Expanding the cavity size: Preparation of 2:1 inclusion complexes based on dinuclear square metallocycles

Article abstract of DOI:10.1021/jo901034c

(Chemical Equation Presented) The self-assembly of two new ligands based on the trans-1,2-bis(4-pyridyl)ethylene motif with palladium or platinum complexes led to quadrangular metallocycles. 1,1′-Methylenebis(4-((E)-2-(pyridin-4- yl)vinyl)pyridinium gave

Full text of DOI:10.1021/jo901034c

pubs.acs.org/joc
Expanding the Cavity Size: Preparation of 2:1 Inclusion Complexes Based
on Dinuclear Square Metallocycles
†
Vıctor Blanco, Albert Gutierrez, Carlos Platas-Iglesias, Carlos Peinador,* and
ꢀ
ꢀ
Jose M. Quintela*
´
~
Departamento de Quımica Fundamental, Facultad de Ciencias, Universidade da Coruna, Campus A
ꢁ
†
Zapateira, 15071, A Corun~a, Spain. Current address: Departament de Quımica Inorganica, Universitat de
´
Barcelona, c/Martı i Franques 1-11, 08028 Barcelona, Spain.
´
ꢁ
capeveqo@udc.es
Received May 18, 2009
The self-assembly of two new ligands based on the trans-1,2-bis(4-pyridyl)ethylene motif with
palladium or platinum complexes led to quadrangular metallocycles. 1,10-Methylenebis(4-((E)-
2-(pyridin-4-yl)vinyl)pyridinium gave the square metallocycles, while the second ligand, which is
less symmetrical, gave a mixture of the regioisomeric metallocyles. The metallocycles display the ideal
disposition of the π-acceptor units to maximize the π-stacking interactions with aromatic guests.
Thus, molecular recognition of π-donor aromatic guests by square metallocycles produced the
corresponding 2:1 inclusion complexes. On the other hand, starting from the mixture of regioisomers,
the incorrect regioisomer rearranged to the correct metallocycle upon the addition of aromatic guests.
On the basis of this behavior, a [3]catenane was obtained regioselectively from the mixture of the
regioisomeric metallocycles and the appropriate cyclophane. The formation of this catenane was
confirmed by NMR and X-ray crystallographic studies.
Introduction
cages have been reported in the last decades.2 Thus, the
shape of the molecular polygon is predetermined by the
The utilization of transition metal centers and dative bond
for directing the formation of two- and three-dimensional
supramolecular structures has proved to be a highly con-
venient self-assembly strategy.1 On the basis of this metho-
dology, a myriad of polygonal metallomacrocyles such as
triangles, squares, pentagons, hexagons, and molecular
ꢀ
ꢀ
ꢀ
ꢀ
(2) (a) Tarkanyi, G.; Jude, H.; Palinkas, G.; Stang, P. J. Org. Lett. 2005, 7,
4971. (b) Janzen, D. E.; Patel, K. N.; VanDerveer, D. G.; Grant, G. J. Chem.
Commun. 2006, 3540. (c) Wu, Z.-Q.; Jiang, X.-K.; Li, Z.-T. Tetrahedron Lett.
ꢀ
2005, 46, 8067. (d) Campos-Fernandez, C. S.; Schottel, B. L.; Chifotides, H.
T.; Bera, J. K.; Bacsa, J.; Koomen, J. M.; Russell, D. H.; Dunbar, K. R.
J. Am. Chem. Soc. 2005, 127, 12909. (e) Jiang, H.; Lin, W. J. Am. Chem. Soc.
2003, 125, 8084. (f) Cho, Y. L.; Uh, H.; Chang, S.-Y.; Chang, H.-Y.; Choi,
M.-G.; Shin, I.; Jeong, K.-S. J. Am. Chem. Soc. 2001, 123, 1258.
(g) O’donnell, J. L.; Zuo, X. B.; Goshe, A. J.; Sarkisov, L.; Snurr, R. Q.;
Hupp, J. T.; Tiede, D. M. J. Am. Chem. Soc. 2007, 129, 1578. (h) Burchell, T.
J.; Puddephatt, R. J. Inorg. Chem. 2005, 44, 3718. (i) Cotton, F. A.; Lin, C.;
Murillo, C. A. Inorg. Chem. 2001, 40, 478. (j) Stulz, E.; Scott, S. M.; Bond, A.
D.; Teat, S. J.; Sanders, J. K. M. Chem.;Eur. J. 2003, 24, 6039. (k) Zhao, L.;
Northrop, B. H.; Stang, P. J. J. Am. Chem. Soc. 2008, 130, 11886. (l) Suzuki,
K.; Iida, J.; Sato, S.; Kawano, M.; Fujita, M. Angew. Chem., Int. Ed. 2008, 47,
5780. (m) Zhao, L.; Northrop, B. H.; Zheng, Y. R.; Yang, H. B.; Lee, H. J.;
Lee, Y. M.; Park, J. Y.; Chi, K. W.; Stang, P. J. J. Org. Chem. 2008, 73, 6580.
(1) (a) Swiegers, G. F.; Malefetse, T. J. Chem. Rev. 2000, 100, 3483.
(b) Fujita, M.; Tominaga, M.; Hori, A.; Therrien, B. Acc. Chem. Res. 2005,
38, 369. (c) Dinolfo, P. H.; Hupp, J. T. Chem. Mater. 2001, 13, 3113.
