Dynamic [2]catenanes based on a hydrogen bonding-mediated bis-zinc porphyrin foldamer tweezer: A case study

Article abstract of DOI:10.1021/jo062523g

(Chemical Equation Presented) This paper describes the self-assembly of a new class of three-component dynamic [2]catenanes, which are driven or stabilized by intramolecular hydrogen bonding, coordination, and electrostatic interaction. One of the component molecules 2, consisting of an aromatic oligoamide spacer and two peripheral zinc porphyrin units, was designed to adopt a folded preorganized conformation, which is stabilized by consecutive intramolecular three-centered hydrogen bonds. Component molecule 3 is a linear secondary ammonium bearing two peripheral pyridine units, which was designed to form a 1:1 complex with 24-crown-8 (5). The ¹H NMR and UV-vis experiments in CDCl₃-CD₃CN (4:1 v/v) revealed that, due to the preorganized U-shaped feature, 2 could efficiently bind 3 through the cooperative zinc-pyridine coordination to generate highly stable 1:1 complex 2·3. Adding 5 to the 1:1 solution of 2 and 3 led to the formation of dynamic three-component [2]catenane 2·3·5 as a result of the threading of 3 through 5. ¹H NMR studies indicated that in the 1:1:1 solution (3 mM) [2]catenane 2·3·5 was generated in 55% yield at 25°C. The yield was increased with the reduction of the temperature and [2]catenane could be produced quantitatively in a 1:1:2 solution ([2] = 3 mM) at -13°C. Replacing 3 with 1,2-bis(4,4′-bipyridinium)ethane (4) in the three-component solution could also give rise to similar dynamic [2]-catenane 2·4·5 albeit in slightly lower yield.

Full text of DOI:10.1021/jo062523g

Dynamic [2]Catenanes Based on a Hydrogen Bonding-Mediated
Bis-Zinc Porphyrin Foldamer Tweezer: A Case Study
Jing Wu,† Fang Fang,‡ Wen-Ya Lu,† Jun-Li Hou,† Chuang Li,† Zong-Quan Wu,†
Xi-Kui Jiang,† Zhan-Ting Li,*,† and Yi-Hua Yu*,‡
State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China, and Key Laboratory
of Optical and Magnetic Resonance Spectroscopy, Ministry of Education, East China Normal UniVersity,
Shanghai 200062, China
ztli@mail.sioc.ac.cn; yhyu@phy.ecnu.edu.cn
ReceiVed December 9, 2006
This paper describes the self-assembly of a new class of three-component dynamic [2]catenanes, which
are driven or stabilized by intramolecular hydrogen bonding, coordination, and electrostatic interaction.
One of the component molecules 2, consisting of an aromatic oligoamide spacer and two peripheral zinc
porphyrin units, was designed to adopt a folded preorganized conformation, which is stabilized by
consecutive intramolecular three-centered hydrogen bonds. Component molecule 3 is a linear secondary
ammonium bearing two peripheral pyridine units, which was designed to form a 1:1 complex with 24-
1
crown-8 (5). The H NMR and UV-vis experiments in CDCl3-CD3CN (4:1 v/v) revealed that, due to
the preorganized U-shaped feature, 2 could efficiently bind 3 through the cooperative zinc-pyridine
coordination to generate highly stable 1:1 complex 2‚3. Adding 5 to the 1:1 solution of 2 and 3 led to
the formation of dynamic three-component [2]catenane 2‚3‚5 as a result of the threading of 3 through 5.
1H NMR studies indicated that in the 1:1:1 solution (3 mM) [2]catenane 2‚3‚5 was generated in 55%
yield at 25 °C. The yield was increased with the reduction of the temperature and [2]catenane could be
produced quantitatively in a 1:1:2 solution ([2] ) 3 mM) at -13 °C. Replacing 3 with 1,2-bis(4,4′-
bipyridinium)ethane (4) in the three-component solution could also give rise to similar dynamic [2]-
catenane 2‚4‚5 albeit in slightly lower yield.
Introduction
chemists.1,2 On the basis of kinetically controlled covalent bond
formation, a vast number of catenanes have been constructed.
Recently, the strategy of dynamic covalent chemistry3 has also
been extensively exploited for the synthesis of discrete types
of catenanes.4 Catenanes generated via both approaches are
kinetically stable,5 that is, the component rings in these
supramolecular structures, once formed, are interlocked irrevers-
ibly. Catenanes incorporating coordination bonds in their
component rings represent another class of structurally unique
supramolecular constructs because their self-assembly is ther-
modynamically controlled and the component rings in these
Because of their unique molecular structures and potential
applications in molecular machines and electronic devices, in
the past two decades the self-assembly of catenanes and related
supramolecular architectures has been of great interest to
† Shanghai Institute of Organic Chemistry.
‡ East China Normal University.
(1) (a) Schill, G. Catenanes, Rotaxanes and Knots; Academic Press: New
York, 1971. (b) Amabilino, D. B.; Stoddart, J. F. Chem. ReV. 1995, 95,
2725. (c) Sauvage, J.-P.; Dietrich-Buchecker, C., Eds. Molecular Catenanes,
Rotaxanes and Knots; Wiley-VCH: Weinheim, Germany, 1999.
10.1021/jo062523g CCC: $37.00 © 2007 American Chemical Society
Published on Web 03/10/2007
J. Org. Chem. 2007, 72, 2897-2905
2897

Wu et al.
catenanes are able to exchange reversibly in solution. Moreover,
they are also potentially useful supramolecular platforms for
exploring new dynamic combinatorial chemistry. However,
examples of catenanes assembled from the formation of
coordination bonds-incorporated rings are relatively few.6-8
Therefore, it remains of importance to develop new efficient
approaches for such types of dynamic interlocked systems.
