Hydrogen bonding-mediated self-assembly of square and triangular metallocyclophanes

Article abstract of DOI:10.1016/j.tetlet.2005.06.173

Intramolecular three-centered hydrogen bonding has been used to induce dipyridyl anthranilamide 5 and diphenylacetylene anthranilamide 11 to adopt rigid straight conformation. Compound 5 reacted with Pd(dppp)(OTf)₂ (12a) or Pt(dppp)(OTf)₂ (12b) in dichloromethane to afford square metallocyclophanes 13a and 13b in 70% and 40% yield, respectively. In contrast, the reaction of 11 with 12b in dichloromethane gave triangular metallocyclophane 14 in 15% yield.

Full text of DOI:10.1016/j.tetlet.2005.06.173

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8067–8070
Hydrogen bonding-mediated self-assembly of square
and triangular metallocyclophanes
Zong-Quan Wu, Xi-Kui Jiang and Zhan-Ting Li*
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
Received 31 March 2005; revised 22 June 2005; accepted 27 June 2005
Available online 29 September 2005
Abstract—Intramolecular three-centered hydrogen bonding has been used to induce dipyridyl anthranilamide 5 and diphenylacet-
ylene anthranilamide 11 to adopt rigid straight conformation. Compound 5 reacted with Pd(dppp)(OTf)2 (12a) or Pt(dppp)(OTf)2
(12b) in dichloromethane to afford square metallocyclophanes 13a and 13b in 70% and 40% yield, respectively. In contrast, the reac-
tion of 11 with 12b in dichloromethane gave triangular metallocyclophane 14 in 15% yield.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Although supramolecular chemistry emerged from the
studies of macrocycles such as crown ethers, cryptands,
and calixarenes,1 in the past decade there has been
increasing interest in constructing new kinds of macro-
cyclic species with well-established structures by making
use of discrete non-covalent forces.2 Among the other
non-covalent forces, the coordination motif between
transition metal ions and organic ligands has proven
itself to be a highly efficient tool for the formation of
new rigid and stable macrocyclic architectures.3 Over
years a large number of metallocyclophanes have been
constructed. In order to overcome the entropic dis-
advantage during macrocyclization and also to achieve
increased assembling efficiency, rigid aromatic molecules
are usually used as ligands, examples of which include
conjugated arylenes, arylene ethynylene, and vinylene
oligomers.4 Nevertheless, in many cases, the synthesis
and modifications of ligands of such kinds are time con-
suming or even difficult, and there is a strong demand
for the development of new kinds of rigid ligands for
construction of new generation of supramolecular archi-
tectures and also for the investigation of assembling
diversity.
ing or helical conformations of unnatural organic mole-
cules.5 Previously, we had reported that intramolecular
hydrogen bonding could be utilized to induce linear oli-
goanthranilamides to adopt new unfolding, straight, or
zigzag secondary structures in both the solid state and
solutions.6 The zigzag motif of the secondary structure
has also been successfully applied to build new U-typed
ligands for the self-assembly of a number of new planar
and rigid metallocyclophanes, which represent a new
generation of synthetic receptors for saccharide deriva-
tives.7 In this letter, we describe the synthesis of two
new kinds of straight ligands and their applications in
the self-assembly of rigid and planar square and triangu-
lar metallocyclophanes.
Straight conjugated dipyridyl derivatives have been
extensively applied to assemble various metallocyclo-
phanes.4 In order to explore the possibility of making
use of hydrogen bonding-induced non-conjugated
dipyridyl compounds to construct metallocyclophanes,
compound
5 was first designed and synthesized
(Scheme 1). Thus, compound 18 was first converted into
nitrate 2 in 50% yield. The latter was then hydro-
genated with Raney Ni as a catalyst to give amine 3
in quantitative yield. The treatment of excessive
amount of the latter with diacyl chloride 49 in refluxing
chloroform in the presence of triethylamine produced 5
in 80% yield.10
In recent years, there have been increasing applications
of intramolecular hydrogen bonding to control the fold-
Keywords: Coordination; Cyclophane; Hydrogen bonding; Molecular
squares; Self-assembly.
*
Linear compound 11, which is incorporated with two
Corresponding author. Tel.: +86 21 641 63300; fax: +86 21 641
66128; e-mail: ztli@mail.sioc.ac.cn
phenylacetylene units on both ends, was also prepared
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.06.173