(d) Caulder, D. L.; Raymond, K. N. J. Chem. Soc., Dalton Trans. 1999,
1185. (e) Steel, P. J. Acc. Chem. Res. 2005, 38, 243. (f) Leininger, S.; Olenyuk,
€
B.; Stang, P. J. Chem. Rev. 2000, 100, 853. (g) Wurthner, F.; You, C.-C.;
Saha-Moller, C. R. Chem. Soc. Rev. 2004, 133. (h) Collin, J.-P.; Heitz, V.;
€
Bonnet, S.; Sauvage, J.-P. Inorg. Chem. Commun. 2005, 8, 1063. (i) Holliday,
B. J.; Mirkin, C. A. Angew. Chem., Int. Ed. 2001, 40, 2022. (j) Cotton, F. A.;
Lin, C.; Murillo, C. A. Acc. Chem. Res. 2001, 34, 759. (k) Fujita, M. Chem.
Soc. Rev. 1998, 27, 417.
ꢀ
(n) Ferrer, M.; Gutierrez, A.; Mounir, M.; Rossell, O.; Ruiz, E.; Rang, A.;
Engeser, M. Inorg. Chem. 2007, 46, 3395.
DOI: 10.1021/jo901034c
r
Published on Web 08/10/2009
J. Org. Chem. 2009, 74, 6577–6583 6577
2009 American Chemical Society

Blanco et al.
JOCArticle
FIGURE 1. Structures used in this work.
choice of the metal center and ligand geometries that direct
the self-assembly process. The success of the metal-directed
self-assembly approach is mainly due to two reasons: (i) The
access to bond angles unavailable in carbon chemistry and
(ii) a wide range of kinetic lability of the metal-heteroatom
bond, which allows the correction of defect products by
selecting appropriate reaction conditions.
The interactions between aromatic rings control a vast and
fascinating variety of phenomena such as the stabilization of
the DNA double helix,3 the tertiary structure of proteins,4
crystal packing of aromatic molecules,5 and columnar struc-
tures of discotic liquid crystals.6 In discrete supramolecular
systems, π-π interactions have been widely utilized to
synthesize many host-guest complexes7 and other assem-
blies such as catenanes and rotaxanes.8
ability of metallocycles to act as receptors. Taking advantage
of these characteristics, we have recently reported the self-
assembly of inclusion complexes with 1:1 and 2:1 stoichi-
ometry and [2]- and [3]catenanes.9
In this paper we present two new quadrangular metallo-
cycles with elongated sides based on a trans-1,2-bis(4-
pyridyl)ethylene motif. Thus, these longer sides could poten-
tially provide metallocycles with larger cavities, and even-
tually with enhanced selectivity toward larger guests. Both
metallocycles would have an ideal distance between opposite
sides to bind two aromatic rings in the cavity, so the forma-
tion of 2:1 inclusion complexes and [3]catenanes should be
expected.
Results and Discussion
In the last years, our group has reported several molecular
rectangles and squares based on the self-assembly of N-
monoalkylated 4,40-bipyridine ligands and square-planar
metal centers. In most cases the dimensions and shape of
the cavity defined by squares or rectangles, as well as the
π-deficient character of the ligand, allowed the insertion of
aromatic guests into the metallocycle. The complexes are
stabilized by means of a combination of π-stacking, hydro-
gen bonding, and hydrophobic forces. Therefore, the correct
angles at the metal center, the length of the side defined by the
ligand, and its π-complementary character determine the
Molecular components used in this work are depicted in
Figure 1. Ligands 1 2PF6 and 2 PF6 were synthesized by
N-alkylation of trans-1,2-bis(4-pyridyl)ethylene with dibro-
momethane and 4-(4-chloromethylphenyl)pyridine, respec-
tively. Both hexafluorophosphate salts can be converted into
the corresponding water-soluble nitrates with tetrabutylam-
3
3
monium nitrate. It is worthy of note that 1 2PF6 proved to
3
be more resistant to thermal decomposition than its 4,40-
bipyridine analogue.9a No decomposition was detected by
1H NMR after heating a CD3CN solution of the ligand at
75 °C for 2 d.
Addition of 1 equiv of (en)Pd(NO3)2 to a solution of ligand
(3) (a) Hunter, C. A.; Sanders, J. K. M. J. Am. Chem. Soc. 1990, 112, 5525.
(b) Saenger, W. Principles of Nucleic Acid Structure; Springer-Verlag: New
York, 1984. (c) Kool, E. T. Chem. Rev. 1997, 97, 1473.
(4) (a) Burley, S. K.; Petsko, G. A. Science 1985, 229, 23. (b) Hunter,
C. A.; Singh, J.; Thornton, J. M. J. Mol. Biol. 1991, 218, 837.
(5) (a) Anderson, H. L.; Bashall, A.; Henrick, K.; McPartlin, M.; Sanders,
J. K. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 429. (b) Martin, C. B.;
Patrick, O.; Cammers-Goodwin, A. J. Org. Chem. 1999, 64, 7568.
(6) (a) Bushby, R. J.; Lozman, O. R. Curr. Opin. Colloid Interface Sci.
2002, 7, 343.
1 2NO3 (10 mM in D2O) at room temperature resulted in the
3
expected formation of the square metallocycle 4a (Figure 2)
as can be seen from inspection of the 1D and 2D NMR data.
Similar results were obtained in CD3CN solutions upon the
1
self-assembly of (en)Pd(OTf)2 and 1 2PF6. The H NMR
3
spectrum of metallocycle 4a in CD3CN showed the charac-
teristic downfield shifts of protons Ha and Hb due to the
1
coordination of the pyridine ring to the Pd center. The H
NMR spectra in both solvents are compatible with the
(7) (a) Sygula, A.; Fronczek, F. R.; Sygula, R.; Rabideau, P. W.;
Olmstead, M. M. J. Am. Chem. Soc. 2007, 129, 3842. (b) Yoshizawa, M.;
Nakagawa, J.; Kurnazawa, K.; Nagao, M.; Kawano, M.; Ozeki, T.; Fujita,
M. Angew. Chem., Int. Ed. 2005, 44, 1810.
(8) (a) Molecular Catenanes, Rotaxanes and Knots; Sauvage, J.-P.,
Dietrich- Buchecker, C., Eds.; Wiley-VCH: Weinheim, Germany, 1999.