Foldamers are linear molecules that are induced by nonco-
valent forces to adopt rigidified well-established secondary
structures.9 Due to its directionality and strength, hydrogen
bonding is one of the ideal noncovalent forces for constructing
such structurally elegant artificial structures. As a result of the
rigid and planar features of the aromatic amide unit, hydrogen
bonding-induced foldamers with the aromatic oligoamide back-
bonesusuallypossesshighlypredictablecompactconformation.10-21
We recently initiated a program to explore their potentials as a
new generation of preorganized scaffolds for supramolecular
self-assembly.9i Previously, we utilized rationally designed
rigidified aromatic amide oligomers as backbones for construct-
ing fullerene-recognizing supramolecular tweezers.22 More
recently we also assembled a new series of highly stable artificial
heteroduplexes by introducing simple self-binding amide sites
into preorganized aromatic oligoamide skeletons.23 We herein
describe how a foldamer-based bis-zinc porphyrin tweezer is
utilized to efficiently direct the self-assembly of a new series
of dynamic [2]catenanes from three components via two discrete
noncovalent interactions.
Results and Discussion
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2898 J. Org. Chem., Vol. 72, No. 8, 2007

New Class of Three-Component Dynamic [2]Catenanes
CHART 1
FIGURE 1. Self-assembling strategy for the dynamic three-component
[2]catenanes.
bonding to adopt a preorganized U-shaped conformation.
Component B is a linear secondary ammonium, which bears
two peripheral pyridine units. Driven by two coordination bonds,
A is able to efficiently bind B to form macrocylic complex A‚
B, while B can thread through C, 24-crown-8 in the present
study, by the cation-macrocyclic polyether recognition to
generate pseudo[2]rotaxane B‚C.24 If all three different nonco-
valent forces were strong enough, dynamic three-component [2]-
catenane A‚B‚C would be produced from the three-component
solution.
To validate the above concept, compounds 1 and 2 were
designed to possess the rigidified folded conformation of
component A (Chart 1). Compound 3 was related to component
B (Figure 1) and 4 was also prepared because Loeb et al.
reported that this molecule could be driven by intermolecular
N+‚‚‚O ion dipole interactions and C-H‚‚‚O hydrogen bonds
to thread through crown ether 5 to form modestly stable complex
4‚5.25
The synthetic route for 1 and 2 is provided in Scheme 1.
Thus, hydroquinone 6 was first dioctylated in hot DMF to give
7 in 70% yield. The ether was then treated with nitric acid to
produce 8 in 40% yield. Palladium-catalyzed hydrogenation of
8 in THF yielded diamine 9 quantitatively. The latter was then
coupled with 10 in dichloromethane in the presence of DCC to
afford 11 in 70% yield. Compound 11 was again reacted with
1222a with EDCI as condensing reagent to produce 1 in 46%
yield. Finally, porphyrin 1 was treated with zinc acetate in
methanol and dichloromethane to give 2 quantitatively. For the
synthesis of 3 (Scheme 2), prop-2-yn-1-amine 13 was first
treated with di-tert-butyl dicarbonate in aqueous THF to give
14 in 75% yield. The latter was reacted with 3-bromoprop-1-
yne in THF in the presence of sodium hydride to afford 15 in
50% yield. Palladium-catalyzed reaction of 15 with 4-iodopy-
ridine in THF produced dipyridine 16 in 94% yield. The
intermediate was then deprotected in trifluoroacetic acid to give
17,26 which was further hydrogenated to afford amine 18.
Finally, treatment of 18 with trifluoromethanesulfonic acid
produced compound 3.27 Compound 4 was prepared based on
the reported method.25 Compounds 1-3 have been characterized
by the 1H, 13C NMR, and (HR) mass spectroscopy or mi-
croanalysis.
Previous X-ray and spectroscopic investigations have revealed
that the amide protons in 1 and 2 were involved in intramo-
lecular three-centered hydrogen bonding.21a,b,28 To further
evidence the rigidified preorganized conformation of their
aromatic oligoamide moiety, fragment molecules 19 and 20 were
also prepared by the route as shown in Scheme 3. The X-ray
crystal analysis of 19 and 20 showed the existence of consecu-
tive intramolecular hydrogen bonds, which forced their back-
bones to adopt a rigidified planar conformation (Figure 2). The
1H NMR spectrum of 2 in CDCl3-CD3CN (4:1) was of high
resolution and the signals of the amide protons appeared in the
downfield area (9.97 and 10.62 ppm, respectively, 3.0 mM).
Because the skeleton of 2 might be regarded as a combination
of 19 and 20, these results support that zinc porphyrin 2 adopts
the proposed rigidified U-shaped conformation.
CPK modeling showed that the two porphyrin units of 2 in
the folded state were roughly parallel to each other, forming a
rigid molecular tweezer with a spatial separation of ca. 2 nm
between the porphyrin units. Such a distance is suitable for
complexing 3 or 4 through two Zn-N coordination bonds.
Adding 1 equiv of 2 to the solution of 3 caused all the signals
of 3 in the 1H NMR spectrum to shift upfield greatly
(Figure 3), supporting strong complexation occurring between
two compounds.29 The Job’s plot obtained from the UV-vis
experiments revealed a 1:1 binding stoichiometry.30 UV-vis
(26) The salt of this amine was originally designed as the linear
component, but found to be unstable at room temperature.
(27) The basicity of secondary amines is substantially stronger than that
of 4-alkylatedpyridines (∆pKa ≈ 7). Therefore, monoprotonation of
compound 3 should occur on the central nitrogen atom, see: (a) Bordwell,
F. G.; Hughes, D. I. J. Am. Chem. Soc. 1986, 108, 7300. (b) Brown, H. C.;
McDaniel, D. H.; Ha¨flinger, O. Determination of Organic Structures by
Physical Methods; Academic Press: New York, 1955; Vol. 1, p 567.
(28) Gong, B. Chem. Eur. J. 2001, 7, 4337.
(24) (a) Glink, P. T.; Schiavo, C.; Stoddart, J. F.; Williams, D. J. Chem.
Commun. 1996, 1483. (b) Clifford, T.; Abushamleh, A.; Busch, D. H. Proc.
Natl. Acad. Sci. U.S.A. 2002, 99, 4830. (c) Schalley, C. A.; Weilandt, T.;
Brueggemann, J.; Vo¨gtle, F. Top. Curr. Chem. 2005, 248, 141.
(25) Tiburcio, J.; Davidson, G. J. E.; Loeb, S. J. Chem. Commun. 2002,
1282.
