A Covalent and Modular Synthesis of Homo- And Hetero[ n]rotaxanes

Article abstract of DOI:10.1021/acs.joc.9b03030

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.

Full text of DOI:10.1021/acs.joc.9b03030

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Article
A covalent and modular synthesis of homo and hetero [n]rotaxanes
Milo D. Cornelissen, Simone Pilon, Luuk Steemers, Martin J Wanner, Steven Frölke, Ed
Zuidinga, Steen Ingemann Jorgensen, Jarl Ivar van der Vlugt, and Jan H. van Maarseveen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b03030 • Publication Date (Web): 22 Jan 2020
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A covalent and modular synthesis of homo- and hetero[n]rotaxanes
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Milo D. Cornelissen, Simone Pilon, Luuk Steemers, Martin J. Wanner, Steven Frölke, Ed Zuidinga,
Steen Ingemann Jørgensen, Jarl Ivar van der Vlugt and Jan H. van Maarseveen*
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Van ‘t Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH
Amsterdam, The Netherlands
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E-mail: j.h.vanmaarseveen@uva.nl
Abstract: 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, give 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 provides efficient access to [n]rotaxanes. The
applicability and modular nature of this novel approach was demonstrated by the synthesis of a series of [2]-,
[3]- and [4]rotaxanes. Furthermore, it was shown that the prerotaxanes allow late-stage functionalization of
the ring fragment introducing further structural diversity.
Introduction
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 rely on non-covalent 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 Schill5 back in 1964 and a [2]rotaxane by
Harrison6 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 1).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.
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 1). This capping-type methodology
provides facile access to a series 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
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using supramolecular methodology.15 Especially, hetero[n]rotaxanes poses a challenge that has
been solved by using several orthogonal host-guest systems16,17 or with an iterative active metal
template approach.18 In these approaches the former methodology is limited by the number of
available orthogonal non-covalent recognition elements and the latter by the necessity of
stoppering units in between the rings to avoid dethreading during build up 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 applications as molecular
switches or motors.
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Previous work:
R
tBu
OH
CO2H
O
O
O
O
Clipping
O
O
O
CO2H
OH
O
R
tBu
Capping
[2]rotaxane
This work:
R
O
O
Capping
OH
1: R = tBu
4: R = Br
6: R = Ph
HO
O
n
O
[n+2]rotaxanes
prerotaxane
R
Scheme 1. Outline of the work described in the previous letter and in this work.
As outlined in Figure 1, the phenolic hydroxyl groups at the terephthalic ester 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 was 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.
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Figure 1. 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 2).
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% yield 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 follow-up Pd(0)-catalyzed removal of the allyl protective groups leading to the
macrocyclic ring precursor 13a in 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 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
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the macrocycle (see Figure 2a). This is a prerequisite for arriving at a mechanically interlocked
structure through further capping-type installation of additional functional thread elements and
stoppers.
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R
R
1)
Br
, Mg
( )4
H
H
2) Et3SiH,
BF3•OEt2
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OH
O
OH O
8a: R = tBu
8b: R = Br
9a (84%)
9b (56%)
1) R1-X, K2CO3,
DMF
CO2Me
OH
CO2C6F5
OR1
1) Cs2CO3,, CH3CN
2) R1 = All:
Pd(PPh3)4, Et2NH
2) KOH, H2O,
R1O
HO
THF, MeOH
3) (COCl)2,
DMF, THF
CO2Me
CO2C6F5
10
11: R1 = All (33% from 10)
12: R1 = Me (45% from 10)
4) F5C6OH,
DiPEA, THF
R
R
( )5
( )5
O
1) Grubbs 2nd gen.
(5-10 mol%),
O
O
O
OR1
OR1
CH2Cl2, reflux
2) H2, Pd/C
THF/EtOH (1) or
H2, PtO2, THF
(14)
R1O
R1O
O
O
O
R
O
( )
( )
5
5
R
1: R1 = H, R = tBu (93%)
13a: R1 = H, R = tBu
(72%, from 11)
13b: R1 = Me, R = Br
(86%, from 12)
14: R1 = Me, R = Br (50%)
4: R1 = H, R = Br (99%)
15: R1 = Me, R = Ph (96%)
6: R1 = H, R = Ph (97%)
PhB(OH)2,
Pd(0)
BBr3
BBr3
Scheme 2. Synthesis of the prerotaxanes.
As a 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 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 3). 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.
