, which were mixed v/v as specified. Compounds 5a9c and 79e
were synthesized according to our previously reported procedures. All
other reagents were obtained from commercial suppliers and used as
received. CH2Cl2 and THF were dried by a Glass Contour solvent
purification system prior to use.
General Procedure A: Rotaxane Formation. DB24C8 (1.1−1.5
equiv) was added to a suspension of the hexafluorophosphate salt (1
equiv) in dichloromethane (∼0.1 M) to give a homogeneous reaction
mixture. A solution of anhydride stopper 7 (2.1 equiv) in
dichloromethane was then added at −20 °C (final concn ∼0.05 M)
followed by tri-n-butylphosphine (0.4 equiv). The mixture was stirred
under an atmosphere of nitrogen at −20 °C for 3−5 h after which time
it was stirred at ambient temperature for 1−2 h. The solvent was then
removed under reduced pressure, and the resulting crude product was
subjected to column chromatography to give the desired rotaxane
(8a−8d).
afford the desired hexafluorophosphate salt (5b−5d), which was used
in the next step without further purification.
8a. Hexafluorophosphate salt 5a (50.0 mg, 0.0803 mmol) was
treated according to General Procedure A. The crude product was
subjected twice to column chromatography (column 1: silica gel,
CHCl3/EtOAc [6:1] then CHCl3/CH3OH [10:1]; column 2: silica
gel, acetone/CH2Cl2 [1:20]) to give the desired rotaxane 8a as a
colorless foam (0.106 g, 70%). Rf = 0.44 (acetone/CH2Cl2 [1:20]).
Mp 106−109 °C. 1H NMR (400 MHz, CDCl3) δH (ppm) 8.20 (d, J =
1.2 Hz, 2 H), 8.19 (d, J = 1.1 Hz, 2 H), 7.83 (d, J = 6.2 Hz, 2H), 7.68−
7.54 (br m, 2 H), 7.42 (d, J = 8.1 Hz, 2 H), 7.32−7.24 (m, 4 H), 7.24−
7.17 (br m, 2 H), 7.12−7.03 (br m, 2 H), 6.85−6.69 (m, 8 H), 5.38 (s,
2 H), 5.29 (s, 2 H), 4.73−4.57 (br m, 4 H), 4.42−4.19 (br m, 4 H),
4.15−4.02 (m, 8 H), 3.86−3.71 (m, 8 H), 3.52 (s, 8 H), 1.52−1.36
(overlapping m, 12 H), 1.47 (s, 9 H), 1.09 (d, J = 1.0 Hz, 36 H), 1.07
(d, J = 1.0 Hz, 36 H). 13C NMR (100 MHz, CDCl3) δC (ppm) 167.3
(CO), 167.1 (CO), 156.0 (CO), 147.4 (ArC), 147.2 (ArCH), 147.0
(ArCH), 139.4 (ArC), 137.8 (ArC), 137.0 (ArCH), 136.6 (ArCH),
136.5 (ArCH), 135.7 (ArC), 134.3 (ArC), 134.2 (ArC), 131.4 (ArC),
130.8 (ArC), 129.47 (ArCH), 129.45 (ArCH), 128.3 (ArC), 128.2
(ArC), 128.1 (ArCH), 127.9 (ArCH), 121.7 (ArCH), 112.6 (ArCH),
80.4 (Cq), 70.8 (CH2), 70.3 (CH2), 68.1 (CH2), 66.1 (CH2), 65.7
(CH2), 52.4 (CH2), 49.7 (CH2), 49.1 (CH2), 28.5 (CH3), 18.6 (CH3),
10.84 (CH), 10.82 (CH) (four carbon signals obscured or
overlapping). IR (KBr, cm−1) 3431, 3145, 2944, 2890, 2866, 1721,
1695, 1505, 1461, 1267, 1252, 1129, 844. MS (FAB+) m/z = 1758 [M
− PF6]+. Anal. Calcd for C103H157F6N2O14PSi4: C 64.95, H 8.31, N
1.49. Found: C 65.24, H 8.12, N 1.16.
1a. Rotaxane 8a (50.0 mg, 0.0263 mmol) was treated according to
General Procedure B to provide the desired bis-hexfluorophosphate
1
salt 1a as an off-white solid (45.9 mg, 90%). Mp 118−120 °C. H
NMR (400 MHz, CDCl3) δH (ppm) 8.20 (d, J = 0.7 Hz, 2 H), 8.19 (d,
J = 0.8 Hz, 2 H), 7.86−7.81 (m, 2 H), 7.80−7.62 (br m, 6 H), 7.59−
7.47 (br m, 4 H), 7.46−7.38 (m, 2 H), 7.28 (d, J = 8.1 Hz, 2 H), 7.22
(d, J = 8.1 Hz, 2 H), 6.77 (s, 8 H), 5.38 (s, 2 H), 5.31 (s, 2 H), 4.69−
4.60 (m, 2 H), 4.49−4.41 (m, 2 H), 4.34 (br s, 2 H), 4.17−3.98
(overlapping m, 10 H), 3.82−3.65 (m, 8 H), 3.45−3.27 (8 H), 1.51−
1.35 (m, 12 H), 1.07 (d, J = 7.5 Hz, 72 H). 13C NMR (100 MHz,
CDCl3) δC (ppm) 167.3 (CO), 167.1 (CO), 147.6 (ArC), 147.3
(ArCH), 147.2 (ArCH), 138.6 (ArC), 138.0 (ArC), 136.7 (ArCH),
136.5 (ArCH), 134.4 (ArC), 134.3 (ArC), 133.3 (ArC), 131.6 (ArC),
131.2 (ArC), 131.1 (ArC), 131.0 (ArCH), 130.3 (ArCH), 129.4
(ArCH), 128.4 (ArCH), 128.2 (ArC), 128.1 (ArC), 127.8 (ArCH),
122.0 (ArCH), 113.2 (ArCH), 70.7 (CH2), 70.3 (CH2), 68.5 (CH2),
65.8 (CH2), 65.7 (CH2), 52.6 (CH2), 52.5 (CH2), 52.3 (CH2), 51.2
(CH2), 18.6 (two overlapping CH3 signals), 10.9 (two overlapping
CH signals) (one ArCH signal obscured or overlapping). IR (KBr,
cm−1) 3421, 2944, 2889, 2866, 1721, 1506, 1457, 1267, 1252, 1130,
849. MS (FAB+) m/z = 1658 [M − 2PF6 − H]+. Anal. Calcd for
C98H150F12N2O12P2Si4: C, 60.35; H, 7.75; N, 1.44. Found: C, 60.26; H,
8.15; N, 1.45.
