Templated synthesis of desymmetrized [2]catenanes with excellent translational selectivity

Article abstract of DOI:10.1021/ol070970s

Desymmetrized [2]catenanes ware synthesized and shown to exhibit excellent translational selectivity. The templated synthesis takes effect from the formation of pseudorotaxanes between π-rich crown ethers and a π-deficient pyromellitic (Pml) unit, followed by macrocyclization around the crown ethers with the creation of a bipyridinium (BPy) unit. The crown ethers preferably encircle the BPy unit In the resulting [2]catenanes in both solution and the solid state, as indicated by various spectroscopic analyses.

Full text of DOI:10.1021/ol070970s

ORGANIC
LETTERS
2007
Vol. 9, No. 13
2577-2580
Templated Synthesis of Desymmetrized
[2]Catenanes with Excellent
Translational Selectivity†
Yi Liu,*,‡ Liana M. Klivansky,‡ Saeed I. Khan,# and Xiyun Zhang§
The Molecular Foundry, Lawrence Berkeley National Laboratory,
Berkeley, California 94720, Department of Chemistry and Biochemistry, UniVersity of
California, Los Angeles, California 90095, and Codexis, Inc., 200 Penobscot DriVe,
Redwood City, California 94063
yliu@lbl.goV
Received April 25, 2007
ABSTRACT
Desymmetrized [2]catenanes were synthesized and shown to exhibit excellent translational selectivity. The templated synthesis takes effect
from the formation of pseudorotaxanes between -rich crown ethers and a -deficient pyromellitic (PmI) unit, followed by macrocyclization
π
π
around the crown ethers with the creation of a bipyridinium (BPy) unit. The crown ethers preferably encircle the BPy unit in the resulting
[2]catenanes in both solution and the solid state, as indicated by various spectroscopic analyses.
Since the first templated synthesis1 of [2]catenanes, inter-
locked molecular systems2 can now be obtained efficiently
relying on supramolecular assistance to covalent synthesis.
Molecular recognition forces, such as donor-acceptor in-
teractions,3 metal-ligand coordination,4 and amide hydrogen-
bonding interactions,5 have been well adapted in the tem-
plated synthesis of interlocked molecules. Synthesis of the
donor-acceptor [2]catenane 1·4PF6 (Scheme 1) that was
pioneered by Stoddart et al. represents6 an important
milestone in this field. The two macrocyclic components of
1·4PF6 are held together at large by living donor-acceptor
interactions between a π-electron deficient bipyridinium
(BPy) cyclophane and a π-electron-rich crown ether mac-
rocycle. Mechanical motions generated from intercomponent
movements render these nanoscale objects ideal candidates
for molecular level switches. Indeed, molecular machines7
† Dedicated to Prof. J. Fraser Stoddart on the occasion of his 65th
birthday.
‡ The Molecular Foundry, Lawrence Berkeley National Laboratory.
# University of California, Los Angeles.
§ Codexis, Inc., Redwood City.
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Wiley-VCH: Weinheim, Germany, 1999.
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10.1021/ol070970s CCC: $37.00
© 2007 American Chemical Society
Published on Web 05/27/2007

