Selective synthesis of [2]- and [3]catenane tuned by ring size and concentration

Article abstract of DOI:10.1021/jo400239h

The syntheses of [2]- and [3]catenanes by olefin metathesis and oxidative acetylide coupling have been studied in detail. Pseudorotaxanes that were obtained by mixing crown ether and ammonium salts containing two terminal reactive end-groups were converte

Full text of DOI:10.1021/jo400239h

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Article
Selective Synthesis of [2]- and [3]Catenane
Tuned by Ring Size and Concentration
Hajime Iwamoto, Wataru Takizawa, Koji Itoh, Tatsuya
Hagiwara, Eiji Tayama, Eietsu Hasegawa, and Takeharu Haino
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo400239h • Publication Date (Web): 06 May 2013
Downloaded from http://pubs.acs.org on May 11, 2013
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Selective Synthesis of [2]- and [3]Catenane Tuned by Ring Size and Concentration
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Hajime Iwamoto†*, Wataru Takizawa†, Koji Itoh‡, Tatsuya Hagiwara†, Eiji Tayama†, Eietsu Hasegawa†,
and Takeharu Haino‡
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† Graduate School of Science and Technology, Niigata University, 2-8050 Ikarashi, Nishi-ku, Niigata 950-
2181, Japan
‡
Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526,
Japan
iwamoto@chem.sc.niigataꢀu.ac.jp
Table of Contents/Abstract Graphic
Abstract
The syntheses of [2]ꢀ and [3]catenanes by olefin metathesis and oxidative acetylide coupling have been
studied in detail. Pseudorotaxanes that were obtained by mixing crown ether and ammonium salts
containing two terminal reactive endꢀgroups were converted to [2]ꢀ and [3]catenane. Their yields were
influenced not only by the chain length of the ammonium salts but also by the concentration of the crown
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ether and the ammonium salts. The strain energies of [2]catenane were responsible for the formation of
[2]catenane.
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Introduction
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Catenanes, which consist of two or more interlocked macrocycles, are of great interest in the field of
supramolecular chemistry.1 The macrocycles are not covalently connected but are linked by mechanical
bonds. The mechanical bonds result in a unique molecular motion of the catenanes in which the
macrocycles rotate around one another and change their spatial relationship to each other. This motion does
not occur in molecules formed by covalent bonds, suggesting the potential for the application of catenanes
in new materials and nanoscale molecular devices.2 The synthesis of catenanes has been extensively
studied, and sophisticated molecular devices based on catenanes have been developed.
One of the general synthetic strategies for catenanes is that a linear molecule threads into a macrocycle to
form a pseudorotaxane, and the linear molecule is then cyclized to form a new macrocycle. Using this
strategy, the first catenane was synthesized by Wasserman in 1960.3 In that report, acyloin condensation of
a diester in the presence of a macrocycle that had no specific interaction with the diester and statistically
formed a pseudorotaxane with the diester yielded catenane in only 0.0001% yield. Statistical approaches
have been inefficient. Therefore, rational and strategic approaches are necessary for the synthesis of
catenanes. Three key steps are involved in this strategy. First, a linear molecule is threaded into a
macrocycle. Second, the linear molecule is cyclized while maintaining the structure in which the linear
molecule is threaded into the macrocycle. Last, the competing intraꢀ or interꢀmolecular reactions, which can
be a potential challenge for the cyclization process, are controlled. To obtain catenanes, these three crucial
steps must be performed.
Hostꢀguest chemistry provides clever solutions for threading a linear molecule into a macrocycle without
using statistical threading. In 1989, Stoddard developed pseudorotaxanes promoted by donorꢀacceptor
interactions between electronꢀrich aromatics and paraquats to afford catenanes.4 Since this pioneering work,
many intermolecular forces, such as hydrogen bonding interactions,5 donorꢀacceptor interactions,6 and
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hydrophobic interactions1d,7 between the linear molecule and the macrocycle, have been employed in the
formation of pseudorotaxanes to form catenanes (e.g., crown ethers and ammonium salts, cyclodextrins and
biphenyl, and cyclic tetraamides and amides). Metal coordination, another method for synthesizing
pseudorotaxane, was first used in catenane synthesis by DietrichꢀBuchecker and Sauvage in 1983.8 The
metal coordination process results in the formation of more stable pseudorotaxanes compared to the weak
intermolecular interactions. Since stable pseudorotaxanes permit the use of a variety of reaction conditions
for macrocyclization, metal coordination is a favorable method for catenane synthesis.9 In addition, the
formation of stable pseudorotaxanes from low concentrations of each component, linear molecule and
macrocycle, is advantageous for intramolecular cyclization. Complexations between Cu+ and
phenanthrolineꢀbased ligands, Ru2+ and terpyridyl ligands, and Pd(II) and pyridyl ligands can also be
effective for catenane synthesis.
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Reaction conditions keeping pseudorotaxane formed by weak interactions or metal coordination are
necessary for catenane synthesis. Alkene metathesis10a,9c,10bꢀd,9g,10eꢀi is one of the most successful reactions
for catenane synthesis. Olefin metathesis reactions occur under neutral conditions and near room
temperature. These mild conditions prevent the dissociation of the hostꢀguest complex and the
decomposition of the coordination bond. Oxidative acetylide coupling of two terminal alkynes,11
condensation of amines with acid chlorides,12 imine formation/reductive amination,13 quaternization of
aromatic amines,14 Williamson ether synthesis,15 and the Huisgen reaction16 are also employed in the
cyclization process.
The presence of competitive intraꢀ or interꢀmolecular reactions is a fundamental and inevitable issue in
the synthesis of macrocycles.17 The synthesis of catenanes, including the macrocyclization process, may
also be subject to this potential problem. In general, a lower concentration of substrate for macrocyclization
results in intramolecular reactions to yield cyclic products, while a higher concentration facilitates
intermolecular reactions to yield dimers, trimers, and oligomers. Although the intramolecular cyclization of
pseudorotaxanes under lower concentrations appears to afford catenanes in good yield, lower
pseudorotaxane concentrations result in their dissociation, particularly for pseudorotaxanes formed via
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weak intermolecular interaction, resulting in a low yield of catenanes. The concentrations of substrates
influence not only the selectivity of the intraꢀ or interꢀmolecular reaction but also the stability of the
pseudorotaxanes, yielding opposing effects.
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We have previously reported the synthesis of catenanes composed of a crown ether and ammonium salts
using olefin metathesis.18 The selectivity of [2]ꢀ and [3]catenanes is influenced not only by the
concentrations of the crown ether and ammonium salts but also by the length of the ammonium salts.
Although several studies have investigated the selectivities of [2]ꢀ and [3]catenanes,19 no relationships
between the concentrations of the substrates and the selectivities of [2]ꢀ and [3]catenanes have been
described. In the course of our study, oxidative acetylide coupling was applied to the selective synthesis of
catenanes. Herein, we provide a detailed description of the selective synthesis of [2]ꢀ and [3]catenanes via
olefin metathesis and oxidative acetylide coupling controlled by the concentration of the crown ether and
the ammonium salts as well as the length of the ammonium salts (Figure 1).
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Figure 1. [2]Catenanes (1a-b, 3a-b) and [3]catenanes (2a-b, 4a-b).
Results and discussion
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Synthesis of Ammonium Salts. The syntheses of ammonium salts 9a-b, which are the precursors for
olefin metathesis, and 9c-d, which are the precursors for the oxidative acetylide coupling, are shown in
Scheme 1. Etherification of diol 520 with NaH and tosylate 6a-d in DMF yielded 7a-d. The deprotection of
the BOC group with TFA afforded secondary amine 8a-d. Treatment with hydrochloric acid followed by
anion exchange from the chloride to the hexafluorophosphate yielded 9a-d.
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Scheme 1. Reagents and conditions: (a) 5, NaH, DMF; (b) TFA, CH2Cl2; (c) 6 M HCl, acetone, then
NH4PF6, CH2Cl2, acetone.
Determination of the Association Constants for Crown Ether-Ammonium Salt Complexation. To
study the binding behavior of ammonium salt 9a and dibenzo[24]crownꢀ8 (DB24C) (10), a standard
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titration experiment was performed using H NMR spectroscopy at room temperature in dichloromethaneꢀ
d2 (Figure 2). Simple mixing of the compounds yielded wellꢀresolved signals resulting from the free and
bound states, whose equilibrium was in slow exchange on the NMR timescale. Methylene protons Hi
adjacent to the ammonium moiety shifted downfield, whereas upfield shifts were observed for aromatic
protons Hg and Hh and methylene protons He and Hf adjacent to the etherꢀoxygen, suggesting that these
protons were shielded by the two aromatic rings connected to the crown ring. All of the protons on the
crown ether were shifted upfield. These chemical shift changes are evidence of the formation of a
pseudorotaxane composed of 9a and 10 in which NH+–O interactions and π–π interactions between the
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secondary ammonium salt and the crown ether cooperatively stabilize the complex.21 Signals of the free
state of 9a are slightly shifted compared with those of standard 1H NMR spectra of 9a. It is probably due to
the faceꢀtoꢀface interaction between 9a and 10. Proton Hf at several concentrations of 9a and 10 was
integrated in the free and bound states, and the binding constant (Ka) of the hostꢀguest complex was
determined to be 4,700 ± 900 L mol–1 based on their ratio.22
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Figure 2. Partial 1H NMR spectra (700 MHz) in CD2Cl2 at 23 °C of (a) DB24C 10, (b) 10 (1.70 × 10–3 mol
L–1) + ammonium salt 9a (1.29 × 10–3 mol L–1) and (c) 9a.