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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 2b).
a) Prerotaxane 1
b) Prerotaxane 7
Figure 2. Connectivity plots as determined by X-ray crystallography of prerotaxanes 1 (a) and 7 (b). The
macrocycle respective para t-butyl or phenyl substituents in 1 or 7 have been omitted for clarity.
Functionalization of the terephthalic template with the tethered azides and alkynes affected
the H NMR spectra of compounds 2 and 3, now showing broad signals as a result of different
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interconverting conformations of the ring and positioning of the template within the macrocycle.
1
To clarify these spectral features, H NMR spectra were recorded at elevated temperatures in
deuterated toluene (see 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 protons on the terminal alkynes
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appeared as a beacon in the complex room temperature H 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).
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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 1621 (Scheme 4). After subsequent NaBH4 reduction,
an Appel reaction and nucleophilic substitution, azide-functionalized stopper A was obtained in 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 83% yield (over the two steps).
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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 5). After optimization it was found that reaction of 0.4 equiv of stopper with respect to the
prerotaxane prevented formation of the bis-stoppered prerotaxanes, selectively providing the
mono-stoppered prerotaxanes a2 and A2.
tBu
tBu
A
a
2
A2
a2
tBu
R
(88% brsm) tBu
(66% brsm)
tBu
B
B
5 or 7
3
B3
B5 (R = Br, 84% brsm)
B7 (R = Ph, 63% brsm)
tBu
R
(52% brsm)
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.
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CuAAC reaction of bis-alkyne functionalized prerotaxane 2 with 0.4 equiv stopper a or A gave
the mono-stoppered prerotaxanes a2 and A2 in 88% and 66% yield, based on 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 stopper B in 52% yield
(brsm). To allow the synthesis of a hetero[n]rotaxane featuring different ring substitution, 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% yield (brsm) in pure form.
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First, the capping-type synthesis of [2]rotaxanes was undertaken (Scheme 6). 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]rotaxanes a2a or A2A in 77% and
88% yield, 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 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 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 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.
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Next, the covalent approach to MiMs was expanded to the [3]rotaxane series (Scheme 7). 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 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]rotaxanes a25B and a27B were obtained as the tetra methylesters
in overall yields of 31% and 56%.
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tBu
tBu
B3,
i-iii
A23B
A2
(tetraester)
28%
(3 steps)
tBu
tBu
tBu
tBu
tBu
tBu
L, iv, ii
a2
a2L2a
(tetra-acid)
66%
2 steps)
B5, v, 31% (3 steps)
ii, iii
B7, v, ii, iii
56% (3 steps)
Ph
tBu
Br
tBu
a25B
(tetra-
ester)
a27B
(tetra-
ester)
Br
tBu
Ph
tBu
Scheme 7. Synthesis of homo- and hetero[3]rotaxanes. 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 8). Reaction of a25B with phenyl boronic acid
under classical Suzuki conditions in a sealed vessel at 120 °C for 3 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 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 9).
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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)
pre-coated with silica gel 60 F254. Flask column chromatography was performed using SilaFlash P60 (40-63
m) under 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 N2 atmosphere. Bruker DRX-300, 400, and 500
MHz instruments were used to record NMR spectra. Chemical shifts () 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 ( = 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 40000 FWHM. FD/FI
probe was equipped with FD Emitter, Carbotec, FD 10 μm. Current rate 51.2 mA/min over 1.2 min, using field
desorption (FD) as 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 hours. The mixture was then cooled to room temperature and added dropwise to a solution of 8a20
(2.84 g, 13.7 mmol, 1.0 equiv) in dry THF (60 mL) at 0 C under N2 atmosphere. The reaction mixture was
stirred and heated under reflux overnight, and subsequently quenched with H2O (5 mL). The mixture was
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diluted with Et2O (100 mL) and 1M HCl (100 mL), after which the aqueous layer was extracted with 2 x 20 mL
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 eq.) was dissolved in dry CH2Cl2 (50 mL) under N2
.
atmosphere, 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 1h to the stirred reaction mixture, 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.
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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 heated to reflux for 2.5 h. The mixture was then cooled to room temperature and
added dropwise to a solution of 8b22 (4.00 g, 17.5 mmol, 1 equiv) in dry THF (50 mL) at 0 °C under N2
atmosphere. The reaction mixture was stirred for 1 hour, 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 1M HCl (50 mL), after which the aqueous layer was extracted with 2 x 50 mL 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 N2 atmosphere,
.
