Incorporation of 2,5-dihydroxyterephthalate as a covalent scaffold in the axis of a 30-membered all-carbon macrocycle provides access to a modular series of rotaxanes. Installment of tethered alkynes or azides onto the terephthalic phenolic hydroxyl functionalities, which are situated at opposite sides of the macrocycle, gives versatile prerotaxane building blocks. The corresponding [2]rotaxanes are obtained by introduction of bulky stoppering ("capping") units at the tethers and subsequent cleavage of the covalent ring/thread ester linkages. Extension of this strategy via coupling of two prerotaxanes bearing complementary linker functionalities (i.e., azide and alkyne) and follow-up attachment of stopper groups provide efficient access to [n]rotaxanes. The applicability and modular nature of this novel approach were demonstrated by the synthesis of a series of [2]-, [3]-, and [4]rotaxanes. Furthermore, it is shown that the prerotaxanes allow late-stage functionalization of the ring fragment introducing further structural diversity.
Incorporation of 2,5-dihydroxyterephthalate as a covalent scaffold in the axis of a 30-membered all-carbon macrocycle provides access to a modular series of rotaxanes. Installment of tethered alkynes or azides onto the terephthalic phenolic hydroxyl functionalities, which are situated at opposite sides of the macrocycle, gives versatile prerotaxane building blocks. The corresponding [2]rotaxanes are obtained by introduction of bulky stoppering ("capping") units at the tethers and subsequent cleavage of the covalent ring/thread ester linkages. Extension of this strategy via coupling of two prerotaxanes bearing complementary linker functionalities (i.e., azide and alkyne) and follow-up attachment of stopper groups provide efficient access to [n]rotaxanes. The applicability and modular nature of this novel approach were demonstrated by the synthesis of a series of [2]-, [3]-, and [4]rotaxanes. Furthermore, it is shown that the prerotaxanes allow late-stage functionalization of the ring fragment introducing further structural diversity.
Mechanically interlocked
molecules (MiMs) such as rotaxanes or
catenanes attract attention because of their fascinating structural
features and aesthetic architecture[1,2] as well as
their application as molecular switches or as components of molecular
machines.[3] Over the last three decades,
several robust methodologies for the synthesis of MiMs have been developed.[4] In the case of rotaxanes, the vast majority of
these approaches relies on noncovalent preorganization of the ring
and thread fragments. The key mechanical bond is made by (i) slipping
of the macrocycle over the thread fragment followed by introduction
of stoppering groups at the thread end or (ii) clipping of the ring
precursor over the thread and subsequent macrocyclization. By using
covalent approaches, the synthesis of so-called “impossible”
rotaxanes, which lack the supramolecular elements required to preorganize
the ring and thread fragments, has also been established. Ironically,
in the first two decades after the first synthesis of a [2]catenane
by Schill et al.[5] back in 1964 and a [2]rotaxane
by Harrison et al.[6] in 1967, the field
was solely based on covalent and statistical approaches. Over the
last years, covalent approaches reappeared on the scene, widening
the structural diversity of MiMs.[7−13] In a recent letter, we described the covalent synthesis of a [2]rotaxane
using a terephthalic acid-centered thread on which the ring-precursor
fragments were esterified followed by clipping-type macrocyclization
around the end-stoppered thread to give a prerotaxane (Scheme ).[14] Saponification of the terephthalic esters liberated the [2]rotaxane
featuring an all-carbon ring fragment that would be inaccessible using
the common supramolecular approaches.
Scheme 1
Outline of the Work
Described in the Previous Letter and in This
Work
We have now shortened our previous
clipping-type covalent route
to obtain similar “impossible” MiMs, starting from the
common prerotaxane synthons 1, 4, and 6, differing in the substitution pattern at the ring phenyl para-positions (Scheme ). This capping-type methodology provides facile access
to a series of homo- and hetero[n]rotaxanes
featuring a combination of different rings, thread fragments, and
stoppers. Both homo- and hetero[n]rotaxanes have
been made before using supramolecular methodology.[15] Especially, hetero[n]rotaxanes pose a
challenge that has been solved by using several orthogonal host–guest
systems[16,17] or with an iterative active-metal template
approach.[18] In these approaches, the former
methodology is limited by the number of available orthogonal noncovalent
recognition elements and the latter by the necessity of stoppering
units in between the rings to avoid dethreading during building of
the [n]rotaxane sequence. Our capping-type synthesis
from covalently linked prerotaxane building blocks overcomes these
drawbacks. In addition, we have deliberately chosen 4-bromo phenyl
groups in the ring fragment of prerotaxane 4 to demonstrate
the possibility for late-stage installation of functional stations
via versatile cross-coupling chemistry for future application as molecular
switches or motors.As outlined in Figure , the phenolic hydroxyl groups at the terephthalicester template
are located at opposite sides of the macrocycle and thus ideally placed
for introduction of thread fragments. Installation of tethered alkynes
or azides at 1, 4, and 6 gives
prerotaxanes 2, 3, 5, and 7 from which, in combination with the three stoppers a,[14]A, and B and a linking fragment L,[19] a diverse series of nine homo-, and hetero[2]-, [3]-, and
[4]rotaxanes were obtained. Connection of the different fragments
is carried out via a Lego-like building approach relying on the Cu(I)-catalyzed
azide-alkyne cycloaddition (CuAAC) reaction without the need for protecting
groups.
Figure 1
Ring, thread, and stopper building blocks for modular [n]rotaxane synthesis.
Ring, thread, and stopper building blocks for modular [n]rotaxane synthesis.
Results and Discussion
The synthesis of the ring fragment of prerotaxanes 1 and 4 commences with a Grignard reaction of hex-5-en-1-ylmagnesium
bromide and 5-(tert-butyl)-2-hydroxyisophthalaldehyde 8a or 5-bromo-2-hydroxyisophthalaldehyde 8b.
The latter two were conveniently made by a double Duff reaction from
4-(tert-butyl)phenol or 4-bromophenol.[20] The Grignard reaction was followed by Et3SiH-mediated reductive removal of the resulting benzylic hydroxyl
groups to give macrocycle precursors 9a or 9b in 84 and 56% overall yields, respectively (Scheme ).
Scheme 2
Synthesis of the Prerotaxanes
The central terephthalic templates, which are
also part of the
thread fragment, were prepared by double allylation or methylation
of dimethyl 2,5-dihydroxyterephthalate (10) followed
by saponification to give the diacids. These were subsequently converted
into the bis-acid chlorides and further transformed into the shelf-stable
and crystalline bispentafluorophenyl esters 11 and 12 in 33% and 45% yields over the four steps, respectively.
Transesterification of pentafluorophenol ester 11 with
phenol 9a by stirring in acetonitrile in the presence
of Cs2CO3 as the base went smoothly with a follow-up
Pd(0)-catalyzed removal of the allyl protective groups leading to
the macrocyclic ring precursor 13a in a 72% isolated
yield. It should be noted here that all attempts to couple the sterically
hindered phenol 9a directly to either the diacid chloride
derivative of phthalic acid of 11 or through the use
of carboxylic-acid activating reagents gave significantly lower yields.
Similarly, activated ester 12 and phenol 9b gave ring-closing metathesis (RCM) precursor 13b in
an 86% isolated yield. A double RCM macrocycloolefination of 13a and 13b, using the second-generation Grubbs
catalyst, gave the macrocyles as a mixture of E/Z isomers.[21] Subsequent catalytic
hydrogenation led to the key prerotaxanes 1 and 14 in yields of 93 and 50%, respectively, over the two steps.These results demonstrate the optimal preorganization of the terminal
olefins for the anticipated macrocyclization reaction by the phthalate
template. Both the 1H and 13C NMR spectra of
prerotaxanes 1 and 14 showed sharp signals,
pointing to a rigid and symmetric conformation. Although we were able
to grow single crystals of prerotaxane 1, their quality
proved to be insufficient for full refinement by X-ray crystallographic
analysis. However, the obtained connectivity plot unequivocally demonstrates
that the phthalate template prevents collapsing of the macrocycle
but also effectively positions the two phenolic hydroxyl groups at
opposite sides of the macrocycle (see Figure a). This is a prerequisite for arriving at
a mechanically interlocked structure through further capping-type
installation of additional functional thread elements and stoppers.
Figure 2
Connectivity
plots as determined by X-ray crystallography of prerotaxanes
(a) 1 and (b) 7. The macrocycle respective para t-butyl or phenyl substituents in 1 or 7 have been omitted for clarity.
Connectivity
plots as determined by X-ray crystallography of prerotaxanes
(a) 1 and (b) 7. The macrocycle respective para t-butyl or phenyl substituents in 1 or 7 have been omitted for clarity.As proof to show the feasibility of this approach for the future
synthesis of functional rotaxanes, the bromides in prerotaxane 14 were substituted by phenyl groups using the Pd-mediated
Suzuki-Miyaura coupling reaction giving 15 in a 96% yield.
BBr3-mediated cleavage of the aryl methyl ethers in 14 and 15 went smoothly and gave bisphenols 4 and 6 in yields of 99 and 97%, respectively.
It is noteworthy that, in comparison to prerotaxane 1 carrying two tBu groups, prerotaxanes 4 and 6 show considerably lower solubility in the common
solvents.To allow for installation of stopper units via the
CuAAC reaction,
prerotaxanes 1, 4, and 6 were
functionalized with tethered alkynes or azides. Introduction of alkynes
was conducted by Williamson-type alkylation of the phenolic hydroxyl
groups in 1 using pent-4-yn-1-yl methanesulfonate as
the electrophile and K2CO3 as the base (Scheme ). Most probably
due to steric hindrance encountered at the axis within the macrocycle
wheel, elevated temperature was required to obtain prerotaxane 2. Complementary azide groups were installed into prerotaxanes 1, 4, and 6 using the same protocols,
starting from 3-azidopropyl methanesulfonate as the electrophile,
to give 3, 5, and 7 in yields
of 92, 100, and 71%, respectively.
Scheme 3
Attachment of the Tethered Alkyne
and Azide Thread Components To
Give the Four Prerotaxane Building Blocks
Gratifyingly, single crystals of prerotaxane 7 featuring
the propyl tethered azides could be obtained. Similarly as encountered
for prerotaxane 1, full refinement of the X-ray crystallographic
data of 7 was not possible due to weak diffraction. However,
the connectivity plot resembled the conformation of the phthalic ester
within the macrocyle of prerotaxane 1, thus positioning
the tethered azides at opposite sides of the ring (see Figure b).Functionalization
of the terephthalic template with the tethered
azides and alkynes affected the 1H NMR spectra of compounds 2 and 3, now showing broad signals as a result
of different interconverting conformations of the ring and positioning
of the template within the macrocycle. To clarify these spectral features, 1H NMR spectra were recorded at elevated temperatures in deuterated
toluene (see the Supporting Information). At higher temperatures, the increased conformational freedom results
in coalescence of the different peaks of the template thread protons
and a less complex spectrum. In prerotaxane 2, the hydrogens
on the terminal alkynes appeared as a beacon in the complex room-temperature 1H NMR spectra. The corresponding isolated terminal alkyne-CH
singlet around 1.95 ppm proved to be useful for identification of
the mono- and di-stoppered prerotaxanes resulting from CuAAC reactions
(vide infra).As a last task, the stoppers had to be prepared.
Besides bulky
stopper a, which has been previously described by us,[14] new stoppers A and B were successfully prepared via a short route from the known common
terphenylaldehyde 16(22) (Scheme ). After subsequent
NaBH4 reduction, an Appel reaction, and nucleophilic substitution,
azide-functionalized stopper A was obtained in a 93%
overall yield. Using the reliable two-step Corey–Fuchs protocol,
the same aldehyde 16 was transformed into the terminal
alkyne-functionalized stopper B in a 83% yield (over
the two steps).
Scheme 4
Synthesis of the Azide and Alkyne Stoppers A and B
With the four prerotaxanes 2, 3, 5, and 7, the
three stoppers a, A, and B,
and the reported 1,4-bis(azidomethyl)benzene L as a linking
connector in hand, we were ready for the Lego-type
construction of a series of nine [n]rotaxanes. The
synthesis of hetero[n]rotaxanes employing different
stoppers or rings required the availability of the respective mono-stoppered
prerotaxanes (Scheme ). After optimization, it was found that the reaction of 0.4 equiv
of the stopper with respect to the prerotaxane prevented the formation
of the bis-stoppered prerotaxanes, selectively providing the mono-stoppered
prerotaxanes a2 and A2.
Scheme 5
Synthesis of the
Half-Stoppered Prerotaxanes
Reaction conditions:
prerotaxane 2, 3, 5, or 7 (1 equiv),
stopper A or B (0.4 equiv), TBTA (0.2 equiv),
Cu(CH3CN)4BF4 (0.2 equiv), CH2Cl2, rt, overnight.
Synthesis of the
Half-Stoppered Prerotaxanes
Reaction conditions:
prerotaxane 2, 3, 5, or 7 (1 equiv),
stopper A or B (0.4 equiv), TBTA (0.2 equiv),
Cu(CH3CN)4BF4 (0.2 equiv), CH2Cl2, rt, overnight.The
CuAAC reaction of bis-alkyne functionalized prerotaxane 2 with 0.4 equiv of stopper a or A gave
the mono-stoppered prerotaxanes a2 and A2 in 88 and 66% yields based on the recovered starting material (brsm).
The azide-functionalized mono-stoppered prerotaxane B3 was obtained after the CuAAC reaction of the bis-azide-threaded
prerotaxane 3 with 0.4 equiv of stopper B in a 52% yield (brsm). To allow the synthesis of a hetero[n]rotaxane featuring different ring substitutions, the mono-stoppered
prerotaxanes B5 and B7 were made in a similar
way. By reaction of prerotaxane 5 and 7 with
0.4 equiv of stopper B, mono-stoppered prerotaxanes B5 and B7 were obtained in 84 and 63% yields
(brsm) in their pure form.First, the capping-type synthesis
of [2]rotaxanes was undertaken
(Scheme ). CuAAC-type
coupling of alkyne-tether functionalized prerotaxane 2 with 2.2 equiv of azide stoppers a or A gave the homo[2]prerotaxanes of a2a or A2A in yields of 56 and 51%, respectively. Saponification of the temporal
linking terephthalate ester linkages liberated the [2]rotaxanesa2a or A2A in 77 and 88% yields, respectively.