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The association constants between 9a-d and 10 are summarized in Table 1. In all cases, signals resulting
from the free and bound states were observed. The exchange rate of the free and bound states was slower
than the NMR timescale, regardless of the chain length of the ammonium salts. The length of the
ammonium salt as well as terminal functional groups, double bonds, and triple bonds do not play an
important role in the stability of crownꢀammonium salt complexes. The obtained association constants
suggest that the pseudorotaxanes should be formed on a millimolar scale.
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Table 1. Association constantsa (Ka/L mol–1) for the hostꢀguest complexation of ammonium salts 9a-d with
crown ether 10 in dichrolomethaneꢀd2 at 298 K.
Ammonium salt
Association constants Ka [L mol–1]
4,700 ± 900
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9b
9c
5,800 ± 700
8,600 ± 800
6,100 ± 400
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Mixtures of 9a-d (1.56ꢀ3.92 x 10–3 M) and 10 (1.27ꢀ2.72 x 10–3 M) were used for the association
constants.
Synthesis of Catenanes. Catenanes were synthesized by olefin metathesis according to Scheme 2(a). The
treatment of pseudorotaxane 9a•10 derived from mixing DB24C 10 (0.002 M) and an ammonium salt
containing two terminal olefin 9a (0.002 M) in dichloromethane with 10 mol% of the firstꢀgeneration
Grubbs catalyst23 yielded catenation products with undefined oligomeric byꢀproducts. The catenation
products were purified by column chromatography and gel permeation chromatography (GPC).
[2]Catenane 1a and [3]catenane 2a were obtained in 56% and 2% yields. For the short ammonium salt 9b,
the same conditions yielded only [3]catenane 2b in 25% yield.
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Scheme 2. Syntheses of catenanes. Reagents and conditions: (a) the firstꢀgeneration Grubbs catalyst 11,
CH2Cl2, reflux; (b) Cu(OAc)2, pyridine, CH2Cl2, reflux.
The synthesis of catenane by oxidative acetylide coupling was performed according to Scheme 2(b). The
treatment of pseudorotaxane 9c•10 derived from mixing DB24C 10 (0.002 M) and an ammonium salt
containing two terminal CꢀC triple bonds 9c (0.002 M) in dichloromethane with three equivalents of
Cu(OAc)2 and one equivalent of pyridine yielded catenation products with undefined oligomeric byꢀ
products. The catenation products were purified by column chromatography and GPC. [2]Catenane 3a and
[3]catenane 4a were obtained in 23% and 4% yields. For the short ammonium salt 9d, the same conditions
yielded [2]catenane 3b and [3]catenane 4b in 4% and 6% yields.
Mass Spectrometry and NMR Studies of Catenanes. The [2]ꢀ and [3]catenanes were characterized by
ESI mass spectrometry. The positive ESI mass spectra of [2]catenane 1a, [3]catenane 2a, and [3]catenane
2b are provided in Figure 3, and the positive ESI mass spectra of [2]catenane 3a, [3]catenane 4a,
[2]catenane 3b, and [3]catenane 4b are provided in Figure 4. [2]Catenane 1a exhibited signals
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corresponding to singly positively charged ions resulting from the loss of one hexafluorophosphate ion.
However, [3]catenanes produced signals corresponding to doubly charged ions resulting from the loss of
two hexafluorophosphate ions. These observed isotopic distributions were similar to the theoretical ones.
These results suggest a structure in which the ammonium salts and the crown ethers are mechanically
interlocked with each other. The number of ion charges indicates the number of macrocycles present in the
obtained compounds.
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Figure 3. Positive ESI mass spectra of (a) [2]catenane 1a, (b) [3]catenane 2a, and (c) [3]catenane 2b.
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Figure 4. Positive ESI mass spectra of (a) [2]catenane 3a, (b) [3]catenane 4a, (c) [2]catenane 3b, and (d)
[3]catenane 4b.
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The H NMR spectra of [2]ꢀ and [3]catenanes obtained from olefin metathesis are shown in Figure 5.
Olefin metathesis usually yields a mixture of alkene structural isomers. Therefore, NMR studies of
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mixtures of the Eꢀ and Zꢀisomers of catenanes were performed. The HꢀNMR signal of the vinylic protons
was observed at approximately 5.4 ppm. In [3]catenane 2b, two sets of signals for the vinylic protons were
observed. The Eꢀ and Zꢀisomers were most likely obtained in the synthesis of the catenanes, but the E/Z
ratio was not determined. For [3]catenane 2a, the broadened signals of the vinylic protons also suggested a
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mixture of Eꢀ and Zꢀisomers. The mixtures of Eꢀ and Zꢀisomers are consistent with the broadened signals of
the allylic protons, which are observed at approximately 2.0 ppm. The signals observed for the vinylic
protons of [2]catenane 1a appear to be a single set. Therefore, one isomer was obtained as a major product
in the reaction. Although the spectra were nearly identical, slight differences were observed. The vinylic
and allylic protons of [2]catenane 1a were shifted upfield relative to those of [3]catenane 2a, and the
aromatic protons of the ammonium macrocycle of [2]catenane 1a, which were observed in the range of 7.1ꢀ
7.3 ppm, were shifted downfield relative to those of [3]catenane 2a. These results suggest that the smaller
ammonium macrocycle of [2]catenane 1a is more strongly influenced by the crown ether than the larger
diammonium macrocycle of [3]catenane 2a.
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Figure 5. Partial H NMR spectra (300 MHz) in CDCl3 of (a) [2]catenane 1a, (b) [3]catenane 2a, and (c)
[3]catenane 2b.
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The H NMR spectra of [2]ꢀ and [3]catenanes obtained from oxidative acetylide coupling are shown in
Figure 6. In contrast to the results of olefin metathesis, all of the signals clearly correspond to a single
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isomer. Although the spectra are nearly identical, slight differences were observed. The propargylic protons
of [2]catenanes 3a and 3b, which were observed at approximately 2.2 ppm, were shifted upfield relative to
those of [3]catenanes 4a and 4b, and the aromatic protons of the ammonium macrocycle of [2]catenanes 3a
and 3b, which were observed in the range of 7.1ꢀ7.3 ppm, were shifted downfield relative to those of
[3]catenanes 4a and 4b. These trends were similar to those observed for olefin metathesis. In particular, the
signals of [2]catenane 3b, which contains a shorter ammonium macrocycle, were shifted more than those of
[2]catenane 3a, which contains a longer ammonium macrocycle. These results suggest that the smaller
ammonium macrocycle of 3b is more influenced by the crown ether than the longer ammonium macrocycle
of 3a.
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Figure 6. Partial H NMR spectra (700 MHz) in CDCl3 of (a) [2]catenane 3a, (b) [3]catenane 4a, (c)
[2]catenane 3b, and (d) [3]catenane 4b.
Concentration Dependence of the [2]- and [3]Catenane Selectivity. Catenane synthesis is significantly
influenced by the concentration of the substrate. As the pseudorotaxane concentration decreases, the
pseudorotaxane undergoes an intramolecular reaction to yield [2]catenanes. However, pseudorotaxane can
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dissociate and reduce the yield of [2]catenanes. As the pseudorotaxane concentration increases, the
pseudorotaxane undergoes an intermolecular reaction to afford [3]catenanes. However, the formation of
other products, such as oligomeric linear molecules and catenanes with more than three rings, via the
intermolecular reaction is also increased.
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To investigate the concentration dependence of the substrates, olefin metathesis was performed under
various concentrations of crown ethers and ammonium salts (Table 2). When the concentration of 9a and
10 was 0.002 M in a dichloromethane solution, [2]catenane 1a was obtained in 56% yield, and [3]catenane
2a was obtained in 2% yield. By increasing the substrate concentrations, the yield of [3]catenane 2a
increased, while that of [2]catenane 1a decreased. Variation in the concentration of short ammonium salt
9b yielded only [3]catenane 2b under any of the tested concentration conditions.
Table 2. Yields of [2]catenanes 1a-b and [3]catenanes 2a-b and the ratio of the chemical yields of
[2]catenane to [3]catenane.
Ammonium Concentration Yield
Ratio of chemical yields
salt
[M]a
[2]catenane (%)
[3]catenane (%)
0.002
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0.02
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9b
0
0
0
0
a Both DB24C 10 and ammonium salt 9a and 9b were prepared at the same concentration.
