Introduction of useful peripheral functional groups on [2]catenanes by combining Cu(i) template synthesis with click chemistry

Article abstract of DOI:10.1039/b9nj00486f

Two protocols based on Cu(i) template synthesis and click reactions for the synthesis of functionalized [2]catenanes are described. A straightforward procedure, involving high dilution conditions at high temperatures (70 °C), affords [2]catenanes bearing two identical peripheral groups in high yields. For the preparation of non-symmetrically functionalized [2]catenanes, a second milder and simpler protocol was developed, generalizing and extending the method. The introduction of peripheral functional groups into the catenane structure opens up possibilities of using [2]catenanes as building blocks for preparation of even more complex structures.

Full text of DOI:10.1039/b9nj00486f

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Introduction of useful peripheral functional groups on [2]catenanes
by combining Cu(I) template synthesis with ‘‘click’’ chemistryw
Jackson D. Megiatto, Jr.* and David I. Schuster*
Received (in Montpellier, France) 15th September 2009, Accepted 19th October 2009
First published as an Advance Article on the web 11th November 2009
DOI: 10.1039/b9nj00486f
Two protocols based on Cu(I) template synthesis and ‘‘click’’ reactions for the synthesis of
functionalized [2]catenanes are described. A straightforward procedure, involving high dilution
conditions at high temperatures (70 1C), affords [2]catenanes bearing two identical peripheral
groups in high yields. For the preparation of non-symmetrically functionalized [2]catenanes,
a second milder and simpler protocol was developed, generalizing and extending the method.
The introduction of peripheral functional groups into the catenane structure opens up possibilities
of using [2]catenanes as building blocks for preparation of even more complex structures.
(phen) ligands, which form a pseudotetrahedral (phen)2–Cu(I)
1. Introduction
complex, generating the cross-over points needed for inter-
locked structure formation. Sauvage and co-workers8 have
Recent developments in the synthesis of interlocked molecules
have allowed the preparation of a great variety of rotaxanes,
elegantly demonstrated that catenanes can be prepared by two
catenanes and more complex structures, such as three foil
different basic strategies using Cu(I) template synthesis. In the
knots.1 The easy access to such interlocked molecules has
one-step approach (strategy A, Scheme 1), the two phen
allowed an extensive exploration of their interesting submolecular
ligands assemble around the Cu(I) ion, and the subsequent
motion properties as principles for construction of molecular
pairwise connection of the reaction centers leads to catenanes.
machines, molecular muscles, nanoelectromechanical systems
In the step-wise approach (strategy B, Scheme 1), which is one
and nanovehicles.2 This flourishing field of research has
step longer but results in better yields than strategy A, a
also impacted other fields such as artificial photosynthetic
‘‘threading’’ reaction of a phen-string-like fragment through
systems,3 catalysis,4 and drug delivery.5
a previously synthesized phen-containing ring, promoted by
The preparation of interlocked molecules relies on two key
binding to the Cu(I) center, generates a pseudorotaxane
steps: (i) recognition and arrangement of the non-interlocked
precursor, which can be subjected to cyclization reactions,
components in an entwined orientation, and (ii) covalent
affording catenanes.
bond-forming reactions, which prevent the fragments from
The biggest challenge in the preparation of interlocked
disentangling, creating
a mechanical bond between the
molecules using Cu(I) template synthesis is the ring closure
of the pre-oriented phen moieties. The precursor (phen)2–Cu(I)
complex is inherently unstable,8 since it may dissociate from
the metal core when subjected to changes in temperature,
solvent polarity, or the presence of strong bases or competing
complexation ligands. Kinetically controlled reactions, where
the (phen)2–Cu(I) pseudotetrahedral configuration is retained
subunits.6 Different templates based on non-covalent bonding
interactions, including hydrogen bonding, donor–acceptor
interactions, and metal complexation, have been successfully
used as synthetic tools to organize the motifs in the orthogonal
arrangement necessary to afford interlocked molecules.1
For the final covalent bond-forming step, different reactions
have been explored as protocols for stoppering (rotaxanes) or
cyclization (catenanes) reactions. Ring closing metathesis
(RCM), imine formation, oxidative coupling of alkynes, and
Huisgen copper(I)-catalyzed alkyne–azide 1,3-dipolar cyclo-
addition (the CuAAC or ‘‘click’’ reaction) have proved to be
efficient methodologies for the final step in the synthesis of
interlocked molecules.1a,7
Among the entwined templates described in the literature,
the metal-template approach, developed by Sauvage and
co-workers,8 is a highly effective strategy for the preparation
of catenanes, rotaxanes and knots. This idea is based on the
strong preference of Cu(I) ions for two bidentate phenanthroline
Chemistry Department, New York University, New York, NY 10003,
USA. E-mail: david.schuster@nyu.edu, jackson.megiatto@nyu.edu
w Dedicated to Jean-Pierre Sauvage on the occasion of his 65th
birthday.
Scheme 1 Sauvage’s Cu(I) template synthesis principle.8
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in the transition state, minimize this dissociation problem and
give mechanically interlocked compounds in high yields.
The CuAAC or ‘‘click’’ reaction9 has emerged as a powerful
and robust synthetic tool for construction of complex materials
due to its unusual tolerance towards functional groups,
regioselectivity and often quantitative yields. Synthesis of
elaborate structures, such as dendrimers, macrocycles,
polymers, donor–acceptor materials, as well as derivatization
of biological substrates (e.g., virus particles, enzymes and
proteins), has been efficiently accomplished using the CuAAC
reaction.10
given in the Experimental). Another important aspect of the
cyclization reaction shown in Scheme 2 is that sulfonated
bathophenanthroline (SBP), a so-called ‘‘click’’ additive,10g,h
must be employed as part of the ‘‘click brew’’. In biological
systems, SBP has been used previously to sequester Cu(I) ions
from the reaction medium, thereby preventing damage to
substrate molecules, such as peptides and proteins.10g Due to
the ability of 1 to complex Cu(I) ions, the absence of SBP as an
auxiliary ligand results in a complex product mixture, which
contains only 7% of target macrocycle 3 along with other
unidentified products.
Inspired by these promising results, we have developed
effective straightforward strategies based on ‘‘click’’ chemistry
and Sauvage’s Cu(I) template technique, for preparation of
interlocked molecules, such as [2] and [3]catenanes.11 Taking
advantage of the mild conditions employed in these protocols,
we have been able to introduce useful functional groups on
the periphery of the interlocked rings, which allow further
structural elaboration.