Although accurate mass determination unequivocally confirms the integrity
of the [2]rotaxane architecture of a2a, for comparison
reasons, we have also made the separate ring and thread fragments
(see the Supporting Information). Simple
TLC analysis of the ring and thread fragments and the [2]rotaxane
clearly established their different physical properties. While the
apolar macrocycle runs high on TLC using EtOAc/hexanes as the eluent,
the thread component shows the lowest polarity due to the presence
of the two carboxylic acid and triazole moieties. Comparison of the 1H NMR spectra of [2]rotaxane a2a, the loose thread,
and the corresponding ring fragment as well as an equimolar mixture
of the latter two compounds shows subtle but significant differences
(see the Supporting Information). In [2]rotaxane a2a, almost all protons in the thread fragment, including
the triazole CH, show a slight upfield shift. This is also the case
for the aliphatic protons on the ring fragment. Remarkably, the singlet
of the two protons at the phthalate phenyl ring did not shift although
they are located in the center of the ring of the rotaxane skeleton.
These results show that the terephthalate template not only allows
for the clipping approach that was previously published by us but
also enables a more convergent capping strategy to arrive at mechanically
interlocked structures. Similarly, from prerotaxane a2, hetero[2]rotaxane a2A was readily obtained in a 54%
overall yield, now after CuAAc-coupling with stopper A followed by saponification. After having confirmed the feasibility
of this new synthetic pathway, homo[2]rotaxane B3B was
made by coupling prerotaxane 3 and stopper B via the same two-step sequence. To facilitate chromatographic purification,
the crude carboxylic acids were converted into their methyl esters
by heating in methanol using HCl as the catalyst to give B3B as the diester in an overall yield of 36% over the three steps.
Scheme 6
Synthesis of Homo- and Hetero[2]rotaxanes
Reaction conditions: (i) prerotaxane 2 or 3, stopper a, A or B (2.2 equiv),
TBTA (0.2 equiv), Cu(CH3CN)4BF4 (0.2
equiv), rt, 5-14 h. (ii) prerotaxane a2, stopper A (1.2 equiv), TBTA (0.2 equiv),
Cu(CH3CN)4BF4 (0.2 equiv), rt, overnight.
(iii) Tesser’s base (1,4-dioxane/MeOH/2M NaOH, 3:1:0.1), 50
°C, overnight. (iv) MeOH, HCl, 40 °C, 5 h.
Synthesis of Homo- and Hetero[2]rotaxanes
Reaction conditions: (i) prerotaxane 2 or 3, stopper a, A or B (2.2 equiv),
TBTA (0.2 equiv), Cu(CH3CN)4BF4 (0.2
equiv), rt, 5-14 h. (ii) prerotaxane a2, stopper A (1.2 equiv), TBTA (0.2 equiv),
Cu(CH3CN)4BF4 (0.2 equiv), rt, overnight.
(iii) Tesser’s base (1,4-dioxane/MeOH/2M NaOH, 3:1:0.1), 50
°C, overnight. (iv) MeOH, HCl, 40 °C, 5 h.Next, the covalent approach to MiMs was expanded to the
[3]rotaxane
series (Scheme ).
A [3]rotaxane could be made by directly connecting two half-stoppered
[2]rotaxanes. Coupling/saponification/esterification of the half-stoppered
[2]prerotaxanes A2 and B3 went uneventfully
and gave homo[3]rotaxane A23B (28% yield over 3 steps).
Alternatively, connecting two half-stoppered alkyne-functionalized
prerotaxanes a2 via diazide-functionalized linker L followed by saponification gave homo[3]rotaxane a2L2a in a 66% overall yield. By coupling of prerotaxane a2 with the two different prerotaxanes B5 or B7 followed by saponification and esterification, the two hetero[3]rotaxanesa25B and a27B were obtained as the tetramethylesters
in overall yields of 31 and 56%.
Reaction conditions: (i) prerotaxane A2 (1 equiv), prerotaxane B3 (2 equiv), TBTA
(0.68 equiv), Cu(CH3CN)4BF4 (0.2
equiv), rt, overnight. (ii) Tesser’s base (1,4-dioxane/MeOH/2M
NaOH, 3:1:0.1), 50 °C, overnight. (iii) MeOH, HCl, 40 °C,
5 h. (iv) prerotaxane a2 (2.2 equiv), linker L (1 equiv), TBTA (0.68 equiv), Cu(CH3CN)4BF4 (0.2 equiv), rt, overnight. (v) prerotaxane a2 (1 equiv), prerotaxane B5 or B7 (1–1.1
equiv), TBTA (0.2 equiv), Cu(CH3CN)4BF4 (0.2 equiv), rt, overnight.To show the
applicability of our covalent approach toward the synthesis
of functional hetero[n]rotaxanes via late-stage decoration,
prerotaxane a25B was transformed to prerotaxane a27B by the robust Suzuki-Miyaura reaction (Scheme ). Reaction of a25B with phenyl boronic acid under classical Suzuki conditions in a
sealed vessel at 120 °C for three days followed by purification
gave prerotaxane a27B in an isolated yield of 43%.
Scheme 8
Late-Stage Ring Decoration via the Suzuki-Miyaura Reaction
As a final effort, homo[4]rotaxane a232a was conveniently
prepared in a 62% overall yield just by clicking the alkyne-functionalized
half-stoppered [2]rotaxanes a2 and the bisazide-equipped
[2]prerotaxane 3 together followed by saponification
(Scheme ).
Scheme 9
Synthesis
of a [4]Rotaxane.
Conclusions
With
nine homo- and hetero[n]rotaxanes in hand,
we have shown that, although covalent routes per definition require
more synthetic steps than a supramolecular route (i.e., making and
breaking the covalent connection between the ring/thread fragments),
this approach may be a viable and complementary alternative, particularly
to arrive at hetero[n]rotaxanes with different stoppers,
rings, and thread components. Both the covalent and supramolecular
approaches require specific functional groups for preorganization
of the ring/thread fragments, making them complementary. We have presented
here a modular approach to hetero[n]rotaxanes that
is amenable for further installation of functional stations in both
the thread and ring fragments. These stations may also be introduced
at a late stage of the synthesis as was shown by installation of two
phenyl groups at the rim of the ring fragment by a Suzuki-Miyaura
coupling reaction. The synthesis of functional MiMs using this methodology
is currently undertaken by us.
Experimental Section
General
Methods and Materials
Reactions were carried
out under air and without additional measures such as drying unless
stated otherwise. Heating and stirring was performed using an oil
bath and standard thermostatized stirring plates and teflon stirring
beans. Thin-layer chromatography (TLC) was performed on Merck TLC
plates (0.25 mm) precoated with silica gel 60 F254. Flask column chromatography
was performed using SilaFlash P60 (40–63 μm) under a
compressed air flow. Starting materials and reagents were used as
supplied by commercial vendors. Anhydrous CH2Cl2 and CH3CN were freshly distilled from CaH2. Dried THF was obtained through distillation with sodium, and dried
solvents were stored under a N2 atmosphere. Bruker DRX-300,
400, and 500 MHz instruments were used to record NMR spectra. Chemical
shifts (δ) are reported in ppm relative to residual undeuterated
solvent peaks. Data of the recorded 1H NMR spectra are
described as follows: chemical shift (multiplicity, coupling constant
when applicable, number of H). The following abbreviations are used
to report the multiplicities: s (singlet), d (doublet), t (triplet),
q (quartet), quint (quintet), dd (doublet of doublet), m (multiplet),
br m (broad multiplet). All reflection intensities were measured with
a Bruker D8 Quest Eco diffractometer equipped with a Triumph monochromator
(λ = 0.71073 Å) and a CMOS Photon 50 detector at 150(2)
K. Intensity data were integrated with the Bruker APEX2. High-resolution
mass spectra (HRMS) were recorded on an AccuTOF GC v 4g, JMS-T100GCV
mass spectrometer (JEOL, Japan) and HR-ToF Bruker Daltonik GmbH (Bremen,
Germany) Impact II, an ESI-ToF MS capable of resolution of at least
40,000 FWHM. The FD/FI probe was equipped with an FD Emitter, Carbotec,
FD = 10 μm. Current rate = 51.2 mA/min over 1.2 min using field
desorption (FD) as an ionization method.
4-(tert-Butyl)-2,6-di(hept-6-en-1-yl)phenol
(9a)
This compound has been made previously
by us but the procedure has been optimized.[14] Magnesium turnings (1.51 g, 62.1 mmol, 4.5 equiv) were suspended
in dry THF (60 mL) in an oven-dried flask. 6-Bromo-1-hexene (8.3 mL,
61.9 mmol, 4.5 equiv) was added dropwise to the stirred solution and
heated under reflux for 3 h. The mixture was then cooled to room temperature
and added dropwise to a solution of 8a(20) (2.84 g, 13.7 mmol, 1.0 equiv) in dry THF (60 mL) at 0
°C under a N2 atmosphere. The reaction mixture was
stirred and heated under reflux overnight and subsequently quenched
with H2O (5 mL). The mixture was diluted with Et2O (100 mL) and 1 M HCl (100 mL), and after which, the aqueous layer
was extracted with 2× 20 mL of Et2O. The combined
organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo to give a yellow oil. The residue
(2.22 g, 5.93 mmol, 1 equiv) was dissolved in dry CH2Cl2 (50 mL) under a N2 atmosphere and cooled to −78
°C, and Et3SiH (3.78 mL, 23.7 mmol, 4.0 equiv) was
added. BF3·Et2O (2.93 mL, 23.7 mmol, 4.0
equiv) was added slowly over the course of 1 h to the stirred reaction
mixture, and after which, the dry-ice bath was removed. After the
solution had returned to room temperature, it was quenched with water
then the organic layer was separated, dried over Na2SO4, and concentrated in vacuo. The crude product was purified
by Kugelrohr distillation (180–190 °C, 0.04 mbar) to give 9a (1.71 g, 5.00 mmol, 84%). 1H NMR (400 MHz, CDCl3) δ 6.99 (s, 2H), 5.84 (quint, J =
17.0, 10.1, 6.7 Hz, 2H), 5.11–4.86 (m, 4H), 4.53 (s, 1H), 2.72–2.46
(m, 4H), 2.08 (q, J = 7.1, 6.6 Hz, 4H), 1.68–1.61
(m, 4H), 1.52–1.34 (m, 8H), 1.31 (s, 9H). For further spectral
data, see ref (14).
4-(Bromo)-2,6-di(hept-6-en-1-yl)phenol (9b)
A solution of 6-bromo-1-hexene (9.97 g, 61 mmol, 3.5 equiv) in dry
THF (20 mL) was added dropwise to magnesium turnings (1.70 g, 70 mmol,
4 equiv) at a rate to maintain reflux. Then, more dry THF (15 mL)
was added, and the reaction was heated to reflux for 2.5 h. The mixture
was then cooled to room temperature and added dropwise to a solution
of 8b(22) (4.00 g, 17.5 mmol,
1 equiv) in dry THF (50 mL) at 0 °C under a N2 atmosphere.
The reaction mixture was stirred for 1 h then warmed to room temperature
and stirred for an additional 3.5 h. The reaction mixture was subsequently
quenched with H2O (5 mL) and diluted with Et2O (50 mL) and 1 M HCl (50 mL), and after which, the aqueous layer
was extracted with 2× 50 mL of Et2O. The combined
organic phases were washed with brine, dried over MgSO4, and concentrated in vacuo. The mixture was purified by column chromatography
(PE/EtOAc 19:1 → 9:1 → 8:2) to give the diol as a yellow
oil (5.87 g, 14.7 mmol, 84%). This diol (4.21 g, 10.6 mmol, 1 equiv)
was dissolved in dry CH2Cl2 (100 mL) under a
N2 atmosphere and cooled to 0 °C, and Et3SiH (51 mL, 317 mmol, 30 equiv) was added. BF3·Et2O (3.9 mL, 31.8 mmol, 3 equiv) was added dropwise, and after
which, the reaction mixture was stirred for 5 h at 0 °C. The
reaction mixture was then quenched by dropwise addition of H2O (20 mL) and warmed to room temperature. Additional H2O (80 mL) was then added, and the mixture was extracted with 3×
50 mL of CH2Cl2. The reunited organic phases
were washed with brine, dried over MgSO4, and concentrated
in vacuo. The residue was dissolved in THF (40 mL), and MeOH (40 mL)
was added followed by NH4F (3.53 g, 95.4 mmol, 9 equiv),
and the mixture was stirred for 45 min. The mixture was then concentrated
and subsequently diluted in EtOAc (100 mL) and H2O (100
mL). The aqueous layer was extracted with 2× 50 mL of EtOAc,
and the reunited organic phases were washed with brine, dried over
MgSO4, and concentrated in vacuo. Column chromatography
(PE/Et2O 80:1 → 40:1) afforded 9b (2.60
g, 7.10 mmol, 67%). 1H NMR (300 MHz, CDCl3)
δ 7.10 (s, 2H), 5.83 (m, 2H), 5.02 (dd, 2H), 4.97 (d, 2H), 4.60
(s, 1H), 2.56 (t, 4H), 2.08 (td, 4H), 1.62 (m, 4H), 1.52–1.34
(m, 8H). 13C {1H} NMR (75 MHz, CDCl3) δ 150.5, 138.9, 130.2, 130.0, 114.4, 112.4, 33.6, 29.9, 29.3,
28.9, 28.7. IR (cm–1): 3582, 3075, 2975, 2926, 2855,
1640, 1459, 1184, 993, 910, 864. HRMS (FD+) m/z calcd for C20H29Br1O1 (M·+) 364.1396, found
364.1396.