When the concentrations of ammonium salt 9a and crown ether 10 were 0.002, 0.01, and 0.02 M, 73%,
86%, and 90% of 9a and 10 were estimated to form the pseudorotaxane 9a•10 based on the determined Ka.
Therefore, if these statistical distributions influence the products, all of the reaction conditions should
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sufficiently yield catenation products. In fact, the total yields of the obtained catenanes were 58, 57, and
51%. Although the dynamic equilibrium for the formation of pseudorotaxane is attainable during the
reaction, the static stability of the pseudorotaxane plays an important, determining role in catenane
formation.
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The concentration of pseudorotaxane 9a•10 influences the selectivity of the intraꢀ or intermolecular
reaction. The cyclization of 9a•10 is an intramolecular process that produces [2]catenane 1a, whereas the
intermolecular metathesis of 9a•10 followed by intramolecular metathesis yields [3]catenane 2a. Although
the formation of [3]catenanes involves an intramolecular process in the final step, the ratios of [2]catenanes
to [3]catenanes may indicate the relative rate of the intraꢀ and intermolecular processes in the cyclization
reaction of 9a•10.24 The ratio at the lowest concentration (0.002 M) was the largest (i.e., 28) observed in the
reactions of 9a and 10, suggesting that the intramolecular process is preferred over the intermolecular
process. As the substrate concentrations increased, the ratio decreased. The intermolecular process is
favored over the intramolecular processes as the concentration of pseudorotaxane 9a•10 increases.
However, the ratio of [2]catenanes to [3]catenanes is greater than 1.0 for a concentration range of 0.002 to
0.02 M, and the intramolecular process most likely dominates under these conditions.
No [2]catenane 1b was detected under any of the studied conditions. At a range of concentrations (i.e.,
0.002, 0.01, and 0.02 M), only [3]catenane 2b was obtained, in 25%, 33%, and 35% yield. In comparison to
using ammonium salt 1a, the intermolecular process was preferred over the intramolecular processes in the
concentration range studied. The crown ether moiety could interfere with the intramolecular cyclization of
pseudorotaxane 9b•10 due to the short length of the ammonium salt. 9b•10 most likely underwent an
intermolecular reaction to yield [3]catenane 2b, or it could have dethreaded followed by intramolecular
cyclization to afford an ammonium macrocycle without a crown ether. The yield increased as the
concentration of pseudorotaxane 9b•10 increased, suggesting that the formation of [3]catenane was
preferred over the intermolecular cyclization involving dethreading of the ammonium salt at high
concentrations.
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Table 3 shows the yields of [2]ꢀ and [3]catenanes obtained from oxidative acetylide coupling at several
concentrations of crown ethers and ammonium salts. When the concentration of 9c and 10 was 0.002 M in
a dichloromethane solution, [2]catenane 3a was obtained in 23% yield, and [3]catenane 4a was obtained in
4% yield. By increasing the concentrations to 0.01 M, the yield of [3]catenane 4a increased, but the yield of
[2]catenane 3a slightly decreased. For short ammonium salt 9d, the yield of [3]catenane 4b was higher than
that of [2]catenane 3b under any of the concentrations tested.
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Table 3. Yields of [2]catenanes 3a-b and [3]catenanes 4a-b and the ratio of the chemical yields of
[2]catenane to [3]catenane.
Ammonium salt
Concentration [M]a Yield
[2]catenane (%)
23
Ratio
of
chemical yields
[3]catenane (%)
0.002
0.01
0.02
0.002
0.01
0.02
4
5.8
9c
21
12
4
12
8
1.8
1.5
6
0.67
0.40
0.38
9d
6
15
13
5
a Dibenzo[24]crownꢀ8 (DB24C) 10 and ammonium salt 9c and 9d were prepared at the same concentration.
In comparison to olefin metathesis, the total yields of the catenation products were lower under all of the
reaction conditions. The association constants (Ka) between 9c-d and 10 were nearly equal to those of 9a-b.
The static stabilities of pseudorotaxane most likely exhibited the same trends as in the olefin metathesis
reaction. However, in the presence of pyridine, the hydrogen bonding interaction (N+–H•••O) between 9c-d
and 10 is probably weakened to destabilize pseudorotaxane 9c-d•10. Cuꢀcrown ether interaction most likely
disturbed the complexation between ammonium salt and crown ether as well. The dethreading process
competes with intraꢀ and intermolecular oxidative acetylide coupling, resulting in a decrease in the
formation of catenation products.
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The correlation of the pseudorotaxane 9c-d•10 concentrations with the ratios of [2]catenane to
[3]catenane was evaluated. As the concentration of 9c•10 increased from 0.002 to 0.02 M, the ratio
decreased from 5.8 to 1.5. This trend was similar to that of olefin metathesis. Intramolecular processes
involving pseudorotaxane 9c-d•10 are preferred over intermolecular processes in the concentration range of
0.002 to 0.02 M. 9d yielded [3]catenane 4b as the major product25 with ratios of 0.67, 0.40, and 0.38 when
the concentrations of the substrates were 0.002, 0.01, and 0.02, respectively. As 9d•10 was concentrated,
the ratio decreased, indicating a concentration dependence that was similar to that observed in other
experiments. In the concentration range used in this study, the ratio was less than 1.0, indicating that the
intramolecular process was preferred over the intramolecular process due to the short length of the
ammonium salt.
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Computational Studies of [2]Catenanes. Catenane formation results from the competition between intraꢀ
and intermolecular reactions. The intramolecular cyclization of pseudorotaxane 9a-d•10 that yields
[2]catenanes 1a-b and 3a-b competes with the intermolecular reactions resulting in [3]catenane formation,
[n]catenane formation, and intermolecular oligoꢀ and polymerization. Although the catenane formation
process is too complicated to be understood in detail, the rate of [2]catenane formation may be explained in
terms of activation energies and the probability of endꢀtoꢀend encounters.26
Activation energies are thought to reflect the strain energy for the formation of small and medium rings,
while the ring strain of largeꢀmembered cyclic systems is commonly negligible.27 In the formation process
of [2]catenane, the crown ether should play an important role in steric repulsive forces. Therefore, the strain
energies of [2]catenanes 1a-b and 3a-b may be informative. Endꢀtoꢀend encounters, which are associated
with the entropic contribution of the reaction, likely decrease as the distance between the two reactive ends
increases. Therefore, an increase in the length of the ammonium salts reduces the probability of the
encounter between the two terminal olefins or acetylenes required for formation of [2]catenanes. The
probabilities are also influenced by the flexibility of pseudorotaxanes 9a-d•10. An increase in the length of
the ammonium salts increases the flexibility of the pseudorotaxane, resulting in an increased entropic cost
for the formation of [2]catenanes.
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To estimate the steric interaction during the cyclization of pseudorotaxanes 9a-d•10, molecular
mechanics calculations of the [2]catenanes were performed using MacroModel V9.1.28 The initial
geometries were generated using the Monte Carlo/lowꢀmode search mixed method, and the structural
optimizations were performed using the OPLS2005 force field with the GB/SA solvation parameters for
chloroform.29 A characteristic example of the calculated structures of [2]catenane 3b is shown in Figure 7.
The ammonium salt forms hydrogen bonding interactions with the crown ethers, which acquires a Uꢀ
shaped conformation to wrap around one of the aromatic rings of the ammonium macrocycle. The cavities
in the crown ether and the ammonium macrocycle are filled by each other, which suggests that the size of
the ammonium macrocycle should be minimal for the formation of [2]catenane.
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Figure 7. Stereo plots of the calculated structure of [2]catenane 3b: ball and stick model (upper) and space
filling model (lower).
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It is well known that the ring strain of cyclized products is closely associated with the ease of cyclization
of the chain molecules.30 Therefore, the strain of the catenanes might govern the ease of cyclization. The
5
6
ring strain energies of the catenanes can be estimated from the energy differences (ꢀH) obtained from the
7
8
9
energies of the catenanes and their components, which include cyclized ammonium macrocycles and crown
ether 10. The energies were calculated using density functional theory (DFT) calculations as implemented
in Gaussian 09.31 The initial geometries determined by the molecular mechanics method mentioned above
were subjected to geometry optimization with B3LYP using the ccꢀpVTZ basis set (Table 4). The
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calculated
ꢀ
H values were large negative values, suggesting that all of the cyclization processes are
H, suggesting an ease of
enthalpically favorable. 1a experienced the largest increase (–154.06 kJ/mol) in
ꢀ
cyclization for [2]catenanes. This result is consistent with the fact that the ratio of the chemical yields of
[2]catenane 1a and [3]catenane 2a is higher than those of the other catenanes. The enthalpic favorability
should overcome the entropic disadvantage caused by the long length of the ammonium salt to afford
[2]catenane 1a in good yield.
1a, which decreases the enthalpic advantage for the formation of 1b. For oxidative acetylide coupling, 3a,
which contains a large ammonium macrocycle, has a calculated H of –143.64 kJ/mol, which indicates an
enthalpic preference for the formation of [2]catenanes, rather than entropic difficulty. 3b, which has an
estimated H of –144.89 kJ/mol, was more stable than 3a. In addition to an entropic advantage, this
enthalpic advantage most likely plays an important role in the formation of [2]catenane 3b.