3b. Diamine 2b (0.865 g, 1.701 mmol) was treated according to
General Procedure C. Purification by column chromatography (silica
gel, CH2Cl2/acetone [20:1 to 1:1]) provided the desired mono-Boc-
protected product 3b (0.550 g, 53%) and the di-Boc-protected
product 9 (0.423 g, 35%) both as colorless oils. Compound 3b: Rf =
0.25 (acetone/CH2Cl2 [1:10]). 1H NMR (400 MHz, CDCl3) δH
(ppm) 8.03−7.98 (m, 4 H), 7.58−7.52 (m, 4 H), 7.44 (d, J = 8.2 Hz, 2
H), 7.41 (d, J = 8.1 Hz, 2 H), 7.34−7.20 (br m, 4 H), 4.49 (br s, 2 H),
4.42 (br s, 2 H), 3.908 (s, 3 H), 3.905 (s, 3 H), 3.89 (s, 2 H), 3.84 (s, 2
H), 1.74 (s, 1 H), 1.50 (br s, 9 H). 13C NMR (100 MHz, CDCl3) δC
(ppm) 167.0 (CO), 166.9 (CO), 155.9 (CO), 145.7 (ArC),
143.5 (ArC), 140.1 (ArC), 139.6 (ArC), 139.3 (ArC), 136.7 (ArC),
129.9 (ArCH), 129.8 (ArCH), 129.2 (ArC), 128.9 (ArC), 128.6
(ArCH), 128.5 (ArC), 128.0 (ArC), 127.8 (ArC), 127.2 (ArC), 127.1
(ArC), 80.4 (Cq), 52.9 (CH2), 52.8 (CH2), 52.1 (CH3), 52.0 (CH3),
49.4 (CH2), 49.1 (CH2), 28.4 (CH3). IR (KBr, cm−1) 3418, 2976,
2950, 1720, 1693, 1279, 1163, 753. MS (FAB+) m/z = 609 [M + H]+.
HRMS (FAB+) m/z calcd for C37H41N2O6 [M + H]+ 609.2965, found
609.2969. Compound 9: Rf = 0.81 (acetone/CH2Cl2 [1:10]). 1H
General Procedure B: Boc-Deprotection. Under an atmosphere of
nitrogen, trifluoroacetic acid (0.2 mL) was added to a solution of
rotaxane (8a−8d) in dichloromethane (1 mL). After the reaction
mixture was stirred at ambient temperature for 2 h, it was poured onto
saturated aqueous NH4PF6 (20 mL) and then extracted with
dichloromethane (3 × 15 mL). The combined organics were washed
with saturated aqueous NH4PF6 (30 mL), dried (MgSO4), and then
concentrated under reduced pressure. The crude product thus
obtained was triturated with hexane to provide the desired bis-
hexfluorophosphate salt (1a−1d).
General Procedure C: Mono Boc-Protection. Under an atmosphere
of nitrogen, Boc-anhydride (1 equiv) and N,N-(dimethylamino)-
pyridine (0.05 equiv) were added to a solution of diamine (1 equiv) in
dichloromethane. The reaction mixture was stirred at ambient
temperature for 3 h and was then concentrated under reduced
pressure. Purification by column chromatography provided the desired
mono-Boc-protected product (3b−3d) and the di-Boc-protected
product (9−11).
General Procedure D: Ester Reduction. Under an atmosphere of
nitrogen, a solution of mono-Boc compound (1 equiv) in
tetrahydrofuran was added dropwise to a suspension of lithium
aluminum hydride (3 equiv) in tetrahydrofuran at 0 °C over 5 min.
The reaction mixture was stirred at 0 °C for 30 min and then slowly
warmed to ambient temperature. After 30 min TLC showed complete
consumption of the starting material, and the reaction was quenched
with ice−water (30 mL) at 0 °C and then extracted with
CHCl3/iPrOH (3:1 v/v, 5 × 30 mL). The combined organic layers
were dried (MgSO4) and then concentrated under reduced pressure.
The crude product obtained was subsequently purified by column
chromatography to afford the desired diol (4b−4d).
General Procedure E: Hexfluorophosphate Salt Formation.
Saturated aqueous NH4PF6 (1 mL) was added dropwise to a solution
of diol (4b−4d) in acetone (3 mL). A precipitate immediately formed.