Dimethyl 2,5-dihydroxyterephthalate (10)[14] (10.04 g, 44.4 mmol, 1 equiv), allyl bromide
(13.4 g, 111.0 mmol, 2.5 equiv), and K2CO3 (15.3
g, 111.0 mmol, 2.5 equiv) were dissolved in 90 mL of DMF, and the
solution was stirred at 100 °C overnight. Then, the solution
was diluted with 300 mL of EtOAc and 300 mL of water. The aqueous
layer was washed with 2× 200 mL of EtOAc, and the organic layers
were combined and evaporated in vacuo. The crude product was precipitated
with 25 mL of EtOAc and 40 mL of PE to yield dimethyl 2,5-bis(allyloxy)terephthalate
as a white solid (8.14 g, 26.58 mmol, 61%). 1H NMR (300
MHz, CDCl3) δ 7.42 (s, 2H), 6.07 (ddt, J = 17.2, 10.2, 4.9 Hz, 2H), 5.64–5.39 (m, 2H), 5.38–5.27
(m, 2H), 4.69–4.57 (m, 4H), 3.93 (s, 6H). 13C {1H} NMR (75 MHz, CDCl3) δ 166.1, 151.7, 132.8,
124.8, 117.7, 117.5, 70.6, 52.5.For saponification of the methylesters, dimethyl 2,5-bis(allyloxy)terephthalate (8.14 g, 26.6 mmol,
1 equiv) and KOH (5.96 g, 106 mmol, 4 equiv) were dissolved in 130
mL of THF:MeOH:H2O (2:1:1), and the solution was stirred
overnight at room temperature. Subsequently, the solution was acidified
with 15 mL of HCl (37%) then concentrated in vacuo and then diluted
again with 200 mL of water and was extracted with 2× 200 mL of
EtOAc. The organic layer was washed with brine, dried with MgSO4, filtered, and evaporated in vacuo to give 2,5-bisallyloxyterephthalic
acid as a white solid (5.25 g, 18.9 mmol, 71%). 1H NMR
(300 MHz, CD3OD) δ 7.49 (s, 2H), 6.09 (ddt, J = 17.2, 10.3, 5.0 Hz, 2H), 5.61–5.40 (m, 2H), 5.39–5.16
(m, 2H), 4.74–4.61 (m, 4H). 13C {1H}
NMR (75 MHz, CD3OD) δ 168.6, 152.6, 134.2, 126.4,
118.2, 118.0, 71.6.The synthesis of the bis acid chloride and
subsequent transformation
into the bis pentafluorophenol ester was conducted by dissolving 2,5-bisallyloxyterephthalic
acid (5.25 g, 18.9 mmol, 1 equiv) in 100 mL of dry THF and oxalyl
chloride (6.5 mL), and subsequently, a droplet of DMF was added to
the solution. The solution was stirred at room temperature overnight.
The solution was then concentrated in vacuo, and after which, it was
dissolved again in 20 mL of dry THF. The resulting solution was added
dropwise to a solution of pentafluorophenol (7.94 g, 56.7 mmol, 3
equiv) and DIPEA (7.90 mL, 45.4 mmol, 2.4 equiv) in 90 mL of dry THF.
The solution was stirred at 0 °C for 1 h and at room temperature
for 3 h. Subsequently, the solution was concentrated in vacuo and
then dissolved in EtOAc and extracted with HCl (1 M), water, saturated
NHCO3 solution, and then brine. The organic layer was washed
with MgSO4, filtered, and evaporated in vacuo to yield
terephthalic ester template 11 as a white solid (8.71
g, 14.3 mmol, 76%). 1H NMR (300 MHz, CDCl3)
δ 7.69 (s, 2H), 6.08 (ddt, J = 17.2, 10.3,
5.0 Hz, 2H), 5.62–5.45 (m, 2H), 5.41–5.27 (m, 2H), 4.82–4.65
(m, 4H). 13C {1H} NMR (75 MHz, CDCl3) δ 160.8, 152.7, 132.1, 122.6, 118.4, 118.0, 70.8.
Dimethyl
2,5-dihydroxyterephthalate (10)
(5.40 g, 23.9 mmol, 1 equiv) and K2CO3 (9.91
g, 71.7 mmol, 3 equiv) were dissolved in DMF (24 mL), and MeI (6.0
mL, 95.6 mmol, 4 equiv) was added dropwise. The solution was then
stirred overnight at room temperature and subsequently diluted with
saturated NH4Cl in H2O (40 mL) and extracted
with 4× 25 mL of CH2Cl2. The reunited organic
phases were then washed with 3× 75 mL of H2O and brine,
dried over MgSO4, and concentrated in vacuo to give dimethyl
2,5-dimethoxyterephthalate (5.91 g, 23.3 mmol, 97%), which was used
without further purification. 1H NMR (400 MHz, CDCl3) δ 7.42 (s, 2H), 3.95 (s, 6H), 3.92 (s, 6H). No additional
spectral data were acquired (known compound).[14]Dimethyl 2,5-dimethoxyterephthalate (5.91 g, 23.3 mmol, 1
equiv) and KOH (5.22 g, 93 mmol, 4 equiv) were dissolved in 180 mL
of THF:MeOH:H2O (4:3:2), and the solution was stirred overnight
at room temperature. Subsequently, the solution was acidified to pH
1 with HCl (37%), diluted with 250 mL of ice-cold H2O,
and filtered, and the filtrate was extracted with 3× 150 mL of
EtOAc. The reunited organic phases were washed with brine, dried over
MgSO4, and concentrated in vacuo, and the residue was triturated
with Et2O to give 2,5-dimethoxyterephthalic acid (3.54
g, 15.6 mmol, 67%). 1H NMR (400 MHz, CD3OD)
δ 7.53 (s, 2H), 3.92 (s, 6H). No additional spectral data were
acquired (known compound).[23]2,5-Dimethoxyterephthalic
acid (3.54 g, 15.6 mmol, 1 equiv) was
suspended in dry THF (200 mL), and DIPEA (11 mL, 62 mmol, 4 equiv),
pentafluorophenol (7.18 g, 39.0 mmol, 2.5 equiv), and HBTU (17.8 g,
46.9 mmol, 3 equiv) were added. The resulting mixture was stirred
at room temperature overnight then dry-loaded on SiO2 and
purified by column chromatography (Et2O → Et2O/EtOAc 5:1). Traces of pentafluorophenol were removed from
the final product by trituration with PE, giving terephthalic ester
template 12 as a yellow solid (6.00 g, 10.8 mmol, 69%). 1H NMR (300 MHz, CDCl3) δ 7.69 (s, 2H), 4.01
(s, 6H). 13C {1H} NMR (75 MHz, CDCl3) δ 160.6, 153.5, 122.0, 116.3, 56.9. IR (cm–1): 1761, 1729, 1516, 1505, 1468, 1445, 1386, 1328, 1308, 1238, 1201,
1183, 1153, 1090, 1029, 1009, 993, 886, 861, 792, 770, 712, 652, 628,
592, 576, 451. HRMS (FD+) m/z calcd for C22H8F10O6 (M·+) 558.0156, found 558.0145. mp: 169.6–170.8
°C.
Compound 9b (2.60 g, 7.10
mmol, 2 equiv), Cs2CO3 (4.63 g, 14.2 mmol, 4
equiv), bis(perfluorophenyl) 2,5-dimethoxyterephthalate 12 (1.98 g, 3.55 mmol, 1 equiv), and 4 Å molecular sieves (3.5
g) were suspended in dry CH3CN (70 mL), and the reaction
was stirred overnight at 50 °C under a N2 atmosphere.
The reaction mixture was then filtered over celite, concentrated in
vacuo, and purified by column chromatography (PE/EtOAc 25:1 →
20:1) to give the bisaryl ester 13b (2.81 g, 3.06 mmol,
86%) as a colorless oil, which slowly crystallized in the fridge. 1H NMR (300 MHz, CDCl3) δ 7.61 (s, 2H), 7.30
(s, 4H), 5.78 (m, 4H), 4.97 (dd, 4H), 4.92 (d, 4H), 3.97 (s, 6H),
2.55 (t, 8H), 2.04 (td, 8H), 1.63 (m, 8H), 1.48–1.27(m, 16H). 13C {1H} NMR (75 MHz, CDCl3) δ
163.8, 152.8, 146.5, 138.8, 137.1, 130.5, 123.7, 119.4, 115.6, 114.4,
56.7, 33.6, 30.3, 29.6, 29.0, 28.7. IR (cm–1): 3075,
2926, 2855, 1750, 1720, 1640, 1600, 1572, 1502, 1459, 1394, 1229,
1206, 1151, 1079, 1032, 908, 865. HRMS (FD+) m/z calcd for C50H6479Br81BrO6 (M·+) 920.3044,
found 920.3057.
Prerotaxane 1
Compound 13a (1.16 g, 1.37 mmol, 1.0 equiv) was dissolved in dry CH2Cl2 (270 mL), and the solution was degassed with
five
vacuum/N2 cycles. A Grubbs second-generation catalyst (116
mg, 0.137 mmol, 0.10 equiv) was then added, and the mixture was stirred
overnight at 40 °C under a N2 atmosphere. The 1H NMR spectrum of the crude reaction mixture revealed that
approximately 15% terminal alkene was still present. The solution
was again degassed with five vacuum/N2 cycles, 58 mg of
Grubbs II was added, and the reaction was stirred overnight at 40
°C under a N2 atmosphere. The mixture was concentrated
in vacuo and purified by column chromatography (PE/CH2Cl2 1:1). A colorless oil of 1.06 g was obtained, which was dissolved
in dry THF (50 mL), and Pd(C) (400 mg, 10 wt % Pd) was added. H2 was bubbled through the mixture for 5 min, and the reaction
was subsequently stirred overnight at 50 °C under a H2 atmosphere (balloon). The mixture was filtered and concentrated
in vacuo. The residue was triturated in MeOH to give 1 (1.01 g, 1.27 mmol, 93%) as a yellow crystalline solid. Slow evaporation
of a saturated solution in MeOH gave crystals that were suitable for
X-ray crystallographic analysis. 1H NMR (400 MHz, CDCl3) δ 10.14 (s, 2H), 7.87 (s, 2H), 7.17 (s, 4H), 2.56–2.42
(m, 8H), 1.69–1.64 (m, 4H), 1.35–1.28 (m, 32H), 1.15
(s, 14H), 1.02 (s, 8H). 13C {1H} NMR (100 MHz,
CDCl3) δ 168.0, 153.6, 149.6, 144.1, 134.2, 125.3,
118.3, 118.0, 34.4, 31.4, 30.4, 30.4, 29.6, 29.2, 28.9, 28.1. HRMS
(FD+) m/z calcd for C52H74O6 (M·+) 794.5480, found 794.5497.
Prerotaxane 14
Compound 13b (2.81 g, 3.06 mmol, 1 equiv) was dissolved in dry CH2Cl2 (1500 mL), and the solution was purged with
N2 for 1 h. A Grubbs second-generation catalyst (130 mg,
0.150
mmol, 5 mol %) was then added, and the mixture was purged with N2 for 15 min before being warmed to 40 °C and stirred
for two days. Then, more of the Grubbs second-generation catalyst
(65 mg, 0.075 mmol, 2.5 mol %) was added, and the resulting mixture
stirred overnight. The reaction mixture was concentrated, and the
residue was suspended in boiling EtOAc (10 mL), cooled, and then filtered,
affording the macrocyclic prerotaxane tetradehydro 14 (1.42 g, 1.64 mmol, 54%) as a gray powder. 1H NMR (300
MHz, CDCl3) δ 7.76 (s, 2H), 7.30 (s, 4H), 5.18 (m,
2H), 5.11 (m, 2H), 3.99 (s, 6H), 2.70–2.36 (m, 8H), 1.95–1.76
(m, 8H), 1.74–1.49 (m, 8H), 1.46–1.15 (m, 16H). 13C {1H} NMR (75 MHz, CDCl3) δ
163.3, 153.3, 153.1, 146.5, 137.6, 137.6, 131.0, 130.9, 129.9, 129.7,
123.1, 123.0, 119.4, 116.4, 116.2, 56.6, 32.5, 32.3, 30.1, 28.9, 28.7,
28.4, 28.3. IR (cm–1): 2926, 2853, 1750, 1720, 1572,
1502, 1459, 1395, 1304, 1231, 1207, 1156, 1081. HRMS (FD+) m/z calcd for C46H5679Br81BrO6 (M·+) 864.2424, found 864.2385.Prerotaxane tetradehydro 14 (1.42 g, 1.64 mmol, 1 equiv) was dissolved in dry THF (400
mL) under a N2 atmosphere, and PtO2 (56.0 mg,
0.247 mmol, 15 mol %) was added to the resulting solution. The reaction
mixture was purged with H2 for 30 min and stirred for three
days at room temperature under a H2 atmosphere (balloon).
Then, further PtO2 (37.3 mg, 0.165 mmol, 10 mol %) was
added, and the reaction was stirred overnight. The mixture was filtered
over celite and concentrated in vacuo. The residue was triturated
in a 1:1 EtOAc/PE mixture (6 mL) to give prerotaxane 14 (1.31 g, , 92%) as a white solid. mp: 256.6–258.8 °C. 1H NMR (300 MHz, CDCl3) δ 7.78 (s, 2H), 7.29
(s, 4H), 4.01 (s, 6H), 2.69–2.35 (m, 8H), 1.72–1.47
(m, 8H), 1.42–1.26 (m, 8H), 1.25–0.90 (m, 24H). 13C {1H} NMR (75 MHz, CDCl3) δ
163.2, 153.4, 153.2, 146.6, 137.7, 130.9, 123.3, 123.2, 119.4, 116.6,
116.4, 56.7, 30.0, 29.9, 29.8, 29.4, 29.4, 29.0, 28.9, 28.1. IR (cm–1): 2923, 2852, 1718, 1572, 1502, 1461, 1395, 1302,
1230, 1207, 1154, 1033, 732. HRMS (FD+) m/z calcd for C46H6079Br81BrO6 (M·+) 868.2731,
found 868.2771.
Prerotaxane 4
Compound 15 (434 mg, 0.500 mmol, 1 equiv) was dissolved in dry CH2Cl2 (125 mL) and subsequently cooled to 0 °C.
Then,
a 1 M BBr3 solution in CH2Cl2 (4.0
mL, 4.0 mmol, 8 equiv) was added dropwise. Once addition was complete,
the mixture was allowed to warm to room temperature and stirred overnight.