When a highly dilute equimolar mixture of 1 and 2 in 9 : 1
EtOH–toluene solvent mixture was added dropwise over
10 hours to a mixture containing CuI, sodium ascorbate
(SA), DBU and SBP in an oxygen-free 7 : 3 : 1 EtOH–H2O–
toluene solvent mixture at 70 1C, macrocycle 3 was obtained in
70% isolated yield. The structure of 3 was unambiguously
confirmed by its 1H NMR spectrum (Fig. 1) and by
MALDI-TOF analysis (Fig. 2), which showed a molecular
ion peak at m/z 979.20 [M + H]+. Remarkably, higher cyclic
compounds, oligomers and linear structures were not formed
under these conditions, confirming the specificity of our
cyclization protocol.
We have explored both Cu(I) template strategies (A and B,
Scheme 1) in conjunction with the CuAAC reaction for
preparation of functionalized interlocked molecules. In a
previous communication,11a we reported that formation of a
bis-diethynyl(phen)2–Cu(I) complex, according to one-step
strategy A (Scheme 1), followed by ‘‘double click’’ ring closure
at 70 1C with functionalized 3,5-aryl-diazides under high
dilution conditions, afforded [2]catenanes with identical
functionalized rings. Catenanes with two different interlocked
rings are appealing targets since they open up the possibility of
using interlocked structures as building blocks for preparation
of even more complex materials. To prepare such materials,
we first attempted the step-wise Cu(I) approach B (Scheme 1)
using our previous methodology.11a Analysis of the product
mixtures revealed that the pseudorotaxane precursor
(phen)2–Cu(I) complex dissociates from the metal core under
these conditions.11a To minimize this dissociation problem, a
slightly different and simpler procedure, which does not
require high dilution conditions, had to be developed.11b,c
Indeed, employing milder conditions allowed the preparation
of non-symmetrical-functionalized [2]catenanes in high yields,
as illustrated below by the synthesis of a non-symmetrical
[2]catenane bearing peripheral styrene and benzaldehyde
groups.
This promising result encouraged us to explore other
variants of this methodology. We envisaged the straight-
forward preparation of a symmetrical-functionalized [2]catenane
based on the Cu(I) template one-step strategy depicted in
Scheme 3. The reaction was carried out as follows:
bis-diethynyl(phen)2–Cu(I) complex 4, prepared following the
one-step strategy A (Scheme 1), was added to a 7 : 3 : 1
EtOH–H2O–toluene mixture of DBU, SA, SBP and CuI at
70 1C. A highly dilute solution of 2 in 9 : 1 EtOH–toluene was
then added dropwise over 12 h, affording the symmetrically
functionalized catenand 5 in 90% yield.
The material obtained after the workup procedure, which
involved washing with ammonium hydroxide,10a,b was surpris-
ingly the copper-free catenane. Its 1H NMR spectrum is quite
similar to that of the analogous macrocycle shown in Fig. 1;
however, MALDI-TOF analysis (m/z calculated for 5:
1956.86; found: 1957.48 [M + 1]+, Fig. 3) confirmed the
Cu-free catenane structure.11a Presumably, the cuprous ion
was removed by complexation with ammonium hydroxide
present in the reaction brew. No higher catenanes were formed
under these conditions, demonstrating the remarkable
efficiency of the final ‘‘double click’’ cyclization procedure.
2. Results and discussion
Synthesis of symmetrical-functionalized [2]catenanes
Synthesis of non-symmetrical-functionalized [2]catenanes
At the outset of this study, it was anticipated that the mild
conditions and the unusual tolerance of ‘‘click’’ reactions9
toward the substrate would allow the introduction of useful
functional groups into interlocked structures. We first studied
a model reaction between the bis-ethynyl derivative 1 and
the 3,5-diazidoaryl acetal 2 to afford phen-macrocycle 3
(see Scheme 2).
We found11a that the CuAAC cyclization reaction between 1
and 2 to give 3 in good yields requires high temperature
(70 1C), high dilution conditions and the presence of the base
1,8-diaza[5.4.0]bicycloundec-7-ene (DBU) (full details are
We next turned our attention to the preparation of a
non-symmetrically functionalized [2]catenane (Scheme 4).
The synthesis of a [2]catenane bearing peripheral styrene and
aldehyde groups was particularly appealing, since it would
allow the preparation of more complex structures using well
established methodologies, such as radical polymerization,12a
olefin metathesis,12b Wittig12c or Schiff base12d reactions.
The synthetic pathway outlined in Scheme 4 is based on
Sauvage’s step-wise Cu(I) template approach (Scheme 1),
which is expected to afford catenanes with two different
interlocked rings.8 Macrocycle 6 was prepared as described
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Scheme 2 Building blocks and ‘‘double click’’ macrocyclization model reaction between diethynylphenanthroline derivative 1 and 3,5-diazidoaryl
acetal 2 to afford macrocycle 3. (a) Neopentylglycol, p-toluenesulfonic acid, THF, reflux, 8 h, quantitative; (b) NaN3, sodium ascorbate (SA),
N,N-dimethylethylenediamine, CuI, EtOH–H2O, reflux, 3 h, 60% yield; (c) CuI, SA, SBP, H2O–EtOH–toluene, high dilution, 70 1C, 30 h, 70%
yield.
elsewhere.11b Reduction followed by oxidation of the
peripheral carboxymethyl ester group, using LiAlH4 and
MnO2, respectively, resulted in aldehyde 7. The threading of
the diethynylphenanthroline derivative 1 through the macro-
cycle 6 gave precursor 8. Compound 10 was prepared in two
steps: Wittig reaction between 3,5-dibromobenzaldehyde
and methyl triphenyl phosphonium bromide in presence of
potassium tert-butoxide (t-BuOK) yielded 3,5-dibromostyrene
9, which then was converted to 10 using NaN3 following a
literature procedure.13
The final cyclization reaction between 8 and 10 using
the same ‘‘click’’ conditions described for 3 did not yield the
desired catenate 11 after the usual workup. Instead, the
symmetric bis-styrene-functionalized [2]catenate 12 (Scheme 5)
was isolated in 35% yield together with the styrene-macrocycle
13 (10%) along with other unidentified byproducts, indicating
that under these conditions unthreading of 8 took place.
Fig. 1 1H NMR spectrum (400 MHz, CDCl3, 300 K) of macrocycle 3.
A plausible explanation14 for the formation of catenate 12 is
shown in Scheme 5, involving decomposition of the precursor
8 followed by the formation of the symmetrical complex 4,
which then undergoes ‘‘click’’ reactions with 10 to form 12.
The starting macrocycle 7 was not identified in the product
mixture, suggesting that the peripheral aldehyde group on 7
may undergo side reactions under the reaction conditions.
These results indicate that the conditions used for the final
cyclization reaction are too harsh, resulting in unthreading of
8 before the CuAAC reactions with 10 took place.8,14 In order
to minimize the detrimental unthreading process, the reaction
medium had to be adjusted to stabilize precursor 8, while
simultaneously the kinetics of the critical cycloaddition
reactions must be accelerated to prevent side reactions with
the peripheral functional groups.