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, after which the reaction mixture was stirred for 5 hours 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 extracted with 3 x 50 mL 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 minutes. The mixture was then concentrated and subsequently diluted in EtOAc (100 mL) and H2O
(100 mL). The aqueous layer was extracted with 2 x 50 mL EtOAc and the reunited organic phases 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.
bis(perfluorophenyl) 2,5-bis(allyloxy)terephthalate (11)
Dimethyl 2,5-dihydroxyterephthalate 1014 (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 DMF, and the solution was
stirred at 100 °C overnight. Then, the solution was diluted with 300 mL EtOAc and 300 mL water. The aqueous
layer was washed with 2 × 200 mL EtOAc, and the organic layers were combined and evaporated in vacuo.
The crude product was precipitated with 25 mL EtOAc and 40 mL 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 methyl esters, 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 THF:MeOH:H2O (2:1:1), and the solution was
stirred overnight at room temperature. Subsequently the solution was acidified with 15 mL HCl (37%), then
concentrated in vacuo and then diluted again with 200 mL water and was extracted with 2 × 200 mL 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,
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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 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, after which it was
dissolved again in 20 mL 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 dry THF.
The solution was stirred at 0 °C for 1 hour and at room temperature for 3 h. Subsequently, the solution was
concentrated in vacuo and then dissolved in EtOAc, extracted with HCl (1M), 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.
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bis(perfluorophenyl) 2,5-bis(methoxy)terephthalate (12)
Dimethyl 2,5-dihydroxyterephthalate 10 (5.40 g, 23.9 mmol, 1 equiv), 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 x 25 mL CH2Cl2. The reunited organic phases were then washed with 3 x 75 mL 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 additonal 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 ice cold H2O, filtered and
the filtrate was extracted with 3 x 150 mL EtOAc. The reunited organic phases were washed with brine, dried
over MgSO4, concentrated in vacuo and the residue 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. m.p.: 169.6-170.8 °C.
bis(4-(tert-butyl)-2,6-di(hept-6-en-1-yl)phenyl) 2,5-bis(hydroxy)terephthalate (13a)
Compound 9a (0.57 g, 1.65 mmol, 2.2 equiv), Cs2CO3 (0.73 g, 2.23 mmol, 3.0 equiv), and bis(perfluorophenyl)
2,5-bis(allyloxy)terephthalate 11 (0.45 g, 0.74 mmol, 1.0 equiv) were dissolved in dry CH3CN (9 mL) and the
reaction was stirred overnight at 50 C under N2 atmosphere. The reaction mixture was concentrated in vacuo
and purified by column chromatography (PE/CH2Cl2 5:1  3:1  1:1  1:2) to give the bisaryl ester (0.616
g, 0.66 mmol, 89%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.62 (s, 2H), 7.12 (s, 4H), 6.08-5.98 (m, 2H),
5.80-5.70 (m, 4H), 5.46 (dd, J = 17.3, 1.7 Hz, 2H), 5.26 (dd, J = 10.6, 1.6 Hz, 2H), 4.97-4.86 (m, 8H), 4.68-4.66
(m, 4H), 2.54 (t, J = 7.9 Hz, 8H), 2.00 (q, J = 6.8 Hz, 8H), 1.62 (q, J = 7.6 Hz, 8H), 1.33 (s, 34H). 13C{1H} NMR (75
MHz, CDCl3) δ 164.1, 152.0, 148.7, 145.2, 139.0, 133.9, 132.6, 124.9, 124.6, 118.1, 117.5, 114.4, 70.6, 34.5,
33.8, 32.7, 31.6, 30.9, 30.1, 29.2, 28.8, 27.9, 27.7, 25.3.
The thus obtained bis arylester (391 mg, 0.422 mmol) was dissolved in dry 1,4-dioxane (4 mL) under N2
atmosphere. Et2NH (0.18 mL, 1.69 mmol, 4.0 equiv) and Pd(PPh3)4 (24 mg, 0.021 mmol, 0.05 equiv) were
added and the reaction was stirred overnight at room temperature. The mixture was diluted with EtOAc (20
mL) and 1M HCl (10 mL), after which the organic layer was washed with brine (10 mL), dried over MgSO4,
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concentrated in vacuo and purified by column chromatography (PE/CH2Cl2 7:1  5:1) to give 13a (345 mg,
0.407 mmol, 97%) as a yellow crystalline solid. 1H NMR (400 MHz, CDCl3) δ 10.07 (s, 2H), 7.83 (s, 2H), 7.17 (s,
4H), 5.83-5.73 (m, 4H), 5.01-4.89 (m, 8H), 2.50 (t, J = 7.8 Hz, 8H), 2.03 (q, J = 6.9 Hz, 8H), 1.61 (t, J = 7.7 Hz,
8H), 1.44-1.30 (m, 34H). mp 88.2-92.8°C. 13C{1H} NMR (75 MHz, CDCl3) δ 168.1, 153.9, 149.5, 144.5, 138.9,
133.7, 125.1, 118.4, 118.3, 114.4, 34.6, 33.7, 32.7, 31.6, 30.8, 30.1, 29.0, 28.7, 25.3. HRMS (FD+) m/z calcd for
C56H78O6 (M•+) 846.5793, found 846.5814.