(29) (a) Sanders, J. K. M.; Bampos, N.; Clyde-Watson, Z.; Darling,
S. L.; Hawley, J. C.; Kim, H.-J.; Mak, C. C.; Webb, S. J. The Porphyrin
Handbook; Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic
Press: New York, 2000; Vol. 3, p 1. (b) Shao, X.-B.; Jiang, X.-K.; Zhao,
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J. Org. Chem, Vol. 72, No. 8, 2007 2899

Wu et al.
SCHEME 1
SCHEME 2
SCHEME 3
titration experiments (Figure 4) were then performed. Fitting
the data to a 1:1 binding mode gave rise to an association
constant Kassoc of 5.7((0.7) × 106 M-1 for complex 2‚3.31 The
value is impressive considering the increased polarity of the
binary solvent used compared to chloroform,32 indicating the
efficiency of the intramolecular hydrogen bonding-induced
preorganization of 2. Also on the base of UV-vis titration
experiments, the Kassoc of complex 2‚4 in CDCl3-CD3CN (4:
1, v/v) was determined to be ca. 7.9((0.9) × 104 M-1, which
is considerably smaller than that of 2‚3 possibly as a result of
the electron-withdrawing effect of the pyridinium units.
The recognition between secondary ammonium ions and
crown ethers has been established to be an efficient templation
for the synthesis of rotaxanes.24 Mixing 3 and 5 (3 mM) resulted
in pronounced change of the chemical shifting of 3 (∆δ: 0.33
and 0.16 ppm for NH and NCH2, respectively) in the 1H NMR
experiments, a Kassoc of ca. 180 M-1 was determined for complex
3‚5. In a similar way, a notably larger Kassoc value (ca. 260 M-1
)
was also established for the complex of 3 with dibenzo-24-
1
crown-8. Because 5 displayed only one single peak in the H
NMR spectrum, which is perfect as a dynamic probe, we chose
5, instead of dibenzo-24-crown-8, for the self-assembly of the
dynamic [2]catenane.
The 1H NMR spectrum in CDCl3-CD3CN (4:1, v/v) revealed
that, in the presence of 2 and 3 (1:1), crown ether 5 displayed
two single signals (3.48 and 2.83 ppm). Gradient experiments
(Figure 5) established that the two signals corresponded to the
free and catenated species 2‚3‚5 (Figure 6), respectively. 2D-
NOESY experiments revealed a NOE connection of modest
1
spectrum (Figure 3). On the basis of the H NMR dilution
(31) Conners, K. A. Binding Constants: The Measurement of Molecular
Complex Stability; Wiley: New York, 1987.
(32) Satake, A.; Kobuke, Y. Tetrahedron 2005, 61, 13.
2900 J. Org. Chem., Vol. 72, No. 8, 2007

New Class of Three-Component Dynamic [2]Catenanes
FIGURE 2. The solid-state structures of compounds 19 (upper) and
20 (down), highlighting the intramolecular hydrogen bonding and
rigidified planar conformation.
1
FIGURE 5. Partial H NMR spectra (400 MHz) of (a) 2 + 3 (1:1, 3
mM), (b) 5 (3 mM), (c) 2 (3 mM) + 3 + 5 (1:1:0.2), (d) 2 (3 mM) +
3 + 5 (1:1:0.6), (e) 2 (3 mM) + 3 + 5 (1:1:1), (f) 2 (3 mM) + 3 +
5 + DABCO (1:1:1:1), (g) 2 (3 mM) + 3 + 5 + DABCO (1:1:1:5),
(h) 2 (3 mM) + 3 + 5 (1:1:2) at 25 °C, and (i) 2 (3 mM) + 3 + 5
(1:1:2) at -13 °C in CDCl3-CD3CN (4:1, v/v).
even at a concentration of 5.0 mM. Adding 1 equiv of DABCO
to the 1:1:1 solution of 2, 3, and 5 caused a remarkable decrease
of the intensity of the signal of 5 at 2.83 ppm (Figure 5f). Upon
addition of 5 equiv of DABCO, the signal of 5 at 2.83 ppm
vanished completely (Figure 5g). All these observations sup-
ported that the signal at 2.83 ppm was that of the crown ether
threaded by linear 3. Addition of DABCO caused de-protonation
of 3 to yield neutral amine 18 and consequently de-threading
of 5 from it, as shown in Figure 6.34 Because 24-crown-8 5
displayed only one signal in the 1:1 solution of 3 and 5 of the
same concentration in the same solvent (Figure 3d) and
compounds 2 and 3 could form a very stable complex, the above
results supported that interlocked dynamic [2]catenane 2‚3‚5
was generated in the three-component solution through Ap-
proach A shown in Figure 1 and the exchange between the free
and catenated 5 was slow on the NMR time scale. The result
also suggested that catenation substantially increased the kinetic
barrier of threading and de-threading of 3 through 5. On the
base of the integrated intensity, we determined that the dynamic
[2]catenane was formed in ca. 55% and 84% yield in the 1:1:1
and 1:1:2 solution (Figure 5, parts e and h). Variable 1H NMR
investigations revealed that reducing the temperature remarkably
1
FIGURE 3. Partial H NMR spectra (400 MHz) of the solution (3
mM) of (a) 2, (b) 2 + 3 (1:1), (c) 3, (d) 3 + 5 (1:1), and (e) 5 in
CDCl3-CD3CN (4:1, v/v) at 25 °C.
FIGURE 4. Absorption spectral changes of 2 (1.8 × 10-6 M-1) on
titration with 3 (0-5.0 × 10-5 M-1) in CDCl3-MeCN (4:1, v/v) at
25 °C.
intensity between the signal of 5 at 2.83 ppm and the â-H signal
of the pyridine units of 3 (Figure 6).33 No such connection was
displayed for the signal of 5 at 3.48 ppm. Under identical
conditions, the 1:1 solution of 3 and 5 did not give similar NOE
(34) Because DABCO is also a strong ligand, the de-catenation may also
result from its competitive coordination to the zinc porphyrin units of 2.
Nevertheless, the result from both routes supported the formation of the
dynamic [2]catenane in the solution.