Argon gas was then bubbled through the reaction suspension with
stirring at ambient temperature for 2 h. The reaction mixture was then
concentrated and partitioned between water (20 mL) and
CHCl3/iPrOH (3:1 v/v, 4 × 20 mL). The combined organic layers
were dried (MgSO4) and then concentrated under reduced pressure to
7903
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NMR (400 MHz, CDCl3) δH (ppm) 8.01 (d, J = 8.2 Hz, 4 H), 7.55 (d,
J = 8.2 Hz, 4 H), 7.38−7.19 (br m, 8 H), 4.50 (br s, 4 H), 4.43 (br s, 4
H), 3.91 (s, 6 H), 1.50 (s, 18 H). 13C NMR (100 MHz, CDCl3) δC
(ppm) 166.8 (CO), 155.9 (CO), 143.5 (ArC), 139.9 (ArC),
136.9 (ArC), 129.9 (ArCH), 129.2 (ArC), 128.5 (ArCH), 128.0
(ArCH), 127.2 (ArCH), 80.4 (Cq), 52.0 (CH3), 49.5 (CH2), 49.1
(CH2), 28.4 (CH3). IR (KBr, cm−1) 3437, 2974, 1715, 1695, 1284,
1164, 1130, 1107, 891, 750. MS (FAB+) m/z = 708 [M]+. HRMS
(FAB+) m/z calcd for C42H48N2O8 [M]+ 708.3411, found 708.3426.
4b. Mono-Boc compound 3b (0.550 g, 0.9035 mmol) was treated
according to General Procedure D. Purification by column
chromatography (silica gel, acetone/CH2Cl2 [1:20 to 3:1]) gave the
desired diol 4b as a colorless oil (0.447 g, 89%). Rf = 0.21 (acetone/
147.2 (ArCH), 141.3 (ArC), 140.9 (ArC), 138.6 (ArC), 137.9 (ArC),
136.6 (ArCH), 136.5 (ArCH), 134.4 (ArC), 134.3 (ArC), 131.6
(ArC), 131.0 (ArC), 130.8 (ArCH), 130.7 (ArCH), 129.8 (ArCH),
129.43 (ArCH), 129.35 (ArC), 129.1 (ArC), 128.5 (ArCH), 128.2
(ArC), 128.1 (ArC), 129.0 (ArCH), 127.9 (ArCH), 127.3 (ArCH),
121.9 (ArCH), 112.8 (ArCH), 70.8 (CH2), 70.4 (CH2), 68.2 (CH2),
65.8 (two overlapping CH2 signals observed in HMQC), 52.44 (CH2),
52.39 (CH2), 51.9 (CH2), 51.5 (CH2), 18.6 (two overlapping CH
signals), 10.9 (two overlapping CH3 signals). IR (KBr, cm−1) 3437,
2943, 2866, 1721, 1505, 1459, 1267, 1130, 841, 559. MS (FAB+) m/z
= 1734 [M − 2PF6 − H]+. Anal. Calcd for C104H154F12N2O12P2Si4: C,
61.64; H, 7.66; N, 1.38. Found: C, 61.25; H, 7.70; N, 1.41.
3c. Diamine 2c (0.142 g, 0.242 mmol) was treated according to
General Procedure C. Purification by column chromatography (silica
gel, EtOAc/hexane [4:1 to neat EtOAc]) and evaporation of
appropriate fractions gave the desired mono-Boc-protected product
3c (85.8 mg, 52%) as a colorless oil and the di-Boc-protected product
10 (53.3 mg, 28%) as a colorless solid. Compound 3c: Rf = 0.56
(EtOAc/hexane [4:1]). 1H NMR (400 MHz, CDCl3) δH (ppm) 8.05−
7.98 (m, 4 H), 7.87 (s, 4 H), 7.64−7.58 (m, 4 H), 7.47−7.41 (m, 4 H),
7.29 (br s, 4 H), 4.56−4.35 (2 overlapping br s, 4 H), 3.93−3.92 (2
overlapping s, 6 H), 3.91 (s, 2 H), 3.87 (s, 2 H), 1.73 (br s, 1 H), 1.51
(s, 9 H). 13C NMR (100 MHz, CDCl3) δC (ppm) 167.1, 166.9, 156.0,
145.8, 143.6, 139.94, 139.87, 139.6, 139.5, 139.4, 136.9, 129.9, 129.8,
129.3, 129.0, 128.7, 128.6, 128.1, 127.8, 127.5, 127.4, 127.2, 127.1,
80.5, 52.93, 52.87, 52.1, 52.1, 49.6, 49.2, 28.5. IR (KBr, cm−1) 3422,
3027, 2976, 2951, 2840, 1721, 1691, 1612, 1280, 1164, 1109, 805, 755.
MS (FAB+) m/z = 685 [M + H]+. HRMS (FAB+) m/z calcd for
C43H45N2O6 [M + H]+ 685.3278, found 685.3260. Compound 10: Rf
= 0.92 (EtOAc/hexane [4:1]). Mp 186−187 °C. 1H NMR (400 MHz,
CDCl3) δH (ppm) 8.01 (d, J = 8.3 Hz, 4 H), 7.68 (s, 4 H), 7.61 (d, J =
8.2 Hz, 4 H), 7.30 (br s, 8 H), 4.57−4.35 (2 overlapping br s, 8 H),
3.92 (s, 6 H), 1.51 (s, 18 H). 13C NMR (100 MHz, CDCl3) δC (ppm)
166.9, 156.0, 143.6, 139.9, 139.8, 137.0, 130.0, 129.3, 128.6, 128.0,
127.5, 127.3, 80.5, 52.1, 49.6, 49.3, 28.5. IR (KBr, cm−1) 3430, 2978,
1693, 1612, 1466, 1281, 1250, 1131, 964, 761, 491. MS (FAB+) m/z =
784 [M]+. HRMS (FAB+) m/z calcd for C48H52N2O8 [M]+ 784.3724,
found 784.3752.