(b) Amabilino, D. B.; Stoddart, J. F. Chem. Rev. 1995, 95, 2725. (c) Badjic,
J. D.; Ronconi, C. M.; Stoddart, J. F.; Balzani, V.; Silvi, S.; Credi, A. J. Am. Chem.
Soc. 2006, 128, 1489. (d) Payer, D.; Rauschenbach, S.; Malinowski, N.; Konuma,
M.; Virojanadara, C.; Starke, U.; Dietrich-Buchecker, C.; Collin, J. P.; Sauvage,
J. P.; Lin, N.; Kern, K. J. Am. Chem. Soc. 2007, 129, 15662.
(9) (a) Blanco, V.; Chas, M.; Abella, D.; Peinador, C.; Quintela, J. M.
J. Am. Chem. Soc. 2007, 129, 13978. (b) Chas, M.; Blanco, V.; Peinador, C.;
Quintela, J. M. Org. Lett. 2007, 9, 675. (c) Chas, M.; Pıa, E.; Toba, R.;
Peinador, C.; Quintela, J. M. Inorg. Chem. 2006, 45, 6117. (d) Abella, D.;
Blanco, V.; Pıa, E.; Chas, M.; Platas-Iglesias, C.; Peinador, C.; Quintela,
J. M. Chem. Commun. 2008, 2879. (e) Peinador, C.; Blanco, V.; Quintela,
J. M. J. Am. Chem. Soc. 2009, 131, 920.
6578 J. Org. Chem. Vol. 74, No. 17, 2009

Blanco et al.
JOCArticle
FIGURE 2. Structures of metallocycles 4-6.
the planar one. The diagonals measured in the centrosym-
metric conformer are 14.3 (distance between methylene
˚
groups) and 21.1 A (distance between Pd atoms), while those
˚
in the puckered isomer amount to 15.2 and 19.2 A, respectively.
Platinum metallocycle 4b 8PF6 was synthesized in 65%
3
yield by the thermodynamically driven self-assembly reac-
tion at 70 °C to take advantage of the “molecular lock”
strategy. The NMR data showed spectroscopic character-
istics very similar to the corresponding palladium analogue.
The HRMS-ESI supported the proposed structure showing
m/z values and isotopic pattern distributions in excellent
agreement with the calculated ones (see the Supporting
Information). The platinum macrocycle could also be iso-
lated as its nitrate salt 4b 8NO3 by adding an excess of
3
tetrabutylammonium nitrate to an acetonitrile solution of
4b 8PF6.
3
FIGURE 3. Solid-state structures of the puckered (top) and flat
(bottom) conformers of 4a 4OTf 4PF6.
In a previous work, we reported the formation of 2:1
inclusion complexes between aromatic guests and a square
metallocycle with 4,40-bipyridine sides.10 Although the in-
troduction of the double bond between the bipyridine units
3
3
presence of either a single compound or two or more species
that are in fast equilibrium on the 1H NMR time scale. We
carried out dilution studies to support the presence of the
metallocycle 4a as a single species in solution. The spectra
remain unchanged in the 5.0-1.25 mM (CD3CN) and 5.0-
0.25 mM (D2O) concentration range. Above these limits,
new resonances appear, which can be attributed to some kind
of aggregation.
in ligand 1 2PF6 extends slightly the sides of the metallo-
3
cycle, we expected that this metallocycle could also lead to
the formation of 2:1 inclusion complexes. Indeed, the self-
assembly of ligand 1 2PF6, (en)Pd(OTf)2, and compounds 7
3
or 9a in CD3CN produced changes in their 1H NMR spectra
that are consistent with the formation of the corresponding
inclusion complexes, as the signals due to aromatic protons
of the naphthalene units shifted to shorter frequencies
(averaged shift: Δδ=-0.15 ppm). However, the chemical
shifts of the metallocycle protons were hardly affected. This
fact can be ascribed to two opposite effects, as the pyridine
units parallel to the naphthalene units are expected to
experience a shielding effect, while the pyridine units ortho-
Single crystals of metallocycle 4a 4OTf 4PF6 were ob-
3
3
tained from a solution of ligand 1 2PF6 and (en)Pd(OTf)2 in
3
acetonitrile. Unfortunately, the crystals were of limited
quality and the resulting data are somewhat poor due to a
triflate counterion that is disordered, although the unambi-
guous assignment of the metallocycle moiety was possible.
The crystal structure shows the presence of two conformers
of metallocycle 4a with a rhombic cavity (Figure 3).
gonal to the guests are deshielded due to [C-H π] inter-
3 3 3
actions. Because the complexation-decomplexation process
is fast in the NMR time scale, the signals for the orthogonal
and parallel pyridines are averaged and the two effects are
mutually canceled.
In one conformer one corner of the rhomboid is out of
plane, with the metallocycle showing a puckered conforma-
tion, with the angles between planes being 49° and 39° for the
two planes defined by PtCH2Pt corners and the two planes
defined by CH2PtCH2, respectively. The second conformer
present in the crystal is centrosymmetric with a planar
disposition of the four corners of the metallocycle. The Pd
atoms show a square-planar coordination environment with
Pd-N(pyridine) bond distances ranging between 2.018 and
On the contrary, the addition of 2 equiv of substrate 8a to a
5 mM solution of 4a 4OTf 4PF6 in acetonitrile resulted in a
3
3
1
color change from intense blue to green. However, the H
NMR spectrum did not reveal significant changes in the
chemical shifts of the free components.