Thus,
a new strategy to prepare non-symmetrical-
functionalized [2]catenanes was required, shown in Scheme 6.
To overcome the precursor stability problem, a heterogeneous
reaction medium was used, composed of dichloromethane
(DCM) and aqueous ethanol. The Cu(I)–(phen)2 complex is
Fig. 2 MALDI-TOF mass spectrum of macrocycle 3 (positive mode,
a-cyano-4-hydroxycinnamic acid (CCA) matrix).
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Scheme 3 One-step strategy to the preparation of symmetrical-functionalized [2]catenand 5, (a) Cu(CH3CN)4][PF6], DCM–CH3CN, rt, 30 min;
quantitative; (b) (ii) 2, CuI, SA, SBP, H2O–EtOH–toluene, high dilution, 70 1C, 30 h; (ii) DCM–H2O–NH4OH, rt, 12 h, 90% yield.
groups. Thus, the diazido phen string-like fragment 1411b
and 3,5-diethynylstyrene 15 were synthesized and used as
building blocks for the preparation of the target [2]catenate
17. Compound 15 (Scheme 6) was prepared by a Sonogashira
coupling reaction between 9 and a large excess of (trimethylsilyl)-
acetylene,15 followed by treatment with tetrabutylammonium
fluoride (TBAF) in THF at rt, affording compound 15 in 70%
overall yield. The threading reaction of 14 through macrocycle 7,
using Cu(I) ion as template,8 afforded the pseudorotaxane
precursor 16 in quantitative yield.
The final macrocyclization reaction was carried out as
follows:11b CuI, SA and SBP were dissolved in degassed
aqueous ethanol (1 : 1, v/v), and the pink suspension was
heated at reflux for 2 min under nitrogen in order to increase
the solubility of the catalyst brew before being cooled to room
Fig.
[2]catenand
(CCA) matrix).
3
MALDI-TOF mass spectrum of triazole-linked Cu-free
temperature. The red DCM–acetonitrile solution containing
16 was then diluted to 10 mL with degassed DCM and added
by syringe to the reaction flask. Finally, diethynylstyrene
derivative 15, dissolved in 3 mL of degassed DCM, and
DBU were added and the resulting red mixture was stirred
under nitrogen for 12 h at rt. The crude mixture was washed
with 10% aqueous HCl solution, then water, and finally
extracted with DCM. The organic phase was then stirred for
3 h with a saturated methanol solution of KPF6 to effect the
anion exchange. Final purification was achieved by column
chromatography (silica gel) using DCM–methanol (99/1 v/v)
as eluent, affording 17 as a red solid in 60% yield.
5
(positive mode, a-cyano-4-hydroxycinnamic acid
less susceptible to unthreading in the DCM phase, while the
other CuAAC reagents remain mainly in the aqueous phase;
since the reaction to connect the pieces takes place at the
interface, high dilution conditions are not required in this new
scenario.
To enhance the reaction kinetics, we again used the ‘‘click
additives’’ SBP and the base DBU.10h,11 Switching the azide
and alkyne positions on the building blocks allowed the final
CuAAC cyclization reactions to occur at room temperature,
increasing the tolerance toward the peripheral functional
The MALDI-TOF spectrum (Fig. 4) shows a peak at m/z
1623.12, corresponding to the target structure 17 (M ꢁ PF6)+.
Scheme 4 Building blocks and unsuccessful attempt to synthesize non-symmetrical-functionalized [2]catenate 11; (a) (i) LiAlH4, THF, rt, 6 h,
quantitative; (ii) MnO2, DCM, reflux, 12 h, 65% overall yield; (b) two steps: (i) [Cu(CH3CN)4][PF6], DCM–CH3CN, rt, 30 min; (ii) 1, rt, 3 h,
quantitative; (c) CuI, SA, SBP, H2O–EtOH–toluene, high dilution, 70 1C, 30 h; (d) (i) methyltriphenylphosphonium bromide, t-BuOK, THF, 0 1C,
30 min; (ii) ꢁ78 1C, 9, then rt, 1 h, yield 45%; (e) NaN3, SA, N,N-dimethylethylenediamine, CuI, EtOH–H2O, reflux, 3 h, 55% yield.
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Scheme 5 Proposed synthetic pathway leading to formation of symmetrical-functionalized [2]catenate 12 and macrocycle 13 under the conditions
explored for the synthesis of target catenate 11.
Scheme 6 Strategy for preparation of non-symmetrical-functionalized [2]catenate 17, (a) (i) Pd(Ph3P)2Cl2, CuI, Et3N, (trimethylsilyl)acetylene,
50 1C; (b) TBAF, THF, rt, 30 min, 70% overall yield; (c) (i) [Cu(CH3CN)4][PF6], DCM–CH3CN, rt, 30 min; (ii) 14, rt, 3 h, quantitative; (d) 15,
CuI, SA, SBP, DBU, DCM–H2O–EtOH, rt, 12 h, 78% yield; (e) KCN, DCM–H2O, rt, 30 min, quantitative yield.
The fragmentation pattern observed in the mass spectrum,
which can be unambiguously assigned to the individual
macrocycles, is very characteristic of catenane structures.16
Loss of N2 from the triazole rings17 was also observed in the
spectrum, suggesting that fragmentation of the styrene-
containing ring occurs through cleavage of the triazole moieties.
The absence of fragments between the molecular ion peak and
the peaks corresponding to the individual macrocycles
confirms the assigned catenate structure 17, possessing two
different functionalized interlocked rings.
1H NMR analysis (Fig. 5) clearly supports the non-symmetrical
interlocked structure 17 depicted in Scheme 6. The aldehyde
proton is observed at 9.63 ppm, while those belonging to the
olefinic moiety are at 6.36, 5.51, and 4.90 ppm (identified as f 0
and g0 in Fig. 5). The methylene groups adjacent to the triazole
ring appear at 4.57 ppm, while the resonance of the proton on
the triazole ring itself is at 7.91 ppm (identified as b0 and c0
in Fig. 5).11a The expected upfield shift for the phenyl
protons on the two phen fragments entwined around the
Cu(I) core8 is observed, while the protons attached to
the phenanthroline moieties give signals at the expected
regions for a Cu(I) catenate.8 The protons on the trioxoethyl
linkers appear in the usual region between 4.40 and 3.00 ppm.
Interestingly, the corresponding protons of the styrene
moiety (labeled as d0 and e0, in Fig. 5) give peaks at
significantly higher field, which can be explained by a
deshielding effect exerted by the two triazole rings at the meta
positions of the styrene ring.18
Removing the Cu(I) ion in 17, following the classical KCN
procedure,8 resulted in the Cu-free catenand 18 (Scheme 6),
which was isolated as a waxy material in quantitative yield.