8068
Z.-Q. Wu et al. / Tetrahedron Letters 46 (2005) 8067–8070
compound 7 with iodine in ethanol in the presence of sil-
NO2
OMe
OMe
ver sulfate in 90% yield.12 Compound 7 was then cou-
pled with acetylene 8 in triethylamine in the presence
of Pd(PPh3)4 to afford aniline 9 in 90% yield. The reac-
tion of 4 with excessive amount of 9 in refluxing chloro-
form with triethylamine as base produced compound 10
in 86% yield. Finally, treatment of 10 with potassium
carbonate in dichloromethane and methanol afforded
11 in 96% yield.
HNO3, HOAc
H2 (40 atm.)
+
+
N
O-
r.t. to 80 C
20 h, 50%
Raney Ni, MeOH
40 C, 3 h, 98%
N
O-
2
1
O
Cl
Cl
N
C6H13
O
MeO
N
O
O
1H NMR spectrum (400 MHz) in chloroform-d revealed
that all the NH protons of compounds 5, 10, and 11
are involved in the three-centered hydrogen bonding
because their signals were displayed typically at the very
downfield area (10.72, 12.20, and 12.21 ppm, respec-
OC6H13
H
O
NH2
N
C6H13
4
O
OMe
NEt3, CHCl3, reflux
2 h, 80%
OC6H13
H
3
N
N
1
tively). H NMR dilution experiments in chloroform-d
OMe
5
at 25 ꢁC revealed very small concentration dependence
(<0.008 ppm) within the range of 30–0.4 mM for com-
pounds 5 and 11. Temperature-variable 1H NMR experi-
Scheme 1. Synthetic route of compound 5.
ments also showed
a relatively low temperature
dependence for the chemical shifts of the amide protons
of both 5 and 11 (<3.5 · 10À3 ppm/K within the range
of À10 to 50 ꢁC investigated in chloroform-d).13 In addi-
tion, the NH stretching frequencies (m) of their IR spec-
trum, obtained both with the KBr disk method or in
chloroform (5 mM), are <3315 cmÀ1 and independent
of the concentration changes in chloroform.14 All these
observations support that these linear compounds adopt
rigid planar conformations due to the existence of the
NH2
NH2
CO2Et
I2, Ag2SO4, EtOH
CO2Et
r.t., 1 h, 90%
I
7
6
SiMe3
H
SiMe3
8
Pd(PPh3)4, CuI, NEt3
50 C, 4 h, 90%
9
H2N
CO2Et
OEt
Ph
Ph
P
P
M
12a: M = Pd
12b: M = Pt
SiMe3
Ph
Ph
TfO OTf
O
H
C6H13
O
N
O
4, NEt3, CHCl3
5
CH2Cl2, r.t., 5 h
Me
reflux, 2 h, 86%
Ph
P
O
O
Ph
N
C6H13
O H
OC6H13
10
H
O
Ph
Ph
O
N
N
N
M
P
Ph
P
Ph
M
N
P
O
N
Ph
Me3Si
OEt
H OC6H13
Ph
H
OEt
N
O
MeO
Me
O
H
N
O
H
MeO
C6H13
O
N
N
O
O
K2CO3
C6H13
O
H
CH2Cl2, MeOH
O
C6H13
O
O
OC6H13
r.t., 3 h, 96%
H
N
H
O
N
N
11
OC6H13
OC H13
H 6
OMe
N
O
Me
O
OMe
H
OEt
H
N
Ph
C6H13
O
N
O
N
N
Scheme 2. Synthetic route of compound 11.
P
Ph
M
P
Ph
N
O
Ph
Ph
Ph
P
M
H
OC6H13
as shown in Scheme 2. Previous studies have demon-
strated that straight conjugated diphenylacetylene deriv-
atives are very efficient precursors for the construction
of new metallocyclophanes.6,11 The synthesis of 11
started from amine 6, which was first converted into
P Ph
Ph
O
Me
13a: M = Pd (70%)
13b: M = Pt (40%)
Scheme 3. Synthetic route of metallocyclophanes 13a and 13b.

