A switchable palladium-complexed molecular shuttle and its metastable positional isomers

Article abstract of DOI:10.1021/ja076570h

We report the design, synthesis, characterization, and operation of a [2]rotaxane in which a palladium-complexed macrocycle can be translocated between 4-dimethylaminopyridine and pyridine monodentate ligand sites via reversible protonation, the metal rem

Full text of DOI:10.1021/ja076570h

Published on Web 11/09/2007
A Switchable Palladium-Complexed Molecular Shuttle and Its
Metastable Positional Isomers
James D. Crowley,† David A. Leigh,*,† Paul J. Lusby,† Roy T. McBurney,†
Laure-Emmanuelle Perret-Aebi,† Christiane Petzold,† Alexandra M. Z. Slawin,‡ and
Mark D. Symes†
Contribution from the School of Chemistry, UniVersity of Edinburgh, The King’s Buildings,
West Mains Road, Edinburgh EH9 3JJ, United Kingdom, and the School of Chemistry,
UniVersity of St. Andrews, Purdie Building, St. Andrews, Fife KY16 9ST, United Kingdom
Received August 31, 2007; E-mail: David.Leigh@ed.ac.uk
Abstract: We report the design, synthesis, characterization, and operation of a [2]rotaxane in which a
palladium-complexed macrocycle can be translocated between 4-dimethylaminopyridine and pyridine
monodentate ligand sites via reversible protonation, the metal remaining coordinated to the macrocycle
throughout. The substitution pattern of the ligands and the kinetic stability of the Pd-N bond means that
changing the chemical state of the thread does not automatically cause a change in the macrocycle’s
position in the absence of an additional input (heat and/or coordinating solvent/anion). Accordingly, under
ambient conditions any of the four sets of protonated and neutral, stable, and metastable co-conformers
of the [2]rotaxane can be selected, manipulated, isolated, and characterized.
Introduction
a simple-to-assemble-and-operate [2]rotaxane in which a pal-
ladium-complexed macrocycle can be translocated between
Despite the success and influence of the redox-responsive
Cu(I)/Cu(II) catenane and rotaxane systems developed in
Strasbourg,1,2 there are no other examples of stimuli-switchable
molecular shuttles3 based on the manipulation of metal-ligand
interactions between the components.4,5 This lack of switchable
metal coordination motifs for interlocked molecules may be set
to change, however, following the recognition of the need to
vary the kinetics of binding events and transportation pathways
(e.g., ratcheting and escapement6) in any mechanical molecular
machine more sophisticated than a switch,7 and the crucial role
played by metastability in the functioning of rotaxanes currently
being investigated for molecular electronics.8 Here we describe
4-dimethylaminopyridine (DMAP) and pyridine (Py) ligand sites
via reversible protonation (the metal remaining coordinated to
(3) (a) Bissell, R. A.; Co´rdova, E.; Kaifer, A. E.; Stoddart, J. F. Nature 1994,
369, 133-136. For other examples of pH-responsive molecular shuttles
see: (b) Mart´ınez-D´ıaz, M.-V.; Spencer, N.; Stoddart, J. F. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1904-1907. (c) Ashton, P. R.; Ballardini, R.;
Balzani, V.; Baxter, I.; Credi, A.; Fyfe, M. C. T.; Gandolfi, M. T.; Go´mez-
Lo´pez, M.; Mart´ınez-D´ıaz, M.-V.; Piersanti, A.; Spencer, N.; Stoddart, J.
F.; Venturi, M.; White, A. J. P.; Williams, D. J. J. Am. Chem. Soc. 1998,
120, 11932-11942. (d) Elizarov, A. M.; Chiu, S.-H.; Stoddart, J. F. J.
Org. Chem. 2002, 67, 9175-9181. (e) Badjic´, J. D.; Balzani, V.; Credi,
A.; Silvi, S.; Stoddart, J. F. Science 2004, 303, 1845-1849. (f) Keaveney,
C. M.; Leigh, D. A. Angew. Chem., Int. Ed. 2004, 43, 1222-1224. (g)
Garaude´e, S.; Silvi, S.; Venturi, M.; Credi, A.; Flood, A. H.; Stoddart, J.
F. ChemPhysChem. 2005, 6, 2145-2152. (h) Badjic´, J. D.; Ronconi, C.
M.; Stoddart, J. F.; Balzani, V.; Silvi, S.; Credi, A. J. Am. Chem. Soc.
2006, 128, 1489-1499. (i) Tokunaga, Y.; Nakamura, T.; Yoshioka, M.;
Shimomura, Y. Tetrahedron Lett. 2006, 47, 5901-5904. (j) Leigh, D. A.;
Thomson, A. R. Org. Lett. 2006, 8, 5377-5379.
(4) For ruthenium-coordinated catenanes and rotaxanes which undergo pho-
toinduced decomplexation of the components, see: (a) Mobian, P.; Kern,
J.-M.; Sauvage, J.-P. Angew. Chem., Int. Ed. 2004, 43, 2392-2395. (b)
Collin, J.-P.; Jouvenot, D.; Koizumi, M.; Sauvage, J.-P. Eur. J. Inorg. Chem.