1
CH2Cl2 [3:1]). H NMR (400 MHz, CDCl3) δH (ppm) 7.57−7.50
(m, 4 H), 7.36 (d, J = 8.1 Hz, 2 H), 7.32−7.28 (overlapping m, 2 H),
7.28 (s, 4 H), 7.28−7.14 (br overlapping m, 4 H), 4.62 (s, 2 H), 4.61
(s, 2 H), 4.45−4.30 (2 br overlapping s, 4 H), 3.78 (s, 2 H), 3.77 (s, 2
H), 2.52 (br s, 2 H), 1.49 (s, 9 H). One × NH not observed. 13C NMR
(100 MHz, CDCl3) δC (ppm) 156.1 (CO), 140.3 (ArC), 140.1
(ArC), 139.9 (ArC), 139.6 (ArC), 139.2 (ArC), 139.1 (ArC), 137.2
(ArC), 137.0 (ArC), 128.7 (ArCH), 128.4 (ArCH), 128.3 (ArCH),
127.8 (ArCH), 127.24 (ArCH), 127.19 (ArCH), 127.16 (ArCH),
127.1 (ArCH), 80.3 (Cq), 64.81 (CH2), 64.75 (CH2), 52.8 (CH2),
52.7 (CH2), 49.1 (CH2), 48.9 (CH2), 28.5 (CH3). IR (KBr, cm−1)
3297, 3024, 2975, 2863, 1690, 1678, 1412, 1162, 805. MS (FAB+) m/
z = 553 [M + H]+. HRMS (FAB+) m/z calcd for C35H41N2O4 [M +
H]+ 553.3066, found 553.3068.
5b. Compound 4b (0.351 g, 0.6351 mmol) was treated according to
General Procedure E to afford the desired hexafluorophosphate salt 5b
as a colorless foam (0.337 g, 76%), which was used in the next step
without further purification.
8b. Hexafluorophosphate salt 5b (70.0 mg, 0.100 mmol) was
treated according to General Procedure A. The crude product was
subjected twice to column chromatography (column 1: silica gel,
CHCl3/EtOAc [10:1 to 5:1]; column 2: silica gel, acetone/CH2Cl2
[1:20]) to give the desired rotaxane 8b as a colorless foam (0.127 g,
64%). Rf = 0.28 (acetone/CH2Cl2 [1:20]). Mp 105−106 °C. 1H NMR
(400 MHz, CDCl3) δH (ppm) 8.21 (d, J = 1.1 Hz, 2 H), 8.19 (d, J =
1.1 Hz, 2 H), 7.86−7.81 (m, 2 H), 7.72−7.60 (br m, 2 H), 7.49 (d, J =
8.2 Hz, 2 H), 7.47−7.40 (m, 4 H), 7.37 (d, J = 8.2 Hz, 2 H), 7.33−
7.21 (overlapping m, 8 H), 6.85−6.71 (m, 8 H), 5.39 (s, 2 H), 5.30 (s,
2 H), 4.71−4.59 (m, 4 H), 4.45 (br s, 2 H), 4.39 (br s, 2 H), 4.16−
4.03 (m, 8 H), 3.85−3.72 (m, 8 H), 3.56−3.44 (m, 8 H), 1.51 (s, 9 H),
1.43 (sept, J = 2.5 Hz, 12 H), 1.08 (d, J = 2.5 Hz, 36 H), 1.07 (d, J =
2.5 Hz, 36 H). 13C NMR (100 MHz, CDCl3) δC (ppm) 167.3 (C
O), 167.0 (CO), 156.0 (CO), 147.5 (ArC), 147.2 (ArCH), 147.0
(ArCH), 141.6 (ArC), 138.9 (ArC), 138.8 (ArC), 137.7 (ArC), 136.54
(ArCH), 136.46 (ArCH), 135.6 (ArC), 134.3 (ArC), 134.1 (ArC),
131.4 (ArC), 130.5 (ArC), 129.7 (ArCH), 129.4 (ArCH), 128.4
(ArCH observed in DEPT), 128.3 (ArC), 128.1 (ArC), 128.0
(ArCH), 127.9 (ArCH), 127.6 (ArCH), 127.2 (ArCH), 127.1
(ArCH), 121.7 (ArCH), 112.7 (ArCH), 80.3 (Cq), 70.7 (CH2), 70.3
(CH2), 68.2 (CH2), 66.1 (CH2), 65.4 (CH2), 52.3 (two overlapping
CH2 signals), 49.3 (CH2), 48.9 (CH2), 28.5 (CH3), 18.5 (two
overlapping CH3 signals), 10.79 (CH), 10.77 (CH) (one carbon signal
obscured or overlapping). IR (KBr, cm−1) 3437, 2944, 2866, 1721,
1696, 1505, 1459, 1267, 1129, 844. MS (FAB+) m/z = 1835 [M −
PF6]+. Anal. Calcd for C109H161F6N2O14PSi4: C, 66.09; H, 8.19; N,
1.41. Found: C, 66.37; H, 8.18; N, 1.41.
4c. Mono-Boc compound 3c (0.402 g, 0.587 mmol) was treated
according to General Procedure D to give the desired diol 4c as a
colorless foam (0.337 g, 91%). Rf = 0.31 (CHCl3/CH3OH). Mp 55−
1
56 °C. H NMR (400 MHz, CDCl3) δH (ppm) 7.68 (s, 4 H), 7.65−
7.58 (m, 4 H), 7.42 (d, J = 8.1 Hz, 2 H), 7.38−7.18 (br overlapping m,
8 H), 7.34 (s, 2 H), 4.67 (s, 2 H), 4.66 (s, 2 H), 4.52−4.33 (2 br
overlapping s, 4 H), 3.83 (s, 2 H), 3.82 (s, 2 H), 1.53 (s, 9 H). One ×
NH, 2 × OH not observed. 13C NMR (100 MHz, CDCl3) δC (ppm)
156.2, 140.3, 140.1, 139.9, 139.8, 139.5, 139.3, 139.2, 137.3, 137.2,
128.8, 128.5, 128.3, 128.1, 127.7, 127.48, 127.46, 127.3, 127.2, 127.1,
80.4, 65.00, 64.95, 52.9, 52.7, 49.2, 49.0, 28.6 (one carbon signal
obscured or overlapping). IR (KBr, cm−1) 3382, 3026, 2975, 2927,
2868, 1688, 1492, 1459, 1407, 1365, 1246, 1162, 804. MS (FAB+) m/
z = 629 [M + H]+. HRMS (FAB+) m/z calcd for C41H45N2O4 [M +
H]+ 629.3379, found 629.3389.