The mixture was then cooled in an ice/salt bath, and MeOH (25 mL)
was added dropwise followed by dilution in MeOH (100 mL) and concentration
in vacuo. The residue was reconcentrated from MeOH (125 mL) two more
times, giving prerotaxane 4 (416 mg, 0.495 mmol, 99%)
as a yellow powder. 1H NMR (300 MHz, CDCl3)
δ 9.95 (s, 2H), 7.86 (s, 2H), 7.32 (s, 4H), 2.56–2.35
(m, 8H), 1.72–1.46 (m, 8H), 1.41–1.21 (m, 8H), 1.20–0.82
(m, 24H). 13C {1H} NMR spectroscopy of the same
sample failed due to the insolubility in CDCl3 leading
to a too low concentration. IR (cm–1): 3282, 2920,
2850, 1691, 1572, 1497, 1457, 1358, 1324, 1184, 1149, 1082, 1067,
857, 829, 811, 786, 636, 422. HRMS (FD+) m/z calcd for C44H5679Br81BrO6 (M·+) 840.2418,
found 840.2480.
Prerotaxane 15
Aryl
bromide 14 (217 mg, 0.250 mmol, 1 equiv) and phenylboronic
acid (122 mg, 1.00
mmol, 4 equiv) were dissolved in THF (10 mL), and the resulting solution
was purged with N2 for 30 min. Then, a degassed 2 M solution
of Na2CO3 in H2O (1.9 mL, 3.75 mmol,
15 equiv) was added followed by Pd(PPh3)4 (28.9
mg, 0.025 mmol, 10 mol %), and the mixture was heated at reflux overnight
under a N2 atmosphere. The mixture was concentrated in
vacuo and diluted in CH2Cl2 (30 mL), the organic
layer was washed with brine, dried over MgSO4, and concentrated
in vacuo. The solid residue was triturated with EtOAc/PE (1:1) to
give compound prerotaxane 15 (207 mg, 0.239 mmol, 96%)
as a brown powder. mp: 285.9–288.2 °C (decomposition). 1H NMR (300 MHz, CDCl3) δ 7.85 (s, 2H), 7.63
(d, 4H), 7.47 (t, 4H), 7.41–7.33 (m, 6H), 4.05 (s, 6H), 2.80–2.49
(m, 8H), 1.79–1.56 (m, 8H), 1.46–0.94 (m, 32H). 13C {1H} NMR (75 MHz, CDCl3) δ
163.6, 153.4, 153.3, 147.0, 140.9, 139.4, 135.7, 128.7, 127.2, 127.1,
127.03, 127.0, 123.5, 116.6, 116.5, 56.8, 30.3, 30.0, 29.8, 29.7,
29.5, 29.4, 29.2, 29.1, 28.2. IR (cm–1): 2923, 2852,
1712, 1577, 1496, 1462, 1396, 1297, 1229, 1205, 1148, 1105, 1031,
905, 882, 804, 781, 761, 732, 696, 641. HRMS (FD+) m/z calcd for C58H70O6 (M·+) 862.5167, found 862.5156.
Prerotaxane 6
Compound 15 (207
mg, 0.239 mmol, 1 equiv) was dissolved in dry CH2Cl2 (40 mL) and subsequently cooled to 0 °C. Then,
a 1 M BBr3 solution in CH2Cl2 (1.9
mL, 1.9 mmol, 8 equiv) was added dropwise. Once addition was complete,
the mixture was allowed to warm to room temperature and stirred overnight.
The mixture was then cooled in an ice/salt bath, and MeOH (8 mL) was
added dropwise followed by dilution in MeOH (32 mL) and concentration
in vacuo. The residue was reconcentrated from MeOH (50 mL) two more
times, giving 6 (195 mg, 0.233 mmol, 97%) as a yellow
powder. 1H NMR (300 MHz, CDCl3) δ 10.10
(s, 2H), 7.93 (s, 2H), 7.62 (d, 4H), 7.47 (t, 4H), 7.42–7.35
(m, 6H), 2.70–2.46 (m, 8H), 1.80–1.52 (m, 8H), 1.44–1.32
(m, 8H), 1.18 (s, 16H), 1.04 (s, 8H). Due to low solubility, the 13C {1H} NMR spectrum was not obtained. IR (cm–1): 3261, 2921, 2851, 1687, 1497, 1460, 1360, 1324,
1219, 1183, 1146, 1080, 1028, 887, 874, 810, 786, 762, 723, 698, 642,
601, 583, 541, 597. HRMS (FD+) m/z calcd for C56H66O6 (M·+) 834.4854, found 834.4887.
Prerotaxane 2
Diol 1 (180
mg, 0.226 mmol, 1.0 equiv), K2CO3 (166 mg, 1.20
mmol, 5.3 equiv), and pent-4-yn-1-ylmethanesulfonate (0.133 g, 0.70
mmol, 2.6 equiv) were dissolved in dry DMF (2 mL), and the reaction
was stirred for 20 h at 90 °C. The mixture was cooled to room
temperature and diluted with Et2O (60 mL) and H2O (60 mL). The aqueous layer was extracted twice with Et2O (20 mL), and the combined organic layers were washed with saturated
NH4Cl (40 mL), twice with H2O (20 mL), and brine
(20 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was triturated with MeOH
to give 2 (173 mg, 0.187 mmol, 82%) as a solid. 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 9.4 Hz, 1H), 7.78 (d, J = 8.8 Hz, 1H),
7.16 (s, 4H), 4.31–4.23 (m, 4H), 2.73–2.42 (m, 12H),
2.09 (br m, 4H), 1.96 (s, 2H), 1.65 (br m, 6H), 1.36 (br m, 30H),
1.19 (br m, 16H), 1.04 (br m, 6H). 13C {1H}
NMR (100 MHz, CDCl3) δ 165.5, 161.7, 148.9, 148.6,
145.3, 134.4, 134.1, 125.2, 123.7, 118.3, 116.9, 83.5, 83.1, 69.1,
68.8, 67.9, 67.7, 34.3, 31.4, 30.5, 30.1, 29.8, 29.5, 29.3, 29.2,
29.0, 28.2, 28.0, 15.1. HRMS (FD+) m/z calcd for C55H90O11 (M·+) 926.6478, found 926.6470.
Prerotaxane 3
Dry DMF (20 mL) was added
to diol 1 (400 mg, 0.503 mmol, 1.0 equiv), 3-azidopropyl
methanesulfonate (450 mg, 1.76 mmol, 3.5 equiv), KI (8.4 mg, 0.0506
mmol, 0.10 equiv), and K2CO3 (173 mg, 1.25 mmol,
2.5 equiv), and the reaction mixture was stirred overnight at 100
°C. The mixture was cooled to room temperature and diluted with
Et2O (70 mL) and H2O (70 mL). The aqueous layer
was extracted twice with Et2O (20 mL), and the combined
organic layers were washed with saturated NH4Cl (40 mL),
twice with H2O (20 mL), and with brine (20 mL). The organic
layer was dried over MgSO4 and concentrated in vacuo. The
residue was triturated in MeOH to give 3 (443 mg, 0.461
mmol, 92%) as a white crystalline solid. 1H NMR (400 MHz,
CDCl3) δ 7.87 (s, 1H), 7.75 (d, J = 7.1 Hz, 1H), 7.16 (s, 4H), 4.32–4.11 (m, 4H), 3.71–3.46
(m, 4H), 2.72–2.35 (m, 8H), 2.12 (br m, 4H), 1.63 (br m, 6H),
1.35 (br m, 30H), 1.19 (br m, 16H), 1.02 (br m, 6H). 13C {1H} NMR (75 MHz, CDCl3) δ 165.4, 161.8,
153.4, 153.1, 152.1, 151.8, 149.1, 148.9, 145.3, 144.7, 144.7, 134.5,
134.2, 134.1, 125.4, 125.2, 124.0, 123.6, 118.4, 118.2, 117.0, 116.6,
66.2, 48.1, 48.0, 34.5, 31.6, 30.6, 30.3, 29.9, 29.6, 29.5, 29.5,
29.1, 29.0, 28.9, 28.2. HRMS (FD+) m/z calcd for C58H84N6O6 (M·+) 960.6447, found 960.6400.
Prerotaxane 5
Dry DMF (12.5 mL) was added
to diol 4 (210 mg, 0.250 mmol, 1 equiv), 3-azidopropyl
methanesulfonate (179 mg, 1.00 mmol, 4 equiv), and K2CO3 (345 mg, 2.50 mmol, 10 equiv), and the reaction mixture was
stirred overnight at 90 °C. The mixture was cooled to room temperature
and diluted with H2O (25 mL) and EtOAc (25 mL). The aqueous
layer was extracted twice with EtOAc (25 mL), and the reunited organic
phases were washed with 3× 25 mL of H2O and brine.
The organic layer was dried over MgSO4 and concentrated
in vacuo. Purification by column chromatography (PE/EtOAc 19:1 →
9:1) afforded prerotaxane 5 (252 mg, 0.250 mmol, 100%)
as a white solid. mp: 171.2–174.5 °C. 1H NMR
(300 MHz, CDCl3) δ 7.86 (s, 1H), 7.77 (s, 1H), 7.31
(s, 4H), 4.24 (m, 4H), 3.64 (m, 2H), 3.54 (m, 2H), 2.73–2.32
(m, 8H), 2.12 (m, 4H), 1.71–1.49 (m, 8H), 1.44–0.83
(m, 32H). 13C {1H} NMR (75 MHz, CDCl3) δ 164.9, 161.2, 153.5, 153.2, 152.1, 151.8, 146.6, 146.1,
137.7, 137.5, 131.0, 123.6, 123.4, 123.2, 123.0, 119.6, 118.5, 118.2,
116.9, 116.4, 66.1, 47.9, 30.2, 29.9, 29.9, 29.8, 29.7, 29.6, 29.4,
29.0, 28.8, 28.8, 28.7, 28.3, 28.2, 28.0. IR (cm–1): 2922, 2851, 2096, 1745, 1718, 1601, 1572, 1502, 1459, 1411, 1385,
1301, 1264, 1227, 1192, 1048, 730. HRMS (FD+) m/z calcd for C50H6679Br81BrN6O6 (M·+) 1006.3385, found 1006.3425.
Prerotaxane 7
Dry DMF (5 mL) was added
to diol 6 (195 mg, 0.233 mmol, 1 equiv), 3-azidopropyl
methanesulfonate (167 mg, 0.932 mmol, 4 equiv), and K2CO3 (322 mg, 2.33 mmol, 10 equiv), and the reaction mixture was
stirred overnight at 90 °C. The mixture was cooled to room temperature
and diluted with H2O (25 mL) and CH2Cl2 (25 mL). The aqueous layer was extracted twice with CH2Cl2 (25 mL), and the reunited organic phases were washed
with 3× 25 mL of H2O and brine. The organic layer
was dried over MgSO4 and concentrated in vacuo. The residue
was triturated with PE/EtOAc (2:1) to give prerotaxane 7 (152 mg, 0.152 mmol, 71%) as a yellow solid. To obtain crystals
that were suitable for X-ray diffraction, a concentrated solution
of 7 in CH2Cl2 was transferred
into an NMR tube. A layer of petroleum ether was carefully added on
top of this solution. The crystals were grown after slow diffusion
of petroleum ether into the CH2Cl2 layer. mp:
212.0–214.8 °C. 1H NMR (300 MHz, CDCl3) δ 7.94 (s, 1H), 7.84 (s, 0.5H), 7.82 (s, 0.5H), 7.64 (d,
4H), 7.51–7.35 (m, 10H), 4.36–4.23 (m, 4H), 3.73–3.54
(m, 4H), 2.85–2.45 (m, 8H), 2.25–2.06 (m, 4H), 1.80–1.57
(m, 8H), 1.49–0.87 (m, 32H). 13C {1H}
NMR (75 MHz, CDCl3) δ 165.3, 161.7, 153.5, 153.2,
152.2, 151.9, 147.1, 146.5, 140.8, 139.6, 139.5, 135.7, 135.5, 135.4,
128.7, 127.2, 127.1, 123.8, 123.7, 123.5, 123.3, 118.5, 118.25, 117.0,
116.6, 66.4, 66.3, 66.2, 48.0, 30.5, 30.4, 30.1, 30.0, 29.6, 29.5,
29.2, 29.0, 28.9, 28.4, 28.3, 28.1. IR (cm–1): 2922,
2851, 2095, 1741, 1715, 1598, 1576, 1501, 1461, 1410, 1384, 1346,
1300, 1261, 1222, 1188, 1142, 1106, 1083, 1047, 1007, 971, 908, 883,
830, 781, 762, 729, 697, 669, 648. HRMS (FD+) m/z calcd for C62H76N6O6 (M·+) 1000.5821, found 1000.5802.
5′-(Azidomethyl)-4,4″-di-tert-butyl-1,1′:3′,1″-terphenyl A
Carbaldehyde 16(22) (1.85
g, 5.00 mmol, 1 equiv) was dissolved in absolute ethanol (30 mL) and
dry THF (30 mL), and the solution was cooled to 0 °C. NaBH4 (378 mg, 10.0 mmol, 2 equiv) was added, and after which,
the solution was stirred for 1 h. The reaction mixture was then concentrated
in vacuo and partitioned between Et2O (40 mL) and H2O (40 mL). The aqueous layer was extracted with Et2O (20 mL), and after which, the combined organic layers were washed
with brine (20 mL), dried over MgSO4, and concentrated
in vacuo to give a colorless film. The residue was dissolved in CH2Cl2 (30 mL), and the mixture was purged with N2 for 30 min and cooled to 0 °C. Subsequently, PPh3 (1.57 g, 6.00 mmol, 1.2 equiv) was added followed by NBS
(1.07 g, 6.00 mmol, 1.2 equiv). The reaction mixture was stirred at
0 °C for 30 min then at room temperature for 30 min and concentrated
in vacuo. The crude mixture was dry-loaded on silica and purified
by column chromatography (PE/EtOAc 200:1 → 100:1) to give the
bromide (2.05 g, 4.70 mmol, 94%) as a colorless foam. 1H NMR (300 MHz, CDCl3) δ 7.80–7.72 (m, 1H),
7.66–7.56 (m, 6H), 7.52 (d, J = 8.4 Hz, 4H),
4.64 (s, 2H), 1.41 (s, 18H).The bromide (871 mg, 2.00 mmol,
1 equiv) was dissolved in acetone (16 mL), and after which, a solution
of NaN3 (195 mg, 3.00 mmol, 1.5 equiv) in H2O (4 mL) was added. The reaction mixture was stirred overnight at
room temperature and subsequently diluted with Et2O (40
mL) and H2O (40 mL). The aqueous layer was extracted with
Et2O (10 mL), and after which, the combined organic layers
were washed with brine (20 mL), dried over MgSO4, and concentrated
in vacuo to give A (784 mg, 1.97 mmol, 99%) as a thick
colorless oil. 1H NMR (300 MHz, CDCl3) δ
7.87–7.77 (m, 1H), 7.64 (d, J = 7.1 Hz, 4H),
7.59–7.45 (m, 6H), 4.50 (s, 2H), 1.43 (s, 18H). 13C {1H} NMR (75 MHz, CDCl3) δ 150.7, 142.3,
137.8, 136.3, 127.0, 125.9, 125.5, 55.0, 34.6, 31.4. HRMS (FD+) m/z calcd for C27H31N3 (M·+) 397.2513,
found 397.2525.