The complexation process was also studied in aqu-
eous solution. In this solvent the hydrophobic forces and
˚
2.056 A. The NCN angles at the methylene corners are 111°
and 109° in the puckered and the planar conformers, respec-
tively. The angles at the Pd corners of N(Py)PdN(Py)
amount to 89° and 92° in the angular conformer and 88° in
(10) Blanco, V.; Chas, M.; Abella, D.; Pıa, E.; Platas-Iglesias, C.;
Peinador, C.; Quintela, J. M. Org. Lett. 2008, 10, 409.
J. Org. Chem. Vol. 74, No. 17, 2009 6579

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TABLE 1. Selected 1H and 13C NMR Chemical Shift Data (Δδ) for Inclusion Complexes in D2O and [3]Catenane 12 6PF6 (5 mM in CD3CN)a
3
metallocycle protonsb
guest protonsc
compd
(7)24a 8NO3
(8a)24a 8NO3
b
c
d
k
l
o
o0
m
p
0.00
0.00
0.00
-0.04
-0.03
-0.37
-0.2
-0.43
-0.3
-0.49
-0.3
-0.66
-1.9
0.00
-0.04
-0.04
-0.17
-0.09
-1.06
-1.8
-1.15
-1.4
-1.3
-2.2
-0.02
-0.08
-0.06
-0.22
-0.10
-1.24
-1.7
-1.3
-1.9
-1.45
-2.3
-1.19
-2.7
-0.32
-0.20
-0.13
-0.24
-0.21
-0.19
-0.54
-0.23
-0.13
-0.25
-0.17
3
-0.27
-0.14
3
(8b)24a 8NO3
3
(9a)24a 8NO3
(9b)24a 8NO3
(8a)25a 6NO3
-0.21
-0.16
3
3
d
d
d
H
C
H
C
H
C
H
C
0.4
-0.3
0.27
0.1
0.32
0.1
0.1
0.4
0.35
0.2
0.31
0.1
0.32
0.1
0.19
0.4
-
-
-
-
-
3
d
d
d
-
(9a)25a 6NO3
3
-0.45
-0.5
-0.68
0.0
-0.73
-0.7
(10)25a 6NO3
3
12 6PF6
3
-1.16
-2.8
-0.96
-1.3
aHydrogen and carbon labels are defined in Figure 1. bThe δ values are compared to those of the corresponding free metallocycle (4a 8NO3,
3
5a 6NO3). cThe δ values are compared to those of the corresponding free guest (7-10). dNot determined because of line broadening.
3
π-stacking should favor the insertion of the aromatic guests
into the cavity of the metallocycle.11 Thus, the addition of 2
equiv of 8a to a 1 mM solution of 4a 8NO3 and sonication
3
for 2 h changed the color of the solution from pale red to
intense red. The 1H NMR spectra of the inclusion complexes
(7)24a 8NO3, (8a)24a 8NO3, and (9a)24a 8NO3 exhibited
3
3
3
larger upfield shifts for the aromatic protons of the guests
than in acetonitrile solution (Table 1). The same color
changes and chemical shift tendencies were observed upon
sonication for the corresponding platinum inclusion com-
plexes. The continuous variation method (Job plot) con-
firmed the stoichiometry of complex formation in solution
between 9a and metallocycle 4b 8NO3 to be 2:1 (guest:host)
3
(Figure 4).12 The UV-vis titrations method was used to
determine association constants in aqueous media for the
inclusion complexes (8b)24a 8NO3, (9a)24a 8NO3, and
3
3
(9b)24a 8NO3 (Ka = 478 ( 84, 315 ( 89, and 120 ( 23,
3
FIGURE 4. Job plot showing the 2:1 (H:G) stoichiometry of a
complex formed between guest 9a and 4b 8NO3 (total concentra-
respectively).13 All of the titration curves were well fitted to
the 2:1 binding model.14
Surprisingly, the self-assembly of ligand 2 NO3 and pal-
ladium complex 3b in D2O led to a mixture of two species in a
1:1 ratio, which were assigned as the two 2 þ 2 isomeric
metallocycles 5a 6NO3 and 6a 6NO3 (Figure 2). The hexa-
3
0
tion 2 mM). The induced change in the chemical shift of Ho is
plotted versus the molar fraction of 9a.
3
Mass spectrometry supported the structure of the square
metallocycles. The HRMS-ESI spectrum of the platinum
analogues 5b,6b showed peaks resulting from the loss of
three to six hexafluorophosphate anions.
3
3
fluorophosphate salts of 5a and 6a could be precipitated
from the corresponding nitrates by addition of potassium
hexafluorophosphate. The NMR spectra recorded upon
redissolution of the solid in CD3CN indicated that both
isomeric metallocycles persist in solution with a 1:1 ratio.
The 1H NMR spectra of the mixture of 5a,6a remained
unaltered upon dilution (concentration range 2.5-0.25 and
5.0-0.25 mM in D2O and CD3CN, respectively). In addi-
tion, the DOSY experiments provided very similar diffusion
coefficients for the two species. These results indicate that the
two species present in solution have a very similar size, in
agreement with the proposed structures. Similar results were
obtained from the self-assembly of the platinum complexes.
Aiming to obtain information on the solution structure of
the 5a,6a metallocycles, these systems were characterized by
means of DFT calculations (B3LYP model).15,16 In these
calculations the 6-31G(d) basis set was used for the ligand
atoms, while for Pd atoms the effective core potential of
Wadt and Hay (Los Alamos ECP) included in the LanL2DZ
basis set was applied.17 Our calculations provide two
minimum energy conformations with nearly undistorted
C2 symmetries (Figure 5).18 These minimum energy confor-
mations correspond to two isomeric rhombic metallocycles
that differ in the relative arrangement of the two ligands.
Indeed, in 5a each PdII ion is coordinated by a 4-phenylpyr-
idine and a 4-vinylpyridine unit, while in 6a one of the PdII
ions is coordinated to two 4-phenylpyridine moieties, and the
(11) (a) Smithrud, F.; Diederich, F. J. Am. Chem. Soc. 1990, 112, 339.