ꢀH for 1b was estimated to be –150.30 kJ/mol, which is larger than that of
ꢀ
ꢀ
Table 4. Calculated steric energy,
ꢀ
Ha [kJ/mol], of catenanes 1a-b and 3a-b.
Catenane
ꢀ
H
–154.06
–150.30
–143.64
–144.89
1a
1b
3a
3b
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a The calculated values were obtained using the following equation:
ꢀH = Hcatenane – (Hmacrocyclic ammonium salt +
1
2
3
4
Hcrown ether).
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Conclusion
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We have demonstrated the synthesis of [2]ꢀ and [3]catenanes under olefin metathesis and oxidative
acetylide coupling conditions. Long ammonium salts containing two terminal reactive endꢀgroups yielded
[2]catenanes as the major products, while short ammonium salts afforded [3]catenanes as the major
products. The concentrations of the starting substrates influenced the ratio of [2]catenane to [3]catenane.
An increase in the concentration resulted in a decrease in the ratio. Molecular mechanics calculations and
density functional theory explained the selective formation of [2]catenanes in terms of the steric factors
affecting macrocyclization. This calculation method does not perfectly rationalize the selectivity of [2]ꢀ and
[3]catenane formation but does provides some insight into estimating the selectivity.
Experimental section
1
13
General Information. H and C NMR spectra at high field were measured on a 700 MHz spectrometer
(1H: 700 MHz, 13C: 175 MHz), a 400 MHz spectrometer (1H: 400 MHz, 13C: 100 MHz), and a 300 MHz
1
spectrometer (1H: 300 MHz, 13C: 75 MHz). H NMR chemical shifts (
δ
) are given in ppm using
) are given in ppm from internal
= 77.0). The melting points were obtained on a micro melting apparatus and are
tetramethylsilane as the internal standard. 13C NMR chemical shifts (
chloroformꢀd (
δ
δ
uncorrected. The IR spectra were measured on an FT/IR spectrophotometer. The mass spectra were
recorded with a highꢀresolution doubleꢀfocusing mass spectrometer.
All of the reactions were performed under an argon atmosphere unless otherwise noted. Tetrahydrofuran
(THF) was purchased as an anhydrous solvent and used directly. Dichloromethane was freshly distilled
over P2O5. Column chromatography was performed using silica gel (particle size 100–210
reagents were of commercial grade and were used without further purification.
ꢁm). All
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Synthesis of
N-(tert-Butoxycarbonyl)bis[4-[(dec-9-en-1-yloxy)methyl]benzyl]amine (7a). To a solution
3
4
5
6
7
8
9
of NaH (55% dispersion in oil, 960 mg, 22.0 mmol) prewashed with hexane in DMF (20 mL), Nꢀ(tertꢀ
butoxycarbonyl)bis[4ꢀ(hydroxymethyl)benzyl]amine 5 (1.72 g, 4.79 mmol) in DMF (10 mL) was added at
0 °C. Then, a solution of decꢀ9ꢀenꢀ1ꢀyl tolueneꢀ4ꢀsulfonate (6a) (4.37 g, 14.1 mmol) in DMF (15 mL) was
added to the reaction mixture. After being stirred for 24 h at 50 °C, the reaction mixture was poured into
aqueous NH4Cl. The aqueous layer was extracted with ethyl acetate. The organic layer was washed with
saturated NaHCO3 and brine and then dried over anhydrous Na2SO4. After removing the Na2SO4 by
filtration, the solvent was concentrated in vacuo. The crude product was purified by column
chromatography on silica gel with 20% ethyl acetate in hexane to yield Nꢀ(tertꢀbutoxycarbonyl)bis[4ꢀ[(decꢀ
10
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1
9ꢀenꢀ1ꢀyloxy)methyl]benzyl]amine (7a) (2.65 g, 4.19 mmol, 88%). H NMR (300 MHz, CDCl3): δ = 7.31
(d, J = 8.1 Hz, 4H), 7.19 (br, 4H), 5.81 (ddt, J = 17.1, 10.2, 6.6 Hz, 2H), 4.99 (ddt, J = 17.1, 2.1, 1.5 Hz,
2H), 4.93 (ddt, J = 10.2, 2.1, 1.2 Hz, 2H), 4.49 (s, 4H), 4.39 (br s, 2H), 4.31 (br s, 2H), 3.47 (t, J = 6.6 Hz,
4H), 2.04 (m, 4H), 1.62 (tt, J = 7.2, 6.6 Hz, 4H), 1.49 (s, 9H), 1.43ꢀ1.26 ppm (m, 20H); 13C NMR (75 MHz,
CDCl3): δ = 156,0, 139.2, 137.7, 137.2, 128.0, 127.9, 127.4, 114.1, 80.0, 72.6, 70.6, 48.9, 48.6, 33.8, 29.8,
29.4, 29.1, 28.9, 28.4, 26.2 ppm; IR (neat): 1/λ = 3074, 2975, 2927, 2854, 1698, 1640, 1513, 1456, 1408,
1365, 1241, 1164, 1101, 1020 cm–1; ESIꢀHRMS m/z calcd for C41H63NO4 [M + Na]+: 656.4655; found:
656.4673.
Synthesis of Bis[4-[(dec-9-en-1-yloxy)methyl]benzyl]amine (8a). To
a
solution of Nꢀ(tertꢀ
butoxycarbonyl)bis[4ꢀ[(decꢀ9ꢀenꢀ1ꢀyloxy)methyl]benzyl]amine (7a) (487 mg, 0.77 mmol) in CH2Cl2 (10
mL), trifluoroacetic acid (2.0 mL, 26.1 mmol) was added dropwise at 0 °C. After being stirred for 12 h at
room temperature, the reaction mixture was poured into an aqueous 10% solution of NaOH. The aqueous
layer was extracted with CHCl3. After removal of the solvent in vacuo, the crude product was purified by
column chromatography on silica gel with 20% ethyl acetate in hexane to yield bis[4ꢀ[(decꢀ9ꢀenꢀ1ꢀ
1
yloxy)methyl]benzyl]amine (8a) (353 mg, 0.66 mmol, 86%). H NMR (300 MHz, CDCl3):
δ = 7.31 (m,
8H), 5.81 (ddt, J = 17.1, 10.2, 6.6 Hz, 2H), 4.99 (ddt, J = 17.1, 2.1, 1.5 Hz, 2H), 4.92 (ddt, J = 10.2, 2.1, 1.2
Hz, 2H), 4.48 (s, 4H), 3.79 (s, 4H), 3.45 (t, J = 6.6 Hz, 4H), 2.04 (m, 4H), 1.63ꢀ1.56 (m, 4H), 1.36ꢀ1.23
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ppm (m, 20H); 13C NMR (75 MHz, CDCl3):
δ
= 139.5, 139.2, 137.4, 128.1, 127.8, 114.1, 72.6, 70.5, 52.8,
= 3075, 2926, 2854, 1640, 1513, 1458, 1359, 1099,
1
2
3
33.8, 29.7, 29.4, 29.1, 28.9, 26.2 ppm; IR (neat): 1/
λ
4
5
6
7
8
1020, 993, 909, 810 cm–1; ESIꢀHRMS m/z calcd for C36H55NO2 [M + H]+: 534.4311; found: 534.4304.
Synthesis of Bis[4-[(dec-9-en-1-yloxy)methyl]benzyl]ammonium Hexafluorophosphate (9a). To a
solution of bis[4ꢀ[(decꢀ9ꢀenꢀ1ꢀyloxy)methyl]benzyl]amine (8a) (114 mg, 0.21 mmol) in acetone (5 mL), 6
M HCl was added dropwise at room temperature. After being stirred for 2 h, evaporation of the solvents
produced a white solid that was dissolved in acetone (5 mL) and H2O (20 mL). Excess NH4PF6 was added
to the solution. After being stirred for 10 h, the reaction mixture was concentrated in vacuo. The aqueous
layer was extracted with CHCl3 and dried over anhydrous Na2SO4. After removing the Na2SO4 by
filtration, the solvent was concentrated in vacuo. The crude product was purified by precipitation with
9
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hexane from CHCl3 to yield bis[4ꢀ[(decꢀ9ꢀenꢀ1ꢀyloxy)methyl]benzyl]ammonium hexafluorophosphate (9a)
1
(131 mg, 0.19 mmol, 92%) as a white solid. m.p.: 81ꢀ83 °C; H NMR (300 MHz, CDCl3):
δ = 7.38 (d, J =
8.4 Hz, 4H), 7.33 (d, J = 8.4 Hz, 4H), 5.81 (ddt, J = 17.1, 10.2, 6.6 Hz, 2H), 4.98 (ddt, J = 17.1, 2.1, 1.5 Hz,
2H), 4.92 (ddt, J = 10.2, 2.1, 1.5 Hz, 2H), 4.46 (s, 4H), 4.11 (s, 4H), 3.47 (t, J = 6.6 Hz, 4H), 2.03 (m, 4H),
1.61 (m, 4H), 1.37ꢀ1.25 ppm (m, 20H); 13C NMR (75 MHz, CDCl3):
δ
= 141.2, 139.2, 129.9, 128.5, 127.9,
= 3246, 3225, 2923, 2852,
114.1, 72.0, 71.0, 50.8, 33.8, 29.7, 29.7, 29.4, 29.1, 28.9, 26.1; IR (KBr): 1/
λ
2793, 1642, 1467, 1417, 1362, 1104, 838 cm–1; ESIꢀHRMS m/z calcd for C36H56F6NO2P [M – PF6]+:
534.4311; found: 534.4307.