assembly. A nice example is8a the switchable [2]catenane
2‚4PF6 (Scheme 1). By differentiating the two π-donors on
the crown ether macrocycle, precise translational selectivity
was achieved to give a nearly “all-or-nothing” situation.
Another way to implement control over the translational
isomerism is to include two different π-accepting units.
Neutral π-deficient units, such as pyromellitic diimide (PmI)
and naphtho-diimide (NpI), have been used13 as π-acceptors
in [2]catenane synthesis. The considerably different π-ac-
cepting ability between PmI and BPy units13d,14 prompts us
to designate desymmetrized [2]catenanes incorporating these
components. Here we report (1) the templated syntheses of
two such [2]catenanes that (2) exist as a single translational
isomer as expressed in the form of a preference for crown
ether component to encircle the BPy unit in both solution
and solid states.
Scheme 1. Introducing Translational Isomerism by Varying
the Donors or Acceptors in the [2]Catenane 1‚4PF6
and molecular switches8 of such kinds have found many
applications, including molecular memories,9 nanovalves,10
and molecular muscles.11
Scheme 2. Synthesis of Two [2]Catenanes and the Related
Translational Isomerism
Desymmetrized [2]catenanes12 serve as a role model of
controllable molecular motors.7d Efficient rotary movements
can be implemented only if precise control of translational
isomerism is achieved. The synthesis of such compounds
remains challenging as it requires the selection of the right
recognition pairs with different strength and their proper
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V.; Lee, C.-F.; Kay, E. R.; Leigh, D. A. Nature 2007, 445, 523-527.
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K.; Sampaio, J.; Raymo, F. M.; Stoddart, J. F.; Heath, J. R. Science 2000,
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A.; DeIonno, E.; Ho, G.; Perkins, J.; Tseng, H.-R.; Yamamoto, T.; Stoddart,
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Stoddart, J. F.; Steuerman, D. W.; Heath, J. F. Science 2004, 306, 2055-
2056. (d) Green, J. E.; Choi, J. W.; Boukai, A.; Bunimovich, Y.; Johnston-
Halperin, E.; DeIonno, E.; Luo, Y.; Sheriff, B. A.; Xu, K.; Shin, Y. S.;
Tseng, H.-R.; Stoddart, J. F.; Heath, J. R. Nature 2007, 445, 414-417.
(10) (a) Nguyen, T. D.; Tseng, H.-R.; Celestre, P. C.; Flood, A. H.; Liu,
Y.; Zink, J. I.; Stoddart, J. F. Proc. Natl. Acad. Sci. U.S.A. 2005, 102,
10029-10034. (b) Nguyen, T. D.; Liu, Y.; Saha, S.; Leung, K. C.-F.;
Stoddart, J. F.; Zink, J. I. J. Am. Chem. Soc. 2007, 129, 626-634.
(11) (a) Huang, T. J.; Brough, B.; Ho, C.-M.; Liu, Y.; Flood, A. H.;
Bonvallet, P. A.; Vignon, S. A.; Tseng, H.-R.; Stoddart, J. F.; Baller, M.;
Magonov, S. Appl. Phys. Lett. 2004, 85, 5391-5393. (b) Liu, Y.; Flood,
A. H.; Bonvallet, P. A.; Vignon, S. A.; Northrop, B. H.; Tseng, H.-R.;
Jeppesen, J. O.; Huang, T. J.; Brough, B.; Baller, M.; Magonov, S.; Solares,
S. D.; Goddard, W. A.; Ho, C.-M.; Stoddart, J. F. J. Am. Chem. Soc. 2005,
127, 9745-9759.
The synthesis (Scheme 2) was first attempted by reacting
a PmI containing dibromide 3, 4,4′-bipyridine (4), and a
hydroquinone (HQ) containing crown ether, bis-p-phenylene-
[34]crown-10 (BPP34C10), in DMF for 3 days. Although
no noticeable color change occurred upon mixing the
dibromide 3 and BPP34C10 owing to weak donor-acceptor
interactions, a red color gradually developed overnight,
suggesting the formation of bipyridium and its inclusion in
the BPP34C10 cavity. After counterion exchange with an
acetone/NH4PF6 mixture, the [2]catenane 5‚2PF6 was isolated
as a red solid in 30% yield. Similarly, when the more
(13) (a) Hamilton, D. G.; Davies, J. E.; Prodi, L.; Sanders, J. K. M. Chem.
Eur. J. 1998, 4, 608-617. (b) Hamilton, D. G.; Montalti, M.; Prodi, L.;
Fontani, M.; Zanello, P.; Sanders, J. K. M. Chem. Eur. J. 2000, 6, 608-
617. (c) Hansen, J. G.; Feeder, N.; Hamilton, D. G.; Gunter, M. J.; Becher,
J.; Sanders, J. K. M. Org. Lett. 2000, 2, 449-452. (d) Kaiser, G.; Jarrosson,
T.; Otto, S.; Ng, Y.-F.; Bond, A. D.; Sanders, J. K. M. Angew. Chem., Int.
Ed. 2004, 43, 1959-1962. (e) Vignon, S. A.; Jarrosson, T.; Iijima, T.; Tseng,
H.-R.; Sanders, J. K. M.; Stoddart, J. F. J. Am. Chem. Soc. 2004, 126, 9884-
9885. (f) Iijima, T.; Vignon, S. A.; Tseng, H.-R.; Jarrosson, T.; Sanders, J.
K. M.; Marchioni, F.; Venturi, M.; Apostoli, E.; Balzani, V.; Stoddart, J.
F. Chem. Eur. J. 2004, 10, 6375-6392.
(12) For examples of desymmetrized [2]catenanes with various degrees
of control on translational selectivity, see: (a) Ashton, P. R.; Perez-Garcia,
L.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Angew. Chem., Int. Ed.
Engl. 1995, 34, 571-574. (b) Baumann, F.; Livoreil, A.; Kaim, W.;
Sauvage, J.-P. Chem. Commun. 1997, 35-36. (c) Balzani, V.; Credi, A.;
Langford, S. J.; Raymo, F. M.; Stoddart, J. F.; Venturi, M. J. Am. Chem.
Soc. 2000, 122, 3542-3543. (d) Tseng, H.-R.; Vignon, S. A.; Celestre, P.
C.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 2003, 9,
543-556. (e) Hernandez, J. V.; Kay, E. R.; Leigh, D. A. Science 2004,
306, 1532-1537.
(14) Credi, A.; Montalti, M.; Balzani, V.; Langford, S. J.; Raymo, F.
M.; Stoddart, J. F. New J. Chem. 1998, 22, 1061-1065.
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Org. Lett., Vol. 9, No. 13, 2007