(b) Ferguson, S. B.; Sanford, E. M.; Seward, E. M.; Diederich, F. J. Am.
Chem. Soc. 1991, 113, 5410. (c) Cubberley, M. S.; Iverson, B. L. J. Am. Chem.
Soc. 2001, 123, 7560.
(12) Job, P. Ann. Chim. 1928, 9, 113.
(15) Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
(13) (a) Connors, K. A. Binding Constants; Wiley: New York, 1987.
(b) Schneider, H.-J.; Yatsimirsky, A. K. Principles and Methods in Supramole-
cular Chemistry; John Wiley & Sons: New York, 2000.
(14) Compouds 7, 8a, and 10 are sparingly soluble in water and the
determination of their binding constants was not possible.
(16) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
(17) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270.
(18) The stationary points found on the potential energy surfaces as a
result of the geometry optimizations have been tested to represent energy
minima rather than saddle points via frequency analysis.
6580 J. Org. Chem. Vol. 74, No. 17, 2009

Blanco et al.
JOCArticle
FIGURE 5. Calculated structures of metallocycles 5a (left) and 6a
(right).
second metal is coordinated by two 4-vinylpyridine ones.
Both 5a and 6a possess similar cavity dimensions, with
FIGURE 6. Crystal structure of catenane 12 6PF6. The color
3
labeling scheme is as follows: nitrogen (blue), oxygen (red), palla-
dium (yellow), and carbon (gray). Solvent molecules, hydrogen
atoms, and counterions have been omitted for clarity.
˚
Pd Pd distances of ca. 18.8 A, and CH2 CH2 distances
3 3 3
3 3 3
˚
of ca. 14.5 A. In 5a the C2 symmetry axis is perpendicular to
the plane described by the four vertexes of the rhombic cavity
defined by the two Pd atoms and the two methylenic carbon
atoms. On the contrary, in 6a the C2 symmetry axis contains
the two Pd atoms. Thus, the two minimum energy conforma-
tions obtained from our DFT calculations show the same
symmetry properties, and therefore they are expected to
provide very similar NMR spectral patterns. Our calcula-
tions predict a small energy difference between 5a and 6a, the
in vacuo relative free energy, ΔG°298K=G°5a-G°6a, amount-
Finally, metallocycles 5a,6a provide a new example of
regioselective catenation as a result of the template directed
reorganization described above.20 It was necessary to add
10 equiv of cyclophane 11 (Figure 1) to a solution (5 mM) of
metallocycles 5a,6a 6PF6 in CD3CN to achieve the reorga-
3
1
nization to the single [3]catenane 12 6PF6. The H NMR
spectrum of 12 6PF6 shows that the exchange between the
3
3
“inside” and “alongside” hydroquinol rings in the [3]cate-
nane is fast at room temperature, resulting in an averaged
signal (δ=5.71 ppm) for the aromatic protons of 11. The
ing to -0.54 kcal mol .
-1 19 These results are in line with the
3
formation of both 5a and 6a in solution with nearly identical
populations.
diffusion coefficients of catenane 12 6PF6 and metallocycles
3
5a,b 6PF6 obtained from DOSY experiments showed that
Addition of guests 8-10 to a solution of 5a,6a 6NO3 in
3
3
the catenane is significantly larger than its components. The
signals due to the metallocycle and the fraction of macro-
cycle 11 forming part of the catenane showed the same
diffusion coefficients, indicating that these components
diffuse as a whole. In contrast, the excess of free 11 displayed
a diffusion coefficient significantly larger than that of
D2O resulted in the total reorganization of the incorrect
metallocycle 6a 6NO3. Most likely, the reorganization of
3
the system toward one species is driven by the π-π stacking
interactions and facilitated by the kinetic lability of Pd-N
bonds. Indeed, metallocycle 6a 6NO3 does not display the
3
correct disposition of the aromatic systems to maximize
the π-π stacking interactions, as the better π-acceptor
di(pyridin-4-yl)ethene systems are in adjacent sides. Further-
12 6PF6 (see the Supporting Information).
3
Single crystals of catenane 12 6PF6 suitable for X-ray
3
crystallography were obtained by slow diffusion of ethyl
ether (4-5 days) into a solution of metallocycles 5a,6a 6PF6
and 11 (10 equiv) in acetonitrile. The crystal structure shows
more, the opposite sides of rhomboid 6a 6NO3 are not
3
parallel, as shown by the DFT calculated structure
1
(Figure 5). The H NMR spectra are compatible with the
3
the hexacationic metallocycle 5a interlocked by two mole-
cules of cyclophane 11 with two parallel π π stacking
presence of the inclusion complexes of the metallocycle
5a 6NO3. Thus, the protons of the di(pyridin-4-yl)ethene
sides are shielded (Hb, Hc, and Hd, see Table 1) while those of
the phenylpyridine side are deshielded (Hk and Hl). This
tendency is consistent with previously reported findings,10
and suggests that the phenylpyridine units are involved in
3 3 3
3
dispositions of three aromatic systems: HQout/PYET/HQin,
where PYET, HQout, and HQin stand for the di(pyridin-
4-yl)ethene unit and the alongside and inside hydroquinol
rings, respectively (Figure 6). As a consequence, the di-
(pyridin-4-yl)ethene systems are coplanar, while the 4-phenyl-
pyridine moiety has a torsion angle of 33°. The interplanar
[C-H π] interactions with the aromatic protons of the
3 3 3
guests.