The mass spectrum shows the ion peaks corresponding to
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Cu-free catenand 18 and the two different macrocyclic
components, revealing again the characteristic fragmentation
pattern of catenated species under the ionization conditions of
MALDI-TOF mass spectrometry.16
The 1H NMR spectrum of 18 indicates that, upon
demetalation of 17, the two interlocked rings undergo a
reorientation relative to one another (Fig. 5). In particular,
the signals of protons o and o0, and m and m0 of the phenyl
substituent of the phenanthroline moieties move downfield,
indicating that the two chelates are no longer entwined around
the Cu(I) ion template.8 These assignments were made with the
help of 2D COSY 1H NMR spectral data. The protons on the
styrene ring are shifted upfield, reflecting proximity to other
aromatic residues.14 These considerations suggest that 18
adopts a conformation similar to that shown in Scheme 6, in
agreement with conformations previously reported for other
demetalated catenands.8
Fig. 4 MALDI-TOF mass spectrum of styrene-aldehyde-Cu(I)-[2]-
catenate 17 (positive mode, a-cyano-4-hydroxycinnamic acid (CCA)
matrix). K = Cu(I) ion.
Fig. 5 1H NMR spectra (400 MHz, CDCl3, 298 K) of benzaldehyde-macrocycle 7, styrene-benzaldehyde-Cu(I)-[2]catenate 17 and Cu-free
[2]catenand 18. K = Cu(I) ion andE = solvent peak.
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The 1H NMR spectrum of 18 shows no concentration
dependence in CDCl3 at room temperature, implying no
significant intermolecular p–p stacking.14,19 Variable tempera-
an abbreviation for aromatic ring. Mass spectra were obtained
on an Agilent 1100 Series Capillary LCMSD Trap XCT
Spectrometer in positive or negative-ion mode and
a
1
ture H NMR studies (298–233 K) in the same solvent show
ThermoFinnigan PolarisQ ion-trap GCMS Spectrometer.
MALDI-TOF mass spectra were recorded in a Bruker
OmniFLEX MALDI-TOF MS Spectrometer. This instrument
was operated at an accelerating potential of 20 kV in linear
mode. The mass spectra represent an average over 256
consecutive laser shots. The mass scale was calibrated using
the matrix peaks and the calibration software available
from Bruker OmniFLEX. The mentioned m/z values
correspond to monoisotopic masses. The compound solutions
(10ꢁ3 mol Lꢁ1) were prepared in THF. Matrix compound was
purchased from Aldrich and used without further purification.
The matrix, a-cyano-4-hydroxycinnamic acid (CCA), was
dissolved (10 g Lꢁ1) in a solvent mixture composed of
H2O–CH3CN–TFA (25/75/1, v/v). Two microlitres of
compound solution were mixed with 10 mL of matrix solution.
The final solution was deposited onto the sample target and
allowed to dry in air. All chemicals were purchased from
Sigma-Aldrich and Alfa Aesar and used without further
purification. For moisture sensitive reactions, solvents were
freshly distilled. Methylene chloride (DCM) and acetonitrile
(CH3CN) were dried over calcium hydride while tetrahydro-
furan (THF) was dried using sodium–benzophenone.
Anhydrous dimethylformamide (DMF) was used as received.
All syntheses were carried out using Schlenk line techniques.
Moisture sensitive liquids were transferred by canula or
syringe. The progress of the reactions was monitored by
thin-layer chromatography (TLC) whenever possible. TLC
was performed using precoated glass plates (Silica gel 60,
0.25 mm thickness) containing a 254 nm fluorescent indicator.
Column chromatography was carried out using Merck
Silica gel 60 (0.063–0.200 mm). Macrocycle 6 and diazido
phenanthroline derivative 14 were prepared in accordance
with previously reported procedures.11b
only increasing broadening of the peaks as the temperature is
lowered, indicating that the molecule exists in several inter-
converting conformations.14 Presumably, this lack of order is
a result of the large size and shape of the macrocycle compo-
nents (42 and 37-atom membered rings) of catenand 18. The
two rings are apparently free to reorient around and through
one another at a rate which is fast on the 1H NMR time scale,
even at low temperatures (213 K) in CDCl3.
These results clearly demonstrate that the introduction of
peripheral styrene and aldehyde groups and the presence of
triazole rings does not noticeably alter the physical properties
of the [2]catenane in solution.8,14,19 The free circumrotation of
one ring within the other and the relatively facile conforma-
tional changes are desirable features, since the peripheral
groups are available for further reactions, opening up the
possibility of using functionalized catenanes as synthetic
building blocks, even after removing the metal-template ion
needed to assemble the structure.
3. Conclusions
Two ‘‘click’’ protocols for the preparation of functionalized
[2]catenanes, using a Cu(I) template synthesis, are described. A
straightforward strategy allowed the synthesis of symmetrical-
functionalized [2]catenanes, although it failed for the synthesis
of non-symmetrical [2]functionalized catenanes. A different
strategy using milder conditions, which is compatible with
the instability of precursors and the presence of peripheral
functional groups, was developed for the preparation of
non-symmetrical-functionalized [2]catenanes in high yields.
The introduction of peripheral functional groups into
[2]catenane structures will be useful for the preparation of
structurally elaborated materials, such as polymers, dendri-
mers, mechanically linked donor–acceptor systems and higher
interlocked structures. The large size of the macrocycle
components allows the interlocked structure to adopt different
conformations after removing the central Cu(I) ion needed for
structural assembly, suggesting that the metal-free system
should be suitable for further reactions to prepare more
complex purely organic systems. These possibilities are under
current investigation.