(33) NOE connections could not be confirmed between the signal of 5
at 2.83 ppm and the signals of the methylene units of 3 due to overlapping
of the methylene signals with other signals at the upfield area.
J. Org. Chem, Vol. 72, No. 8, 2007 2901

Wu et al.
FIGURE 7. Partial 1H NMR spectra (400 MHz) of the solution of (a)
2 (3.0 mM), (b) 3 + 5 (1:1), (c) 2 + 3 + 5 (0.2:1:1), (d) 2 + 3 + 5
(0.6:1:1), and (f) 2 + 3 + 5 (1:1:1) in CDCl3-CD3CN (4:1, v/v) at
25 °C ([3] ) [5] ) 3.0 mM).
complexed and free 5, respectively, are greatly different.
Considering the large difference in molecular size of 2, 3, and
5, these results well supported that 2, 3, and the complexed 5
were bound tightly in the form of one single entity, i.e., the
proposed dynamic [2]catenane.
Addition of an incremental amount of compound 2 to the
1:1 solution of 3 and 5 also caused 5 to display two signals in
the 1H NMR spectrum (Figure 7), which are obviously produced
by the uncatenated and catenated species, respectively (Ap-
proach B, Figure 1). The signal of the catenated species is broad
when the amount of 2 is low and became increasingly sharp
and shifted upfield with the increase of 2. This result could be
rationalized by considering an increasingly enhanced coordina-
tion between the zinc porphyrins of 2 and the peripheral
pyridines of 3, which led to an increased shielding effect for 2
on 5 in the dynamic [2]catenane. In contrast, the chemical shift
of the signal of the uncatenated 5 was not significantly affected
by the addition of 2.
FIGURE 6. Proposed structures of dynamic [2]catenane 2‚3‚5 and
de-catenation by the addition of DABCO. The intermolecular NOE
connection between 3 and 5 is shown in the [2]catenane.
increased the yield of the dynamic [2]catenane. Quantitative
formation of the dynamic [2]catenane was realized at -13 °C,
as was evidenced by the 1:1 ratio of the integrated intensity of
the signal of the free and catenated 5, for the 1:1:2 solution
(Figure 5i). At the same temperature, the yield of the dynamic
[2]catenane was estimated to be ca. 75% for the 1:1:1 solution.
Increasing the temperature of the mixture solution to 60 °C did
not cause the two signals of 5 to coalesce, implying that the
dynamic three-component [2]catenane was stable even at
increased temperature.
Numerous attempts to detect the ion peak of the three-
component assembly by the mass spectroscopy were unsuc-
cessful. To collect more evidence for the formation of the
dynamic [2]catenane, two-dimensional diffusion-ordered NMR
(DOSY) investigations have been performed,35 which gave rise
to diffusion coefficients (D) of 3.9 × e-9, 3.9 × e-9, 4.3 ×
e-9, and 6.0 × e-9 m2/s for 2, 3, and the two species of 5,
respectively (see the Supporting Information). It can be found
that the first three values are quite close. However, the latter
two values, which were produced from the two species of
It was reported that compounds 4 and 5 could form [2]-
pseudorotaxane 4‚5, which was stabilized by intermolecular N+‚
‚‚O ion dipole interactions and C-H‚‚‚O hydrogen bonds.25,36
Therefore, the possibility of the formation of a dynamic [2]-
catenane from 2, 4, and 5 was also explored in CDCl3-CD3-
CN (4:3, v/v) (Figure 8). The content of CD3CN in the binary
solvent was increased to achieve a relatively high solubility for
compound 4. Different from the result of the 1:1 solution of 3
and 5 in CDCl3-CD3CN (4:1, v/v), which revealed a singlet
for 24-crown-8 5 in the 1H NMR spectrum (Figure 3d), the 1H
NMR spectrum of the 1:1 solution of 4 and 5 in CDCl3-CD3-
CN (4:3, v/v) gave rise to two singlets (3.34 and 3.27 ppm) for
5 (Figure 8c), which corresponded to the free and threaded 5,
respectively. This observation implied that the exchanging
process between the threading and de-threading 4 through 5
1
1
was slow on the H NMR time scale. The H NMR spectra of
the solution of 2, 4, and a variable amount of 5 in CDCl3-
CD3CN (4:3, v/v) are provided in Figure 8. Similar to the
observations in the system of 2, 3, and 5, crown ether 5 in the
presence of 2 and 4 also displayed two single signals obviously
(35) (a) Gafni, A.; Cohen, Y. J. Org. Chem. 1997, 62, 120. (b) Gafni,
A.; Cohen, Y. J. Org. Chem. 2002, 67, 2639. (c) Zhao, T.; Beckham,
H. W.; Gibson, H. W. Macromolecules 2003, 36, 4833.
(36) (a) Loeb, S. J.; Wisner, J. A. Angew. Chem., Int. Ed. 1998, 37,
2838. (b) Loeb, S. J.; Tiburcio, J.; Vella, S. J.; Wisner, J. A. Org. & Biomol.
Chem. 2006, 4, 667.
2902 J. Org. Chem., Vol. 72, No. 8, 2007

New Class of Three-Component Dynamic [2]Catenanes
Although three different noncovalent interactions are introduced
and a coordination bond-incorporated macrocycle of 48 atoms
is involved, the thermodynamically controlled creation of the
new series of interlocked architectures is remarkably efficient.37
The dynamic [2]catenane could be assembled quantitatively
albeit at lowered temperature. The result demonstrates the
potential of rigidified aromatic amide oligomers in supramo-
lecular self-assembly. The extension of this strategy to the self-
assembly of dynamic [3]catenanes and reversibly regulated
interlocked architectures is currently under investigation.