5c. Compound 4c (0.335 g, 0.533 mmol) was treated according to
General Procedure E to afford the desired hexafluorophosphate salt 5c
as a colorless foam (0.412 g, quant), which was used in the next step
without further purification.
8c. Hexafluorophosphate salt 5c (87.9 mg, 0.0113 mmol) was
treated according to General Procedure A. The crude product was
subjected twice to column chromatography (column 1: silica gel,
CHCl3/EtOAc [6:1 then CHCl3/CH3OH [20:1]; column 2: silica
gel;, acetone/CH2Cl2 [1:20]] to give the desired rotaxane 8c as a
colorless foam (0.159 g, 68%). Rf = 0.28 (acetone/CH2Cl2 [1:20]),
0.34 (CHCl3/CH3OH [20:1]). Mp 113−115 °C. 1H NMR (400
MHz, CDCl3) δH (ppm) 8.21 (d, J = 1.0 Hz, 2 H), 8.19 (d, J = 1.0 Hz,
2 H), 7.90−7.84 (m, 2 H), 7.73−7.58 (overlapping m, 8 H), 7.50 (d, J
= 5.0 Hz, 2 H), 7.44 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.2 Hz, 2 H),
7.36−7.23 (overlapping m, 8 H), 6.85−6.72 (m, 8 H), 5.39 (s, 2 H),
5.30 (s, 2 H), 4.72−4.60 (br m, 4 H), 4.53−4.35 (2 overlapping br s, 4
H), 4.17−4.04 (m, 8 H), 3.86−3.73 (m, 8 H), 3.51 (s, 8 H), 1.51 (s, 9
1b. Rotaxane 8b (0.121 g, 0.0611 mmol) was treated according to
General Procedure B to provide the desired bis-hexfluorophosphate
1
salt 1b as an off-white foam (0.117 g, 94%). Mp 131−132 °C. H
NMR (400 MHz, CDCl3) δH (ppm) 8.21−8.16 (m, 4 H), 7.86−7.81
(m, 2 H), 7.70−7.56 (overlapping br m, 2 H), 7.60 (d, J = 8.2 Hz, 2
H), 7.54 (d, J = 8.3 Hz, 2 H), 7.51−7.44 (m, 4 H), 7.37−7.24 (m, 8
H), 6.83−6.68 (m, 8 H), 5.34 (s, 2 H), 5.29 (s, 2 H), 4.71−4.57 (m, 4
H), 4.37 (s, 2 H), 4.26 (s, 2 H), 4.15−4.00 (m, 8 H), 3.84−3.70 (m, 8
H), 3.56−3.40 (m, 8 H), 1.50−1.34 (m, 12 H), 1.08 (d, J = 1.0 Hz, 36
H), 1.06 (d, J = 1.0 Hz, 36 H). 13C NMR (100 MHz, CDCl3) δC
(ppm) 167.3 (CO), 167.2 (CO), 147.5 (ArC), 147.3 (ArCH),
7904
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H), 1.44 (sept, J = 3.1 Hz, 12 H), 1.09 (d, J = 3.1 Hz, 36 H), 1.07 (d, J
= 3.1 Hz, 36 H). 13C NMR (100 MHz, CDCl3) δC (ppm) 167.3,
167.1, 156.1, 147.5, 147.2, 147.1, 136.6, 136.5, 129.5, 128.1, 127.9,
127.5, 127.3, 127.1, 121.8, 112.7, 80.3, 70.8, 70.3, 68.2, 66.2, 65.7, 52.4,
49.2, 49.0, 28.6, 18.6, 10.9, 10.8 (four carbon signals obscured or
overlapping). IR (KBr, cm−1) 3438, 3150, 2944, 2866, 1721, 1697,
1505, 1460, 1266, 1129, 844. MS (FAB+) m/z = 1911 [M − PF6]+.
Anal. Calcd for C115H165F6N2O14PS4: C, 67.15; H, 8.09; N, 1.36.
Found: C, 66.93; H, 8.33; N, 1.36.
4d. Mono-Boc compound 3d (0.250 g, 0.329 mmol) was treated
according to General Procedure D. Purification by column
chromatography (silica gel, acetone/CH2Cl2 [1:10 to 1:1]) afforded
the desired diol 4d as an off-white solid (0.167 g, 72%). Rf = 0.27
(acetone/CH2Cl2 [1:1]). Mp 117−119 °C. 1H NMR (400 MHz,
CDCl3/CD3OD [10:1]) δH (ppm) 7.75−7.67 (m, 8 H), 7.64 (d, J =
8.1 Hz, 2 H), 7.62 (d, J = 8.1 Hz, 2 H), 7.40 (d, J = 8.2 Hz, 2 H),
7.38−7.30 (m, 6 H), 7.30−7.16 (br m, 4 H), 4.642 (s, 2 H), 4.637 (s, 2
H), 4.45 (br s, 2 H), 4.39 (br s, 4 H), 3.82 (s, 2 H), 3.81 (s, 2 H), 1.52
(s, 9 H). 13C NMR (100 MHz, CDCl3) δC (ppm) 156.3 (CO),
140.3 (ArC), 140.2 (ArC), 139.7 (ArC), 139.6 (ArC), 139.5 (ArC),
139.43 (ArC), 139.40 (ArC), 138.2 (ArC), 138.1 (ArC), 136.9 (ArC),
136.7 (ArC), 136.6 (ArC), 128.8 (ArCH), 128.3 (ArCH), 127.8
(ArCH), 127.4 (ArCH), 127.3 (ArCH), 127.2 (ArCH), 127.10
(ArCH), 127.07 (ArCH), 127.02 (ArCH), 126.98 (ArCH), 80.5 (Cq),
64.13 (CH2), 64.09 (CH2), 52.4 (CH2), 52.2 (CH2), 49.1 (CH2
observed in DEPT), 48.8 (CH2 observed in DEPT), 28.2 (CH3) (two
carbon signals obscured or overlapping). IR (KBr, cm−1) 3421, 2931,
1683, 1489, 1244, 1160, 805. MS (FAB+) m/z = 705 [M + H]+.