4,4″-Di-tert-butyl-5′-ethynyl-1,1′:3′,1″-terphenyl B
A solution of CBr4 (1.51 g, 4.56 mmol,
2 equiv) and PPh3 (2.39 g, 9.12 mmol, 4 equiv) in dry CH2Cl2 (25 mL) under a nitrogen atmosphere was cooled
to 0 °C and stirred for 15 min. Carbaldehyde 16 (846
mg, 2.28 mmol, 1 equiv) was added to the yellow solution then the
mixture was stirred cooled at 0 °C for 1 h and concentrated in
vacuo. The crude mixture was dry-loaded on silica and purified by
column chromatography (PE/EtOAc 100:1 → 99:1) to give the dibromovinyl
(1.10 g, 2.09 mmol, 92%). The residue was dissolved in dry THF (20
mL) and cooled to −78 °C under a nitrogen atmosphere.
Then, BuLi (2.5 M, 2.1 mL, 5.23 mmol, 2.5 equiv) was added slowly
to the cooled solution, which was subsequently stirred for 1 h at
−78 °C and 1 h at room temperature. The reaction was quenched
with H2O (5 mL), and the aqueous layer was extracted with
Et2O (5 mL). The combined organic layers were washed with
H2O (10 mL) and brine (10 mL), dried over MgSO4, and concentrated in vacuo. The crude mixture was purified by column
chromatography (PE/EtOAc 100:0 → 99:1) to give B (712 mg, 1.88 mmol, 90%) as a white solid. 1H NMR (300
MHz, CDCl3) δ 7.83 (s, 1H), 7.73 (s, 2H), 7.61 (d, J = 8.5 Hz, 4H), 7.53 (d, J = 8.4 Hz, 4H),
3.16 (s, 1H), 1.42 (s, 18H). 13C {1H} NMR (75
MHz, CDCl3) δ 151.0, 141.9, 137.5, 129.4, 127.0,
126.6, 126.0, 122.9, 83.9, 34.7, 31.5. HRMS (FD+) m/z calcd for C28H30 (M·+) 366.2342, found 366.2354.
Half-Stoppered
Prerotaxane a2
Diyne 2 (200 mg,
0.216 mmol, 1.0 equiv), stopper 4,4′,4″-(3-azidopropane-1,1,1-triyl)tris(tert-butylbenzene) a(14) (42 mg, 0.087 mmol, 0.40 equiv), and TBTA (23 mg, 0.043 mmol, 0.20
equiv) were dissolved in dry CH2Cl2 (23 mL),
and the solution was degassed with five vacuum/N2 cycles.
Cu(CH3CN)4BF4 (14 mg, 0.045 mmol,
0.21 equiv) was added, and the reaction was stirred overnight at room
temperature under a N2 atmosphere. The mixture was concentrated
in vacuo and purified by column chromatography (PE/EtOAC 14:1 →
12:1 → 10:1) to give a2 (57 mg, 0.0405 mmol, 19%)
as a white foam. Also, 140 mg of 2 (0.151 mol, 70%) was
retrieved (yield brsm 63%). 1H NMR (400 MHz, CDCl3) δ 7.88–7.84 (m, 1H), 7.80–7.69 (m, 1H), 7.31
(d, J = 8.2 Hz, 6H), 7.23 (d, J =
8.4 Hz, 6H), 7.14 (s, 4H), 6.94 (d, J = 9.0 Hz, 1H),
4.22 (t, J = 20.1 Hz, 4H), 4.05 (br m, 2H), 3.20–3.08
(m, 2H), 2.96–2.91 (m, 2H), 2.67 (br m 2H), 2.57–2.43
(m, 8H), 2.27 (br m, 2H), 2.07 (br m, 2H), 1.95 (s, 1H), 1.55 (br
m, 4H), 1.33 (br m, 47H), 1.16 (br m, 16H), 1.00 (br m, 6H), 0.88
(br m, 12H). 13C {1H} NMR (100 MHz, CDCl3) δ 148.7, 143.1, 134.4, 128.4, 124.9, 54.1, 47.8, 34.3,
34.3, 31.5, 31.3, 30.5, 30.1, 29.8, 29.0, 28.2, 15.1. HRMS (FD+) m/z calcd for C95H129N3O6 (M·+) 1407.9876, found 1407.9941.
Half-Stoppered Prerotaxane A2
Diyne 2 (130 mg, 0.140 mmol, 1.0
equiv), 5′-(azidomethyl)-4,4″-di-tert-butyl-1,1′:3′,1″-terphenyl (22
mg, 0.055 mmol, 0.39 equiv), and TBTA (15 mg, 0.028 mmol, 0.20 equiv)
were dissolved in dry CH2Cl2 (3 mL), and the
solution was degassed with five vacuum/N2 cycles. Cu(CH3CN)4BF4 (13 mg, 0.041 mmol, 0.29 equiv)
was added, and the reaction was stirred for 18 h at room temperature
under a N2 atmosphere. The mixture was concentrated in
vacuo and purified by column chromatography (PE/EtOAc 10:1 →
4:1 → 2:1) to give A2 (60 mg, 0.0453 mmol, 32%)
as a white solid. Also, 66 mg of prerotaxane 2 (0.0712
mmol, 51%) was retrieved (yield brsm A2 66%). 1H NMR (400 MHz, CDCl3) δ 7.94–7.66 (m, 3H),
7.54 (d, J = 8.1 Hz, 4H), 7.49 (d, J = 8.3 Hz, 4H), 7.39 (d, J = 15.1 Hz, 2H), 7.20–7.06
(m, 4H), 7.00–6.96 (m, 1H), 5.63–5.49 (m, 2H), 4.22–4.18
(m, 4H), 2.95 (d, J = 21.4 Hz, 2H), 2.49 (br m, 8H),
2.07 (br m, 2H), 1.94 (s, 1H), 1.38 (s, 18H), 1.28 (br m, 40H), 0.91
(br m, 32H). 13C {1H} NMR (100 MHz, CDCl3) δ 176.3, 126.8, 126.0, 125.7, 125.2, 125.0, 77.2,
77.1, 76.9, 76.6, 70.4, 69.2, 68.7, 62.9, 47.1, 34.5, 34.3, 31.6,
31.4, 31.2, 30.4, 29.7, 29.6, 29.5, 25.4, 22.5, 13.9, 11.7. HRMS (ESI+) m/z calcd for C89H118N3O6 [M+H]+ 1324.9015,
found 1324.8976.
Half-Stoppered Prerotaxane B3
Diazide 3 (117 mg, 0.127 mmol, 1 equiv), stopper B (24.5
mg, 0.051 mmol, 0.4 equiv), and TBTA (13.5 mg, 0.025 mmol, 0.2 equiv)
were dissolved in dry CH2Cl2 (10 mL), and the
solution was purged with N2 for 30 min. Then, Cu(CH3CN)4BF4 (8.0 mg, 0.025 mmol, 0.2 equiv)
was added, and the mixture was purged with N2 for an additional
10 min and stirred overnight at room temperature under a N2 atmosphere. The crude mixture was dry-loaded on silica (ca. 600
mg) and purified by column chromatography (EtOAc/PE 1:14 →
1:10) to give starting material 3 (68.7 mg, 0.074 mmol,
58%) and mono-stoppered product B3 (54.4 mg, 0.039 mmol,
30%) as a colorless film. The procedure was repeated on the recovered
starting material to afford again B3 (33.1 mg, 0.023
mmol, 32%). 1H NMR (300 MHz, CDCl3) δ
7.98–7.67 (m, 2H), 7.36–7.20 (m, 12.5H), 7.20–7.10
(s, 4H), 7.01–6.90 (m, 0.5H), 4.34–3.98 (m, 6H), 3.22–3.09
(m, 2H), 3.04–2.87 (m, 2H), 2.78–2.35 (m, 10H), 2.35–2.21
(m, 2H), 2.15–2.02 (m, 2H), 1.95 (s, 1H), 1.75–1.50
(m, 8H), 1.47–0.82 (m, 77H). 13C {1H}
NMR (75 MHz, CDCl3) δ 165.6, 165.4, 162.0, 153.2,
152.1, 149.0, 148.8, 146.8, 145.6, 145.4, 144.7, 143.2, 140.6, 134.5,
134.3, 133.9, 128.8, 128.5, 125.5, 125.3, 125.0, 123.9, 123.6, 123.4,
121.1, 120.7, 118.4, 118.2, 116.7, 83.6, 83.2, 69.1, 68.9, 68.7, 68.0,
54.2, 47.9, 40.8, 40.1, 34.6, 34.5, 34.4, 34.4, 32.7, 31.8, 31.7,
31.6, 31.4, 30.6, 30.2, 29.9, 29.7, 29.7, 29.6, 29.3, 29.1, 28.7,
28.3, 25.2, 22.7, 22.1, 15.2, 14.1. IR (cm–1): 3312,
3032, 2955, 2924, 2854, 2098, 1745, 1718, 1599, 1504, 1463, 1410,
1384, 1363, 1303, 1269, 1228, 1199, 1165, 1116, 1088, 1051, 1015,
958, 910, 880, 824, 782, 732, 701, 646, 588, 541. HRMS (FD+) m/z calcd for C95H129N3O6 (M·+) 1407.9876, found 1407.9951.
Half-Stoppered Prerotaxane B5
Diazide 5 (252 mg, 0.250 mmol, 1
equiv), stopper B (36.6
mg, 0.100 mmol, 0.4 equiv), and TBTA (26.5 mg, 0.050 mmol, 0.2 equiv)
were dissolved in dry CH2Cl2 (20 mL), and the
solution was purged with N2 for 30 min. Then, Cu(CH3CN)4BF4 (15.7 mg, 0.050 mmol, 0.2 equiv)
was added, and the mixture was purged with N2 for an additional
10 min and stirred overnight at room temperature under a N2 atmosphere. The crude mixture was dry-loaded on silica (ca. 700
mg) and purified by column chromatography (CH2Cl2/PE 1:1 → 7:3 → 8:2 → 9:1 → CH2Cl2) to give starting material 5 (152 mg,
0.151 mmol, 60%) and half-stoppered prerotaxane B5 (82.6
mg, 0.060 mmol, 24%) as a colorless film. The procedure was repeated
on the recovered starting material to afford an additional portion
of B5 (64.5 mg, 0.047 mmol, 31%). 1H NMR (300
MHz, CDCl3) δ 8.03–7.95 (m, 2H), 7.87–7.72
(m, 3H), 7.69–7.50 (m, 9H), 7.34–7.28 (m, 4H), 4.83–4.60
(m, 2H), 4.35–4.14 (m, 4H), 3.69–3.49 (m, 2H), 2.78–2.32
(m, 10H), 2.19–2.06 (m, 2H), 1.75–0.81 (m, 58H). 13C {1H} NMR (75 MHz, CDCl3) δ
165.1, 164.8, 162.6, 161.6, 161.1, 154.4, 153.4, 153.1, 152.8, 152.7,
152.3, 152.0, 151.8, 151.5, 150.6, 147.9, 147.4, 146.6, 146.0, 142.3,
142.1, 138.0, 138.0, 137.7, 137.5, 137.4, 137.0, 131.5, 131.1, 131.0,
130.7, 130.5, 127.0, 125.8, 125.6, 125.4, 123.8, 123.3, 123.2, 122.7,
121.3, 121.2, 120.0, 119.8, 119.6, 119.4, 118.7, 118.4, 118.2, 117.0,
116.9, 116.7, 116. 5, 69.9, 66.3, 65.6, 62.5, 62.2, 48.4, 48.2, 48.0,
47.9, 47.0, 46.6, 34.6, 31.4, 30.2, 30.1, 29.9, 29.8, 29.7, 29.6,
29.4, 29.3, 29.1, 29.1, 28.9, 28.8, 28.3, 28.2, 28.0. IR (cm–1): 2924, 2853, 2098, 1743, 1720, 1599, 1572, 1502, 1460, 1411, 1386,
1302, 1270, 1228, 1195, 1154, 1051, 909, 832, 781, 732. HRMS (FD+) m/z calcd for C78H96Br2N6O6 (M·+) 1370.5753, found 1370.5797.
Half-Stoppered Prerotaxane B7
Diazide 7 (152 mg, 152 μmol,
1 equiv), stopper B (22.2 mg, 60.6 μmol, 0.4 equiv),
and TBTA (16.1 mg, 30.4 μmol,
0.2 equiv) were dissolved in dry CH2Cl2 (10
mL), and the solution was purged with N2 for 30 min. Then,
Cu(CH3CN)4BF4 (9.6 mg, 30.4 μmol,
0.2 equiv) was added, and the mixture was purged with N2 for an additional 10 min and stirred overnight at room temperature
under a N2 atmosphere. The crude mixture was dry-loaded
on silica (ca. 500 mg) and purified by column chromatography (CH2Cl2/PE 8:2 → 9:1 → CH2Cl2) to give starting material 7 (76.0 mg,
76.0 μmol, 50%) and mono-stoppered product B7 (26.9
mg, 20.0 μmol, 13%) as a colorless film. The procedure was repeated
on the recovered starting material to afford again 7 (49.1
mg, 49.1 μmol, 65%) and B7 (32.3 mg, 23.6 μmol,
31%). 1H NMR (300 MHz, CDCl3) δ 8.07–7.88
(m, 4H), 7.85–7.76 (m, 2H), 7.68–7.59 (m, 8H), 7.58–7.33
(m, 14H), 4.87–4.66 (m, 2H), 4.37–4.19 (m, 4H), 3.71–3.54
(m, 2H), 2.91–2.44 (m, 10H), 2.23–2.08 (m, 2H), 1.81–1.56
(m, 8H), 1.48–0.85 (m, 50H). 13C {1H}
NMR (75 MHz, CDCl3) δ 165.1, 162.1, 161.6, 153.4,
152.7, 150.5, 147.4, 147.1, 146.9, 146.4, 142.1, 140.8, 140.7, 139.8,
139.6, 139.5, 138.0, 135.7, 135.4, 131.5, 128.7, 128.7, 127.2, 127.1,
126.9, 125.7, 125.6, 123.6, 123.2, 117.1, 66.3, 65.5, 48.0, 46.7,
34.6, 31.4, 30.5, 30.4, 30.0, 29.9, 29.7, 29.7, 29.0, 28.9, 28.3,
28.1. IR (cm–1): 2923, 2852, 2097, 1741, 1718, 1597,
1501, 1462, 1410, 1385, 1302, 1268, 1223, 1191, 1145, 1106, 1084,
1051, 968, 883, 831, 803, 782, 762, 735, 699. HRMS (FD+) m/z calcd for C90H106N6O6 (M·+) 1366.8169, found 1366.8131.