2005, 1850-1855. For other types of rotaxanes and catenanes which feature
intercomponent metal-ligand coordination, see: (c) Hutin, M.; Schalley,
C. A.; Bernardinelli, G.; Nitschke, J. R. Chem.sEur. J. 2006, 12, 4069-
4076. (d) Blight, B. A.; Wisner, J. A.; Jennings, M. C. Chem. Commun.
2006, 4593-4595. (e) Blight, B. A.; Wisner, J. A.; Jennings, M. C. Angew.
Chem., Int. Ed. 2007, 46, 2835-2838.
† University of Edinburgh.
‡ University of St Andrews.
(1) For macrocycle translocation in Cu(I)/Cu(II)-coordinated rotaxanes, see:
(a) Gavin˜a, P.; Sauvage, J.-P. Tetrahedron Lett. 1997, 38, 3521-3524. (b)
Armaroli, N.; Balzani, V.; Collin, J.-P.; Gavin˜a, P.; Sauvage, J.-P.; Ventura,
B. J. Am. Chem. Soc. 1999, 121, 4397-4408. (c) Durola, F.; Sauvage,
J.-P. Angew. Chem., Int. Ed. 2007, 46, 3537-3540. For macrocycle
translocation in Cu(I)/Cu(II)-coordinated catenanes, see: (d) Livoreil, A.;
Dietrich-Buchecker, C. O.; Sauvage, J.-P. J. Am. Chem. Soc. 1994, 116,
9399-9400. (e) Ca´rdenas, D. J.; Livoreil, A.; Sauvage, J.-P. J. Am. Chem.
Soc. 1996, 118, 11980-11981. (f) Livoreil, A.; Sauvage, J.-P.; Armaroli,
N.; Balzani, V.; Flamigni, L.; Ventura, B. J. Am. Chem. Soc. 1997, 119,
12114-12124. For macrocycle rotation in Cu(I)/Cu(II)-coordinated rotax-
anes, see: (g) Raehm, L.; Kern, J.-M.; Sauvage, J.-P. Chem.sEur. J. 1999,
5, 3310-3317. (h) Weber, N.; Hamann, C.; Kern, J.-M.; Sauvage, J.-P.
Inorg. Chem. 2003, 42, 6780-6792. (i) Poleschak, I.; Kern, J.-M.; Sauvage,
J.-P. Chem. Commun. 2004, 474-476. (j) Le´tinois-Halbes, U.; Hanss, D.;
Beierle, J. M.; Collin, J.-P.; Sauvage, J.-P. Org. Lett. 2005, 7, 5753-5756.
For a recent review of transition metal complexed molecular machines,
see: (k) Bonnet, S.; Collin, J.-P.; Koizumi, M.; Mobian, P.; Sauvage, J.-P.
AdV. Mater. 2006, 18, 1239-1250.
(5) For examples of rotaxanes and catenanes which utilize transition metal
ions to switch on/off other types of intercomponent interaction, see: (a)
Korybut-Daszkiewicz, B.; Wie¸ckowska, A.; Bilewicz, R.; Domagaa˜, S.;
Woz´niak, K. Angew. Chem., Int. Ed. 2004, 43, 1668-1672. (b) Jiang, L.;
Okano, J.; Orita, A.; Otera, J. Angew. Chem., Int. Ed. 2004, 43, 2121-
2124. (c) Leigh, D. A.; Lusby, P. J.; Slawin, A. M. Z.; Walker, D. B. Angew.
Chem., Int. Ed. 2005, 44, 4557-4564. (d) Leigh, D. A.; Lusby, P. J.; Slawin,
A. M. Z.; Walker, D. B. Chem. Commun. 2005, 4919-4921. (e) Marlin,
D. S.; Gonza´lez Cabrera, D.; Leigh, D. A.; Slawin, A. M. Z. Angew. Chem.,
Int. Ed. 2006, 45, 77-83. (f) Marlin, D. S.; Gonza´lez Cabrera, D.; Leigh,
D. A.; Slawin, A. M. Z. Angew. Chem., Int. Ed. 2006, 45, 1385-1390.
(6) Chatterjee, M. N.; Kay, E. R.; Leigh, D. A. J. Am. Chem. Soc. 2006, 128,
4058-4073.
(2) For contraction/stretching in a rotaxane dimer through Cu(I)-Zn(II)
exchange, see: (a) Jime´nez, M. C.; Dietrich-Buchecker, C.; Sauvage, J.-P.
Angew. Chem., Int. Ed. 2000, 39, 3284-3287. (b) Jime´nez-Molero, M.
C.; Dietrich-Buchecker, C.; Sauvage, J.-P. Chem.sEur. J. 2002, 8, 1456-
1466.
(7) (a) Kay, E. R.; Leigh, D. A. Nature 2006, 440, 286-287. (b) Kay, E. R.;
Leigh, D. A.; Zerbetto, F. Angew. Chem., Int. Ed. 2007, 46, 72-191.