Experimental Section
Compound 7. To a stirred solution of 6 (9.00 g, 82.0 mmol)
and n-octyl bromide (30 mL, 0.17 mol) in DMF (90 mL) was added
potassium carbonate (34.0 g, 0.25 mol). The suspension was stirred
at 100 °C for 7 h and then cooled to room temperature. The solid
was filtered and the filtrate was concentrated under reduced
pressure. The resulting residue was triturated with ethyl acetate (200
mL). The organic phase was washed with saturated sodium
bicarbonate solution (100 mL), water (3 × 100 mL), and brine (100
mL) and dried over sodium sulfate. The solvent was then removed
under reduced pressure. The resulting crude product was recrystal-
lized from ethyl acetate and petroleum ether to give compound 7
as a white solid (19.0 g, 70%). Mp 55-57 °C [lit.38 mp 56 °C]. 1H
NMR (300 MHz, CDCl3): δ 0.88-1.44 (m, 22 H), 1.59-1.56 (m,
4 H), 1.76-1.72 (m, 4 H), 3.91 (t, J ) 6.6 Hz, 4 H), 6.83 (s, 4 H).
MS (EI) m/z: 334 [M]+.
FIGURE 8. Partial 1H NMR spectra (400 MHz) of the CDCl3-CD3-
CN (4:3, v/v) solution of (a) 2 + 4 (1:1), (b) 5 (3.0 mM), (c) 4 + 5
(1:1), (d) 2 + 4 + 5 (1:1:0.2), (e) 2 + 4 + 5 (1:1:0.6), and (f) 2 +
4 + 5 (1:1:1) at 25 °C and (g) 2 + 4 + 5 (1:1:1) at -13 °C ([2] )
[4] ) 3.0 mM).
Compound 8. To a stirred solution of compound 7 (17.0 g, 0.10
mol) in acetic acid (350 mL) was added slowly concentrated nitric
acid (20 mL) at room temperature. The mixture was then stirred at
80 °C for 0.5 h and cooled to room temperature. The yellow
precipitate formed was filtered and washed with water thoroughly.
The solid was dried in vacuo and then recrystallized from ethyl
acetate to give compound 8 as a yellow solid (6.00 g, 40%). Mp
89-91 °C. 1H NMR (300 MHz, CDCl3): δ 0.88-1.47 (m, 22 H),
1.59-1.54 (m, 4 H), 1.86-1.90 (m, 4 H), 4.09 (t, J ) 6.3 Hz, 4
H), 7.51 (s, 2 H). MS (EI) m/z: 424 [M]+. Anal. Calcd for
C22H36N2O6: C, 62.24; H, 8.55; N, 6.60. Found: C, 62.23; H, 8.44;
N, 6.49.
CHART 2
Compound 9. A suspension of compound 8 (0.50 g, 1.20 mmol)
and Pd-C (10%, 50 mg) in THF (10 mL) was stirred under an
atmosphere of hydrogen gas (1 atm) at room temperature for 1.5
h. The solid was then filtered off and the solution was concentrated
in vacuo to give the desired compound as a white solid (0.44 g,
100%). The product was unstable in the air and used for the next
1
step without further purification. H NMR (300 MHz, CDCl3): δ
0.85-1.46 (m, 22 H), 1.75-1.71 (t, 4 H), 2.07-2.03 (t, 4 H), 3.85
(t, J ) 6.6 Hz, 4 H), 6.35 (t, J ) 3.3 Hz, 2 H).
as a result of the formation of dynamic [2]catenane 2‚4‚5 (Chart
2), which corresponded to the signal at 2.72 ppm. Moreover,
upon addition of a small amount of 2, the signal of 5 at 3.27
ppm in the two-component complex 4‚5 disappeared (Figure
8d). This result reflects that the formation of the dynamic [2]-
catenae was quite favored. By comparing the integrated intensity
of the two signals of 5, we established that the yields of dynamic
[2]catenane 2‚4‚5 in the 1:1:1 mixture solution (3.0 mM) at 25
and -13 °C were ca. 50% and 62%, respectively. These results
show that compound 4 is slightly less efficient as an axle than
3 for the creation of the new series of dynamic [2]catenanes.
Compound 11. At room temperature, to a stirred solution of
compound 1039 (88 mg, 0.45 mmol), HOBt (0.12 g, 0.90 mmol),
and DCC (0.19 g, 0.90 mmol) in dichloromethane (20 mL) was
added a solution of compound 9 (0.34 g, 0.90 mmol) in dichlo-
romethane (10 mL). The solution was then stirred at room
temperature for 12 h and concentrated under reduced pressure. The
resulting residue was subjected to column chromatography (dichlo-
romethane/methanol 200:1) to give compound 11 as a white solid
1
(0.25 g, 70%). Mp 29-31 °C. H NMR (300 MHz, CDCl3): δ
(37) Several dynamic [2]rotaxanes with zinc porphyrin units as stoppers
have been reported, see: (a) Gunter, M. J.; Farquhar, S. M.; Mullen, K. M.
New J. Chem. 2004, 28, 1443. (b) Johnstone, K. D.; Yamaguchi, K.; Gunter,
M. J. Org. & Biomol. Chem. 2005, 3, 3008. (c) Gunter, M. J. Eur. J. Org.
Chem. 2004, 1655. (d) Ikeda, T.; Asakawa, M.; Shimizu, T. New J. Chem.
2004, 28, 870.
(38) Nierengarten, J.-F.; Gu, T.; Hadziioannou, G.; Tsamouras, D.;
Krasnikov, V. HelV. Chim. Acta 2004, 87, 2948.
(39) Venimadhavan, S.; Shelly, K. P.; Stewart, R. J. Org. Chem. 1989,
54, 2483.
Conclusion
In summary, we have in this work illustrated a new concept
of assembling dynamic [2]catenanes by making use of the
preorganization of the hydrogen bonding-mediated oligoamide
backbone to create the tweezer-styled key building block.
J. Org. Chem, Vol. 72, No. 8, 2007 2903

Wu et al.
0.79-1.47 (m, 24 H), 1.82-1.78 (m, 8 H), 3.78 (s, 3 H), 4.00 (t,
J ) 18.6 Hz, 8 H), 6.40 (s, 2 H), 7.39 (t, J ) 8.1 Hz, 1 H), 8.17
(s, 2 H), 8.25 (d, J ) 7.5 Hz, 2 H). 13C NMR (300 MHz, CDCl3):
δ 14.0, 14.1, 22.6, 22.6, 26.0, 26.1, 29.2, 29.3, 29.3, 29.4, 29.5,
31.7, 31.8, 64.2, 69.2, 69.7, 100.5, 106.6, 119.1, 125.2, 128.4, 132.8,
134.6, 140.3, 142.7, 155.9, 161.9. MS (MALDI-TOF) m/z: 890
[M + H]+, 902 [M + Na]+. Anal. Calcd for C53H84N4O7: C, 71.58;
H, 9.52; N, 6.30. Found: C, 71.40; H, 9.54; N, 6.07.