Prerotaxane a2a
Diyne 2 (46
mg, 0.050 mmol), stopper a (53 mg, 0.110 mmol, 2.2 equiv),
and TBTA (6 mg, 0.010 mmol, 0.20 equiv) were dissolved in dry CH2Cl2 (45 mL), and the solution was degassed with
five vacuum/N2 cycles. Cu(CH3CN)4BF4 (3 mg, 0.010 mmol, 0.20 equiv) was added, and the
reaction was stirred overnight at room temperature under a N2 atmosphere. The mixture was concentrated in vacuo and purified by
column chromatography (PE/EtOAC 14:1 → 12:1 → 10:1)
to give a2a (53 mg, 0.028 mmol, 56%) as a colorless foam.
Spectral data of a2a matched those reported in the literature.[14]
[2]Rotaxane a2a (Diacid)
Prerotaxane a2a (190 mg, 0.100 mmol) was dissolved in
8 mL of Tesser’s
base (1,4-dioxane/MeOH/2 M NaOH, 3:1:0.1), and the reaction was stirred
overnight at 50 °C. The mixture was subsequently diluted with
EtOAc (15 mL) and a saturated KHSO4 solution (15 mL). The
organic layer was washed with brine (10 mL), dried over MgSO4, and concentrated in vacuo to give [2]rotaxane a2a (149
mg, 0.0773 mmol, 77%) as a colorless film. 1H NMR (400
MHz, CDCl3) δ 7.72 (s, 2H), 7.31 (d, J = 7.9 Hz, 12H), 7.23 (d, J = 8.3 Hz, 12H), 7.15
(s, 2H), 6.98 (s, 4H), 4.21 (t, J = 6.3 Hz, 4H),
4.15–4.02 (m, 4H), 3.22–3.09 (m, 4H), 2.88 (t, J = 7.4 Hz, 4H), 2.61 (t, J = 8.1 Hz, 8H),
2.23 (quint, J = 6.9 Hz, 4H), 1.59–1.48 (m,
8H), 1.30 (br m, 78H), 1.09 (br m, 26H). 13C {1H} NMR (100 MHz, CDCl3) δ 165.0, 151.3, 149.5, 148.8,
148.8, 145.7, 143.0, 142.6, 129.0, 128.4, 124.9, 124.4, 123.4, 121.2,
117.0, 69.3, 67.0, 54.0, 53.3, 48.1, 40.7, 34.3, 33.9, 31.6, 31.6,
31.3, 31.1, 30.8, 30.5, 29.6, 29.6, 29.3, 29.2, 29.1, 28.5, 21.4.
MS (FD+) m/z calcd for
C128H176N6O8 (M·+) 1925.4, found 1925.4.
Prerotaxane A2A
Diyne 2 (50
mg, 0.0539 mmol, 1.0 equiv), stopper A (47 mg, 0.118
mmol, 2.2 equiv), and TBTA (6 mg, 0.011 mmol, 0.20 equiv) were dissolved
in dry CH2Cl2 (10 mL), and the solution was
degassed with five vacuum/N2 cycles. Cu(CH3CN)4BF4 (4 mg, 0.013 mmol, 0.24 equiv) was added, and
the reaction was stirred overnight at room temperature under a N2 atmosphere. The mixture was concentrated in vacuo and purified
by column chromatography (PE/EtOAC 5:1 → 4:1 → 3:1→
1:1) to give A2A (47 mg, 0.273 mmol, 51%) as a yellow
solid. 1H NMR (400 MHz, CDCl3) δ 7.84–7.66
(m, 4H), 7.55 (d, J = 8.2 Hz, 8H), 7.50 (d, J = 8.2 Hz, 8H), 7.40 (d, J = 14.9 Hz,
4H), 7.11 (d, J = 15.2 Hz, 4H), 6.98 (d, J = 15.7 Hz, 2H), 5.63–5.46 (m, 4H), 4.30–4.16
(m, 4H), 3.06–2.85 (m, 4H), 2.68–2.23 (m, 12H), 1.39
(s, 36H), 1.29 (br m, 34H), 1.12 (br m, 12H), 0.93 (br m, 12H). 13C {1H} NMR (100 MHz, CDCl3) δ
176.3, 153.2, 152.9, 152.0, 151.8, 150.8, 150.7, 148.9, 148.7, 147.7,
147.5, 145.3, 144.6, 144.6, 142.4, 137.4, 137.4, 135.7, 135.7, 134.4,
134.2, 134.1, 126.8, 126.0, 125.7, 125.2, 125.2, 125.0, 79.4, 69.8,
68.9, 68.8, 68.6, 68.4, 34.7, 34.5, 34.3, 34.0, 33.7, 31.9, 31.7,
31.6, 31.4, 31.3, 31.1, 30.4, 30.3, 30.0, 29.7, 29.6, 29.6, 29.6,
29.5, 29.4, 29.4, 29.3, 29.1, 29.0, 28.9, 28.8, 28.4, 28.4, 28.2,
28.1, 28.0, 27.9, 25.4, 23.8, 23.1, 22.6, 22.3, 22.2, 22.1, 22.0,
14.6, 14.1. HRMS (FD+) m/z calcd for C116H148N6O6 (M·+) 1721.1455, found 1721.1524.
[2]Rotaxane A2A (Diacid)
Prerotaxane A2A (71 mg,
0.0412 mmol) was dissolved in 4 mL of Tesser’s
base (1,4-dioxane/MeOH/2 M NaOH, 3:1:0.1), and the reaction was stirred
overnight at 50 °C. The mixture was subsequently diluted with
EtOAc (10 mL) and a saturated KHSO4 solution (10 mL). The
organic layer was washed with brine (10 mL), dried over MgSO4, and concentrated in vacuo to give [2]rotaxane A2A (64
mg, 0.0364 mmol, 88%) as a yellow solid. 1H NMR (400 MHz,
CDCl3) δ 7.81 (d, J = 6.8 Hz, 2H),
7.69 (d, J = 12.2 Hz, 2H), 7.62–7.30 (m, 26H),
7.01 (s, 4H), 5.63–5.53 (m, 4H), 4.35–4.20 (m, 6H),
2.95–2.87 (m, 4H), 2.65–2.57 (m, 8H), 2.37–2.23
(m, 4H), 1.74–1.43 (m, 12H), 1.43–1.10 (m, 54H), 1.09–0.76
(m, 24H). 13C {1H} NMR (125 MHz, CDCl3) δ 176.4, 165.0, 151.4, 151.4, 151.0, 150.9, 149.6, 146.5,
146.4, 142.7, 142.6, 142.6, 137.4, 135.4, 128.9, 127.4, 126.9, 126.9,
126.2, 126.1, 125.9, 125.9, 125.6, 125.5, 124.7, 124.5, 123.4, 123.4,
121.5, 121.3, 117.2, 117.1, 70.6, 69.6, 69.5, 69.4, 63.1, 54.4, 54.3,
47.2, 34.6, 34.5, 34.0, 32.0, 31.7, 31.7, 31.7, 31.6, 31.4, 31.1,
30.8, 30.7, 30.6, 30.4, 30.0, 29.7, 29.7, 29.6, 29.6, 29.5, 29.4,
29.3, 29.2, 29.1, 29.1, 29.0, 28.4, 28.3, 25.5, 25.3, 22.7, 22.7,
22.1, 21.7, 14.2, 14.0, 11.8. HRMS (ESI+) m/z calcd for C116H154N6O8 [M + 2H]2+ 879.5909, found 879.5972.
Prerotaxane B3B
Diazide 3 (75
mg, 0.0759 mmol, 1.0 equiv), stopper B (73 mg,
0.20 mmol, 2.6 equiv), and TBTA (15 mg, 0.028 mmol, 0.37 equiv) were
dissolved in dry CH2Cl2 (3 mL), and the solution
was degassed with five vacuum/N2 cycles. Cu(CH3CN)4BF4 (13 mg, 0.041 mmol, 0.54 equiv) was
added, and the reaction was stirred overnight at room temperature
under a N2 atmosphere. The mixture was concentrated in
vacuo and purified by column chromatography (PE/EtOAC 5:1 →
4:1 → 3:1→ 1:1) to give B3B (91.3 mg, 0.0531
mmol, 70%) as glass. 1H NMR (400 MHz, CDCl3)
δ 8.09–7.93 (m, 5H), 7.93–7.72 (m, 4H), 7.65 (d, J = 6.9 Hz, 8H), 7.54 (d, J = 7.2 Hz, 8H),
7.18 (s, 4H), 4.88–4.63 (m, 4H), 4.39–4.13 (m, 4H),
2.81–2.39 (m, 12H), 1.61 (br m, 11H), 1.43 (s, 35H), 1.38 (s,
14H), 1.31 (br m, 11H), 0.95 (br m, 23H). 13C {1H} NMR (100 MHz, CDCl3) δ 162.1, 152.7, 150.5, 149.3,
147.4, 145.1, 144.5, 142.3, 142.1, 138.1, 134.4, 131.6, 127.0, 125.8,
125.6, 125.4, 123.7, 123.2, 121.4, 116.9, 65.3, 46.7, 34.6, 34.5,
31.6, 31.4, 30.5, 29.7, 29.6, 29.0, 28.3. HRMS (ESI+) m/z calcd for C114H144KN6O6 [M+K]+ 1732.0779, found 1732.0799.
[2]Rotaxane B3B (Tetramethylester)
Prerotaxane B3B (72.0 mg, 0.0419 mmol) was dissolved in a mixture of dioxane
(4 ml) and methanol (1 ml), a solution of NaOH (40 mg) in water (0.5
ml) was added, and the reaction was stirred at 50 °C for 72 h.
The mixture was subsequently diluted with EtOAc (10 mL) and a saturated
KHSO4 solution (10 mL). The organic layer was washed with
brine (10 mL), dried over MgSO4, and concentrated in vacuo
to give the diacid, which was immediately converted to a diester.
A solution of HCl in MeOH (prepared from 8 mL of MeOH and 1.5 mL of
acetyl chloride at 50 °C) was added, and the solution was stirred
at 50 °C for 5 h. The reaction mixture was concentrated in vacuo,
and the residue was co-evaporated with MeOH (3× 5 ml) and purified
by flash chromatography (PE/EtOAc 3:1 and 2:1) to give B3B (37.2 mg, 0.0211 mmol, 51%) as glass. 1H NMR (400 MHz,
CDCl3) δ 8.24 (s, 2H), 8.03 (s, 4H), 7.75 (s, 2H),
7.51 (d, J = 8.1 Hz, 8H), 7.46–7.33 (m, 10H),
7.16 (s, 2H), 7.04 (s, 4H), 4.78 (t, J = 6.7 Hz,
4H), 4.06 (t, J = 5.6 Hz, 4H), 3.86 (s, 6H), 2.63
(t, J = 8.2 Hz, 8H), 2.55 (t, J =
6.1 Hz, 4H), 1.59–1.44 (m, 9H), 1.38 (s, 34H), 1.35 (s, 18H),
1.15 (t, J = 7.4 Hz, 8H), 1.00–0.77 (m, 25H). 13C {1H} NMR (100 MHz, CDCl3) δ
165.4, 151.8, 150.4, 149.8, 147.6, 142.6, 142.2, 138.0, 131.1, 129.3,
127.0, 125.8, 125.7, 124.5, 124.2, 123.3, 121.3, 116.6, 65.6, 52.5,
46.9, 34.6, 34.0, 31.8, 31.4, 31.3, 30.7, 29.8, 29.5, 29.4, 29.0,
29.0. HRMS (ESI+) m/z calcd for C116H153N6O8 [M+H]+ 1758.1744, found 1758.1764.
Prerotaxane a2A
Half-stoppered prerotaxane a2 (54.9 mg, 0.0390
mmol, 1 equiv), stopper A (0.0186 g, 0.0468 mmol, 1.2
equiv), and TBTA (4.13 mg, 0.00779 mmol,
0.2 equiv) were dissolved in 5 mL of dry DCM, and then Cu(CH3CN)4BF4 (2.45 mg, 0.00779 mmol, 0.2 equiv)
was added. The solution was stirred at room temperature under a N2 atmosphere overnight. The solution was concentrated in vacuo,
and the crude product was purified by column chromatography (PE/EtOAc
9:1 → 7:1 → 5:1) to yield prerotaxane a2A as a colorless film (0.039 g, 0.0216 mmol, 56%). 1H NMR
(400 MHz, CDCl3) δ 7.92–7.65 (m, 4H), 7.56
(d, J = 8.3 Hz, 4H), 7.50 (d, J =
8.1 Hz, 4H), 7.40 (d, J = 15.3 Hz, 2H), 7.31 (d, J = 8.2 Hz, 6H), 7.24 (d, J = 8.2 Hz, 6H),
7.19–7.06 (m, 4H), 7.05–6.88 (m, 1H), 5.55–5.44
(m, 2H), 4.34–4.12 (m, 4H), 4.12–3.97 (m, 2H), 3.15
(t, J = 8.4 Hz, 2H), 3.06–2.82 (m, 4H), 2.79–2.17
(m, 12H), 1.60 (br m, 12H), 1.34 (m, 68H), 1.08 (br m, 24H). 13C {1H} NMR (100 MHz, CDCl3) δ
148.7, 143.1, 142.4, 137.4, 128.3, 126.8, 126.0, 125.7, 125.2, 124.8,
54.0, 47.8, 34.5, 34.3, 34.2, 31.4, 31.2, 30.4, 30.0, 29.6, 29.5,
29.0, 28.0. HRMS (FD+) m/z calcd for C122H160N6O6 (M·+) 1805.2394, found 1805.2477.