Synthesis
Bis-ethynylphenanthroline derivative 1. 2,9-Bis(4-{2-[2-
hydroxyethoxy(ethoxy)-(ethoxy)]}phenyl)-1,10-phenanthroline
(4.00 g, 6.380 mmol), prepared in accordance with the literature
procedure,8c and propargyl bromide (15.00 g, 12.740 mmol)
were dissolved in 200 mL of dry DMF and stirred for 15 min
under an argon atmosphere at room temperature. Sodium
hydride (0.450 g, 18.90 mmol) was then added and the reaction
mixture was heated to 80 1C. After 4 h, another portion of
NaH (0.220 g, 9.450 mmol) and propargyl bromide (7.50 g,
6.370 mmol) were added and the reaction mixture was stirred
for an additional 8 h at 80 1C. The reaction was carefully
quenched with cold water and concentrated under reduced
pressure. DCM (300 mL) was added and the organic layer
was then separated. The aqueous phase was extracted with
DCM (3 ꢂ 100 mL). The combined organic layers were
washed with water (3 ꢂ 150 mL), dried over magnesium
sulfate, filtered through paper and concentrated. Final
purification was achieved by column chromatography (SiO2)
using DCM–MeOH as the eluent (gradient from 0 to 3%, v/v),
affording 1 (3.60 g, 85%) as a brown oil. dH (400 MHz;
4. Experimental section
General
NMR spectra were obtained on either a Bruker AVANCE 400
(400 MHz) or an AVANCE 500 (500 MHz) spectrometer
using deuterated solvents as the lock. The spectra were
collected at 25 1C and chemical shifts (d, ppm) were referenced
1
to residual solvent peak. J values are given in Hz. In the H
NMR assignment (d), Ho and Hm refer to the hydrogen atoms
at the ortho and meta positions, respectively, of the phenyl ring
attached to the phenanthroline ring system, whose hydrogen
atoms are numbered H3,8, H4,7, H5,6, respectively. Ar is used as
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CDCl3) 8.34 (4H, d, J = 8.8, 4H, Ho), 8.27 (2H, d, J = 8.5,
4,7), 8.11 (2H, d, J = 8.5, H3,8), 7.76 (2H, s, H5,6), 7.08
extracted with ethyl acetate (3 ꢂ 150 mL). The combined
organic layers were washed with ammonium hydroxide
(2 ꢂ 50 mL) and water (5 ꢂ 150 mL), dried over magnesium
sulfate, filtered through paper and finally evaporated to
dryness. Final purification was achieved by column chromato-
graphy (neutral Al2O3) using DCM–MeOH (99/1) as the
eluent to give macrocycle 3 (0.178 g, 70%) as a colorless solid.
dH (400 MHz; CDCl3) 8.38 (4H, d, J = 9.0, Ho), 8.22 (2H, d,
J = 8.4 Hz, H4,7), 8.03 (2H, d, J = 8.4, H3,8), 7.95 (2H, s,
H-triazole ring), 7.69 (2H, s, H5,6), 7.10–7.00 (6H, m, Hm and
ortho Ar-H), 6.76 (1H, s, para Ar-H), 5.26 (1H, s, Ar-CH-
acetal), 4.73 (4H, s, O-CH2-triazole ring), 4.19–3.60 (24H, m,
all O-CH2-CH2-O), 3.58 (4H, m, acetal CH2); 1.24 and
0.73 (6H, s, CH3 on acetal); m/z (MALDI-TOF) found
979.20 ([M + H]+), C54H58N8O10 requires 978.43.
H
(4H, d, J = 8.8, Hm), 4.20 (4H, t, J = 4.9, Ar-O-CH2), 4.16
(4H, t, J = 4.9, O-CH2-CRCH), 3.86–3.55 (18H, m, O-CH2-
CH2-O), 2.42 (2H, m, O-CH2-CRCH); dc (400 MHz; CDCl3)
phenanthroline nuclei: 159.5, 156.4, 146.0, 136.9, 132.7, 129.0,
127.6, 125.6, 119.2, 114.8, trioxoethyl linker: 72.7, 69.7, 69.5,
69.2, 67.6, 66.0, ethynyl group: 78.2 (CH2-CRCH); 76.2
(CH2-CRCH); 59.9 (CH2-CRCH); m/z (LC-MSD) found
705.40 ([M + H]+), C42H44N2O8 requires 704.31.
2-(3,5-Diazidophenyl)-5,5-dimethyl-1,3-dioxane (2). Commer-
cially available 3,5-dibromobenzaldehyde (1.00 g, 3.780 mmol),
neopentylglycol (0.786 g, 7.56 mmol) and p-toluenesulfonic
acid (0.360 g, 1.890 mmol) were dissolved in 50 mL of dry
THF and heated at reflux for 8 h. The solvent was evaporated
and DCM (200 mL) was added. The crude product
was washed with water (5 ꢂ 100 mL), dried over Na2SO4,
filtered through paper and evaporated to dryness to yield
quantitatively the glycol-protected benzaldehyde 2a as a
colorless oil, which was used in the next step without further
purification. Sodium azide (0.740 g 11.40 mmol), sodium
ascorbate (0.340 g, 1.710 mmol), N,N-dimethylethylenedi-
amine (0.225 g, 2.565 mmol), NaOH (0.034 g, 0.850 mmol),
glycol-protected 3,5-dibromobenzaldehyde (1.00 g, 2.850 mmol)
and CuI (0.162 g, 0.855 mmol) were dissolved in 50 mL of a
degassed (argon for 30 min) EtOH–H2O solvent mixture (7 : 3)
and heated at reflux for 3 h. The crude product was concen-
trated under reduced pressure and extracted with DCM
(3 ꢂ 100 mL). The combined organic phases were washed
with water (3 ꢂ 150 mL), dried over Na2SO4, filtered through
paper and concentrated. Final purification was achieved by
column chromatography using DCM–MeOH (99 : 1) as the
eluent to give the glycol-protected 3,5-diazidobenzaldehyde 2
(0.546 g, 65%) as a gold oil. nmax (KBr)/cmꢁ1 2099 (NQN
stretch); dH (400 MHz; CDCl3) 6.61 (2H, d, J = 2.3, ortho Ar-H),
6.22 (1H, t, J = 2.3, para Ar-H), 5.26 (1H, s, Ar-CH-acetal),
3.85 and 3.55 (4H, d, acetal CH2), 1.27 and 0.79 (6H, s, CH3
on acetal); dc (400 MHz; CDCl3) 140.6 (C3,5), 136.2 (C1), 134.3
(C4), 128.8 (C2,6), 108.32 (Ar-C-O-CH2), 79.1 (O-CH2-C-
CH3), 33.5 (O-CH2-C-CH3), 19.5 (O-CH2-C-CH3).
Catenand 5. In the reaction flask, ethynylphenanthroline 1
(0.148 g, 0.200 mmol) was dissolved in 15 mL of dry DCM
under an argon atmosphere. Cu(CH3CN)4PF6 (0.038 g,
0.100 mmol) dissolved in 5 mL of CH3CN was added to the
flask dropwise by syringe and the resulting dark red solution
was stirred at room temperature for 30 min, generating the
Cu-complex 4. A total of 600 mL of an oxygen-free mixture of
EtOH–H2O–toluene (60/40/10) was then added to the flask,
followed by addition of DBU (0.608 g, 4.00 mmol), sodium
ascorbate (0.160 g, 0.808 mmol) and SBP (0.708 g, 1.2 mmol).
The reaction mixture was stirred for 10 min and CuI (0.076 g,
0.400 mmol) was then added. The solution was stirred for an
additional 30 min at room temperature and heated to 70 1C.
Protected diazidobenzaldehyde 2 (0.055 g, 0.200 mmol) was
dissolved in 180 mL of a degassed (argon for 30 min)
EtOH–toluene (90/10) solvent mixture and transferred by
canula into an addition funnel under an argon atmosphere.