Synthesis of
N-(tert-Butoxycarbonyl)bis[4-[(hex-5-en-1-yloxy)methyl]benzyl]amine (7b). To a solution
of NaH (60% dispersion in oil, 507 mg, 12.7 mmol) prewashed with hexane in DMF (20 mL), Nꢀ(tertꢀ
butoxycarbonyl)bis[4ꢀ(hydroxymethyl)benzyl]amine 5 (1.20 g, 3.36 mmol) in DMF (10 mL) was added at
room temperature. Then, a solution of hexꢀ5ꢀenꢀ1ꢀyl tolueneꢀ4ꢀsulfonate (6b) (1.90 g, 7.47 mmol) in DMF
(10 mL) was added to the reaction mixture. After being stirred for 12 h under reflux conditions, the reaction
mixture was poured into aqueous NH4Cl. The aqueous layer was extracted with ethyl acetate. The organic
layer was washed with saturated NaHCO3 and brine and then dried over anhydrous Na2SO4. After
removing the Na2SO4 by filtration, the solvent was concentrated in vacuo. The crude product was purified
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by column chromatography on silica gel with 20% ethyl acetate in hexane to yield Nꢀ(tertꢀ
1
butoxycarbonyl)bis[4ꢀ[(hexꢀ5ꢀenꢀ1ꢀyloxy)methyl]benzyl]amine (7b) (695 mg, 1.33 mmol, 40%). H NMR
5
6
(300 MHz, CDCl3):
δ = 7.31 (d, J = 8.1 Hz, 4H), 7.19 (br, 4H), 5.82 (ddt, J = 17.1, 10.2, 6.6 Hz, 2H), 5.05
7
8
9
(ddt, J = 17.1, 1.8, 1.5 Hz, 2H), 4.95 (ddt, J = 10.2, 1.8, 1.5 Hz, 2H), 4.49 (s, 4H), 4.40 (br s, 2H), 3.31 (br
s, 2H), 3.49 (t, J = 6.6 Hz, 4H), 2.08 (ddq, J = 6.6, 6.6, 1.5 Hz, 4H), 1.70ꢀ1.60 (m, 4H), 1.49 (s, 9H), 1.43ꢀ
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1.26 ppm (m, 4H); 13C NMR (75 MHz, CDCl3):
δ = 155.9, 138.7, 137.6, 137.2, 128.0, 127.8, 127.4, 114.5,
80.0, 72.6, 70.2, 48.8, 48.5, 33.5, 29.2, 28.4, 25.4 ppm; IR (neat): 1/
λ = 3074, 2975, 2933, 2857, 1695,
1640, 1513, 1455 cm–1; ESIꢀHRMS m/z calcd for C33H47NO4 [M + Na]+: 544.3403; found: 544.3416.
Synthesis of Bis[4-[(hex-5-en-1-yloxy)methyl]benzyl]amine (8b). To
a
solution of Nꢀ(tertꢀ
butoxycarbonyl)bis[4ꢀ[(decꢀ9ꢀenꢀ1ꢀyloxy)methyl]benzyl]amine (7b) (981 mg, 1.88 mmol) in CH2Cl2 (20
mL), trifluoroacetic acid (3.0 mL, 39.2 mmol) was added dropwise at 0 °C. After being stirred for 12 h at
room temperature, the reaction mixture was poured into an aqueous 10% solution of NaOH. The aqueous
layer was extracted with CHCl3. After removal of the solvent in vacuo, the crude product was purified by
column chromatography on silica gel with 20% ethyl acetate in hexane to yield bis[4ꢀ[(hexꢀ5ꢀenꢀ1ꢀ
1
yloxy)methyl]benzyl]amine (8b) (691 mg, 1.64 mmol, 87%). H NMR (300 MHz, CDCl3):
δ = 7.32 (m,
8H), 5.97 (ddt, J = 17.1, 10.5, 5.4 Hz, 2H), 5.22 (ddt, J = 17.1, 1.8, 1.5 Hz, 2H), 4.99 (ddt, J = 10.5, 1.8, 1.5
Hz, 2H), 4.50 (s, 4H), 3.80 (s, 4H), 3.48 (tt, J = 6.3, 1.2 Hz, 4H), 2.08 (m, 4H), 1.65 (m, 4H), 1.50 ppm (m,
4H); 13C NMR (75 MHz, CDCl3):
= 3073, 2934, 2856, 1639, 1455, 1359, 1100, 994, 910, 811 cm–1; ESIꢀHRMS m/z
δ = 139.5, 138.7, 137.3, 128.1, 127.7, 114.4, 72.6, 70.1, 52.7, 33.5, 29.2,
25.4 ppm; IR (neat): 1/
λ
calcd for C28H39NO2 [M + H]+: 422.3059; found: 422.3063.
Synthesis of Bis[4-[(hex-5-en-1-yloxy)methyl]benzyl]ammonium Hexafluorophosphate (9b). To a
solution of bis[4ꢀ[(hexꢀ5ꢀenꢀ1ꢀyloxy)methyl]benzyl]amine (8b) (691 mg, 1.63 mmol) in acetone (10 mL), 6
M HCl was added dropwise at room temperature. After being stirred for 2 h, evaporation of the solvents
produced a white solid that was dissolved in acetone (10 mL) and H2O (40 mL). Excess NH4PF6 was added
to the solution. After being stirred for 10 h, the reaction mixture was concentrated in vacuo. The aqueous
layer was extracted with CHCl3 and dried over anhydrous Na2SO4. After removing the Na2SO4 by
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2
3
4
filtration, the solvent was concentrated in vacuo. The crude product was purified by precipitation with
hexane from CHCl3 to yield bis[4ꢀ[(hexꢀ5ꢀenꢀ1ꢀyloxy)methyl]benzyl]ammonium hexafluorophosphate (9b)
5
6
(878 mg, 1.54 mmol, 94%). m.p.: 77 °C; 1H NMR (300 MHz, CDCl3):
δ = 7.40 (d, J = 8.1 Hz, 4H), 7.33 (d,
7
8
9
J = 8.1 Hz, 4H), 6.74 (br s, 2H), 5.80 (ddt, J = 17.1, 10.2, 6.6 Hz, 2H), 5.00 (ddt, J = 17.1, 2.1, 1.5 Hz, 2H),
4.94 (ddt, J = 10.2, 2.1, 1.5 Hz, 2H), 4.46 (s, 4H), 4.13 (t, J = 5.1 Hz, 4H), 3.47 (t, J = 6.6 Hz, 4H), 2.07 (m,
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60
4H), 1.64 (m, 4H), 1.47 ppm (m, 4H); 13C NMR (75 MHz, CDCl3):
= 3289, 2931, 2854, 2115, 1414, 1106, 842 cm–1; ESIꢀ
HRMS m/z calcd for C28H40F6NO2P [M – PF6]+: 422.3059; found 422.3080.