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J. AM. CHEM. SOC. 2007, 129, 15085-15090
15085

A R T I C L E S
Crowley et al.
Scheme 1. Reversible Substitution of Pyridine and DMAP Ligands
in Macrocycle-Pd Complex L1PdPy/DMAP in DMF-d7 at 298 Ka
(Scheme 1a), we found that the pyridine group of L1PdPy was
rapidly10 and quantitatively substituted for DMAP.11 By adding
an equivalent of p-toluenesulfonic acid (TsOH), the process
could be reversed (Scheme 1b).12 The reasons for the selectivity
in Scheme 1b are quite subtle: although both heterocycles are
“coordinated”sone to Pd(II) and one to H+son both sides of
the equation (Scheme 1b), protonation of the more basic
heterocycle determines the position of equilibrium because the
N-H bond is significantly stronger than the Pd-N bond.13 In
other words, a proton differentiates DMAP and Py more
effectively than does Pd(II). The results suggested that a
palladium-complexed [2]rotaxane incorporating both DMAP and
Py binding sites in the thread could operate as a pH-switchable
molecular shuttle.
Synthesis and Characterization of Palladium-Coordinated
Molecular Shuttle L2Pd. A candidate [2]rotaxane, L2Pd, was
synthesized in nine steps using a “threading-followed-by-
stoppering” strategy14 (Scheme 2). 2,6-Diiodo-4-dimethylami-
nopyridine, 1, was prepared via a modified literature procedure15
(Scheme 2, step a) and subjected to consecutive Sonogashira
cross-coupling reactions,16 first with propargyl alcohol (1 equiv)
and then with decadiyne (5 equiv), to afford the unsymmetrical
DMAP-station17 intermediate 3 (Scheme 2, step c). The synthesis
of the Py-station fragment was achieved by desymmetrization
of commercially available 2,6-dibromopyridine through a So-
nogashira cross-coupling with 1 equiv of propargyl alcohol to
give 2 (Scheme 2, step b), hydrogenation (over PtO2), and
Mitsunobu reaction18 with bulky phenol 419 to give 5 (Scheme
2, step d). The coupling of 3 and 5 via another Pd-catalyzed
Sonogashira reaction, and subsequent hydrogenation over Pd-
(OH)2/C, afforded the saturated monostoppered thread, 6
(Scheme 2, step e). Coordination of the macrocycle-palladium
complex to the DMAP site of 6 occurred upon simple stirring
with L1Pd(CH3CN)9c in dichloromethane (298 K, 1 h). The
resulting threaded pseudo-rotaxane complex was covalently
a Upon mixing the substrates, equilibrium is reached within the time taken
to acquire a 1H NMR spectrum. (a) Neutral conditions; (b) in the presence
of TsOH (1 equiv).
the macrocycle throughout). The substitution pattern of the
ligands and the kinetic stability of the Pd-N bond means that
changing the chemical state of the thread (adding or removing
protons) does not automatically cause a change in the macro-
cycle’s position in the absence of an additional input (heat and/
or coordinating solvent/anion). Accordingly, under ambient
conditions any of the four sets of protonated and neutral, stable,
and metastable co-conformers of the [2]rotaxane can be selected,
manipulated, isolated, and characterized.
Results and Discussion
Basis of the Design: Protonation/Deprotonation-Driven
Ligand Exchange Experiments. The shuttle is based on a
recognition motif previously used to assemble rotaxanes and
catenanes by organizing tridentate pyridine 2,6-dicarboxamide
and appropriately derivatized monodentate pyridine ligands
about a square planar Pd(II) template.9 In a simple exchange
experiment with non-interlocked versions of these ligands
(11) For the exchange of various 4-substituted pyridine ligands at the fourth
coordination site of Pd-pincer complexes, see: (a) van Manen, H.-J.;
Nakashima, K.; Shinkai, S.; Kooijman, H.; Spek, A. L.; van Veggel, F. C.
J. M.; Reinhoudt, D. N. Eur. J. Inorg. Chem. 2000, 2533-2540. The
exchange of DMAP for poly(4-vinylpyridine) at the fourth coordination
site of bimetallic Pd- and Pt-pincer complexes has been exploited in the
chemoresponsive viscosity switching of a metallo-supramolecular network;
see: (b) Loveless, D. M.; Jeon, S. L.; Craig, S. L. J. Mater. Chem. 2007,
17, 56-61.
(12) A proton-driven ligand exchange of diethylamine and lutidine coordinated
to Pd(II) has previously been reported; see: (a) Hamann, C.; Kern, J.-M.;
Sauvage, J.-P. Dalton Trans. 2003, 3770-3775. For the proton-driven
exchange of one amine for another within copper-coordinated imine ligands,
see: (b) Nitschke, J. R. Angew. Chem., Int. Ed. 2004, 43, 3073-3075. (c)
Nitschke, J. R.; Schultz, D.; Bernardinelli, G.; Ge´rard, D. J. Am. Chem.
Soc. 2004, 126, 16538-16543. (d) Schultz, D.; Nitschke, J. R. Proc. Natl.