˚
separation HQin-HQin is 3.75 A, and the distance between
It is interesting to note that larger or smaller aromatic
guests such as pyrene or hydroquinone do not interact with
metallocycles 4a 8NO3 and 5a,6a 6NO3. Thus, the extra
˚
their centroids is 6.20 A; hence one HQin is displaced 4.94 A
˚
with respect to the other, disrupting the HQin-HQin
π
π
3 3 3
3
3
interaction. In addition to the typical [C-H O] bonds21
length provided by the double bond is not enough to allow
the inclusion of pyrene, but it extends the distance between
opposite sides of the cavity, which weakens the interaction
with hydroquinone. Thus, it is reasonable to conclude that
the naphthalene derivatives 7-10 have the appropriate size
for their inclusion in metallocycles 4a 8NO3 and 5a,6a
3 3 3
established between the R-CH bipyridine hydrogens and the
(20) Blanco, V.; Abella, D.; Pıa, E.; Platas-Iglesias, C.; Peinador, C.;
Quintela, J. M. Inorg. Chem. 2009, 48, 4098.
(21) See for example: (a) Ashton, P. R.; Ballardini, R.; Balzani, V.; Credi,
A.; Gandolfi, M. T.; Menzer, S.; Perezgarcia, L.; Prodi, L.; Stoddart, J. F.;
Venturi, M.; White, A. J. P.; Williams, D. J. J. Am. Chem. Soc. 1995, 117,
11171. (b) Asakawa, M.; Ashton, P. R.; Balzani, V.; Brown, C. L.; Credi, A.;
Matthews, O. A.; Newton, S. P.; Raymo, F. M.; Shipway, A. N.; Spencer, N.;
Quick, A.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Chem.;Eur. J.
1999, 5, 860.
3
3
6NO3.
(19) Relative free energies include zero point energy corrections and
thermal terms obtained from frequency analyses.
J. Org. Chem. Vol. 74, No. 17, 2009 6581

Blanco et al.
JOCArticle
oxygen atoms of 11, [N-H O] hydrogen bonds between
(E)-1-(4-(Pyridin-4-yl)benzyl)-4-(2-(pyridin-4-yl)vinyl)pyridinium
Nitrate (2 NO3). Ligand 2 PF6 (100.0 mg, 0.20 mmol) was
dissolved in CH3CN and an excess of Bu4NNO3 was added until
no further precipitation is observed. The white precipitate was
3 3 3
amine protons and the oxygen atoms of the polyether chain
are also detected.22 The dimensions of the metallocycle
3
3
˚
are 18.10ꢀ14.92 A (palladium-palladium and methylene-
filtered and washed with CH3CN to yield 2 NO3 (60.4 mg, 73%).
3
methylene distances, respectively).
Mp 166-168 °Cdec;1HNMR(500MHz, D2O) δ5.82 (2H, s), 7.61
(2H, d, J = 8.3 Hz), 7.61 (1H, d, J = 16.3 Hz), 7.75-7.78 (3H, m),
7.90 (2H, d, J = 8.3 Hz), 7.95 (2H, d, J = 6.3 Hz), 8.16 (2H, d, J =
6.8 Hz), 8.60 (2H, d, J = 6.3 Hz), 8.64 (2H, d, J = 6.6 Hz), 8.83
(2H, d, J = 6.8 Hz); 13C NMR (125 MHz, CD3CN) δ 63.2 (CH2),
122.9 (CH), 123.1 (CH), 125.3 (CH), 128.4 (CH), 128.7 (CH), 129.7
(CH), 135.0 (C), 137.4 (CH), 137.5 (C), 144.2 (CH), 145.0 (C),
145.8 (CH), 147.9 (CH), 151.8 (C), 152.9 (C); MS-ESI (m/z) 350.2
[M - NO3-]þ. Anal. Calcd for C24H20N4O3: C, 69.89; H, 4.89; N,
13.58. Found: C, 70.18; H, 4.63; N, 13.34.
Experimental Section
1,10-Methylenebis(4-((E)-2-(pyridin-4-yl)vinyl))pyridinium Bis-
(hexafluorophosphate) (1 2PF6). A solution of trans-1,2-bis-
3
(4-pyridyl)ethylene (2.00 g, 10.9 mmol) and CH2Br2 (0.77 mL,
10.9 mmol) in CH3CN (100 mL) was refluxed for 48 h. After
being cooled to room temperature, the yellow precipitate was
washed with CH3CN and diethyl ether to afford a solid, which
was dissolved in water (400 mL). An excess of KPF6 was added to
the solution until no further precipitation was observed. The gray
Metallocycle 4a 8NO3. To a solution of 1 2NO3 (4.0 mg,
8.0 ꢀ 10-3mmol) in D2O (4.0 mL) was added (en)Pd(NO3)2 (3b)
3
3
1
(2.3 mg, 8.0 ꢀ 10-3mmol). H NMR (500 MHz, D2O) δ 2.91
solid was filtered and washed with water to afford 1 2PF6 (1.70 g,
3
50%). Mp 195-198 °C dec; 1H NMR (500 MHz, CD3CN) δ 6.84
(2H, s), 7.61 (2H, d, J=16.0 Hz), 7.61 (4H, d, J=6.5 Hz), 7.88
(2H, d, J = 16.0 Hz), 8.25 (4H, d, J = 7.0 Hz), 8.70 (4H, d, J=
6.5 Hz), 8.84 (4H, d, J=7.0 Hz); 13C NMR (125 MHz, CD3CN) δ
77.5 (CH2), 122.9 (CH), 126.8 (CH), 127.8 (CH), 142.4 (CH),
142.8 (C), 145.8 (CH), 151.7 (CH), 157.6 (C); MS-ESI (m/z)
523.15 [M - PF6-]þ, 377.17 [M - Hþ - 2PF6-]þ, 189.09 [M -
(8H, br s), 7.27 (4H, s), 7.61 (4H, d, J = 16.4 Hz), 7.74-7.78
(12H, m), 8.27 (8H, d, J = 7.0 Hz), 8.78 (8H, d, J = 6.8 Hz), 9.17
(8H, d, J = 7.0 Hz); 13C NMR (125 MHz, D2O) δ 46.6 (CH2),
77.1 (CH2), 124.9 (CH), 126.3 (CH), 129.8 (CH), 137.8 (CH),
144.6 (CH), 145.8 (C), 151.4 (CH), 155.6 (C).