The azide solution was added dropwise to the reaction flask
over 10 h with magnetic stirring. At the end of the addition,
the reaction mixture was stirred for another 4 h followed by
removal of the solvents under reduced pressure. Ethyl acetate
(200 mL) and water (50 mL) were added, the organic layer was
separated and the aqueous phase was extracted with ethyl
acetate (3 ꢂ 150 mL). The combined organic layers were
washed with ammonium hydroxide (2 ꢂ 50 mL), then water
(5 ꢂ 150 mL), dried over magnesium sulfate, filtered through
paper and evaporated to dryness. Final purification was
achieved by column chromatography (neutral Al2O3) using
DCM–MeOH (gradient from 0 to 2%) as the eluent to give
catenand 5 (0.360 g, 92%) as a beige solid. dH (400 MHz;
CDCl3) 8.32 (8H, d, J = 9.0, Ho), 8.15 (4H, d, J = 8.4 Hz,
Macrocycle 3. Ethynylphenanthroline derivative 1 (0.200 g,
0.284 mmol) and protected 3,5-diazidobenzaldehyde
2
(0.078 g, 0.284 mmol) were dissolved in 100 mL of a degassed
(argon for 30 min) ethanol–toluene (9/1) solvent mixture and
transferred by canula into an addition funnel. In the three-
neck round-bottomed flask, 1,8-diaza[5.4.0]bicycloundec-7-
ene (DBU) (0.076 g, 4.00 mmol), sodium ascorbate (0.340 g,
1.704 mmol), sulfonated bathophenanthroline SBP (0.670 g,
1.136 mmol) and CuI (0.107 g, 0.568 mmol) were dissolved in
600 mL of a degassed (argon for 30 min) EtOH–H2O–toluene
(60/40/10) solvent mixture under an argon atmosphere. The
resulting dark red solution was then heated to 70 1C and the
solution in the addition funnel was added dropwise over 10 h
(high dilution conditions). The reaction mixture was then
stirred for another 4 h. The solvents were evaporated, and
ethyl acetate (200 mL) and water (50 mL) were added. The
organic layer was separated and the aqueous phase was
H
4,7), 8.01 (4H, d, J = 8.4, H3,8), 7.86 (4H, s, H-triazole ring),
7.24 (4H, s, H5,6), 7.10–6.95 (12H, m, Hm and ortho Ar-H);
6.71 (2H, s, para Ar-H), 5.14 (4H, s, acetal Ar-CH), 4.76
(8H, s, O-CH2-triazole ring), 4.20–3.70 (48H, m, all O-CH2-
CH2-O), 3.51 (8H, m, acetal CH2), 1.22 and 0.71 (12H, s, CH3
on acetal); m/z (MALDI-TOF) found 1957.48 ([M + H]+),
C
108H116N16O20 requires 1956.86.
Macrocycle 7. Macrocycle 6 (0.152 g, 0.20 mmol) was
dissolved in 30 mL of freshly distilled THF under an N2
atmosphere and magnetic stirring. LiAlH4 (2 mL, 1 M solution
in THF) was slowly added by syringe and the blue suspension
ꢀc
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New J. Chem., 2010, 34, 276–286 | 283

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was stirred at rt for 6 h. Ethyl acetate (5 mL) was added to the
mixture which was stirred for 10 min. The solvent was
removed and the remaining solid was redissolved in 50 mL
of CHCl3. The solid was filtered through paper and thoroughly
washed with CHCl3. MnO2 (3.0 g) was added to the filtrate and
the mixture was heated at reflux for 5 h. The slurry solid was
removed by filtration through celite and the solid washed with
fresh CHCl3. The filtrate was dried over Na2SO4 and the solvent
was removed under reduced pressure. Final purification was
achieved by column chromatography (SiO2) using DCM–
EtOAc (90 : 10, v/v) as eluent, affording 7 (0.100 g, 70%) as a
light yellow solid. dH (400 MHz; CDCl3) 9.86 (1H, s, CHO), 8.34
(4H, d, J = 9.0, Ho), 8.26 (2H, d, J = 8.8, H4,7), 8.08 (2H, d,
J = 8.8, H3,8), 7.73 (2H, s, H5,6), 7.11 (4H, d, J = 9.0, Hm), 6.95
(2H, d, J = 8.4, ortho Ar-H), 6.62 (1H, m, J = 8.4, para Ar-H),
4.10 (4H, s, Ar-O-CH2), 4.05–3.50 (20H, m, O-CH2-CH2-O). dc
(400 MHz; CDCl3) benzaldehyde ring: 192.1, 145.6, 136.7,
107.5, 106.3; phenanthroline nuclei: 159.5, 156.4, 146.0, 136.9,
132.7, 129.0, 127.6, 125.6, 119.2, 114.8; trioxoethyl linker:
72.7, 69.7, 69.5, 67.6, 66.0, 61.6; m/z (LC-MSD) found 731.56
([M + H]+), C43H42N2O9 requires 730.29.
3,5-Diethynylstyrene (15). In
a
round-bottomed flask
covered by aluminium foil, triethylamine (12 mL), dibromo-
styrene 9 (0.380 g, 1.45 mmol), Pd(Ph3P)2Cl2 (0.203 g,
0.29 mmol) and trimethylsilylacetylene (0.653 g, 6.70 mmol)
were added under inert atmosphere and the reaction mixture
was heated to 50 1C. After 10 min, CuI (0.041 g, 0.22 mmol)
was added to the reaction flask and the mixture was stirred at
50 1C for 18 h under an N2 atmosphere. The black crude
suspension was then filtered through celite using DCM as
eluent and the solvents were evaporated. The product was
redissolved in THF and tetrabutylammonium fluoride (5 mL)
was added and the solution was stirred for 30 min at room
temperature. THF was evaporated under reduced pressure,
DCM (150 mL) was added and the crude product was washed
with water, dried over Na2SO4, filtered through paper and
concentrated. Final purification was achieved by column
chromatography (SiO2) using hexanes as eluent to afford
3,5-diethynylstyrene 15 (0.154 g, 70%) as a colorless oil. dH
(400 MHz; CDCl3) 7.43 (3H, m, Ar-H), 6.50 (1H, m,
CHQCH2), 5.70 (1H, d, J = 17.4, CHQCH2), 5.24 (1H, d,
J = 10.8, CHQCH2), 2.98 (2H, s, CRCH); dc (400 MHz;
CDCl3) 136.3 (CHQCH2), 135.4 (C4), 134.2 (C1), 129.9 (C2,6),
123.4 (C3,5), 114.2 (CHQCH2), 82.4 (CHRCH), 81.1
(CHRCH); m/z (GC-MS) found 152.9 ([M + H]+), C12H8
requires 152.06.