electron-rich crown ether 1,5-dinaphtho[38]crown-10 (1/
5DN38C10) was used, the [2]catenane 6‚2PF6 was isolated
as a purple solid in 52% yield.
conformation is also stabilized16 by various [C-H‚‚‚O] and
[C-H‚‚‚π] interactions. Similarly, the stacked array of
complementary donor-acceptors is also observed in the
crystal structure of 5·2PF6 (Figure 1b). Intermolecular
packings along the axes of the donor-acceptor stacks are
present in both cases.
15
The electrospray ionization (ESI) mass spectra of 5‚2PF6
and 6‚2PF6 reveal singly charged peaks at m/z 1260.2 and
1359.5, and doubly charged peaks at m/z 557.6 and 607.2,
1H NMR spectroscopy also provided insightful information
for the relative location of the two ring components. The
resonances of spectra of 5·2PF6 or 6·2PF6 are assignable to
one single translational isomer. The “inside” and “outside”
HQ or DNP ring systems in 5·2PF6 or 6·2PF6 are (Figure 2)
clearly discernible, suggesting that the site exchange between
HQ or DNP ring systems is slow at the 1H NMR time scale.
The “inside” and “outside” HQ protons of 5·2PF6 resonate
as two singlets at δ 6.26 and 3.80, respectively. In the case
of 6·2PF6, the resonances of the two DNP ring systems are
expressed in the usual doublet-triplet-doublet coupling
pattern. Characteristically, the H4/8 of the inside DNP ring
system appears as a doublet at δ 2.95 ppm (inset in Figure
2b) as a result of the shielding effect from the nearby
dicationic cyclophane. In contrast to 5·2PF6, all except the
PmI protons of the dicationic cyclophane in 6‚2PF6 become
diastereotopic. The chemical unequivalence occurs13a as a
result of the local C2 symmetry imposed from the DNP ring
system on the dicationic cyclophane.
-
corresponding to the loss of one and two PF6 ions,
respectively. The UV-vis spectrum of 5‚2PF6 in Me2CO
shows a broad charge-transfer (CT) band at λ ) 448 nm (ꢀ
) 230 M-1 dm-1), characteristic for a BPy unit situated in
the cavity of BPP34C10.6 Similarly, the purple solution of
6‚2PF6 has a CT absorption at λ ) 508 nm (ꢀ ) 230 M-1
dm-1), consistent with the BPy unit being included in the
1/5DN38C10 cavity.14
Figure 1. Stick representation of X-ray structures and structural
formula of (a) [2]catenane 62+ and (b) [2]catenane 52+. Hydrogen
atoms and counterions are omitted for clarity.
The preference of a BPy unit being included in the crown’s
cavity is also indicated by X-ray structural analysis.15 The
crystal structure of 6·2PF6 (Figure 1a) indicates that the
dicationic cyclophane is interlocked with the crown ether
such that (1) the 1,5-dioxynaphthalene (DNP) ring system
is sandwiched between the nearly parallelly aligned BPy unit
and the PmI unit with (2) the BPy unit sandwiched between
the parallelly aligned DNP ring systems. The mean inter-
planar separations are 3.3 Å, in keeping with stabilizing
[π-π] stacking interactions. The two pyridinium ring
systems are twisted with an angle of 10.1° and the distance
between the two quatery N+ centers is 7.02 Å. The PmI unit
is not strictly coplanar, with a dihedral angle between the
mean planes of the diimide rings of 5.2°. The distance
between the two N atoms of the PmI unit is 6.75 Å. The
1
Figure 2. Partial H NMR spectra of (a) 5‚2PF6 at 297 K, (b)
6‚2PF6 at 297 K, and (c) 6‚2PF6 at 193 K.
The observation of only one single set of resonances in
both 5·2PF6 and 6·2PF6 implies that one translational isomer
(16) Multiple [C-H‚‚‚O] interactions are observed between several
oxygen atoms in the polyether loops of the crown ether and one R-BPy
proton, one p-phenylene proton, and one methylene proton of the dicationic
cyclophane. The associated [H‚‚‚O] distances are 2.61, 2.50, and 2.47 Å,
respectively. The corresponding [C-H‚‚‚O] angles are 165°, 127°, and 134°.
In addition, there is [C-H‚‚‚π] interaction between one of the H-4/8 protons
of the “inside” DNP ring system and its proximal p-phenylene ring. The
distances between the H atom and the centroid π-electron plane is 2.54 Å,
and the corresponding [C-H‚‚‚π] angle is 149°.
(15) Red crystals suitable for X-ray single crystal analysis were obtained
after diffusion of ether into a Me2CO solution of 5‚2PF6. Purple crystals of
6‚2PF6 were obtained from a MeCN solution after diffusion of diisopropyl
ether. For more crystallographic information, please see the crystallographic
information files in the Supporting Information.
Org. Lett., Vol. 9, No. 13, 2007
2579