δ = 138.6, 130.0, 128.5, 114.6, 72.0,
70.7, 50.8, 33.5, 29.1, 25.4 ppm; IR (KBr): 1/
λ
Synthesis of
N-(tert-Butoxycarbonyl)bis[4-[(dec-9-yn-1-yloxy)methyl]benzyl]amine (7c). To a solution
of NaH (60% dispersion in oil, 2.08 g, 52.0 mmol) prewashed with hexane in DMF (30 mL), Nꢀ(tertꢀ
butoxycarbonyl)bis[4ꢀ(hydroxymethyl)benzyl]amine 5 (3.67 g, 10.3 mmol) in DMF (30 mL) was added at
0 °C under N2. Then, a solution of decꢀ9ꢀynꢀ1ꢀyl tolueneꢀ4ꢀsulfonate (6c) (7.92 g, 25.7 mmol) in DMF (30
mL) and catalytic amounts of tetrabutylammonium iodide were added to the reaction mixture. After being
stirred for 15 h at 50 °C, the reaction mixture was poured into aqueous NH4Cl. The aqueous layer was
extracted with ethyl acetate. The organic layer was washed with saturated NaHCO3 and brine and then
dried over anhydrous Na2SO4. After removing the Na2SO4 by filtration, the solvent was concentrated in
vacuo. The crude product was purified by column chromatography on silica gel with 10% ethyl acetate in
hexane to yield Nꢀ(tertꢀbutoxycarbonyl)bis[4ꢀ[(decꢀ9ꢀynꢀ1ꢀyloxy)methyl]benzyl]amine (7c) (5.38 g, 8.54
1
mmol, 83%). H NMR (400 MHz, CDCl3):
δ = 7.28 (d, J = 8.1 Hz, 4H), 7.16 (br, 4H), 4.47 (s, 4H), 4.37
(br, 2H), 4.28 (br, 2H), 3.45 (t, J = 6.6 Hz, 4H), 2.16 (dt, J = 7.1, 2.6 Hz, 4H), 1.91 (t, J = 2.6 Hz, 2H),
1.66ꢀ1.44 (m, 17H), 1.42ꢀ1.24 ppm (m, 16H); 13C NMR (100 MHz, CDCl3):
δ
= 156.0, 137.7, 137.2, 128.0,
127.8, 127.4, 84.7, 80.0, 72.6, 70.5, 68.1, 48.9, 48.5, 29.7, 29.3, 29.0, 28.7, 28.4, 26.1, 18.4 ppm; IR (neat):
= 3306, 2932, 2856, 2117, 1694, 1242, 1100, 883 cm–1; ESIꢀHRMS: m/z calcd for C41H59NO4 [M +
1/
λ
Na]+: 652.4336; found: 652.4333; elemental analysis calcd (%) for C41H59NO4ꢁ1/2H2O: C 77.07, H 9.47, N
2.19; found: C 77.25, H 9.35, N 2.15.
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Synthesis of Bis[4-[(dec-9-yn-1-yloxy)methyl]benzyl]amine (8c). To
a
solution of Nꢀ(tertꢀ
3
4
5
6
7
8
9
butoxycarbonyl)bis[4ꢀ[(decꢀ9ꢀynꢀ1ꢀyloxy)methyl]benzyl]amine (7c) (4.95 g, 7.86 mmol) in CH2Cl2,
trifluoroacetic acid (5.2 mL, 67.9 mmol) was added dropwise at 0 °C under N2. After being stirred for 4 h at
room temperature, the reaction mixture was poured into aqueous NaHCO3 and basified with NaHCO3
powder. The aqueous layer was extracted with CHCl3. The organic layer was washed with saturated
NaHCO3 and brine and then dried over anhydrous Na2SO4. After removing the Na2SO4 by filtration, the
solvent was concentrated in vacuo. The crude product was purified by column chromatography on silica gel
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45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
with 40% ethyl acetate in hexane to yield bis[4ꢀ[(decꢀ9ꢀynꢀ1ꢀyloxy)methyl]benzyl]amine (8c) (4.00 g, 7.55
1
mmol, 96%). H NMR (400 MHz, CDCl3):
δ = 7.34ꢀ7.29 (m, 8H), 4.48 (s, 4H), 3.79 (s, 4H), 3.45 (t, J =
6.6 Hz, 4H), 2.17 (dt, J = 7.1, 2.7 Hz, 4H), 1.93 (t, J = 2.7 Hz, 2H), 1.62ꢀ1.50 (m, 8H), 1.39ꢀ1.28 ppm (m,
16H); 13C NMR (100 MHz, CDCl3):
δ
= 139.4, 137.4, 128.2, 127.7, 84.7, 72.6, 70.4, 68.1, 52.7, 29.7, 29.3,
= 3294, 2933, 2116, 1703, 1513, 1462, 1097, 814 cm–1;
29.0, 28.7, 28.4, 26.1, 18.4 ppm; IR (neat): 1/
λ
ESIꢀHRMS: m/z calcd for C36H51NO2 [M + H]+: 530.3993; found: 530.3977; elemental analysis calcd (%)
for C36H51NO2ꢁH2O: C 78.93, H 9.75, N 2.56; found: C 78.92, H 9.44, N 2.53.
Synthesis of Bis[4-[(dec-9-yn-1-yloxy)methyl]benzyl]ammonium Hexafluorophosphate (9c). To a
solution of bis[4ꢀ[(decꢀ9ꢀynꢀ1ꢀyloxy)methyl]benzyl]amine (8c) (4.00 g, 7.55 mmol) in acetone (50 mL), 6
M HCl (2.6 mL) was added dropwise at room temperature. After being stirred for 2 h, the reaction mixture
was concentrated in vacuo. Then, acetone (70 mL) and a solution of NH4PF6 (3.04 g, 18.65 mmol) in water
were added to the compound. After being stirred for 4 h, the reaction mixture was concentrated in vacuo.
The aqueous layer was extracted with CHCl3 and dried over anhydrous Na2SO4. After removing the
Na2SO4 by filtration, the solvent was concentrated in vacuo. The crude product was purified by
precipitation with hexane from CHCl3 to yield bis[4ꢀ[(decꢀ9ꢀynꢀ1ꢀyloxy)methyl]benzyl]ammonium
1
hexafluorophosphate (9c) (4.54 g, 6.71 mmol, 89%). m.p.: 103 °C; H NMR (400 MHz, CDCl3):
δ = 7.40ꢀ
7.24 (m, 8H), 4.46 (s, 4H), 4.10 (s, 4H), 3.46 (t, J = 6.5 Hz, 4H), 2.16 (dt, J = 7.1, 2.6 Hz, 4H), 1.92 (t, J =
2.6 Hz, 2H), 1.54ꢀ1.47 (m, 8H), 1.39ꢀ1.28 ppm (m, 16H); 13C NMR (100 MHz, CDCl3):
δ
= 141.1, 129.9,
128.5, 128.0, 84.8, 72.0, 71.0, 68.1, 50.7, 29.7, 29.3, 29.0, 28.7, 28.4, 26.1, 18.4 ppm; IR (KBr): 1/λ =
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3289, 2931, 2854, 2115, 1414, 1106, 842 cm–1; ESIꢀHRMS: m/z calcd for C36H52F6NO2P [M – PF6]+:
1
2
3
4
530.3993; found: 530.3980.
5
6
Synthesis of
N-(tert-Butoxycarbonyl)bis[4-[(hex-5-yn-1-yloxy)methyl]benzyl]amine (7d). To a solution
7
8
9
of NaH (60% dispersion in oil, 3.37 g, 84.3 mmol) prewashed with hexane in DMF (80 mL), Nꢀ(tertꢀ
butoxycarbonyl)bis[4ꢀ(hydroxymethyl)benzyl]amine 5 (5.92 g, 16.6 mmol) in DMF (40 mL) was added at
0 °C under N2. Then, a solution of hexꢀ5ꢀynꢀ1ꢀyl tolueneꢀ4ꢀsulfonate (6d) (9.61 g, 38.1 mmol) in DMF (40
mL) and catalytic amounts of tetrabutylammonium iodide were added to the reaction mixture. After being
stirred for 2 h at 50 °C, the reaction mixture was poured into aqueous NH4Cl. The aqueous layer was
extracted with ethyl acetate. The organic layer was washed with saturated NaHCO3 and brine and then
dried over anhydrous Na2SO4. After removing Na2SO4 by filtration, the solvent was concentrated in vacuo.
The crude product was purified by column chromatography on silica gel with 10% ethyl acetate in hexane
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40
41
42
43
44
45
46
47
48
49
50
51
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53
54
55
56
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59
60
to yield Nꢀ(tertꢀbutoxycarbonyl)bis[4ꢀ[(hexꢀ5ꢀynꢀ1ꢀyloxy)methyl]benzyl]amine (7d) (7.41 g, 14.3 mmol,
1
86%). H NMR (400 MHz, CDCl3):
δ
7.30 (d, J = 8.4 Hz, 4H), 7.20 (br, 4H), 4.49 (s, 4H), 4.39 (br, 2H),
4.30 (br, 2H), 3.50 (t, J = 6.2 Hz, 4H), 2.22 (dt, J = 7.0, 2.6 Hz, 4H), 1.95 (t, J = 2.6 Hz, 2H), 1.80ꢀ1.59 (m,
8H), 1.49 ppm (s, 9H); 13C NMR (100 MHz, CDCl3):
δ
= 156.0, 137.5, 137.3, 128.1, 127.9, 127.5, 84.3,
80.1, 72.6, 69.8, 68.4, 48.9, 48.5, 28.8, 28.5, 25.2, 18.2 ppm; IR (neat): 1/λ = 3295, 2936, 2863, 2116,
1693, 1243, 1113, 883 cm–1; ESIꢀHRMS m/z calcd for C33H43NO4 [M + Na]+: 540.3084; found: 540.3082;
elemental analysis calcd (%) for C33H43NO4ꢁ1/4H2O: C 75.90, H 8.40, N 2.68; found: C 76.08, H 8.43, N
2.65.