HRMS (FAB+) m/z calcd for C47H49N2O4 [M + H]+ 705.3692, found
705.3696.
1c. Rotaxane 8c (0.159 g, 0.0773 mmol) was treated according to
General Procedure B to provide the desired bis-hexfluorophosphate
salt 1c as an off-white solid (0.149 g, 91%). Mp 134−136 °C. 1H NMR
(400 MHz, CDCl3) δH (ppm) 8.19 (d, J = 1.1 Hz, 2 H), 8.18 (d, J =
1.1 Hz, 2 H), 7.85−7.81 (m, 2 H), 7.70−7.61 (br overlapping m, 2 H),
7.59 (d, J = 8.2 Hz, 2 H), 7.53−7.41 (overlapping m, 12 H), 7.38−7.34
(m, 2 H), 7.32−7.22 (m, 4 H), 6.90−6.80 (overlapping br m, 2 H),
6.80−6.69 (m, 8 H), 5.34 (s, 2 H), 5.28 (s, 2 H), 4.73−4.55 (m, 4 H),
4.37 (br s, 2 H), 4.24 (br s, 2 H), 4.16−3.97 (m, 8 H), 3.84−3.66 (m,
8 H), 3.59−3.39 (m, 8 H), 1.47−1.35 (m, 12 H), 1.07 (d, J = 3.3 Hz,
36 H), 1.05 (d, J = 3.3 Hz, 36 H). 13C NMR (100 MHz, CDCl3) δC
(ppm) 167.3 (CO), 167.2 (CO), 147.5 (ArC), 147.3 (ArCH),
147.2 (ArCH), 142.0 (ArC), 141.2 (ArC), 139.20 (ArC), 139.17
(ArC), 138.6 (ArC), 137.8 (ArC), 136.62 (ArCH), 136.55 (ArCH),
134.4 (ArC), 134.3 (ArC), 131.6 (ArC), 130.8 (ArCH), 130.7
(ArCH), 129.9 (ArCH), 129.5 (ArCH), 129.3 (ArC), 128.7 (ArC),
128.5 (ArCH), 128.2 (ArC), 128.1 (ArC), 127.9 (ArCH), 127.8
(ArCH), 127.5 (ArCH), 127.2 (ArCH), 121.8 (ArCH), 112.8
(ArCH), 70.8 (CH2), 70.4 (CH2), 68.20 (CH2), 65.8 (two
overlapping CH2 signals observed in HMQC), 52.5 (CH2), 52.4
(CH2), 51.9 (CH2), 51.6 (CH2), 18.6 (two overlapping CH3 signals),
10.9 (two overlapping CH signals) (one ArC, one ArCH signal).
obscured or overlapping). IR (KBr, cm−1) 3422, 3148, 2944, 2866,
1721, 1505, 1459, 1267, 1130, 846, 558. MS (FAB+) m/z = 1810 [M
− 2PF6 − H]+. Anal. Calcd for C110H158F12N2O12P2Si4: C, 62.83; H,
7.57; N, 1.33. Found: C, 62.90; H, 7.86; N, 1.34.
5d. Compound 4d was treated according to General Procedure E to
afford the desired hexafluorophosphate salt 5d as a pale yellow solid
(0.202 g, quant), which was used in the next step without further
purification.