3,5-Dibromostyrene (9). Methyltriphenylphosphonium bromide
(1.430 g, 4.00 mmol) was dissolved in 15 mL of dry THF under
an N2 atmosphere. The solution was cooled to 0 1C (ice bath)
and potassium tert-butoxide (0.450 g, 4.00 mmol) was added
portionwise (3 ꢂ 0.150 g over 10 min). The resulting red
mixture was warmed to room temperature and stirred for 1 h.
The reaction mixture was then cooled to ꢁ78 1C (ethanol–
liquid N2 bath) and a solution of 3,5-dibromobenzaldehyde
(1.00 g, 3.780 mmol) in 10 mL of dry THF was added
dropwise. The reaction mixture was warmed to room
temperature, stirred for 2 h and carefully quenched with 5%
aqueous HCl solution. The solvent was evaporated and DCM
(100 mL) was added. The organic layer was separated and the
aqueous phase was extracted with DCM (3 ꢂ 150 mL).
The combined organic layers were washed with water
(3 ꢂ 250 mL), dried over Na2SO4, filtered through paper
and evaporated to dryness. Final purification was achieved
by column chromatography (SiO2) using hexanes as eluent to
afford 3,5-dibromostyrene 9 (0.450 g, 45%) as a colorless oil. dH
(400 MHz; CDCl3) 7.45 (1H, t, J = 1.8, Ar-para-H), 7.40 (2H, d,
J = 1.8, Ar-ortho-H), 6.46 (1H, m, CHQCH2), 5.19 (1H, d, J =
17.4, CHQCH2) and 5.26 (1H, d, J = 10.8, CHQCH2); dc
(400 MHz; CDCl3) 139.6 (C1), 135.5 (CHQCH2), 134.2 (C4),
128.5 (C2,6), 123.7 (C3,5), 112.1 (CHQCH2); m/z (GC-MS) found
260.42 ([M + H]+), C8H6Br2 requires 259.88.
Synthesis of Cu(I)-catenate 17. In flask A, macrocycle 7
(0.050 g, 0.068 mmol) was dissolved in 2.0 mL of degassed
DCM–CH3CN (7 : 3, v/v) to which [Cu(CH3CN)4][PF6]
(0.026 g, 0.068 mmol) was added under N2 and the solution
was stirred at rt for 30 min. The azidophenanthroline ligand 14
(0.046 g, 0.068 mmol) was then added as a solid to flask A and
the deep red solution was stirred under N2 at rt for 3 h to
generate precursor 16. Meanwhile, in the reaction flask, CuI
(0.026 g, 0.137 mmol), sodium ascorbate (0.110 g, 0.548 mmol)
and SBP (0.161 g, 0.274 mmol) were dissolved in 20 mL of
degassed aqueous ethanol (1 : 1, v/v). The pink suspension was
heated at reflux for 2 min and cooled back to rt. The deep red
solution in the flask A containing 16 was then diluted to 8 mL
with degassed DCM and added by syringe to the reaction
flask. Finally, 15 (0.013 g, 0.068 mmol), dissolved in 10 mL of
degassed DCM, and DBU (0.031 g, 0.205 mmol) were added
and the resulting purple mixture was stirred under nitrogen for
12 h at rt. The crude mixture was neutralized by adding 5 mL
of 10% HClaq solution and extracted with DCM (3 ꢂ 50 mL).
The organic phase was washed with water (3 ꢂ 100 mL),
concentrated to a volume of 10 mL and then stirred for 3 h
with a saturated methanolic solution of KPF6 to effect the
anion exchange. The solvents were evaporated under reduced
pressure; the remaining insoluble light red solid was extracted
with DCM (3 ꢂ 100 mL) and filtered through paper. The
solvent was evaporated under reduced pressure and the crude
product was purified by column chromatography (SiO2) using
DCM–CH3OH (99/1 v/v) as eluent, affording 17 (0.070 g,
75%) as a red solid. dH (400 MHz; CDCl3) 9.73 (1H, s, CHO),
8.50 (1H, s, CH2QCH-Ar-H at para position), 8.43 (2H, s,
CH2QCH-Ar-H at ortho position), 8.34 (2H, d, J = 8.4 Hz, H4,7),
3,5-Diazidostyrene (10). Compound 10 was synthesized from
9 following the same procedure described for compound 2. After
workup, the crude product was purified by column chromato-
graphy (SiO2) using DCM as eluent to afford compound 10
(0.250 g, 55%) as a gold oil. nmax (KBr)/cmꢁ1 2094 (NQN
stretch); dH (400 MHz; CDCl3) 6.55 (1H, m, CH = CH2), 6.48
(2H, d, J = 2.0, ortho Ar-H), 6.21 (1H, t, J = 2.0, para Ar-H),
5.19 (1H, d, J = 17.4, CHQCH2) and 5.26 (1H, d, J = 10.8,
CHQCH2); dc (400 MHz; CDCl3) 143.1 (C3,5), 137.0
(CHQCH2), 135.9 (C1), 129.4 (C4), 125.0 (C2,6), 112.2
(CHQCH2).
0
8.23 (2H, d, J = 8.4 Hz, H4 ,7 ), 8.03 (2H, s, H-triazole ring),
0
0
7.92 (2H, s, H5,6), 7.76 (2H, s, H5 ,6 ), 7.72 (2H, d, J = 8.4, H3,8),
0
ꢀc
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284 | New J. Chem., 2010, 34, 276–286

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0
7.64 (2H, d, J = 8.4, H3 ,8 ), 7.26 (4H, d, J = 9.0, Ho), 7.21
0
Germany, 2003; (e) A. Credi, M. Montalli, V. Balzani,
S. J. Langford, F. M. Raymo and J. F. Stoddart, New J. Chem.,
1998, 22, 1061–1065.
0
(4H, d, J = 9.0, Ho ), 6.96 (2H, s, CHO-Ar-H at ortho
position), 6.71 (1H, s, CHO-Ar-H at para position), 6.45
(1H, m, CHQCH2), 5.96 (4H, d, J = 9.0, Hm), 5.88 (4H, d,
3 (a) D. J. Cardenas, J.-P. Collin, P. Gavina, J.-P. Sauvage, A. De
Cian, J. Fischer, N. Armaroli, L. Flamigni, V. Vicinelli and
V. Balzani, J. Am. Chem. Soc., 1999, 121, 5481–5488;
(b) H. Sasabe, N. Kihara, Y. Furusho, K. Mizuno, A. Ogawa
and T. Takata, Org. Lett., 2004, 6, 3957–3960; (c) S. Saha,
A. H. Flood, J. F. Stoddart, S. Impellizzeri, S. Silvi, M. Venturi
and A. Credi, J. Am. Chem. Soc., 2007, 129, 12159–12171;
(d) A. S. D. Sandanayaka, N. Watanabe, K.-I. Ikeshita,
Y. Araki, N. Kihara, Y. Furusho, O. Ito and T. Takata, J. Phys.
Chem. B, 2005, 109, 2516–2525; (e) L. Flamigni, N. Amaroli,
F. Barigelletti, J.-C. Chambron, J.-P. Sauvage and N. Solladie,
New J. Chem., 1999, 23, 1151–1158.