[2]Rotaxane a2A (Diacid)
Prerotaxane a2A (39 mg,
0.216 mmol) was dissolved in 2 mL of Tesser’s
base (1,4-dioxane/MeOH/2 M NaOH, 3:1:0.1), and the reaction was stirred
overnight at 50 °C. The mixture was subsequently diluted with
EtOAc (10 mL) and a saturated KHSO4 solution (10 mL). The
organic layer was washed with brine (5 mL), dried over MgSO4, and concentrated in vacuo to give [2]rotaxane a2A (38
mg, 0.0206 mmol, 96%) as a colorless film. 1H NMR (400
MHz, CDCl3) δ 7.81–7.79 (m, 2H), 7.72 (m,
2H), 7.61–7.41 (m, 11H), 7.31 (d, J = 8.0
Hz, 6H), 7.23 (d, J = 8.2 Hz, 6H), 6.99 (s, 4H),
5.63 (s, 2H), 5.54–5.43 (m, 2H), 4.30–4.15 (m, 4H),
4.14–4.03 (m, 2H), 3.23–3.10 (m, 2H), 2.99–2.78
(m, 4H), 2.65–2.53 (m, 6H), 2.23 (s, 4H), 1.58–1.42
(m, 6H), 1.42–1.14 (m, 75H), 1.14–0.65 (m, 24H). 13C {1H} NMR (100 MHz, CDCl3 δ
164.9, 164.7, 151.3, 151.3, 150.9, 150.8, 149.5, 149.4, 149.3, 148.8,
143.0, 142.6, 142.5, 142.4, 137.3, 128.8, 128.3, 126.8, 125.8, 125.7,
125.5, 124.9, 124.4, 124.4, 121.1, 117.0, 117.0, 69.6, 69.3, 67.0,
64.3, 54.2, 54.1, 54.0, 53.3, 48.1, 40.7, 34.5, 34.2, 33.9, 31.6,
31.2, 31.0, 30.4, 29.6, 29.3, 29.1, 29.0, 29.0, 24.7, 22.6. MS (FD+) m/z calcd for C122H164N6O8 (M·+) 1841.3, found 1841.3.
Prerotaxane A23B
Compound A2 (54.5 mg, 0.0411 mmol, 1.0 equiv), B3 (110 mg, 2 equiv),
and TBTA (15 mg, 0.028 mmol, 0.68 equiv) were dissolved in dry CH2Cl2 (3 mL), and the solution was degassed with
five vacuum/N2 cycles. Cu(CH3CN)4BF4 (13 mg, 0.041 mmol, 1.0 equiv) was added, and the
reaction was stirred for 18 h at room temperature under a N2 atmosphere. The mixture was concentrated in vacuo and purified by
column chromatography (PE/EtOAc 8:1 → 5:1 → 2:1) to
give A23B (60.5 mg, 0.0228 mmol, 55%) as glass. 1H NMR (400 MHz, CDCl3) δ 8.02–7.31
(m, 26H), 7.24–7.18 (m, 2H), 7.18–7.06 (m, 8H), 7.04–6.89
(m, 1H), 5.54–5.49 (m, J = 2H), 4.88–4.69
(m, 2H), 4.64–4.44 (m, 2H), 4.27 (t, J = 4.9
Hz, 12H), 4.18 (br m, 6H), 2.91 (br m, 4H), 2.53 (br m, 18H), 1.49
(br m, 8H), 1.39 (br m, 18H), 1.29 (br m, 72H), 1.12 (br m, 18H),
0.91 (br m, 32H). 13C {1H} NMR (125 MHz, CDCl3) δ 176.4, 142.5, 138.0, 134.4, 128.4, 127.9, 126.9,
126.1, 125.8, 125.7, 125.2, 125.1, 123.2, 79.5, 70.6, 69.8, 69.4,
63.0, 47.2, 46.8, 34.6, 34.4, 34.1, 31.9, 31.7, 31.5, 31.4, 31.4,
31.4, 30.5, 30.2, 29.7, 29.7, 29.6, 29.4, 29.1, 28.3, 25.5, 23.1,
22.7, 22.6, 21.7, 21.4, 19.3, 19.2, 19.0, 19.0, 17.8, 14.1, 14.0,
11.8. HRMS (ESI+) m/z calcd for C175H233N9O12 [M + 2H)]2+ 1326.8961, found 1326.8928.
[3]Rotaxane A23B (Tetramethylester)
Prerotaxane A23B (30 mg, 0.0113 mmol) was dissolved in a mixture of dioxane
(4 mL) and methanol (1 mL), a solution of NaOH (40 mg) in water (0.5
ml) was added, and the reaction was stirred at 50 °C during 72
h. The mixture was subsequently diluted with EtOAc (10 mL) and a saturated
KHSO4 solution (10 mL). The organic layer was washed with
brine (5 mL), dried over Na2SO4, and concentrated
in vacuo to give the diacid, which was immediately converted to the
diester. A solution of HCl in MeOH (prepared from 8 mL of MeOH and
1.5 mL of acetyl chloride at 50 °C) was added, and the solution
was stirred at 50 °C for 5 h. The reaction mixture was concentrated
in vacuo, and the residue was co-evaporated with MeOH (3× 5 mL)
and purified by flash chromatography (PE/EtOAc 3:1 and 2:1) to give
[3]rotaxane A23B (16.1 mg, 0.00579 mmol, 51%) as glass.1H NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 8.06–7.96
(m, 2H), 7.77 (s, 1H), 7.73 (s, 1H), 7.51 (d, J =
8.3 Hz, 4H), 7.49–7.44 (m, 7H), 7.44–7.41 (m, 2H), 7.41–7.30
(m, 10H), 7.11 (s, 2H), 7.01 (s, 4H), 6.99 (s, 4H), 5.45 (s, 2H),
4.77 (t, J = 6.8 Hz, 2H), 4.53 (t, J = 6.8 Hz, 2H), 4.17–3.94 (m, 8H), 3.84 (s, 3H), 3.82 (s,
3H), 3.74 (s, 3H), 3.73 (s, 3H), 2.98–2.85 (m, 4H), 2.78–2.48
(m, 18H), 2.41–2.31 (m, 2H), 2.27–2.11 (m, 4H), 1.62–1.46
(m, 20H), 1.38 (s, 18H), 1.36 (s, 18H), 1.32 (s, 18H), 1.30 (s, 20H),
1.27–1.13 (m, 16H), 1.13–0.82 (m, 42H). 13C {1H} NMR (100 MHz, CDCl3) δ 165.8,
165.7, 165.3, 165.1, 151.8, 151.7, 150.7, 150.2, 149.8, 149.7, 147.5,
147.4, 146.9, 142.5, 142.3, 142.0, 137.8, 137.4, 135.6, 130.8, 129.1,
128.9, 126.8, 125.9, 125.7, 125.6, 125.4, 124.3, 124.2, 124.1, 124.0,
123.2, 121.7, 121.3, 121.1, 116.7, 116.6, 77.2, 77.1, 76.9, 76.6,
68.8, 66.0, 65.6, 54.0, 52.4, 52.2, 52.1, 46.9, 46.7, 34.5, 34.4,
33.9, 33.8, 31.8, 31.6, 31.3, 31.2, 31.1, 30.5, 30.4, 29.8, 29.7,
29.6, 29.5, 29.4, 29.3, 29.2, 29.0, 28.9, 22.6, 22.0, 21.9, 14.0.
HRMS (ESI+) m/z calcd
for C179H247N9O16 (M·+) 2779.8819, found 2779.8762.
Prerotaxane a2L2a
Prerotaxane 1 (110 mg, 0.0779
mmol, 2.2 equiv), linker L (6.67 mg,
0.0354 mmol, 1 eq), and TBTA (3.76 mg, 0.00708 mmol, 0.2 equiv) were
dissolved in 10 mL of dry DCM, and then Cu(CH3CN)4BF4 (2.23 mg, 0.00708 mmol, 0.2 equiv) was added to the
solution. The solution was stirred at room temperature under a N2 atmosphere overnight. Subsequently, the solution was concentrated
in vacuo, and the crude product was purified by column chromatography
to yield prerotaxane a2L2a as a white film (0.0790 g,
0.0263 mmol, 74%). 1H NMR (400 MHz, CDCl3) δ
7.91–7.79 (m, 2H), 7.77–7.63 (m, 2H), 7.31 (d, J = 8.3 Hz, 12H), 7.24 (d, J = 8.5 Hz,
12H), 7.21–6.89 (m, 16H), 5.47–5.27 (m, 4H), 4.32–4.12
(m, 8H), 4.12–3.93 (m, 4H), 3.16 (t, J = 8.3
Hz, 4H), 3.05–2.82 (m, 8H), 2.79–2.12 (m, 24H), 1.59
(br m, 16H), 1.34 (m, 110H), 1.06 (br m, 44H). 13C {1H} NMR (100 MHz, CDCl3) δ 148.7, 143.1, 134.4,
128.3, 124.8, 68.6, 54.0, 53.3, 47.8, 40.7, 34.3, 34.2, 31.4, 31.2,
30.5, 30.1, 29.8, 29.6, 29.4, 28.9, 28.2, 28.0, 23.8, 22.0. HRMS (ESI+) m/z calcd for C198H266N12O12Na [M + Na]+ 3027.0465, found 3027.0744.
[3]Rotaxane a2L2a (Tetraacid)
Prerotaxane a2L2a (71 mg, 0.0236
mmol) was dissolved in 7 mL of Tesser’s
base (1,4-dioxane/MeOH/2 M NaOH, 3:1:0.1), and the reaction was stirred
overnight at 50 °C. The mixture was subsequently diluted with
EtOAc (10 mL) and a saturated KHSO4 solution (10 mL). The
organic layer was washed with brine (5 mL), dried over MgSO4, and concentrated in vacuo to give 20 (65 mg, 0.0211
mmol, 89%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 7.71 (s, 2H), 7.67 (s, 2H), 7.62 (s, 1H), 7.34–7.29
(m, 11H), 7.22 (d, J = 8.2 Hz, 14H), 7.19–7.11
(m, 6H), 6.98 (s, 8H), 5.46–5.32 (m, 4H), 4.30–4.14
(m, 8H), 4.13–4.01 (m, 4H), 3.22–3.03 (m, 4H), 2.99–2.82
(m, 8H), 2.64–2.56 (m, 12H), 2.30–2.19 (m, 8H), 2.02–1.54
(m, 12H), 1.52–1.37 (m, 12H), 1.37–1.19 (m, 106H), 1.19–0.83
(m, 44H). 13C {1H} NMR (100 MHz, CDCl3) δ 165.1, 164.9, 151.3, 151.3, 149.4, 148.8, 146.4, 145.6,
143.0, 142.6, 142.6, 135.1, 128.9, 128.8, 128.6, 128.3, 124.9, 124.4,
69.4, 69.2, 67.0, 54.0, 53.4, 48.1, 40.7, 34.2, 33.9, 31.6, 31.5,
31.2, 31.0, 30.5, 29.6, 29.3, 29.2, 29.1, 29.0, 21.5, 21.4. MS (ESI+) m/z calcd for C198H278N12O16 [M + 2H]2+ 1540.1, found 1540.1
Prerotaxane a25B
The
half-stoppered prerotaxanes B5 (85.3 mg, 62.1 μmol,
1 equiv), a2 (87.5
mg, 62.1 μmol, 1 equiv), and TBTA (6.6 mg, 12.4 μmol,
0.2 equiv) were dissolved in dry CH2Cl2 (15
mL), and the solution was purged with N2 for 30 min. Then,
Cu(CH3CN)4BF4 was added, and the
mixture was purged with N2 for an additional 10 min and
stirred overnight at room temperature under a N2 atmosphere.
The crude mixture was dry-loaded on silica and purified by column
chromatography (CH2Cl2/PE/Et2O 6.7:3.3:0.5
→ 5:5:0.5) to give a25B (126 mg, 45.3 μmol,
73%) as a colorless film. 1H NMR (300 MHz, CDCl3) δ 8.03–7.95 (m, 3H), 7.91–7.50 (m, 13.5H),
7.42–7.07 (m, 21H), 6.98–6.92 (m, 0.5H), 4.83–4.71
(m, 1H), 4.70–4.40 (m, 3H), 4.33–4.00 (m, 10H), 3.22–3.11
(m, 2H), 3.04–2.83 (m, 4H), 2.78–2.15 (m, 24H), 1.72–1.50
(m, 16H), 1.46–0.81 (m, 127H). 13C {1H} NMR (75 MHz, CDCl3) δ 164.6, 161.6, 161.3, 153.1,
152.9, 152.1, 150.6, 148.8, 147.4, 147.09, 146.5, 145.9, 145.4, 143.2,
142.3, 142.2, 138.0, 137.6, 137.4, 134.5, 134.3, 131.5, 131.1, 131.1,
128.5, 126.9, 125.8, 125.6, 125.3, 125.0, 123.7, 123.5, 123.2, 121.3,
121.1, 119.8, 119.7, 118.0, 118.3, 117.0, 116.5, 85.3, 84.9, 82.7,
68.8, 66.4, 65.6, 54.2, 47.9, 46.6, 40.9, 40.8, 37.1, 36.7, 34.6,
34.4, 34.4, 31.6, 31.4, 31.4, 30.6, 30.1, 29.9, 29.7, 29.6, 29.5,
29.4, 29.1, 28.8, 28.7, 28.2, 25.2, 23.9, 22.7, 22.7, 22.1, 20.9,
20.6, 17.5, 17.3, 14.7, 14.2, 14.1, 8.0. IR (cm–1): 2954, 2923, 2853, 1742, 1720, 1599, 1572, 1503, 1461, 1410, 1385,
1363, 1303, 1270, 1226, 1197, 1161, 1114, 1086, 1052, 954, 909, 881,
831, 803, 781, 732. HRMS (ESI+) m/z calcd for C172[13]CH225Br2N9O12 (M·+) 2780.5661, found 2780.5746.