Acad. Sci. U.S.A. 2005, 102, 11191-11195. (e) Nitschke, J. R. Acc. Chem.
Res. 2007, 40, 103-112.
(13) (a) Sanderson, R. T. Chemical Bonds & Bond Energy; Academic Press:
New York, 1976. (b) Cotton, F. A.; Wilkinson, G.; Murillo, C.; Bochmann,
M.; Grimes, R.; Murillo, C. A.; Bochmann M. AdVanced Inorganic
Chemistry: A ComprehensiVe Text, 6th ed.; John Wiley & Sons: New
York, 1999. A contributing reason as to why the proton discriminates
DMAP and pyridine better than the Pd-macrocycle complex may be
because the proton is charged while the Pd-macrocycle is not. However,
since this is not the situation in ref 12a, where proton-driven ligand exchange
at Pd(II) also occurs, it is presumably not a major factor in the present
system either.
(14) Amabilino, D. B.; Stoddart, J. F. Chem. ReV. 1995, 95, 2725-2828.
(15) Wayman, K. A.; Sammakia, T. Org. Lett. 2003, 5, 4105-4108.
(16) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16,
4467-4470.
(17) The italicized prefixes DMAP- and Py- denote the position of the macrocycle
on the thread in the rotaxane.
(18) Mitsunobu, O.; Yamada, Y. Bull. Chem. Soc. Jpn. 1967, 40, 2380-2382.
(19) Gibson, H. W.; Lee, S. H.; Engen, P. T.; Lecavalier, P.; Sze, J.; Shen, Y.
X.; Bheda, M. J. Org. Chem. 1993, 58, 3748-3756.
(8) (a) Tseng, H.-R.; Wu, D.; Fang, N. X.; Zhang, X.; Stoddart, J. F.
ChemPhysChem 2004, 5, 111-116. (b) Steuerman, D. W.; Tseng, H.-R.;
Peters, A. J.; Flood, A. H.; Jeppesen, J. O.; Nielsen, K. A.; Stoddart, J. F.;
Health, J. R. Angew. Chem., Int. Ed. 2004, 43, 6486-6491. (c) Flood, A.
H.; Peters, A. J.; Vignon, S. A.; Steuerman, D. W.; Tseng, H. -R.; Kang,
S.; Heath, J. R.; Stoddart, J. F. Chem.sEur. J. 2004, 10, 6558-6564. (d)
Flood, A. H.; Stoddart, J. F.; Steuerman, D. W.; Heath, J. R. Science 2004,
306, 2055-2056. (e) Choi, J. W.; Flood, A. H.; Steuerman, D. W.; Nygaard,
S.; Braunschweig, A. B.; Moonen, N. N. P.; Laursen, B. W.; Luo, Y.;
Delonno, E.; Peters, A. J.; Jeppesen, J. O.; Xe, K.; Stoddart, J. F.; Heath,
J. R. Chem.sEur. J. 2006, 12, 261-279.
(9) (a) Fuller, A.-M.; Leigh, D. A.; Lusby, P. J.; Oswald, I. D. H.; Parsons, S.;
Walker, D. B. Angew. Chem., Int. Ed. 2004, 43, 3914-3918. (b) Furusho,
Y.; Matsuyama, T.; Takata, T.; Moriuchi, T.; Hirao, T. Tetrahedron Lett.
2004, 45, 9593-9597. (c) Fuller, A.-M. L.; Leigh, D. A.; Lusby, P. J.;
Slawin, A. M. Z.; Walker, D. B. J. Am. Chem. Soc. 2005, 127, 12612-
12619. (d) Leigh, D. A.; Lusby, P. J.; Slawin, A. M. Z.; Walker, D. B.
Angew. Chem., Int. Ed. 2005, 44, 4557-4564. (e) Fuller, A.-M. L.; Leigh,
D. A.; Lusby, P. J. Angew. Chem., Int. Ed. 2007, 46, 5015-5019.
(10) Exchange of the unsubstituted heterocycles in CDCl3, C2D2Cl4, or DMF-
d7 was complete within the time frame of mixing the L1PdPy complex
with DMAP and acquiring a 1H NMR spectrum, as was the reverse proton-
driven exchange upon adding TsOH. However, the 2,6-dipropyl substituted
heterocycles did not exchange in CDCl3 even over extended periods (7 d)
or upon heating at reflux. In DMF-d7 at 358 K equilibrium was reached
after 60 min (neutral conditions) or 130 min (in the presence of TsOH).
For full details of the exchange experiments, see the Supporting Information.
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Palladium-Coordinated Molecular Shuttle
A R T I C L E S
Figure 1. 1H NMR spectra (400 MHz, CDCl3, 300 K) of palladium rotaxane L2Pd in its four different protonated and co-conformational states, and for
comparison the free thread: (a) Thread 8; (b) DMAP-L2Pd; (c) DMAP-[L2HPd]OTs; (d) Py-L2Pd; (e) Py-[L2HPd]OTs. The lettering in the figure refers
to the assignments in Scheme 2.
captured with 4 (DIAD, PPh3, THF) to give the [2]rotaxane,
L2Pd, in 26% yield20 after column chromatography (Scheme
2, step f).
heterocycle at the open end of the thread, irrespective of relative
orientation, solvation, or other factors.