4 (a) M. J. Chmielewski, J. J. Davis and P. D. Beer, Org. Biomol.
Chem., 2009, 7, 415–424; (b) P. Thordarson, J. A. Bijsterveld,
A. E. Rowan and R. J. M. Nolte, Nature, 2003, 424, 915–918.
5 K. Patel, S. Angelos, W. R. Dichtel, A. Coskun, Y.-W. Yang,
J. I. Zink and J. F. Stoddart, J. Am. Chem. Soc., 2008, 130,
2382–2383.
6 (a) W. R. Dichtel, O. S. Miljanic, W. Zhang, J. M. Pruell, K. Patel,
I. Aprahamian, J. R. Heath and J. F. Stoddart, Acc. Chem. Res.,
2008, 41, 1750–1761; (b) J.-P. Sauvage and C. O. Dietrich-
Buchecker, Molecular Catenanes, Rotaxanes and Knots,
Wiley-VCH, Weinheim, Germany, 1999; (c) D. B. Amabilino
and J. F. Stoddart, Chem. Rev., 1995, 95, 2725–2828; (d) J. A. G.
Williams, Chem. Soc. Rev., 2009, 38, 1783.
7 (a) B. Mohr, M. Weck, J.-P. Sauvage and R. H. Grubbs, Angew.
Chem., Int. Ed. Engl., 1997, 36, 1308–1310; (b) V. Aucagne,
K. D. Hanni, D. A. Leigh, P. J. Lusby and D. B. Walker, J. Am.
Chem. Soc., 2006, 128, 2186–2187; (c) P. Mobian, J.-P. Collin and
J.-P. Sauvage, Tetrahedron Lett., 2006, 47, 4907–4909;
(d) A. I. Prikhod’ko, F. Durola and J.-P. Sauvage, J. Am. Chem.
Soc., 2008, 130, 448–449; (e) S. Durot, P. Mobian, J.-P. Collin and
J.-P. Sauvage, Tetrahedron, 2008, 64, 8496–8506; (f) V. Aucagne,
J. Berna, J. D. Crowley, S. M. Goldup, K. D. Hanni, D. A. Leigh,
P. J. Lusby, V. E. Ronaldson, A. M. Z. Slawin, A. Viterisi and
D. B. Walker, J. Am. Chem. Soc., 2007, 129, 11950–11963;
(g) W. R. Dichtel, O. S. Miljanic, J. M. Spruell, J. R. Heath and
J. F. Stoddart, J. Am. Chem. Soc., 2006, 128, 10388–10390;
(h) M. Hutin, C. A. Schalley, G. Bernardinelli and
J. R. Nitschke, Chem.–Eur. J., 2006, 12, 4069–4076; (i) Y. Sato,
R. Yamasaki and S. Saito, Angew. Chem., Int. Ed., 2009, 48,
504–508.
0
J = 9.0, Hm ), 5.59 (1H, d, CHQCH2), 4.98 (1H, d,
CHQCH2), 4.65 (4H, s, O-CH2-triazole ring), 4.20–3.00
(44H, m, O-CH2-CH2-O); m/z (MALDI-TOF) found
1623.12 ([M]+), C91H88N10O15Cu requires 1623.57.
Synthesis of Cu-free catenand 18. Catenane 17 (0.050 g,
0.028 mmol) was dissolved in 5 mL of DCM to which was
added a solution of KCN (0.020 g, 0.30 mmol) dissolved in
5 mL of H2O, and the mixture was stirred at room temperature
for 30 min. The deep red solution became colorless and the
organic layer was separated. The aqueous phase was extracted
with DCM (3 ꢂ 50 mL). The combined organic layers were
washed with water (3 ꢂ 50 mL), dried over Na2SO4, filtered
through paper and evaporated to dryness. Final purification
was achieved by column chromatography (SiO2) using
DCM–CH3OH (99/1 v/v) as eluent, affording 17 as a waxy
solid in quantitative yield. dH (400 MHz; CDCl3) 9.75 (1H, s,
0
CHO), 8.44 (4H, d, J = 9.0, Ho), 8.32 (4H, d, J = 9.0, Ho ),
0
0
8.25 (2H, d, J = 8.4 Hz, H4,7), 8.19 (2H, d, J = 8.4 Hz, H4 ,7 ),
8.16 (2H, d, CH2QCH-Ar-H at ortho position), 8.09 (2H, d,
J = 8.4, H3,8), 8.02 (2H, s, H-triazole ring), 8.00 (2H, d, J =
0
0
8.4, H3 ,8 ), 7.93 (1H, s, CH2QCH-Ar-H at para position), 7.73
0
(2H, s, H5,6), 7.71 (2H, s, H5 ,6 ), 7.03 (4H, d, J = 9.0, Hm),
0
0
6.94 (4H, d, J = 9.0, Hm ), 6.89 (1H, m, CHQCH2), 6.90
(2H, s, CHO-Ar-H at ortho position), 6.63 (1H, s, CHO-Ar-H
at para position), 5.92 (1H, d, CHQCH2), 5.35 (4H, s, O-CH2-
triazole ring), 5.30 (1H, d, CHQCH2), 5.20–3.00 (44H, m,
all O-CH2-CH2-O); m/z (MALDI-TOF) found 1600.15
([M + K]+), C91H88N10O15 requires 1560.64.
Acknowledgements
8 (a) C. O. Dietrich-Buchecker and J.-P. Sauvage, Tetrahedron Lett.,
1983, 24, 5095–5098; (b) C. O. Dietrich-Buchecker and
J.-P. Sauvage, J. Am. Chem. Soc., 1984, 106, 3043–3044;
(c) C. O. Dietrich-Buchecker and J.-P. Sauvage, Tetrahedron,
1990, 46, 503–512; (d) C. O. Dietrich-Buchecker and
J.-P. Sauvage, Chem. Rev., 1987, 87, 795–810; (e) J.-P. Collin,
J.-P. Sauvage, Y. Trolez and K. Rissanen, New J. Chem., 2009, 33,
2148–2154.
The authors are deeply grateful to the National Science
Foundation (Grant CHE-0647334) for financial support. This
investigation was conducted in part in a facility constructed
with support from Research Facilities Improvement Grant
Number C06 RR-16572-01 from the National Center for
Research Resources, National Institutes of Health.
9 (a) R. Huisgen, Angew. Chem., Int. Ed. Engl., 1968, 7, 321–328;
(b) H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem.,
Int. Ed., 2001, 40, 2004–2021; (c) M. Meldal and C. W. Tornøe,
Chem. Rev., 2008, 108, 2952–3015.
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