CDCl3): δ 1.46 (s, 9 H), 2.23 (s, 1 H), 3.93 (s, 2 H), 4.73 (br, 1
H). MS (ESI) m/z: 178 [M + Na]+.
Compound 15.41 To a stirred solution of compound 14 (0.45 g,
2.90 mmol) in THF (4 mL) was added sodium hydride (60%, 0.15
g, 3.80 mmol). The suspension was stirred for 0.5 h and then
propargyl bromide (0.59 g, 4.60 mmol) was added dropwise. The
mixture was stirred at room temperature for 5 h and then quenched
with saturated ammonium chloride solution. The solvent was
removed under reduced pressure and the resulting residue triturated
with ethyl acetate (30 mL). The organic phase was then washed
with water (3 × 30 mL and brine (30 mL) and dried over sodium
sulfate. After the solvent was removed in vacuo, the resulting
material was subjected to flash chromatography (petroleum ether/
dichloromethane 2:1) to give compound 15 as pale yellow liquid
(0.28 g, 50%). 1H NMR (300 MHz, CDCl3): δ 1.53 (s, 9 H), 2.22
(s, 2 H), 4.16 (br, 4 H). MS (ESI) m/z: 216 [M + Na]+.
Compound 1. At room temperature, to a stirred solution of
compounds 11 (0.11 g, 0.12 mmol), 12 (0.34 g, 0.32 mmol), and
DMAP (2 mg) in dichloromethane (15 mL) was added EDCI (80
mg). The solution was stirred at room temperature for 12 h and
then another portion of dichloromethane (10 mL) was added. The
solution was washed with saturated sodium bicarbonate solution
(10 mL), water (3 × 10 mL), and brine (10 mL) and then dried
over sodium sulfate. Upon removal of the solvent under reduced
pressure, the resulting residue was subjected to column chroma-
tography (dichloromethane/petroleum ether 8:1) to give porphyrin
1 as a purple solid (0.17 g, 46%). Mp 142-144 °C. 1H NMR (400
MHz, CDCl3): δ 0.56-1.71 (m, 166 H), 1.89 (t, J ) 7.5 Hz, 12
H), 2.07 (t, J ) 8.1 Hz, 8 H), 3.99-4.02 (m, 7 H), 4.17 (t, J ) 6.6
Hz, 4 H), 4.44 (t, J ) 7.2 Hz, 4 H), 7.35 (d, J ) 3.9 Hz, 4 H), 7.72
(s, 6 H), 8.03 (s, 12 H), 8.24 (d, J ) 4.2 Hz, 4 H), 8.40 (s, 2 H),
8.48 (s, 2 H), 8.81 (d, d, J1 ) 12.9 Hz, J2 ) 6.3 Hz, 16 H), 9.08
(d, J ) 2.4 Hz, 2 H), 9.93 (s, 2 H), 10.56 (s, 2 H). 13C NMR (300
MHz, CDCl3): δ 14.0, 14.1, 22.5, 22.6, 22.7, 28.2, 29.2, 29.3, 29.4,
29.6 (d), 29.7, 31.7, 31.8, 31.9, 35.1, 64.5, 69.6, 69.9, 70.3, 105.6,
105.7, 118.3, 121.0, 121.2, 121.5, 121.5, 123.4, 125.0, 128.4, 129.6,
129.8, 130.0, 135.7, 141.3, 141.4, 141.8, 141.9, 148.7, 148.8, 156.2,
156.6, 162.5, 163.4. MS (MALDI-TOF) m/z: 3014 [M + H]+.
Anal. Calcd for C201H256N12O11: C, 80.04; H, 8.55; N, 5.57.
Found: C, 79.81; H, 8.69; N, 5.23.
Compound 16. A suspension of compound 15 (97 mg, 0.50
mmol), 4-iodopyridine hydrochloric acid salt (0.21 g, 1.00 mmol),
Pd(PPh3)2Cl2 (18 mg, 0.025 mmol), cupric iodide (7 mg, 0.0375
mmol), and DIPA (0.5 mL) in THF (2.0 mL) was stirred at room
temperature for 1 h. The solvent was then removed under reduced
pressure and the resulting residue triturated with dichloromethane
(10 mL). The organic phase was washed with water (10 mL) and
brine (10 mL) and dried over sodium sulfate. Upon removal of the
solvent under reduced pressure, the crude product was purified by
column chromatography (dichloromethane/methanol 50:1) to give
compound 16 as pale yellow oil (0.16 g, 94%). Mp 87-88 °C. 1H
NMR (300 MHz, acetone-d6): δ 1.50 (s, 9 H), 4.50 (s, 4 H), 7.35
(d, d, J1 ) 4.5 Hz, J2 ) 1.8 Hz, 4 H), 8.55 (d, d, J1 ) 4.5 Hz,
J2 ) 1.8 Hz, 4 H). 13C NMR (300 MHz, CDCl3): δ 28.4, 36.5,
81.6, 89.4, 125.7, 130.9, 149.8, 154.3. MS (ESI) m/z: 348 [M +
H]+. HRMS (ESI): Anal. Calcd for C21H22N3O2 [M]+ 348.1706,
found 348.1706.
Compound 17. A solution of compound 16 (0.20 g, 0.60 mmol)
in trifluoroacetic acid (2 mL) was stirred at room temperature for
4 h and then concentrated under reduced pressure. The resulting
residue was triturated with dichloromethane (10 mL). The organic
phase was washed with sodium hydroxide solution (1 M, 3 mL),
water (2 × 5 mL), and brine (50 mL) and dried over sodium sulfate.
Upon removal of the solvent in vacuo, the resulting residue was
subjected to flash chromatography (dichloromethane/ methanol 50:
1) to afford compound 17 as a pale yellow solid (0.12 g, 60%).