Macrocycle-to-Py-Station Protonation-Driven Shuttling
Experiments. Switching of the macrocycle position in DMAP-
L2Pd was attempted by the addition of 1 equiv of TsOH in
Mass spectrometry confirmed the product’s constitution as
1
L2Pd, and H NMR spectroscopy (Figure 1b) showed the co-
conformation formed to be exclusively DMAP-L2Pd;17 i.e., the
Pd-macrocycle fragment, L1Pd, was solely coordinated to the
DMAP binding site. A comparison of the spectra of free thread
8 (Figure 1a) and DMAP-L2Pd in CDCl3 (Figure 1b) shows
significant differences between the signals of the DMAP station
(Hd-f) for the rotaxane and thread, while the Py station signals
(Hi-k) of the rotaxane occur at very similar values to those of
the free thread. Interestingly, and for reasons that would become
apparent later, attempting the threading protocol with 7, a close
analogue of 6 in which the positions of the two stations were
reversed (i.e., the Py binding site was closest to the unstoppered
end of the thread; Scheme 2, step g), led exclusively to the
formation of Py-L2Pd! The outcomes of the two threading
reactions indicate that the pyridine and DMAP binding sites
are both astonishingly efficient at capturing the Pd-macrocycle
component from L1Pd(CH3CN) on its initial pass over the
1
CDCl3 (Scheme 3). The H NMR spectrum of the resulting
adduct (Figure 1c) showed significant changes in the Py
resonances, Hi-k, but no discernible shift of the DMAP signals,
Hd-f, indicating that protonation of the Py station had occurred
but the position of the macrocycle had not changed; i.e., the
chemical structure was now DMAP-[L2HPd]OTs (Scheme 3).
No changes to the 1H NMR spectrum of the sample were
observed over several days, indicating that the co-conformer is
effectively stable at room temperature in CDCl3. Somewhat
surprisingly, however, given the results of the exchange
experiments reported in Scheme 1,10 even in neat coordinating
solvents (DMSO-d6 or DMF-d7) no evidence of translocation
of the ring in DMAP-[L2HPd]OTs was observed at room
temperature. Translocation of the palladium macrocycle sub-
component (L1Pd) only takes place at elevated temperatures
(383 K), in both coordinating (DMF-d7) and non-coordinating
solvents (C2D2Cl4), in both cases reaching an equilibrium 89:
11 ratio of Py:DMAP-[L2HPd]OTs (Scheme 3) after 16 h
(DMF-d7) or 36 h (C2D2Cl4).
(20) The modest yield of rotaxane in the stoppering step is probably a
consequence of using a triphenylphosphine-mediated reaction with a Pd-
complexed pseudo-rotaxane. Alternative methodologies are currently being
investigated.
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A R T I C L E S
Crowley et al.
Scheme 2. Synthesis of Palladium-Complexed Molecular Shuttle L2Pda
a Reagents and conditions: (a) BF3‚OEt2, LDA, I2, THF, 40%; (b) propargyl alcohol, Pd(PPh3)4, CuI, Et3N/THF (1:2), 60%; (c) (i) propargyl alcohol,
Pd(PPh3)4, CuI, Et3N/THF, 75%, (ii) 1,9-decadiyne (5 equiv), Pd(PPh3)4, CuI, Et3N/THF, 77%; (d) (i) H2, PtO2, EtOH/Et3N, 94%, (ii) 4, DIAD, PPh3, THF,
61%; (e) (i) Pd(PPh3)4, CuI, Et3N/THF, 66%, (ii) H2, Pd(OH)2/C, THF, 88%; (f) (i) L1Pd(CH3CN), CH2Cl2 (90%), (ii) 4, DIAD, PPh3, THF, 26% (from 6);
(g) (i) L1Pd(CH3CN), CH2Cl2 (67%), (ii) 4, DIAD, PPh3, THF, 21% (from 7); (h) 4, DIAD, PPh3, THF, 25%.
Scheme 3. Operation of the Palladium-Complexed Molecular Shuttle L2Pda
a
† No macrocycle translocation observed over 24 h in DMF-d7 at 298 K or in C2D2Cl4 over 24 h at 383 K; ‡ No macrocycle translocation observed in
either DMF-d7 or C2D2Cl4 at 298 K over 24 h.