Synthesis of Bis[4-[(hex-5-yn-1-yloxy)methyl]benzyl]amine (8d). To
a solution of Nꢀ(tertꢀ
butoxycarbonyl)bis[4ꢀ[(hexꢀ5ꢀynꢀ1ꢀyloxy)methyl]benzyl]amine (7d) (4.61 g, 8.90 mmol) in CH2Cl2,
trifluoroacetic acid (6.8 mL, 88.8 mmol) was added dropwise at 0 °C under N2. After being stirred for 3 h at
room temperature, the reaction mixture was poured into aqueous NaHCO3 and basified with NaHCO3
powder. The aqueous layer was extracted with CHCl3. The organic layer was washed with saturated
NaHCO3 and brine and then dried over anhydrous Na2SO4. After removing Na2SO4 by filtration, the
solvent was concentrated in vacuo. The crude product was purified by column chromatography on silica gel
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with 40% ethyl acetate in hexane to yield bis[4ꢀ[(hexꢀ5ꢀynꢀ1ꢀyloxy)methyl]benzyl]amine (8d) (3.66 g, 8.76
1
3
4
mmol, 98%). H NMR (400 MHz, CDCl3):
δ = 7.32ꢀ7.27 (m, 8H), 4.47 (s, 4H), 3.77 (s, 4H), 3.47 (t, J =
5
6
6.2 Hz, 4H), 2.20 (dt, J = 7.0, 2.6 Hz, 4H), 1.93 (t, J = 2.6 Hz, 2H), 1.79ꢀ1.53 ppm (m, 8H); 13C NMR (100
7
8
9
MHz, CDCl3):
δ = 139.3, 137.3, 128.2, 127.8, 84.3, 72.7, 69.7, 68.4, 52.7, 28.7, 25.2, 18.2 ppm; IR (neat):
= 3305, 2941, 2115, 1643, 1514, 1454, 1093, 808 cm–1; ESIꢀHRMS: m/z calcd for C28H35NO2 [M +
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1/
λ
H]+: 418.2741; found: 418.2729; elemental analysis calcd (%) for C28H35NO2ꢁ1/2H2O: C 78.83, H 8.51, N
3.28; found: C 78.81, H 8.33, N 3.20.
Synthesis of Bis[4-[(hex-5-yn-1-yloxy)methyl]benzyl]ammonium Hexafluorophosphate (9d). To a
solution of bis[4ꢀ[(hexꢀ5ꢀynꢀ1ꢀyloxy)methyl]benzyl]amine (8d) (3.66 g, 8.76 mmol) in acetone (55 mL), 6
M HCl (3 mL) was added dropwise at room temperature. After being stirred for 2 h, the reaction mixture
was concentrated in vacuo. Then, acetone (50 mL) and a solution of NH4PF6 (2.86 g, 17.55 mmol) in water
were added to the compound. After being stirred for 4 h, the reaction mixture was concentrated in vacuo.
The aqueous layer was extracted with CHCl3 and then dried over anhydrous Na2SO4. After removing the
Na2SO4 by filtration, the solvent was concentrated in vacuo. The crude product was purified by
precipitation with hexane from CHCl3 to yield bis[4ꢀ[(hexꢀ5ꢀynꢀ1ꢀyloxy)methyl]benzyl]ammonium
hexafluorophosphate (9d) (4.24 g, 7.52 mmol, 86%). m.p.: 111 °C; 1H NMR (400 MHz, CDCl3):
δ = 7.42ꢀ
7.34 (m, 8H), 4.48 (s, 4H), 4.12 (s, 4H), 3.51 (t, J = 6.3 Hz, 4H), 2.22 (dt, J = 7.0, 2.6 Hz, 4H), 1.95 (t, J =
2.6 Hz, 2H), 1.78ꢀ1.71 (m, 4H), 1.65ꢀ1.59 ppm (m, 4H); 13C NMR (100 MHz, CDCl3):
δ
= 140.5, 130.0,
128.6, 128.4, 84.2, 72.1, 70.2, 68.6, 50.3, 28.6, 25.1, 18.2 ppm; IR (neat): 1/λ = 3286, 2943, 2863, 2114,
1416, 1104, 837 cm–1; ESIꢀHRMS: m/z calcd for C28H36F6NO2P [M – PF6]+: 418.2741; found: 418.2731.
General Procedure of Catenane Synthesis using Olefin Metathesis. To a solution of ammonium
hexafluorophosphate salts 9a-b containing a terminal olefin (1 equiv) and dibenzo[24]crownꢀ8 (DB24C)
(10) (1 equiv) in CH2Cl2, firstꢀgeneration Grubbs catalyst (0.2 equiv) was added at room temperature under
Ar. The concentrations were varied from 0.002 to 0.02 M. After being stirred for 0.5 days under reflux
conditions, the reaction mixture was passed through a silica gel column with 10% methanol in chloroform.
The crude product was purified by GPC with chloroform to yield [2]catenane 1 and [3]catenane 2.
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Synthesis of [2]Catenane 1a and [3]Catenane 2a. Following the above general procedure, bis[4ꢀ[(decꢀ9ꢀ
enꢀ1ꢀyloxy)methyl]benzyl]ammonium hexafluorophosphate (9a) (70 mg, 0.10 mmol), dibenzo[24]crownꢀ8
(DB24C) (10) (45 mg, 0.10 mmol), and Grubbs catalyst 1st (17 mg, 0.021 mmol) in CH2Cl2 (5 mL for 0.02
7
8
M) yielded [2]catenane 1a (35 mg, 0.032 mmol, 31%) and [3]catenane 2a (23 mg, 0.010 mmol, 20%).
9
1
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60
[2]Catenane 1a. H NMR (300 MHz, CDCl3):
δ = 7.55 (br, 2H), 7.28 (d, J = 7.9 Hz, 4H), 7.20 (d, J = 7.9
Hz, 4H), 6.93ꢀ6.88 (m, 4H), 6.82ꢀ6.78 (m, 4H), 5.31ꢀ5.28 (m, 2H), 4.59ꢀ4.55 (m, 4H), 4.42(s, 4H), 4.12ꢀ
4.10 (m, 8H), 3.77ꢀ3.75 (m, 8H), 3.46ꢀ3.41 (m, 12H), 1.93ꢀ1.87 (m, 4H), 1.64ꢀ1.57 (m, 8H), 1.37ꢀ1.25 ppm
(m, 16H); 13C NMR (100 MHz, CDCl3):
δ
= 147.4, 140.2, 130.7, 130.3, 129.3, 127.8, 121.8, 112.8, 72.0,
= 3153, 2929,
70.6, 70.3, 70.1, 68.3, 52.3, 32.4, 29.7, 29.6, 29.5, 29.1, 28.7, 26.4 ppm; IR (CHCl3): 1/
λ
1596, 1504, 1251, 1106, 848, 772 cm–1; ESIꢀHRMS m/z calcd for C58H84F6NO10P [M – PF6]+: 954.6090;
found: 954.6084.
1
[3]Catenane 2a. H NMR (300 MHz, CDCl3):
δ
7.62 (br, 4H), 7.25 (d, J = 8.0 Hz, 8H), 7.17 (d, J = 8.0
Hz, 8H), 6.89ꢀ6.84 (m, 8H), 6.79ꢀ6.75 (m, 8H), 5.38ꢀ5.34 (m, 4H), 4.58ꢀ4.54 (m, 8H), 4.40 (s, 8H), 4.10ꢀ
4.08 (m, 16H), 3.77ꢀ3.75 (m, 16H), 3.45ꢀ3.41 (m, 24H), 2.05ꢀ1.95 (m, 8H), 1.65ꢀ1.56 (m, 16H), 1.35ꢀ1.26
ppm (m, 32H); 13C NMR (175 MHz, CDCl3):
δ
= 147.4, 140.1, 130.6, 130.3, 129.1, 127.5, 121.6, 112.6,
= 3150,
72.0, 70.7, 70.6, 70.1, 68.1, 52.4, 32.5, 29.7, 29.4, 29.4, 29.3, 28.9, 26.1 ppm; IR (CHCl3): 1/
λ
2929, 1596, 1504, 1251, 1104, 848, 771 cm–1; ESIꢀHRMS m/z calcd for C116H168F12N2O20P2 [M – 2PF6]2+:
955.1107; found: 955.1084.
Synthesis of [3]Catenane 2b. Following the above general procedure, bis[4ꢀ[(hexꢀ5ꢀenꢀ1ꢀ
yloxy)methyl]benzyl]ammonium hexafluorophosphate (9b) (70 mg, 0.12 mmol), dibenzo[24]crownꢀ8
(DB24C) (10) (55 mg, 0.12 mmol), and Grubbs catalyst 1st (17 mg, 0.0021 mmol) in CH2Cl2 (6 mL for
1
0.02 M) yielded [3]catenane 2b (42 mg, 0.021 mmol, 35%). H NMR (300 MHz, CDCl3):
δ = 7.62 (br,
4H), 7.23 (d, J = 7.8 Hz, 8H), 7.17 (d, J = 7.8 Hz, 8H), 6.87ꢀ6.84 (m, 8H), 6.79ꢀ6.76 (m, 8H), 5.44ꢀ5.37 (m,
4H), 4.55ꢀ4.51 (m, 8H), 4.41 (s, 8H), 4.09ꢀ4.08 (m, 16H), 3.75ꢀ3.73 (m, 16H), 4.45ꢀ3.41 (m, 24H), 2.11ꢀ
13
1.99 (m, 8H), 1.67ꢀ1.57 (m, 8H), 1.49ꢀ1.39 ppm (m, 8H); C NMR (100 MHz, CDCl3);
δ = 147.4, 140.1,
130.5, 130.3, 129.1, 127.4, 121.6, 112.7, 71.9, 70.6, 70.5, 70.1, 68.2, 52.4, 32.3, 29.1, 26.2 ppm; IR
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(CHCl3): 1/λ
= 3148, 2932, 1596, 1504, 1249, 1108, 847, 776 cm–1; ESIꢀHRMS m/z calcd for
1
2
3
4
C100H136F12N2O20P2 [M – 2PF6]2+: 842.9855; found: 842.9835.