Metallocycle 4a 4OTf 4PF6. To a solution of 1 2PF6 (20.1
3
3
3
mg, 0.030 mmol) in CD3CN (3.0 mL) was added (en)Pd(OTf)2
(3a) (15.3 mg, 0.033 mmol). 1H NMR (500 MHz, CD3CN)
δ 2.83 (8H, br s), 4.25 (8H, s), 6.89 (4H, s), 7.58 (4H, d, J =
16.5 Hz), 7.70-7.73 (12H, m), 8.17 (8H, d, J = 7.0 Hz), 8.78
(8H, d, J = 6.8 Hz), 8.91 (8H, d, J = 7.1 Hz); 13C NMR
(125 MHz, CD3CN) δ 47.7 (CH2), 77.7 (CH2), 125.7 (CH),
127.4 (CH), 131.0 (CH), 138.7 (CH), 146.0 (CH), 146.7 (C),
153.1 (CH), 156.3 (C).
2PF6 ]
- 2þ. Anal. Calcd for C25H22F12N4P2: C, 44.92; H, 3.32; N,
8.38. Found: C, 45.17; H, 3.09; N, 8.52.
1,10-Methylenebis(4-((E)-2-(pyridin-4-yl)vinyl))pyridinium Bis-
(nitrate) (1 2NO3). To a solution of ligand 1 2PF6 (0.62 g,
3
3
0.93 mmol) in CH3CN (100 mL) was added an excess of
Bu4NNO3 until no further precipitation is observed. The red
precipitate was filtered and washed with CH3CN to yield 1 2NO3
3
(0.39 g, 83%). Mp 178-180 °C dec; 1H NMR (500 MHz,
CD3CN) δ 7.27 (2H, s), 7.68 (2H, d, J = 16.4 Hz), 7.76 (4H, d,
J = 5.6 Hz), 7.93 (2H, d, J = 16.4 Hz), 8.36 (4H, d, J = 6.8 Hz),
8.64 (4H, d, J = 6.0 Hz), 9.16 (4H, d, J = 6.8 Hz); 13C NMR
(125 MHz, CD3CN) δ 76.8 (CH2), 122.8 (CH), 126.0 (CH), 127.8
(CH), 140.3 (CH), 143.7 (C), 144.5 (CH), 148.8(CH), 156.5 (CH),
Metallocycle 4b 8PF6. A solution of ligand 1 2PF6 (100.3 mg,
3
3
0.150 mmol) and (en)Pt(OTf)2 (3c) (91.3 mg, 0.165 mmol) in
CH3CN (15 mL) was heated at 70 °C for 5 d. The solvent was
removed under reduced pressure without heating. The crude
product was suspended in water and ion-exchange resin (0.50 g)
was added. The mixture was stirred at room temperature for 24 h.
The resin was removed by filtration and an excess of KPF6 is
added to the filtrate until no further precipitation was observed.
156.3 (C); MS-ESI (m/z) 189.09 [M - 2NO3 ]
- 2þ. Anal. Calcd for
C25H22N6O6: C, 59.76; H, 4.41; N, 16.73. Found: C, 59.51; H,
4.22; N, 16.98.
(E)-1-(4-(Pyridin-4-yl)benzyl)-4-(2-(pyridin-4-yl)vinyl)pyridinium
The solid was filtered and washed with water to yield 4b 8PF6
3
1
as a pink solid (236.8 mg, 65%). Mp 251-253 dec; H NMR
Hexafluorophosphate (2 PF6). A solution of 4-(40-chloromethyl-
(500 MHz, CD3CN) δ 2.76 (8H, br s), 4.79 (8H, s), 6.87 (4H, s),
7.61 (4H, d, J=16.4 Hz), 7.70 (8H, d, J = 6.8 Hz), 7.73 (4H, d,
J = 16.5 Hz), 8.19 (8H, d, J = 6.9 Hz), 8.75 (8H, d, J = 6.8 Hz),
8.86 (8H, d, J = 7.0 Hz); 13C NMR (125 MHz, CD3CN) δ 48.6
(CH2), 77.8 (CH2), 126.1 (CH), 127.4 (CH), 131.1 (CH), 138.5
(CH), 145.9 (CH), 146.7 (C), 153.8 (CH), 156.3 (C). HRMS-ESI
3
phenyl)pyridine (0.84 g, 4.12 mmol) cooled to 0 °C in CH3CN
(50 mL) was slowly added to a solution of trans-1,2-bis(4-pyridyl)-
ethylene (3.00 g, 16.46 mmol) and a catalytic amount of KI in
refluxing CH3CN (70 mL). The reaction was refluxed for 24 h; after
cooling, the solvent was evaporated in vacuo. The resulting residue
was triturated with ethyl ether (6 ꢀ 100 mL) to give a crude product,
which was purified by column chromatography (SiO2, acetone/
NH4Cl 1.5 M/MeOH 5:4:1). The product-containing fractions
were combined and the solvents were removed in vacuo. The
residue was dissolved in H2O/CH3OH (95/5, 900 mL) and an
excess of KPF6 was added until no further precipitation was
(m/z) calcd for [M - 3PF6
[M-4PF6
- 4þ 461.5726, found 461.5746; calcd for [M -5PF6
]
- 3þ 663.7517, found 663.7522; calcd for
- 5þ
]
]
340.2651, found 340.2656. Anal. Calcd for C54H60F48N12-
P8Pt2: C, 26.72; H, 2.49; N, 6.93. Found: C, 26.50; H, 2.66; N, 7.21.