Ligand Exchange Experiments and X-ray Crystallography
Using 2,6-Dialkyl-Substituted Heterocycles. The dramatic
kinetic stability of the DMAP-Pd bond in the protonated [2]-
rotaxane led us to re-examine the kinetics of non-interlocked
ligand exchange, this time using 2,6-dialkyl-substituted hetero-
cycles (Scheme 4). Indeed, using 2,6-dipropylPy and 2,6-
dipropylDMAP as the monodentate components of the L1Pd-
heterocycle complex (Scheme 4) produced the same extremely
slow exchange of ligands observed in the [2]rotaxane. Single
crystals of both L1Pd(2,6-dipropylPy) and L1Pd(2,6-dipropy-
lDMAP) were subsequently grown by vapor diffusion of diethyl
ether into saturated solutions of the complexes in dichlo-
romethane. The X-ray crystal structures of these two complexes
(Figure 2a and 2b) are indicative of the likely coordination mode
and geometry of the macrocycle at the two different binding
sites in the [2]rotaxane. The crystal structures suggest that the
reason for the enhanced kinetic stability of the Pd-coordinated
2,6-dialkylheterocycle units is that the R-hydrogen atoms of the
alkyl substituents block the pathway of incoming nucleophiles
to the Pd center.21
Macrocycle-to-DMAP-Station Deprotonation-Driven Shut-
tling Experiments. Deprotonation of the 89:11 Py:DMAP
equilibrium mixture of [L2HPd]OTs (Na2CO3, CH2Cl2, 30 min)
generated the neutral co-conformers which were readily sepa-
(21) Similar effects have been observed upon increasing the steric bulk about
the coordination sphere in other Pd and Pt complexes. For examples, see:
(a) Atwood, J. D. Inorganic and Organometallic Reaction Mechanisms,
2nd ed.; Wiley-VCH: New York, 1997. (b) Yount, W. C.; Loveless, D.
M.; Craig, S. L. J. Am. Chem. Soc. 2005, 127, 14488-14496.
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Palladium-Coordinated Molecular Shuttle
A R T I C L E S
Scheme 4. Reversible Substitution of 2,6-Dipropylpyridine and
2,6-DipropylDMAP Ligands in Macrocycle-Pd Complex
confirmed the position of the macrocycle in the Py-L2Pd isomer.
Reprotonation of Py-L2Pd (1 equiv of TsOH in CDCl3)
quantitatively generated Py-[L2HPd]OTs (1H NMR spectrum,
Figure 1e), as another kinetically stable, out-of-equilibrium co-
conformer.
a
L1Pd(2,6-dipropylPy)/(2,6-dipropylDMAP) in DMF-d7
To complete the cycle of operations on L2Pd, pure Py-L2Pd
and the nonequilibrium, 11:89, mixture of DMAP/Py-L2Pd were
each heated at 383 K in DMF-d7. After 90 min both had reached
identical 86:14 ratios of DMAP/Py-L2Pd which did not change
upon further heating (Scheme 3). Unlike the proton-driven
translocation, no macrocycle translational isomerization was
observed when Py-L2Pd was heated in C2D2Cl4. Similarly, 2,6-
dipropylDMAP did not undergo a substitution reaction with
L1Pd(2,6-dipropylPy) in non-coordinating solvents (Scheme 4).
Conclusions
The practical realization and mechanistic investigation of
molecular-level systems in which both the kinetics and ther-
modynamics of binding events can be varied and controlled is
profoundly important for the development of sophisticated
molecular machine systems.7b Although nature is clearly able
to achieve this through the rapid manipulation of hydrogen
bonding and electrostatic interactions, the transient nature of
such weak binding events makes it hard to see how to emulate
this in synthetic systems given current levels of understanding
and expertise. We anticipate that metal-ligand coordination (and
dynamic covalent chemistry) will play a prominent role in the
early development of synthetic molecular machine systems.
a
(a) Neutral conditions; (b) in the presence of TsOH (1 equiv). Time
required to reach equilibrium:10 † 60 min at 358 K; ‡ 130 min at 358 K. No
exchange of the 2,6-dipropylheterocycle ligands was observed in CDCl3,
under either neutral conditions or in the presence of TsOH, even under
heating at reflux over 7 d.
Experimental Section
Synthesis of DMAP-L2Pd from 6 and Selected Spectroscopic
Data: To a solution of 6 (0.043 g, 0.046 mmol, 1.0 equiv) in CH2Cl2
(30 mL) was added L1Pd(CH3CN) (0.032 g, 0.046 mmol, 1.0 equiv),
and the solution stirred at RT for 1 h. The solvent was removed under
reduced pressure, and the crude residue was purified by column
chromatography (MeOH/CH2Cl2, 4:96) to give the threaded pseudo-
rotaxane (0.066 g, 90%). To a solution of the pseudo-rotaxane (0.054
g, 0.0304 mmol, 1.0 equiv), PPh3 (0.013 g, 0.0509 mmol, 1.5 equiv),
and 4 (0.026 g, 0.0509 mmol, 1.5 equiv) in THF (10 mL) was added
DIAD (0.010 mL, 0.0509 mmol, 1.5 equiv) Via microsyringe, and the
resulting solution was stirred at RT for 36 h. After removal of the
solvent under reduced pressure, the crude residue was purified by
column chromatography on silica (EtOAc:CH2Cl2 2:3) and washed with
ice-cold CH3CN to yield DMAP-L2Pd as a yellow solid (0.025 g, yield
) 29% from the pre-rotaxane, 26% from 6). Mp 170-172 °C; 1H NMR
(400 MHz, CDCl3): δ ) 1.01-1.43 (m, 84H, tBu-Stopper-H + thread-
alkyl-H + macrocycle-alkyl-H + Hb), 1.61-1.79 (m, 6H, thread-alkyl-H
+ macrocycle-alkyl-H), 2.01 (br, 4H, thread-alkyl-H + Hc), 2.15-
2.25 (m, 2H, Hm), 2.65-3.38 (m, 14H, Ha+e+h+l+C), 3.55 (br, 2H, Hg),
3.80-3.89 (m, 4H, HF), 3.98 (t, J ) 6.3, 2H, Hn), 5.25 (br, 2H, HC′),
5.82 (br, 1H, Hf), 6.40-6.80 (m, 13H, stopper-H + HD+E+d), 6.93-
7.02 (m, 2H, Hi+k), 7.05-7.11 (m, 16H, stopper-H), 7.19-7.25 (m,
12H, stopper-H), 7.45-7.53 (m, 1H, Hj), 7.83 (d, J ) 7.8, 2H, HB),
8.04 (t, J ) 7.8, 1H, HA); LRESI-MS (MeOH/CH2Cl2/TFA): m/z )
2075 [M+]; HR-FABMS (3-NOBA matrix): m/z ) 2075.20724 [M+]
(calcd for C135H168N6O6106Pd, 2075.20601).