5
6
7
8
General Procedure of Catenane Synthesis using Eglinton Coupling. To a solution of ammonium
hexafluorophosphate salts 9c-d containing a terminal alkyne (1 equiv) and dibenzo[24]crownꢀ8 (DB24C)
(10) (1 equiv) in CH2Cl2, Cu(OAc)2 (3 equiv) and pyridine (1 equiv) were added at room temperature under
N2. The concentrations were varied from 0.002 to 0.02 M. After being stirred for 2.5 days at reflux, the
reaction mixture was filtered with Celite. The filtrate was washed with NH4Cl/NaHCO3 aqueous solution, 1
M NaOH, saturated NaHCO3, and brine and dried over anhydrous Na2SO4. After removing the Na2SO4 by
filtration, the solvent was concentrated in vacuo. The residue was dissolved in CH2Cl2 and treated with a
solution of excess NH4PF6 in water at room temperature. After being stirred for 5 h, the aqueous layer was
extracted with CH2Cl2. The organic layer was dried over anhydrous Na2SO4. After removing the Na2SO4 by
filtration, the solvent was concentrated in vacuo. The crude product was purified by column
chromatography on silica gel with 10% methanol in CHCl3 and GPC (CHCl3) to yield [2]catenane 3a-b and
[3]catenane 4a-b.
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Synthesis of [2]Catenane 3a and [3]Catenane 4a. Following the above general procedure, bis[4ꢀ[(decꢀ9ꢀ
ynꢀ1ꢀyloxy)methyl]benzyl]ammonium hexafluorophosphate (9c) (135.3 mg, 0.200 mmol),
dibenzo[24]crownꢀ8 (DB24C) (10) (89.5 mg, 0.200 mmol), Cu(OAc)2 (110.2 mg, 0.607 mmol), and
pyridine (16.5 ꢁl, 0.204 mmol) in CH2Cl2 (10 mL) yielded [2]catenane 3a (28.1 mg, 0.025 mmol, 12%) and
[3]catenane 4a (18.0 mg, 0.008 mmol, 8%).
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[2]Catenane 3a. H NMR (700 MHz, CDCl3):
δ = 7.56 (br, 1H), 7.26 (d, J = 8.0 Hz, 4H), 7.26 (d, J = 8.0
Hz, 4H), 6.88ꢀ6.87 (m, 4H), 6.79ꢀ6.78 (m, 4H), 4.58ꢀ4.57 (m, 4H), 4.39 (s, 4H), 4.10ꢀ4.09 (m, 8H), 3.77ꢀ
3.75 (m, 8H), 3.43ꢀ3.42 (m, 12H), 2.19 (t, J = 6.7 Hz, 4H), 1.59ꢀ1.55 (m, 4H), 1.47ꢀ1.43 (m, 4H), 1.36ꢀ1.25
ppm (m, 16H); 13C NMR (175 MHz, CDCl3):
δ
= 147.4, 140.2, 130.7, 129.2, 127.6, 121.7, 112.8, 77.6,
= 3152,
72.0, 70.6, 70.3, 70.1, 68.2, 65.3, 52.3, 29.7, 29.1, 29.1, 28.4, 28.2, 26.3, 19.0 ppm; IR (CHCl3): 1/
λ
2933, 1595, 1503, 1251, 1106, 850, 758 cm–1; ESIꢀHRMS m/z calcd for C60H82F6NO10P [M – PF6]+:
976.5933; found: 976.5910.
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[3]Catenane 4a. H NMR (700 MHz, CDCl3):
δ = 7.60 (br, 2H), 7.25 (d, J = 7.6 Hz, 8H), 7.16 (d, J = 7.6
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Hz, 8H), 6.86ꢀ6.85 (m, 8H), 6.77ꢀ6.75 (m, 8H), 4.57ꢀ4.55 (m, 8H), 4.39 (s, 8H), 4.09ꢀ4.03 (m, 16H), 3.76ꢀ
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3.75 (m, 16H), 3.46 (s, 16H), 3.42 (t, J = 6.5 Hz, 8H), 2.22 (t, J = 6.8 Hz, 8H), 1.61ꢀ1.57 (m, 8H), 1.51ꢀ1.47
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(m, 8H), 1.39ꢀ1.24 ppm (m, 32H); 13C NMR (175 MHz, CDCl3):
δ = 147.4, 140.1, 130.6, 129.1, 127.5,
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121.6, 112.6, 77.5, 72.0, 70.7, 70.1, 68.1, 65.3, 52.4, 29.6, 29.2, 29.0, 28.6, 28.2, 26.1, 19.1 ppm; IR
= 3151, 2933, 1595, 1504, 1251, 1104, 848, 755 cm–1; ESIꢀHRMS m/z calcd for
(CHCl3): 1/
λ
C120H164F12N2O20P2 [M – 2PF6]2+: 977.0950; found: 977.0935.
Synthesis of [2]Catenane 3b and [3]Catenane 4b. Following the above general procedure, bis[4ꢀ[(hexꢀ5ꢀ
ynꢀ1ꢀyloxy)methyl]benzyl]ammonium hexafluorophosphate (9d) (112.5 mg, 0.200 mmol),
dibenzo[24]crownꢀ8 (DB24C) (10) (89.2 mg, 0.199 mmol), Cu(OAc)2 (110.2 mg, 0.607 mmol), and
pyridine (16.5 ꢁl, 0.204 mmol) in CH2Cl2 (10 mL) yielded [2]catenane 3b (10.1 mg, 0.010 mmol, 5%) and
[3]catenane 4b (26.3 mg, 0.013 mmol, 13%).
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[2]Catenane 3b. H NMR (700 MHz, CDCl3):
δ = 7.44 (br, 1H), 7.31 (d, J = 7.9 Hz, 4H), 7.21 (d, J = 7.9
Hz, 4H), 6.95ꢀ6.94 (m, 4H), 6.89ꢀ6.88 (m, 4H), 4.57ꢀ4.55 (m, 4H), 4.36 (s, 4H), 4.15 (s, 8H), 3.74 (s, 8H),
3.39 (t, J = 5.7 Hz, 4H), 3.36 (s, 8H), 2.18 (t, J = 7.4 Hz, 4H), 1.58ꢀ1.54 (m, 4H), 1.52ꢀ1.45 ppm (m, 4H);
13C NMR (175 MHz, CDCl3):
δ
= 147.7, 139.9, 131.2, 129.8, 129.1, 121.9, 113.2, 77.8, 72.4, 70.5, 70.1,
= 3154, 2932, 1595, 1503, 1252, 1108, 848,
69.2, 68.6, 65.1, 52.3, 29.3, 26.3, 19.0 ppm; IR (CHCl3): 1/
λ
745 cm–1; ESIꢀHRMS m/z calcd for C52H66F6NO10P [M – PF6]+: 864.4681; found: 864.4646.
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[3]Catenane 4b. H NMR (700 MHz, CDCl3):
δ = 7.62 (br, 2H), 7.25 (d, J = 7.8 Hz, 8H), 7.16 (d, J = 7.8
Hz, 8H), 6.87ꢀ6.85 (m, 8H), 6.79ꢀ6.76 (m, 8H), 4.55ꢀ4.53 (m, 8H), 4.39 (s, 8H), 4.09ꢀ4.08 (m, 16H), 3.76ꢀ
3.75 (m, 16H), 3.45ꢀ3.42 (m, 24H), 2.27 (t, J = 7.0 Hz, 8H), 1.71ꢀ1.58 ppm (m, 16H); 13C NMR (175 MHz,
CDCl3):
δ
= 147.4, 139.9, 130.6, 129.1, 127.5, 121.6, 112.7, 77.3, 72.0, 70.6, 70.1, 69.8, 68.2, 65.5, 52.3,
= 3150, 2934, 1595, 1504, 1252, 1107, 848, 751 cm–1; ESIꢀHRMS
28.7, 25.2, 18.9 ppm; IR (CHCl3): 1/
λ
m/z calcd for C104H132F12N2O20P2 [M – 2PF6]2+: 864.9698; found: 864.9670.
Determination of the Association Constants. The association constants for ammonium salts 9a-d and
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crown ether 10 were determined by H NMR titration in dichloromethaneꢀd2. The complexes of 9a-d with
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