Mp 68-70 °C. 1H NMR (300 MHz, CDCl3): δ 3.84 (s, 4 H), 7.29
(d, d, J1 ) 1.6 Hz, J2 ) 4.4 Hz, 4 H), 8.57 (d, d, J1 ) 1.6 Hz, J2
) 4.4 Hz, 4 H). 13C NMR (300 MHz, acetone-d6): δ 38.1, 81.6,
93.4, 126.3, 131.9, 150.8. MS (ESI) m/z: 248 [M + H]+. HRMS
(ESI): Anal. Calcd for C16H14N3 [M]+ 248.1182, found 248.1186.
Compound 18. A suspension of compound 17 (0.12 g, 0.50
mmol) and Pd-C (10%, 60 mg) in THF (5 mL) was stirred under
an atmosphere of hydrogen gas (1 atm) at room temperature for 5
h. The solid was filtered off and the filtrate concentrated under
reduced pressure. The resulting residue was subjected to flash
chromatography (dichloromethane/methanol 50:1) to give com-
pound 18 as a pale yellow oil (0.10 g, 81%). 1H NMR (300 MHz,
CDCl3): δ 2.00 (t, J ) 7.5 Hz, 4 H), 2.65 (t, J ) 7.6 Hz, 4 H),
2.75 (t, J ) 7.2 Hz, 4 H), 7.11 (d, d, J1 ) 0.5 Hz, J2 ) 4.4 Hz, 4
H), 8.49 (d, d, J1 ) 0.5 Hz, J2 ) 4.4 Hz, 4 H). 13C NMR (300
MHz, CDCl3): δ 27.9, 32.3, 48.0, 123.7, 149.6, 149.9. MS (ESI)
m/z: 256 [M + H]+. HRMS (ESI): Anal. Calcd for C16H22N3 [M]+
256.1808, found 256.1807.
Compound 2. A solution of compound 1 (56 mg, 0.016 mmol)
and Zn(OAc)2‚2H2O (39 mg, 0.16 mmol) in methanol and dichlo-
romethane (5 mL, 1:10) was stirred at room temperature for 1 h
and then concentrated in vacuo. The resulting residue was triturated
in dichloromethane (20 mL). The organic phase was washed with
water (2 × 5 mL) and brine (5 mL) and dried over sodium sulfate.
Upon removal of the solvent under reduced pressure, the resulting
solid was subjected to flash chromatography (dichloromethane/
methanol 100:1) to give compound 2 as a purple solid (60 mg,
1
100%). Mp 196-198 °C. H NMR (400 MHz, CDCl3): δ 0.61-
2.00 (m, 178 H), 1.97 (t, J ) 6.0 Hz, 4 H), 2.16 (t, J ) 7.5 Hz, 4
H), 4.03-4.09 (m, 7 H), 4.23 (t, J ) 7.2 Hz, 4 H), 4.53 (t, J ) 7.2
Hz, 4 H), 7.41 (d, J ) 3.0 Hz, 4 H), 7.77 (s, 6 H), 8.09 (s, 12 H),
8.33 (d, d, J1 ) 10.2 Hz, J2 ) 4.2 Hz, 4 H), 8.45 (s, 2 H), 8.52 (s,
2 H), 8.97-9.02 (m, 16 H), 9.06 (d, J ) 2.7 Hz, 2 H), 9.97 (s, 2
H), 10.62 (s, 2 H). 13C NMR (300 MHz, CDCl3): δ 13.9, 14.1,
14.2, 22.5, 22.6, 22.7, 26.0, 26.1, 28.2, 29.2, 29.3, 29.4, 29.6 (d),
31.6, 31.8, 31.9, 35.1, 64.5, 69.6, 69.9, 70.3, 105.6, 105.6, 111.3,
120.7, 121.0, 122.5, 123.3, 128.4, 129.5, 129.7, 129.9, 131.6, 132.1,
132.2, 132.4, 136.3, 138.1, 141.8, 141.9, 141.9, 148.5 (d), 148.6,
150.3, 150.4, 150.5 (d), 156.5, 162.4, 163.5. MS (MALDI-TOF)
m/z: 3138 [M + H]+. HRMS (MALDI-FT): Anal. Calcd for
C
201H252N12O11Zn2 [M + H]+ 3137.8106, found 3137.8082.
Compound 14. At room temperature, to a stirred solution of
propargyl amine 13 (1.10 g, 20.0 mmol) in THF (12 mL) and water
(12 mL) were added saturated sodium bicarbonate solution (1 mL)
and di-tert-butyl dicarbonate (0.42 mL). The solution was stirred
at room temperature for 4 h and then concentrated in vacuo. The
resulting residue was triturated with ethyl acetate (20 mL). The
solution was washed with water (3 × 10 mL) and brine (10 mL)
and dried over sodium sulfate. Upon removal of the solvent in
vacuo, compound 14 was obtained as a pale yellow solid (2.30 g,
Compound 3. Compound 18 (33 mg, 0.13 mmol) was dissolved
in methanol (2 mL). Under stirring, a solution of trifluoromethane-
sulfuric acid (0.22 M, 0.59 mL) in water was added slowly. Stirring
was continued for 10 min and then the solvent was removed under
reduced pressure to give compound 3 as a pale yellow solid (52
mg, 100%). Mp 148-150 °C. 1H NMR (300 MHz, CD3CN-d3): δ
1
75%). Mp 40-42 °C [lit.40 mp 41-42 °C]. H NMR (300 MHz,
(40) Cheng, S.; Tarby, C. M.; Comer, D. D.; Williams, J. P.; Caporale,
L. H. Bioorg. Med. Chem. 1996, 4, 727.
(41) Boger, D. L.; Lee, J. K.; Goldberg, J.; Jin, Q. J. Org. Chem. 2000,
65, 1467.