8d. Hexafluorophosphate salt 5d (87.9 mg, 0.0113 mmol) was
treated according to General Procedure A. The crude product was
subjected twice to column chromatography (column 1: silica gel,
CHCl3/EtOAc [10:1 to 5:1]; column 2: silica gel, acetone/CH2Cl2
[1:20]) to give the desired rotaxane 8d as a colorless solid (0.109 g,
72%). Rf = 0.43 (acetone/CH2Cl2 [20:1]). Mp 119−121 °C. 1H NMR
(400 MHz, CDCl3) δH (ppm) 8.20 (d, J = 8.3 Hz, 4 H), 7.85−7.81
(m, 2 H), 7.75−7.58 (m, 12 H), 7.50 (d, J = 8.3 Hz, 2 H), 7.43 (d, J =
8.1 Hz, 2 H), 7.39 (d, J = 8.2 Hz, 2 H), 7.35−7.20 (m, 8 H), 6.85−
6.70 (m, 8 H), 5.39 (s, 2 H), 5.29 (s, 2 H), 4.73−4.59 (m, 4 H), 4.47
(br s, 2 H), 4.40 (br s, 2 H), 4.18−4.02 (m, 8 H), 3.86−3.71 (m, 8 H),
3.59−3.44 (m, 8 H), 1.51 (s, 9 H), 1.48−1.36 (m, 12 H), 1.08 (d, J =
4.3 Hz, 36 H), 1.06 (d, J = 4.2 Hz, 36 H). 13C NMR (100 MHz,
CDCl3) δC (ppm) 167.4 (CO), 167.2 (CO), 156.2 (CO),
147.5 (ArC), 147.3 (ArCH), 147.1 (ArCH), 141.5 (ArC), 140.1
(ArC), 140.0 (ArC), 139.8 (ArC), 139.5 (ArC), 138.9 (ArC), 138.0
(ArC), 137.9 (ArC), 137.3 (ArC), 136.7 (ArCH), 136.6 (ArCH),
135.7 (ArC), 134.4 (ArCH), 134.2 (ArCH), 131.5 (ArC), 130.7
(ArC), 129.9 (ArCH), 129.5 (ArCH), 128.6 (ArCH), 128.4 (ArC),
128.2 (ArC), 128.1 (ArCH), 128.0 (ArCH), 127.6 (ArCH), 127.53
(ArCH), 127.51 (ArCH), 127.3 (ArCH), 127.2 (ArCH), 121.8
(ArCH), 112.8 (ArCH), 80.4 (Cq), 70.8 (CH2), 70.4 (CH2), 68.2
(CH2), 66.2 (CH2), 65.8 (CH2), 52.5 (two overlapping CH2 signals
observed in HMQC), 49.3 (CH2), 49.0 (CH2), 28.6 (CH3), 18.7 (two
overlapping CH signals), 10.90 (CH), 10.88 (CH) (two ArC signals
obscured or overlapping). IR (KBr, cm−1) 3447, 3148, 2943, 2866,
1721, 1697, 1505, 1459, 1251, 1129, 844. MS (FAB+) m/z = 1986 [M
− PF6]+. Anal. Calcd for C121H169F6N2O14PSi4: C, 68.14; H, 7.99; N,
1.31. Found: C, 68.01; H, 8.00; N, 1.32.
3d. Diamine 2d (0.500 g, 0.757 mmol) was treated according to
General Procedure C. Purification by column chromatography (silica
gel, acetone/CH2Cl2 [1:20 to 10:1]) provided the desired mono-Boc-
protected product 3d (0.261 g, 45%) and the di-Boc-protected
product 11 (0.150 g, 23%), both as pale-yellow solids. Compound 3d:
Rf = 0.52 (acetone/CH2Cl2 [1:10]), 0.27 (acetone/CH2Cl2 [1:20]).
1
Mp 131−133 °C. H NMR (400 MHz, CDCl3) δH (ppm) 8.04−7.98
(m, 4 H), 7.74−7.66 (m, 8 H), 7.64−7.58 (m, 4 H), 7.47−7.40 (m, 4
H), 7.35−7.24 (br m, 4 H), 4.50 (br s, 2 H), 4.43 (br s, 2 H), 3.91 (s,
6 H), 3.90 (s, 2 H), 3.85 (s, 2 H), 1.72 (s, 1 H), 1.50 (s, 9H). 13C
NMR (100 MHz, CDCl3) δC (ppm) 167.0 (CO), 166.9 (CO),
156.0 (CO), 145.7 (ArC), 143.5 (ArC), 139.9 (ArC), 139.8 (ArC),
139.7 (ArC), 139.6 (ArC), 139.5 (ArC), 139.3 (ArC), 136.9 (ArC),
129.9 (ArCH), 129.8 (ArCH), 129.2 (ArC), 128.9 (ArC), 128.8
(ArCH), 128.7 (ArCH), 128.5 (ArCH), 128.0 (ArCH), 127.8
(ArCH), 127.39 (ArCH), 127.36 (ArCH), 127.2 (ArCH), 127.1
(ArCH), 80.5 (Cq), 52.9 (CH2), 52.8 (CH2), 52.1 (CH3), 52.0 (CH3),
49.5 (CH2), 49.1 (CH2), 28.4 (CH3) (two carbon signals obscured or
overlapping). IR (KBr, cm−1) 3422, 2975, 2841, 1721, 1692, 1611,
1280, 1160, 1108, 805, 756. MS (FAB+) m/z = 761 [M + H]+. HRMS
(FAB+) m/z calcd for C49H49N2O6 [M + H]+ 761.3591, found
761.3589. Compound 11: Rf = 0.50 (acetone/CH2Cl2 [1:60]), 0.88
1d. Rotaxane 8d (0.121 g, 0.0567 mmol) was treated according to
General Procedure B to provide the desired bis-hexfluorophosphate
1
salt 1d as an off-white solid (0.114 g, 92%). Mp 146−149 °C. H
NMR (400 MHz, CDCl3) δH (ppm) 8.39−8.23 (br s, 2 H), 8.20 (d, J
= 0.9 Hz, 2 H), 8.18 (d, J = 0.9 Hz, 2 H), 7.85−7.80 (m, 2H), 7.70−
7.42 (m, 20 H), 7.37 (d, J = 8.3 Hz, 2 H), 7.29 (d, J = 8.3 Hz, 2 H),
7.25 (d, J = 8.3 Hz, 2 H), 6.82−6.68 (m, 8 H), 5.32 (s, 2 H), 5.28 (s, 2
H), 4.72−4.55 (br m, 4 H), 4.23−4.13 (br m, 2 H), 4.13−4.08
(overlapping br m, 2 H), 4.11−3.99 (m, 8 H), 3.83−3.69 (m, 8 H),