Metallocycle 4b 8NO3. To a solution of 4b 8PF6 (60.0 mg,
3
3
0.025 mmol) in CH3CN (10 mL) was added an excess of
Bu4NNO3 until no further precipitation is observed. The red
precipitate is filtered and washed with CH3CN to yield 4b 8NO3
observed. The solid was filtered and washed with water to give
1
2 PF6 (0.33 g, 16%) as a white solid. Mp 214-216 °C dec; H
3
3
1
NMR (500 MHz, CD3CN) δ 5.76 (2H, s), 7.63 (2H, d, J = 8.5 Hz),
7.67 (1H, d, J = 16.5 Hz), 7.78-7.81 (3H, m), 7.93 (2H, d, J =
8.4 Hz), 8.04 (2H, d, J = 6.7 Hz), 8.15 (2H, d, J = 6.9 Hz), 8.69
(4H, m), 8.72 (2H, d, J=6.9Hz);13C NMR (125 MHz, CD3CN) δ
64.1 (CH2), 123.9 (CH), 124.6 (CH), 126.6 (CH), 129.7 (CH), 130.3
(CH), 131.0 (CH), 136.9 (C), 137.9 (C), 138.5 (CH), 145.6 (CH),
145.8 (CH), 146.6 (C), 148.7 (CH), 153.9 (C), 154.4 (C); MS-ESI
(m/z) 350.4 [M - PF6-]þ. Anal. Calcd for C24H20F6N3P: C, 58.19;
H, 4.07; N, 8.48. Found: C, 58.38; H, 4.30; N, 8.44.
(35 mg, 82%). H NMR (500 MHz, D2O) δ 2.82 (8H, s), 7.17
(4H, s), 7.53 (4H, d, J = 16.5 Hz), 7.62 (8H, d, J = 6.5 Hz), 7.67
(4H, d, J = 16.0 Hz), 8.18 (8H, d, J = 7.0 Hz), 8.70 (8H, d, J =
6.5 Hz), 9.07 (8H, d, J = 7.0 Hz); 13C NMR (125 MHz, D2O) δ
47.4 (CH2), 77.1 (CH2), 125.3 (CH), 126.3 (CH), 129.8 (CH),
137.6 (CH), 144.6 (CH), 145.7 (C), 152.1 (CH), 155.5 (C). Anal.
Calcd for C54H60N20O24Pt2: C, 36.78; H, 3.43; N, 15.89. Found:
C, 36.49; H, 3.17; N, 15.97.
Catenane 12 6PF6. To a solution of 5a,6a 6PF6 (5.7 mg,
3
3
0.003 mmol) in CD3CN (0.6 mL) was added 11 (32.2 mg,
0.060 mmol). 1H NMR (500 MHz, CD3CN) δ 2.88 (8H, s),
2.96-3.00 (12H, m), 3.15 (8H, m), 3.34-3.36 (12H, m), 3.60 (m,
˚
˚
(22) Distances: [H O] 2.20 A, and [N O] 3.06 A. Angle: [N-H O],
3 3 3 3 3 3 3 3 3
and 156°.
6582 J. Org. Chem. Vol. 74, No. 17, 2009

Blanco et al.
JOCArticle
Acknowledgment. The authors thank Centro de Super-
ꢀ
computacion de Galicia for providing the computer facil-
ities. This research was supported by Xunta de Galicia
ꢀ
(PGIDIT06PXIB103224PR), Ministerio de Educacion y
Cultura, and FEDER (CTQ2007-63839/BQU). V.B. and
excess of 11), 3.74 (m, excess of 11), 3.96 (m, excess of 11), 4.35
(4H, br s), 4.47 (4H, br s), 5.58 (4H, s), 5.71 (16H, s), 6.32 (2H, d,
J = 16.3 Hz), 6.42 (2H, d, J = 16.3 Hz), 6.75 (s, excess of 11),
7.00 (4H, d, J = 6.5 Hz), 7.50 (4H, d, J = 6.6 Hz), 7.58 (4H, d,
J = 8.4 Hz), 7.68 (4H, d, J = 8.4 Hz), 7.78 (4H, d, J = 6.8 Hz),
8.68 (4H, d, J = 6.4 Hz), 8.71 (4H, d, J = 6.6 Hz), 8.86 (4H, d,
J = 6.8 Hz); 13C NMR (125 MHz, CD3CN) δ 47.9 (CH2), 64.1
(CH2), 67.6 (CH2), 68.7 (CH2, excess of 11), 70.3 (CH2), 70.4
(CH2, excess of 11), 70.9 (CH2), 71.2 (CH2, excess of 11), 71.2
(CH2, excess of 11), 114.9 (CH), 116.1 (CH, excess of 11), 124.9
(CH), 125.4 (CH), 126.4 (CH), 128.6 (CH), 129.1 (CH), 130.9
(CH), 133.9 (CH), 137.5 (C), 137.5 (C), 145.8 (CH), 146.3 (C),
151.5 (C), 151.8 (C), 152.6 (CH), 152.8 (C), 153.2 (CH), 153.9 (C,
excess of 11).
ꢀ
A.G. thank the Ministerio de Educacion y Ciencia (FPU
Program) and the Universitat de Barcelona for their pre-
doctoral fellowships.
Supporting Information Available: 1H NMR, 13C NMR,
and 2D experiments for all compounds, crystallographic files
(in CIF format) of metallocycle 4a 4OTf 4PF6 and catenane
3
3
12 6PF6, titrations data, and optimized Cartesian coordi-
3
Single crystals of the catenane 12 6PF6 suitable for X-ray
diffraction were obtained by slow diffusion of ethyl ether into a
solution of 5a,6a 6PF6 and 11 in acetonitrile.
3
nates (BH&H/6-31þG(d) level) for 5a and 6a. This material
is available free of charge via the Internet at http://pubs.
acs.org.
3
J. Org. Chem. Vol. 74, No. 17, 2009 6583