The demonstrated selectivity can be well understood in
terms of the significantly different electronic properties
between PmI and BPy units. An electrostatic potential surface
analysis18 (Figure 3) of two model compounds, Paraquat and
N,N′-dimethylpyromellitic diimide, clearly indicates that a
BPy unit is more electron deficient than a PmI unit.
Correspondingly, the BPy unit is more prone to stack with
the π-donor units from the crown ether component than the
PmI unit. Significantly different binding constants of these
units toward crown ethers are reported previously. For
example, the binding constant for a PmI derivative and
1/5DN38C10 is only 21 M-1 and is increased to 210 M-1 in
-
the presence of LiI,13d while the binding constant for a PF6
salt of dibenzylviologen and 1/5DN38C10 is 20 000 M-1.14
Such noncovalent bonding strength difference matches well
with the acceptors’ electron deficiency and possibly accounts
for the excellent translational selectivity expressed in these
desymmetrized [2]catenanes.
We have developed an efficient synthesis of desymme-
trized [2]catenanes with precise control of translational
isomerization. The engaged recognition units compose a fine
set of modules where a balance is realized between tem-
plating and achieving translational selectivitysthe donor-
acceptor interaction between PmI and crown ether is strong
enough to template the catenation while it is weak enough
to be outperformed by the generated BPy unit. The demon-
strated excellent translational selectivity could lead to high
fidelity molecular switches for usage in the growing field
of molecular electronics. Electrochemical- and photochemi-
cal-switching behavior of these catenanes are currently being
investigated.
Figure 3. Electrostatic potential surfaces of two model compounds,
paraquat (left) and N,N′-dimethylpyromellitic diimide (right). Blue
represents positive electrostatic potential and red stands for negative
electrostatic potential. The surfaces were optimized with the
MMFF94x force field.
is dominant at this temperature, while the possibility cannot
be excluded where the two isomers undergo fast exchange
such that only an averaged spectrum is observed. To verify
that, the temperature is further lowered to -80 °C, at which
point the site exchange should be slow enough17 to capture
possible translational isomers in equilibrium. As shown in
Figure 2c, all the peaks of 6·2PF6 remain sharp in CD3COCD3
and no new peaks are observed, suggesting that the observed
single resonance is not a result of site exchange and indeed
the excellent translational selectivity is maintained through-
out. On the basis of the detection limit of 1H NMR
spectroscopy, a selectivity greater than 97:3 can be estimated
for both [2]catenanes.
Acknowledgment. This work was performed at the
Molecular Foundry, Lawrence Berkeley National Laboratory,
and was supported by the Office of Science, Office of Basic
Energy Sciences, of the U.S. Department of Energy under
contract No. DE-AC02-05 CH11231. We thank Dr. Rudi
Nunlist and Dr. Frederick J. Hollander at the University of
California, Berkeley for their help on variable-temperature
1H NMR spectroscopic measurements and X-ray structural
analysis.
(17) Two mechanisms are possible for the exchange between the two
translational isomers. Either the dicationic cyclophane rotates through the
center of the crown ether component, or the outer DNP ring system can
sweep round the dicationic cyclophane by pirouetting about the included
DNP ring system. According to studies by the Stoddart group on structually
similar [2]catenanes, the latter one is the lower energy process as it requires
least energy for the breakdown of donor-acceptor interactions. The typical
associated activation barrier for Stoddart’s systems is around 12 to 14 kcal
mol-1. Correspondingly, those site exchange processes can be efficiently
“frozen out” below -30 oC. For compounds 5‚2PF6 and 6‚2PF6, such
activation barrier is difficult to measure on account of the absence of other
isomers. However, they should be very similar to those reported systems,
both of which involve the breaking of donor-acceptor interactions between
BPy and the outer aromatic ring system.
Supporting Information Available: Experimental details
for the preparation of 3, 5·2PF6, and 6·2PF6, and UV-vis
spectra and X-ray crystallographic data of 5·2PF6 and 6·2PF6.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL070970S
(18) The electrostatic potential surfaces were generated with MOE2006,
using the MMFF94x force field. MOE2006 is a product of the Chemical
Computing Group, Montreal, Canada.
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Org. Lett., Vol. 9, No. 13, 2007