3.56−3.41 (m, 8 H), 1.50−1.33 (m, 12 H), 1.07 (d, J = 3.3 Hz, 36 H),
1.05 (d, J = 3.3 Hz, 36 H). 13C NMR (100 MHz, CDCl3) δC (ppm)
167.3 (CO), 167.2 (CO), 147.5 (ArC), 147.3 (ArCH), 147.2
(ArCH), 141.8 (ArC), 141.5 (ArC), 134.0 (ArC), 139.7 (ArC), 139.2
(ArC), 138.8 (ArC), 138.2 (ArC), 137.9 (ArC), 136.7 (ArCH), 136.6
(ArCH), 134.4 (ArC), 134.3 (ArC), 131.6 (ArC), 130.8 (ArCH),
130.64 (ArC), 130.62 (ArCH), 129.88 (ArCH), 129.86 (ArC), 129.5
1
(acetone/CH2Cl2 [1:20]). Mp 197−198 °C. H NMR (400 MHz,
CDCl3) δH (ppm) 8.01 (d, J = 8.2 Hz, 4 H), 7.70 (app. q, J = 8.4 Hz, 8
H), 7.61 (d, J = 8.1 Hz, 4 H), 7.39−7.18 (br m, 8 H), 4.51 (br s, 4 H),
4.43 (br s, 4 H), 3.90 (s, 6 H), 1.50 (s, 18 H). 13C NMR (100 MHz,
CDCl3) δC (ppm) 166.9 (CO), 155.9 (CO), 143.5 (ArC), 143.4
(ArC), 139.8 (ArC), 139.6 (ArC), 136.9 (ArC), 129.9 (ArCH), 129.2
(ArC), 128.5 (ArCH), 127.9 (ArCH), 127.44 (ArCH), 127.37
(ArCH), 127.2 (ArCH), 80.4 (Cq), 52.04 (CH3), 49.50 (CH2),
49.12 (CH2), 28.43 (CH3). IR (KBr, cm−1) 3422, 3025, 2978, 2929,
1714, 1699, 1613, 1488, 1397, 1280, 1249, 1165, 1111, 801, 752. MS
(FAB+) m/z = 860 [M]+. HRMS (FAB+) m/z calcd for C54H56N2O8
[M]+ 860.4037, found 860.4016.
7905
dx.doi.org/10.1021/ja412671k | J. Am. Chem. Soc. 2014, 136, 7899−7906

Journal of the American Chemical Society
Article
(ArCH), 129.2 (ArC), 128.4 (ArCH), 128.2 (ArC), 127.9 (ArCH),
127.7 (ArCH), 127.5 (ArCH), 127.5 (ArCH), 127.4 (ArCH), 127.2
(ArCH), 121.9 (ArCH), 112.8 (ArCH), 70.8 (CH2), 70.4 (CH2), 68.2
(CH2), 65.84 (CH2), 65.77 (CH2), 52.5 (CH2), 52.4 (CH2), 50.6
(CH2), 50.4 (CH2), 18.7 (two overlapping CH3 signals), 10.9 (two
overlapping CH signals) (one ArC signal, one ArCH signal obscured
or overlapping). IR (KBr, cm−1) 3421, 3150, 2944, 2866, 1721, 1505,
1459, 1267, 1129, 882. MS (FAB+) m/z = 1886 [M − 2PF6 − H]+.
Anal. Calcd for C116H162F12N2O12P2Si4: C, 63.95; H, 7.49; N, 1.29.
Found: C, 63.85; H, 7.30; N, 1.30.
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ASSOCIATED CONTENT
* Supporting Information
■
(7) (a) Zazza, C.; Mancini, G.; Brancato, G.; Sanna, N.; Barone, V.
Comput. Theor. Chem. 2012, 985, 53−61. (b) Zhang, K.-D.; Zhao, X.;
Wang, G.-T.; Liu, Y.; Zhang, Y.; Lu, H.-J.; Jiang, X.-K.; Li, Z.-T.
Tetrahedron 2012, 68, 4517−4527. (c) Kim, H.; Goddard, W. A., III;
Jang, S. S.; Dichtel, W. R.; Heath, J. R.; Stoddart, J. F. J. Phys. Chem. A
2009, 113, 2136−2143. (d) Phoa, K.; Neaton, J. B.; Subramanian, V.
Nano Lett. 2009, 9, 3225−3229. (e) Jang, S. S.; Jang, Y. H.; Kim, Y. H.;
Goddard, W. A.; Choi, J. W.; Heath, J. R.; Laursen, B. W.; Flood, A.
H.; Stoddart, J. F.; Norgaard, K.; Bjornholm, T. J. Am. Chem. Soc.
2005, 127, 14804−14816.
S
Synthesis of axle precursors 2a−2d, characterization, spectral
data of all new compounds, additional experimental results.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
hirose@chem.es.osaka-u.ac.jp
■
(8) Estimated for 11 and 14 by molecular mechanics using the
OPLS2005 force field by MacroModel.
Notes
(9) (a) Hirose, K. J. Incl. Phenom. Macrocycl. Chem. 2010, 68, 1−24.
(b) Hirose, K.; Ishibashi, K.; Shiba, Y.; Doi, Y.; Tobe, Y. Chem.Eur.
J. 2008, 14, 5803−5811. (c) Hirose, K.; Shiba, Y.; Ishibashi, K.; Doi,
Y.; Tobe, Y. Chem.Eur. J. 2008, 14, 3427−3433. (d) Hirose, K.;
Shiba, Y.; Ishibashi, K.; Doi, Y.; Tobe, Y. Chem.Eur. J. 2008, 14,
981−986. (e) Hirose, K.; Ishibashi, K.; Shiba, Y.; Doi, Y.; Tobe, Y.
Chem. Lett. 2007, 36, 810−811.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research, Platform for Drug Discovery, Informatics, Structural
Life Science from the Ministry of Education, Culture, Sports,
Science, Technology, Japan (21350076, 24651139). P.G.Y.
gratefully acknowledges the JSPS for his fellowship (P11737).
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2012, 3, 3265−3271. (b) Zhu, K.; Vukotic, V. N.; Loeb, S. J. Angew.
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