Z.-Q. Wu et al. / Tetrahedron Letters 46 (2005) 8067–8070
8069
intramolecular three-centered hydrogen bonding,15,16 as
shown in Schemes 1 and 2.
to the rigid precursors, but the amide protons give their
signals at downfield area (>11.0 ppm), indicating that
they are still involved in intramolecular hydrogen
bonding.
The possibility of constructing rigid metallomacrocyclic
structures from 5 and 11 were then investigated. Treat-
ment of dipyridyl 5 with complex 12a17 or 12b18 in
dichloromethane at room temperature afforded molecu-
lar squares 13a and 13b in 70% and 40% yield, respec-
tively (Scheme 3).19 In contrast, compound 11 reacted
with 12b at room temperature in diethylamine in the
presence of cupric iodide gave triangular cyclophane
14 in 15% yield (Scheme 4). No square metallocyclo-
phane or other products were obtained from this reac-
tion. The fact that only triangular cyclophane was
formed might reflect the facts that the steric hindrance
of the acetylene ligand is remarkably reduced compared
to that of the pyridine-based ligand 5 and the formation
of smaller rings is favorable entropically than larger
ones from the same ligand in the absence of templating
effect. Such result has been observed frequently in the
synthesis of crown ethers.20 The low yield of triangular
14 compared with that of square 13a and 13b may be
the result of the fact that the intramolecular hydrogen
bonding-driven straight ligand is still more flexible than
fully conjugative linear ligand.21
In summary, we have demonstrated that intramolecular
three-centered hydrogen bonding can be applied to
rigidify the unfolding conformation of linear dipyridyl
and diphenylacetylene derivatives and consequently
facilitate the self-assembly of two square and one trian-
gular metallocyclophanes. In principle, this non-cova-
lent approach may be further utilized to control
functionalized linear molecules to adopt discrete kinds
of rigid conformations, which should find applications
in constructing new generation of functional supramo-
lecular architectures and for the development of new
synthetic receptors for molecular recognition.
Acknowledgments
We are grateful to the Ministry of Science and Technol-
ogy (G2000078101), the Natural Science Foundation of
China, and the Chinese Academy of Sciences for finan-
cial support.
The structures of the cyclophanes have been character-
ized by 1H NMR and MS spectroscopy, and microanal-
ysis (for 13a and 13b). All the three cyclophanes are
moderately soluble in chloroform but not in polar ace-
tone or methanol. Upon coordination, the resolution
References and notes
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O
H N
EtO
N
H
O
C6H13O
O
O
C6H13
OC6H13
H O
N
OEt
Ph
OC6H13
O
O
H
O
N
OEt
OEt
O
Ph
C6H13
O
H
P
O
N
Ph
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N
O
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P
Ph
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P
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Scheme 4. Synthetic route of triangular metallocyclophane 14.

8070
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19. Experimental procedures: Under an atmosphere of nitro-
gen, to a flask (100 mL) equipped with a stir bar,
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1
as a colorless solid (47 mg, 70%). Mp >250 ꢁC. HNMR
(400 MHz, CDCl3): d 11.32 (s, 8H), 9.17 (d, J = 6.9 Hz,
8H), 8.54 (s, 8H), 8.42 (d, J = 6.6 Hz, 8H), 8.01 (s, 8H),
7.60 (br, 32H), 7.32 (br, 48H), 4.37 (t, J = 7.2 Hz, 16H),
4.20 (s, 24H), 2.77 (br, 8H), 2.01–2.05 (m, 16H), 1.52–1.27
(m, 64H), 0.89 (t, J = 15.3 Hz, 24H). MS (ESI): m/z 1143
[MÀ4OTfÀdppp]4+, 968 [MÀ5OTf]5+. Anal. Calcd for
1
194 ꢁC: H NMR (400 MHz, CDCl3): 10.72 (s, 2H), 8.58
(d, J = 5.1 Hz, 2H), 8.30 (d, J = 3.3 Hz, 4H), 7.99 (s, 2H),
4.29 (t, J = 6.9 Hz, 4H), 4.04 (s, 6H), 2.00 (t, J = 6.6 Hz,
4H), 1.49–1.35 (m, 12H), 0.89 (t, J = 7.2 Hz, 6H). IR (film,
KBr): m 3315, 2955, 2927, 2857, 2677, 2605, 2498, 1670,
1591, 1521, 1482, 1415, 1394, 1232, 1211. MS (EI): m/z 578
[M]+. Anal. Calcd for C32H42N4O6: C, 66.42; H, 7.31; N,
9.68. Found: 66.11; H, 7.38; N, 9.58.
C
244H272F24N16O48P8Pd4S8: C, 52.49; H, 4.91; N, 4.01.
Found: C, 52.77; H, 4.89; N, 3.60. In analogy with the
preparation of compound 13a, treatment of compound 5
(28 mg, 0.5 mmol) with Pt(dppp)(OTf)2 (46 mg, 0.5 mmol)
in dichloromethane (40 mL) at room temperature for 5 h
produced compound 13b as a colorless solid (30 mg, 40%)
after workup. Mp >260 ꢁC. 1H NMR (400 MHz, CDCl3):
d 11.28 (s, 8H), 9.17 (d, J = 6.9 Hz, 8H), 8.58 (s, 8H), 8.43
(d, J = 6.9 Hz, 8H), 8.01 (s, 8H), 7.71–7.75 (m, 32H),
7.44–7.48 (m, 48H), 4.36 (t, J = 6.9 Hz, 16H), 4.19 (s,
24H), 3.20 (br, 16H), 2.56 (br, 8H), 2.02 (t, J = 6.6 Hz,
16H), 1.50–1.34 (m, 48H), 0.91 (t, J = 7.8 Hz, 24H). MS
(ESI): m/z 837 [MÀ6OTf]6+, 593 [MÀ8OTf]8+. Anal.
Calcd for C244H272N16O48F24P8Pt4S8: C, 49.36; H, 4.62;
N, 3.77. Found: C, 49.79; H, 4.99; N, 3.66.
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