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bis(4-bromo-2,6-di(hept-6-en-1-yl)phenyl) 2,5-bis(methoxy)terephthalate (13b)
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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 4Å molecular sieves (3.5 g) were suspended in
dry CH3CN (70 mL) and the reaction was stirred overnight at 50 °C under 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 crystalized 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. Grubbs 2nd generation catalyst (116 mg, 0.137 mmol, 0.10 equiv) was
then added and the mixture was stirred overnight at 40 C under 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 Grubbs II was added, and the reaction was stirred
overnight at 40 C under N2 atmosphere. The mixture was concentrated in vacuo and purified by column
chromatography (PE/CH2Cl2 1:1). 1.06 g of a colorless oil 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. Grubbs 2nd generation catalyst (130 mg, 0.150 mmol, 5 mol%) was then added, and
the mixture purged with N2 for 15 minutes before being warmed to 40 °C and stirred for two days. Then more
Grubbs 2nd 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 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 grey 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 minutes and stirred for 3 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 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. m.p.: 256.6-258.8 °C. 1H NMR
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(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.
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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 1M 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 re-concentrated from MeOH (125 mL) two more times,
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giving prerotaxane 4 (416 mg, 0.495 mmol, 99%) as a yellow powder. H 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 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 purged with N2 for 30 minutes. Then a degassed 2M
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.m.p.: 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., 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 1M 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 re-concentrated 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 a 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 20h 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
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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.
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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), (8.4 mg KI, 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.
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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 x 25 mL 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,
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100%) as a white solid. m.p.: 171.2-174.5 °C. H 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 x 25 mL 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. m.p.: 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
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Carbaldehyde 1617 (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, 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), 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), the mixture was purged with N2 for 30 minutes
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 minutes, then at room temperature for
30 minutes, 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), 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), 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.
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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 nitrogen atmosphere was cooled to 0 °C and stirred for 15 minutes. Carbaldehyde 18 (846 mg, 2.28
mmol, 1 equiv) was added to the yellow solution, then the mixture was stirred cooled at 0 °C for 1h 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 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 1h at -78 °C and 1h at room
temperature. The reaction was quenched with H2O (5 mL) and the aqueous layer 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)
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to give B (712 mg, 1.88 mmol, 90%) as a white solid. H 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)
a14 (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 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
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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 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]+ 1324.902, found 1324.899.
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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
minutes. Then Cu(CH3CN)4BF4 (8.0 mg, 0.025 mmol, 0.2 equiv) was added and the mixture purged with N2 for
additional 10 minutes and stirred overnight at room temperature under N2 atmosphere. The crude mixture
was dry loaded on silica (600 mg ca.) 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
minutes. Then Cu(CH3CN)4BF4 (15.7 mg, 0.050 mmol, 0.2 equiv.) was added and the mixture purged with N2
for additional 10 minutes and stirred overnight at room temperature under N2 atmosphere. The crude
mixture was dry loaded on silica (700 mg ca.) 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
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material to afford an additional portion of B5 (64.5 mg, 0.047 mmol, 31%). H 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 minutes.
Then Cu(CH3CN)4BF4 (9.6 mg, 30.4 μmol, 0.2 equiv.) was added and the mixture purged with N2 for additional
10 minutes and stirred overnight at room temperature under N2 atmosphere. The crude mixture was dry
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loaded on silica (500 mg ca.) 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.
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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 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 literature.14
[2]Rotaxane a2a (di acid)
Prerotaxane a2a (190 mg, 0.100 mmol) was dissolved in 8 mL Tesser’s base (1,4-dioxane/MeOH/2M 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 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 (di acid)
Prerotaxane A2A (71 mg, 0.0412 mmol) was dissolved in 4 mL Tesser’s base (1,4-dioxane/MeOH/2M 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),
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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+ 880.093, found 880.099.