[3]Rotaxane a25B (Tetraester)
Prerotaxane a25B (21.6
mg, 7.76 μmol, 1 equiv) was dissolved in
a mixture of dioxane (3.1 mL) and methanol (1.1 mL), a 4 M solution
of NaOH in water (194 μL, 0.780 mmol, 100 equiv) was added,
and the reaction was stirred at room temperature overnight. The mixture
was subsequently diluted with EtOAc (10 mL) and a 1 M KHSO4 solution (10 mL). The aqueous layer was extracted twice with EtOAc
(10 mL), and the reunited organic phases were washed with brine, dried
over MgSO4, and concentrated in vacuo to give the tetraacid,
which was immediately converted to the tetramethylester. A solution
of HCl in MeOH (prepared from 8 mL of MeOH and 1.5 mL of acetyl chloride)
was added, and the solution was stirred at 50 °C during 4 h.
The reaction mixture was concentrated in vacuo, and the residue was
co-evaporated with MeOH (3× 5 mL) and purified by column chromatography
(CH2Cl2/Et2O 19:1 → 9:1 →
8:2) to give [3]rotaxanea25B (9.6 mg, 3.30 μmol,
43%) as a colorless film. 1H NMR (300 MHz, CDCl3) δ 8.33 (s, 1H), 7.90 (s, 2H), 7.73 (s, 2H), 7.43–7.25
(m, 17H), 7.25–7.15 (m, 7H), 7.16–7.09 (m, 5H), 6.97
(s, 4H), 4.80 (t, 2H), 4.54 (s, 2H), 4.18–3.93 (m, 10H), 3.90–3.67
(m, 12H), 3.13 (s, 2H), 2.92 (s, 4H), 2.80–2.53 (m, 14H), 2.52–2.11
(m, 10H), 1.50–1.47 (m, 8H), 1.38 (s, 18H), 1.31 (s, 27H),
1.28 (s, 18H), 1.22–0.80 (m, 64H). IR (cm–1): 2924, 2853, 1719, 1505, 1461, 1437, 1408, 1386, 1363, 1307, 1237,
1203, 1103, 1040, 975, 909, 877, 831, 791, 732, 649, 588. HRMS (FD+) m/z calcd for C177H24281Br81BrN9O16 [M+H]+ 2911.68, found 2911.59. Only two digits are given
because the peak chosen consists of several isotopic components.
Prerotaxane a27B
Synthesis by late-stage
Suzuki cross coupling: aryl bromide a25B (27.6 mg, 9.91
μmol, 1 equiv) and phenylboronic acid (9.7 mg, 79.3 μmol,
8 equiv) were dissolved in THF (3 mL), and the resulting solution
was purged with N2 for 30 min. Then, a degassed 2 M solution
of Na2CO3 in H2O (79 μL, 159
μmol, 16 equiv) was added followed by Pd(PPh3)4 (2.3 mg, 1.98 μmol, 20 mol %), and the mixture was
heated at 120 °C in a sealed pressure vessel for three days.
The mixture was concentrated in vacuo and diluted in CH2Cl2 (10 mL) and H2O (10 mL), the aqueous layer
was extracted with 2× 10 mL of CH2Cl2,
and the reunited organic phases were washed with brine, dried over
MgSO4, and concentrated in vacuo. Purification by column
chromatography (CH2Cl2/PE/Et2O 6.7:3.3:0.5
→ 5:5:0.5 → 5:5:1) to give a27B (11.7 mg,
4.21 μmol, 43%) as a film. 1H NMR (300 MHz, CDCl3) δ 8.09–7.97 (m, 3H), 7.95–7.72 (m, 5H),
7.70–7.60 (m, 8H), 7.60–7.23 (m, 28H), 7.20–7.11
(m, 4.5H), 7.00–6.94 (m, 0.5H), 4.88–4.44 (m, 4H), 4.39–4.01
(m, 10H), 3.23–3.14 (m, 2H), 3.04–1.98 (m, 28H), 1.75–1.52
(m, 16H), 1.48–0.83 (m, 127H). 13C {1H} NMR (75 MHz, CDCl3) δ 165.6, 165.0, 162.1, 161.7,
153.4, 153.1, 152.9, 152.0, 150.6, 148.9, 147.5, 147.1, 146.9, 146.4,
145.5, 144.7, 143.2, 142.2, 140.7, 139.8, 139.7, 138.0, 135.7, 135.4,
134.5, 134.3, 131.6, 131.3, 128.7, 128.5, 127.2, 127.2, 127.0, 125.8,
125.0, 123.8, 123.2, 121.4, 121.1, 118.7, 118.4, 117.0, 116.6, 85.2,
84.8, 82.6, 68.8, 66.3, 65.5, 54.2, 47.9, 46.7, 41.0, 40.8, 34.6,
34.4, 34.4, 31.6, 31.4, 31.4, 30.6, 30.5, 30.3, 29.9, 29.8, 29.8,
29.7, 29.0, 28.4, 28.1, 24.0, 22.8, 22.7, 22.2, 20.9, 17.6, 17.3,
14.7, 14.2, 14.1, 8.0. IR (cm–1): 2953, 2923, 2853,
1741, 1719, 1598, 1550, 1503, 1462, 1410, 1384, 1363, 1303, 1269,
1225, 1196, 1164, 1147, 1114, 1086, 1052, 954, 909, 882, 832, 803,
782, 763, 732. HRMS (ESI+) m/z calcd for C189H251N9O16Na [M+Na]+ 2925.9002, found 2925.8881.Synthesis
by coupling of prerotaxanes a2 and B7: the
half-stoppered prerotaxanes B7 (59.2 mg, 43.3 μmol,
1 equiv), a2 (65.5 mg, 46.5 μmol, 1.07 equiv),
and TBTA (4.6 mg, 8.67 μmol, 0.2 equiv) were dissolved in dry
CH2Cl2 (10 mL), and the solution was purged
with N2 for 30 min. Then, Cu(CH3CN)4BF4 (2.7 mg, 8.67 μmol, 0.2 equiv) was added, and
the mixture was purged with N2 for an additional 10 min
and stirred overnight at room temperature under a N2 atmosphere.
The crude mixture was dry-loaded on silica (ca. 400 mg) and purified
by column chromatography (CH2Cl2/PE/Et2O 6.7:3.3:0.5 → 5:5:0.5 → 5:5:1) to give a27B (110 mg, 39.8 μmol, 92%) as a colorless film.
[3]Rotaxane a27B (Tetramethylester)
Prerotaxane a27B (49.4 mg, 17.8 μmol, 1 equiv) was dissolved in
a mixture of dioxane (3.1 mL) and methanol (1.1 mL), a 4 M solution
of NaOH in water (220 μL, 0.890 mmol, 50 equiv) was added, and
the reaction was stirred at room temperature overnight. The mixture
was subsequently diluted with EtOAc (10 mL) and a 1 M KHSO4 solution (10 mL). The aqueous layer was extracted twice with EtOAc
(10 mL), and the reunited organic phases were washed with brine, dried
over MgSO4, and concentrated in vacuo to give the tetraacid,
which was immediately converted to the tetramethylester. A solution
of HCl in MeOH (prepared from 8 mL of MeOH and 1.5 mL of acetyl chloride)
was added, and the solution was stirred at 50 °C during 4 h.
The reaction mixture was concentrated in vacuo, and the residue was
co-evaporated with MeOH (3× 5 mL) and purified by column chromatography
(CH2Cl2/PE/Et2O 6.7:3.3:1 →
8:2:1 → 8:2:2) to give a27B (32.7 mg, 11.3 μmol,
63%) as a faint yellow film. 1H NMR (300 MHz, CDCl3) δ 8.30 (s, 0.75H), 8.13 (s, 0.25H), 7.97 (s, 2H),
7.74 (s, 1H), 7.62 (d, 4H), 7.45–7.37 (m, 10H), 7.34–7.11
(m, 26H), 6.98 (s, 4H), 4.79 (t, 2H), 4.49 (t, 2H), 4.13–4.00
(m, 8H), 3.94 (t, 2H), 3.88 (s, 3H), 3.85 (s, 3H), 3.80–3.73
(m, 6H), 3.18–3.09 (m, 2H), 3.01–2.77 (m, 8H), 2.70–2.53
(m, 14H), 2.35–2.13 (m, 6H), 1.58 (m, 16H), 1.37–0.86
(m, 127H). 13C {1H} NMR (75 MHz, CDCl3) δ 165.8, 165.7, 165.2, 152.1, 152.0, 151.9, 151.8, 150.4,
150.0, 148.8, 147.6, 147.0, 143.2, 142.4, 142.2, 141.4, 137.8, 133.0,
130.8, 130.5, 129.5, 129.2, 128.7, 128.5, 126.9, 126.7, 126.4, 126.3,
125.8, 125.0, 124.4, 124.4, 124.1, 124.1, 123.9, 123.2, 121.8, 121.3,
116.7, 116.4, 68.9, 66.1, 65.6, 54.1, 52.6, 52.4, 52.3, 52.2, 48.1,
47.2, 46.8, 40.8, 38.9, 34.4, 34.4, 34.0, 32.0, 31.7, 31.6, 31.4,
31.3, 30.9, 30.6, 30.4, 30.0, 29.7, 29.5, 29.4, 29.2, 29.2, 29.1,
29.0, 29.0, 24.0, 23.0, 22.7, 22.1, 14.2, 14.1. IR (cm–1): 2924, 2853, 1719, 1599, 1505, 1465, 1437, 1408, 1386, 1363, 1301,
1268, 1236, 1205, 1103, 1040, 976, 910, 879, 831, 791, 762, 736, 699,
655. HRMS (ESI+) m/z calcd
for C189H251N9O16Na [M+Na]+ 2925.8996, found 2925.8881.
Prerotaxane a232a
Diazide 3 (40 mg, 0.0416 mmol, 1.0 equiv),
mono-stoppered prerotaxane a2 (171 mg, 0.121 mmol, 2.9
equiv), and TBTA (5 mg, 0.0094
mmol, 0.23 equiv) were dissolved in dry CH2Cl2 (13 mL), and the solution was degassed with five vacuum/N2 cycles. Cu(CH3CN)4BF4 (3 mg, 0.0095
mmol, 0.23 equiv) was added, and the reaction was stirred overnight
at room temperature under a N2 atmosphere. The mixture
was concentrated in vacuo and purified by column chromatography (PE/CH2Cl2 4:1 → 2:1 → 1:1) to give a232a (99 mg, 0.0262 mmol, 63%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.84 (s, 3H), 7.72 (s,
3H), 7.55–7.37 (m, 1H), 7.32 (d, J = 8.3 Hz,
12H), 7.24 (d, J = 8.7 Hz, 12H), 7.20–7.10
(m, 12H), 7.10–6.76 (m, 3H), 4.55 (br m, 4H), 4.21 (br m, 16H),
3.23–3.10 (m, 4H), 3.51 (br m, 42H), 1.55 (br m, 12H), 1.34
(br m, 136H), 1.16 (br m, 49H), 0.96 (br m, 34H). 13C {1H} NMR (100 MHz, CDCl3) δ 176.3, 165.0, 152.1,
151.8, 149.0, 148.9, 148.7, 147.0, 146.7, 145.3, 145.0, 144.6, 144.4,
143.1, 131.7, 130.5, 128.6, 128.3, 128.0, 127.8, 124.9, 124.5, 123.7,
123.5, 123.3, 69.7, 69.0, 68.8, 68.6, 66.1, 53.7, 53.3, 47.8, 46.6,
38.8, 34.8, 34.4, 34.3, 34.2, 34.1, 33.7, 31.8, 31.5, 31.4, 31.3,
31.2, 31.1, 30.5, 30.1, 29.8, 29.5, 29.2, 28.8, 28.3, 28.2, 28.1,
15.1, 14.6, 14.1, 14.0. HRMS (ESI+) m/z calcd for C248H345N12O18 [M + 3H]3+ 1260.5500, found 1260.5468.
[4]Rotaxane a232a (Hexaacid)
Prerotaxane a232a (99 mg, 0.0262 mmol) was dissolved in 7 mL of Tesser’s
base (1,4-dioxane/MeOH/4 M NaOH, 3:1:0.1), and the reaction was stirred
over the weekend at 50 °C. The mixture was subsequently diluted
with EtOAc (10 mL) and a saturated KHSO4 solution (10 mL).
The organic layer was washed with brine (10 mL), dried over MgSO4, and concentrated in vacuo to give [4]rotaxane a232a (101 mg, 0.0260 mmol, 99%) as a yellow solid. 1H NMR
(400 MHz, CDCl3) δ 7.83–7.39 (m, 10H), 7.40–7.29
(m, 12H), 7.26–7.15 (m, 16H), 7.11–6.86 (m, 12H), 4.55
(br s, 4H), 4.30–4.26 (m, 4H), 4.26–4.14 (m, 8H), 3.21–3.09
(m, 4H), 3.03–2.83 (m, 8H), 2.68–2.53 (m, 20H), 2.47–2.18
(m, 16H), 1.71–1.59 (m, 16H), 1.54–1.44 (m, 16H), 1.44–1.21
(m, 136H), 1.21–0.98 (m, 46H), 0.97–0.79 (m, 20H). 13C {1H} NMR (125 MHz, CDCl3) δ
176.4, 151.6, 149.4, 149.1, 148.9, 143.1, 129.2, 128.4, 127.5, 126.9,
125.0, 124.7, 124.5, 121.4, 117.2, 70.6, 69.4, 63.1, 54.1, 48.3, 47.2,
47.0, 40.8, 34.4, 34.0, 31.7, 31.5, 31.4, 31.1, 30.7, 30.6, 30.0,
29.7, 29.6, 29.4, 29.3, 29.2, 29.1, 28.4, 25.5, 25.3, 22.7, 21.6,
15.2, 14.2, 14.0, 11.8. HRMS (ESI+) m/z calcd for C248H356N12O24 [M + 2H]2+ 1944.3531, found 1944.3499.
Authors: Chenfeng Ke; Ronald A Smaldone; Takashi Kikuchi; Hao Li; Anthony P Davis; J Fraser Stoddart Journal: Angew Chem Int Ed Engl Date: 2012-09-13 Impact factor: 15.336
Authors: Oleg Borodin; Yevhenii Shchukin; Craig C Robertson; Stefan Richter; Max von Delius Journal: J Am Chem Soc Date: 2021-09-24 Impact factor: 15.419
Scheme 1
Figure 1
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