Figure 2. X-ray crystal structures of (a) L1Pd(2,6-dipropylPy) and (b)
L1Pd(2,6-dipropylDMAP). Carbon atoms of the macrocycle are shown in
light blue, and those of the monodentate ligands, in orange and green,
respectively; oxygen atoms are red; nitrogen, dark blue; and palladium,
gray. Selected bond lengths [Å] and angles [deg]: (a) N1-Pd 1.94, N2-
Pd 2.03, N3-Pd 2.06, N4-Pd 2.03, N2-Pd-N4 161.6; (b) N1-Pd 1.93,
N2-Pd 2.03, N3-Pd 2.06, N4-Pd 2.02, N2-Pd-N4 161.4.
Preparation of DMAP-[L2HPd]OTs: To a solution of DMAP-L2Pd
(0.0295 g, 0.0142 mmol, 1.0 equiv) in CDCl3 (2 mL) was added TsOH
(0.00270 g, 0.0142 mmol, 1.0 equiv), and the reaction stirred at RT
until all the TsOH had dissolved (5 min). 1H NMR spectroscopy
revealed quantitative formation of DMAP-[L2HPd]OTs. 1H NMR (400
MHz, CDCl3): δ ) 1.00-1.40 (m, 82H, stopper-H + alkyl-thread-H
+ alkyl-macrocycle-H), 1.59-1.77 (m, 10H, thread-alkyl-H + Hb), 2.03
rated by column chromatography to give pure, kinetically stable
samples of both DMAP-L2Pd (minor product) and Py-L2Pd
1
(major product). Their H NMR spectra are shown in Figure
1b and 1d, respectively. As before, the relative shifts of the
resonances of the DMAP and Py stations unambiguously
9
J. AM. CHEM. SOC. VOL. 129, NO. 48, 2007 15089

A R T I C L E S
Crowley et al.
1
(br, 2H, Hc), 2.19-2.31 (m, 5H, tosyl-H + Hm), 2.69-3.42 (m, 14H,
and monitored Via H NMR spectroscopy at regular intervals. A ratio
of 86:14 DMAP:Py-L2Pd was established after 1.5 h, and further heating
did not alter this ratio. Upon heating pure Py-L2Pd to 110 °C in C2D2-
Cl4, no isomerization was observed, even after 7 days of heating at
383 K.
Ha+e+h+l+C), 3.56 (br, 2H, Hg), 3.79-3.94 (m, 6H, Hn+F), 5.23 (br, 2H,
HC’), 5.82 (br, 1H, Hf), 6.39-6.71 (m, 13H, stopper-H + Hd+D+E),
7.05-7.14 (m, 18H, stopper-H + tosyl-H), 7.21-7.24 (m, 12H, stopper-
H), 7.44 (br, 2H, Hi+k), 7.82-7.85 (m, 4H, tosyl-H + HB), 8.02-8.14
(m, 2H, Hj+A).