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Prerotaxane B3B
Diazide 3 (75 mg, 0.0759 mmol, 1.0 equiv), and 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 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
a 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]+ 1732.078, found 1732.081
[2]Rotaxane B3B (tetra methyl ester)
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 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 (10 mL), dried over MgSO4, 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 MeOH and
1.5 ml acetyl chloride at 50 C) was added and the solution was stirred at 50 C during 5 h. The reaction
mixture was concentrated in vacuo, the residue was co-evaporated with MeOH (3x 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]+ 1758.175, found 1758.177
Prerotaxane a2A
Half stoppered prerotaxane a2 (54.9 mg, 0.0390 mmol, 1 equiv), stopper A (0.0186 g, 0.0468 mmol, 1.2 eq)
and TBTA (4.13 mg, 0.00779 mmol, 0.2 equiv) were dissolved in 5 mL 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 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 (di acid)
Prerotaxane a2A (39 mg, 0.216 mmol) was dissolved in 2 mL Tesser’s base (1,4-dioxane/MeOH/2M 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
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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.
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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 18h at room
temperature under 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 a 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 (tetra methyl ester)
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 MeOH and
1.5 ml acetyl chloride at 50 C) was added and the solution was stirred at 50 C during 5 h. The reaction
mixture was concentrated in vacuo, the residue was co-evaporated with MeOH (3x 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 a 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 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 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,
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3027.0744.
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[3]Rotaxane a2L2a (tetra acid)
Prerotaxane a2L2a (71 mg, 0.0236 mmol) was dissolved in 7 mL Tesser’s base (1,4-dioxane/MeOH/2M 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
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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 minutes. Then Cu(CH3CN)4BF4 was added and the mixture purged with N2 for additional 10 minutes and
stirred overnight at room temperature under 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, 127fzH). 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 C17213CH225Br2N9O12 (M•+) 2780.5661, found
2780.5746.
[3]Rotaxane a25B (tetra ester)
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 4M 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 1M
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 tetra acid, which
was immediately converted to the tetra methyl ester. A solution of HCl in MeOH (prepared from 8 mL of
MeOH and 1.5 mL acetyl chloride) was added and the solution was stirred at 50 °C during 4 h. The reaction
mixture was concentrated in vacuo, the residue was co-evaporated with MeOH (3 x 5 mL) and purified by
column chromatography (CH2Cl2/Et2O 19:1  9:1  8:2) to give [3]rotaxane a25B (9.6 mg, 3.30 μmol, 43%)
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as a colorless film. H NMR (300 MHz, CDCl3) δ 8.33 (s, 1H), 7.90 (s, 2H), 7.73 (s, 2fH), 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
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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
purged with N2 for 30 minutes. Then a degassed 2M 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 3 days. The mixture was concentrated in vacuo and diluted in CH2Cl2 (10 mL) and
H2O (10 mL), the aqueous layer was extracted 2 x 10 mL CH2Cl2 and the reunited organic phases were washed
with brine, dried over MgSO4 and concentrated in vacuo. Purification by column chromatography
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(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. H NMR
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(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, 127). 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 minutes. Then Cu(CH3CN)4BF4 (2.7 mg, 8.67 μmol,
0.2 equiv.) was added and the mixture purged with N2 for additional 10 minutes and stirred overnight at
room temperature under 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 (tetra methyl ester)
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 4M 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 1M
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 tetra acid, which
was immediately converted to the tetra methyl ester. A solution of HCl in MeOH (prepared from 8 mL of
MeOH and 1.5 mL acetyl chloride) was added and the solution was stirred at 50 °C during 4 h. The reaction
mixture was concentrated in vacuo, the residue was co-evaporated with MeOH (3 x 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%)
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as a faint yellow film. H 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 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%)
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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.
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[4]Rotaxane a232a (hexa-acid)
Prerotaxane a232a (99 mg, 0.0262 mmol) was dissolved in 7 mL Tesser’s base (1,4-dioxane/MeOH/4M 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
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yellow solid. H 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.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI @: 1H and 13
C
NMR spectra of all new products and intermediates. X-ray crystallographic structures of prerotaxanes 1 and
7 (CIF).
AUTHOR INFORMATION
Corresponding Author
*E-mail: j.h.vanmaarseveen@uva.nl
ORCID
Jan Herman van Maarseveen: 0000-0002-1483-436X
Jarl Ivar van der Vlugt: 0000-0003-0665-9239
Notes
The authors declare no competing financial interest.
Acknowledgement
The authors would like to thank The Netherlands Organization for Scientific Research for financial support
(NWO-CW, ECHO grant numbers 711.014.010 and 711.017.007 to J.v.M).
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