2904 J. Org. Chem., Vol. 72, No. 8, 2007

New Class of Three-Component Dynamic [2]Catenanes
1.93-1.99 (m, 4 H), 2.72 (t, J ) 7.5 Hz, 4 H), 2.99 (t, J ) 7.8 Hz,
4 H), 7.26 (d, d, J1 ) 1.5 Hz, J2 ) 7.5 Hz, 4 H), 8.51 (d, d, J1 )
1.5 Hz, J2 ) 7.5 Hz, 4 H). 13C NMR (300 MHz, CDCl3): δ 27.01,
32.2, 48.4, 118.3, 124.9, 150.5. MS (ESI) m/z: 256 [M + H]+.
HRMS (ESI): Anal. Calcd for C16H22 N3 [M]+ 256.1808, found
256.1808.
solid. Mp 203-205 °C [lit.44 mp 200-210 °C]. 1H NMR (300 MHz,
CDCl3): δ 3.99 (s, 6 H), 7.57 (s, 2 H). MS (EI) m/z: 228 [M]+.
Compound 25. A suspension of compound 24 (0.43 g, 1.90
mmol) and Pd-C (50 mg, 10%) in THF (6 mL) was stirred under
1 atm of hydrogen gas at room temperature for 7 h. The solid was
filtered and the filtrate concentrated to give compound 2543 as a
purple oil (100%). The product was used for the next step without
Compound 19. To a stirred solution of compound 22 (0.63 g,
5.20 mmol) and triethylamine (1 mL) in THF (10 mL) was added
a solution of compound 2142 (0.58 g, 2.50 mmol) at room
temperature. The solution was stirred for 4 h and then concentrated
under reduced pressure. The resulting residue was triturated in
dichloromethane (20 mL). The organic phase was washed with
diluted hydrochloric acid (0.5 M, 10 mL), water (10 mL), saturated
sodium bicarbonate solution (10 mL), and brine (10 mL) and dried
over sodium sulfate. The solvent was then removed under reduced
pressure and the crude product purified by recrystallization from
EtOAc to give compound 19 as a colorless solid (0.81 g, 80%).
Mp 170-172 °C. 1H NMR (300 Hz, CDCl3): δ 3.98 (s, 6 H), 4.03
1
further purification. H NMR (300 Hz, CDCl3): δ 3.76 (s, 6 H),
6.28 (s, 2 H).
Compound 20. To a stirred solution of compound 25 (0.29 g,
1.70 mmol), DMAP (50 mg), and triethylamine (0.5 mL) in THF
(5 mL) was added a solution of compound 26 (0.58 g, 3.40 mmol)
in THF (5 mL). The solution was stirred at room temperature for
12 h and then concentrated under reduced pressure. The residue
was triturated in ethyl acetate (15 mL). The organic solution was
washed successively with dilute hydrochloric acid (0.5 N, 5 mL),
saturated sodium bicarbonate solution (5 mL), water (10 mL), and
brine (10 mL) and dried over sodium sulfate. Upon removal of the
solvent in vacuo, the resulting crude product was purified by flash
chromatography (petroleum ether/EtOAc 5:1) to give compound
20 as a white solid (80%). Mp >220 °C dec. 1H NMR (300 MHz,
CDCl3): δ 4.01 (s, 6 H), 4.08 (s, 6 H), 7.05 (d, J ) 8.2 Hz, 2 H),
7.14 (t, J ) 7.5 Hz, 2 H), 7.49 (d, J ) 7.2 Hz, 2 H), 8.30 (d, d,
(s, 3 H), 6.97 (d, d, J1 ) 1.5 Hz, J ) 7.9 Hz, 2 H), 7.06 (d, t,
2
J1 ) 1.5 Hz, J2 ) 7.7 Hz, 2 H), 7.13 (d, t, J1 ) 1.8 Hz, J2 ) 7.7
Hz, 2 H), 7.43 (t, J ) 7.8 Hz, 1 H), 8.29 (d, J ) 7.8 Hz, 2 H), 8.60
(d, d, J1 ) 1.8 Hz, J2 ) 7.8 Hz, 2 H), 10.08 (s, 1 H). 13C NMR
(300 MHz, CDCl3): δ 55.8, 64.2, 110.2, 120.6, 121.4, 124.2, 125.4,
128.0, 128.3, 135.2, 148.5, 155.9, 162.5. MS (ESI) m/z: 407
[M + H]+, 429 [M + Na]+. Anal. Calcd for C23H22N2O5: C, 67.76;
H, 5.47; N, 6.64. Found: C, 67.97; H, 5.46; N, 6.89.
J1 ) 1.8 Hz, J 2 ) 7.9 Hz, 2 H), 8.52 (s, 2 H), 10.71 (s, 2 H). 13
C
NMR (300 MHz, CDCl3): δ 56.1, 56.8, 77.2, 104.0, 111.6, 121.5,
122.2, 124.0, 132.2, 133.0, 142.3, 157.5, 162.8. MS (ESI) m/z: 436
[M + Na]+.
Compound 24. To a stirred solution of compound 23 (5.00 g,
36.0 mmol) in acetic acid (60 mL) was added concentrated nitric
acid (15 mL) at room temperature. The solution was stirred at 80
°C for 0.5 h and then cooled to room temperature and poured into
cold water (100 mL). The yellow precipitate formed was filtered
and washed with water thoroughly. The crude product was dried
under reduced pressure and then purified by flash chromatography
(petroleum ether/EtOAc 10:1) to afford compound 24 as a yellow
Acknowledgment. We thank the National Natural Science
Foundation (Nos. 20321202, 20332040, 20372080, 20425208,
20572126),theNationalBasicResearchProgram(2007CB808000),
and the Chinese Academy of Sciences for financial support.
Supporting Information Available: The 2D DOSY spectrum
of the solution of 2, 3, and 5 in CDCl3/CD3CN (4:1, v/v), the general
experimental method, and crystallographic information (CIF files)
of compounds 19 and 20. This material is available free of charge
via the Internet at http://pubs.acs.org.
(42) Wagner, P. J.; Meador, M. A.; Park, B.-S. J. Am. Chem. Soc. 1990,
112, 5199.
(43) Nose, M.; Suzuki, H. Synthesis 2000, 1539.
(44) Doornbos, S. Org. Prep. Proced. Int. 1969, 1, 287.
JO062523G
J. Org. Chem, Vol. 72, No. 8, 2007 2905