X-ray Crystallographic Structure Determinations. Single crystals
of L1Pd(2,6-dipropylPy) and L1Pd(2,6-dipropylDMAP) of suitable
quality for X-ray diffraction studies were grown by the vapor diffusion
of Et2O into CH2Cl2 solutions of the complexes. Structural data for
both L1Pd(2,6-dipropylPy) and L1Pd(2,6-dipropylDMAP) were col-
lected at 93 K using a Rigaku Mercury diffractometer (MM007 high-
flux RA/Mo KR radiation, confocal optic). All data collections
employed narrow frames (0.3-1.0) to obtain at least a full hemisphere
of data. Intensities were corrected for Lorentz polarization and
absorption effects (multiple equivalent reflections). The structures were
solved by direct methods, and non-hydrogen atoms were refined
anisotropically with CH protons being refined in riding geometries
(SHELXTL) against F2. L1Pd(2,6-dipropylDMAP): C46H61N5O4Pd, Mr
) 854.40, yellow prism, crystal size ) 0.08 × 0.08 × 0.08 mm3,
monoclinic, P21/c, a ) 18.098(2) Å, b ) 18.151(2) Å, c ) 12.7405-
(14) Å, â ) 91.62(3)°, V ) 4183.6(8) Å3, Z ) 4, Fcalcd ) 1.357 Mg
m-3; µ ) 0.493 mm-1, 27 337 data (7572 unique, Rint ) 0.0510), R )
0.0512 for 6199 observed data, wR2 0.1268, S ) 1.125 for 506
parameters. Residual electron density 1.273 and -1.090 eÅ-3. L1Pd-
(2,6-dipropylPy): C44H56N4O4Pd, Mr ) 811.33, yellow prism, crystal
size ) 0.05 × 0.03 × 0.03 mm3, monoclinic, P21/c, a ) 14.437(6) Å,
b ) 18.314(6) Å, c ) 16.522(6) Å, â ) 112.17(9)°, V ) 4045(3) Å3,
Z ) 4, Fcalcd ) 1.332 Mg m-3; µ ) 0.505 mm-1, 26 021 data (7361
unique Rint ) 0.2872), R ) 0.0937 for 3061 observed data, wR2 )
0.1982 S ) 0.953 for 479 parameters. Residual electron density 1.263
and -0.812 eÅ-3. CCDC 651736 and 651737 contain the supplemen-
tary crystallographic data for this paper. These data can be obtained
free of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Preparation of Py-L2Pd Wia the Protonation-Driven Translational
Isomerization and Subsequent Deprotonation of DMAP-[L2HPd]-
OTs: DMAP-[L2HPd]OTs (0.0322 g, 0.0142 mmol) was dissolved in
1
DMF-d7 (1 g), and a control H NMR spectrum acquired before the
sample was heated at 383 K. The sample was monitored regularly by
1H NMR spectroscopy. An equilibrium ratio of 89:11 Py:DMAP-
[L2HPd]OTs was reached after 16 h and remained unchanged upon
further heating. (Similarly, heating DMAP-[L2HPd]OTs at 383 K in
C2D2Cl4 for 36 h gave the same ratio of isomers, and subsequent heating
did not alter the product distribution.) After removal of DMF-d7 under
reduced pressure, the reaction mixture was redissolved in CH2Cl2 (10
mL) and stirred with a large excess of Na2CO3 (5 g) for 30 min.
Filtration through celite followed by removal of the solvent under
1
reduced pressure gave a yellow solid. H NMR (400 MHz, CDCl3)
analysis revealed that the crude residue was comprised of a mixture of
Py:DMAP-L2Pd in an (unchanged) 89:11 ratio. The two co-conformers
were separated by column chromatography on silica gel (MeOH/CH2-
Cl2 1:19) to give pure samples of both DMAP-L2Pd (identical
spectroscopic and other physical data to the sample previously obtained)
and Py-L2Pd. 1H NMR (400 MHz, CDCl3): δ ) 1.07-1.43 (m, 82H,
stopper-H + thread-alkyl-H + macrocycle-alkyl-H), 1.47-1.72 (m,
10H, thread alkyl-H + macrocycle-alkyl-H + Hg), 2.14-2.23 (m, 2H,
Hb), 2.57-3.00 (m, 12H, Hc+e+g+l), 3.29-3.43 (m, 4H, Hh+C), 3.52-
3.59 (m, 2H, Hn), 3.78-3.88 (m, 4H, HF), 3.93-4.00 (m, 2H, Ha),
4.59 (d, J ) 12.5, 2H, HC′), 6.21-6.23 (m, 2H, Hd+f), 6.44-6.47 (m,
4H, HD), 6.49-6.56 (m, 4H, HE), 6.68-6.79 (m, 4H, stopper-H), 6.92
(d, J ) 7.6, 1H, Hk), 7.05-7.11 (m, 16H, stopper-H), 7.17-7.24 (m,
13H, stopper-H + Hh), 7.79-7.82 (m, 1H, Hj), 7.84-7.87 (m, 2H,
HB), 8.05-8.09 (m, 1H, HA).
Preparation of Pure Py-[L2HPd]OTs: To a solution of Py-L2Pd
(0.0221 g, 0.0106 mmol, 1.0 equiv) in CDCl3 (2 mL) was added TsOH
(0.00202 g, 0.0106 mmol, 1.0 equiv), and the reaction stirred at RT
until all the TsOH had dissolved (5 min). 1H NMR spectroscopy
revealed quantitative formation of Py-[L2HPd]OTs. 1H NMR (400
MHz, CDCl3): δ ) 1.47-1.66 (m, 82H, stopper-H + thread-alkyl-H
+ macrocycle-alkyl-H), 1.58-1.81 (m, 10H, thread-alkyl-H + mac-
rocycle-alkyl-H + Hm), 2.16-2.32 (m, 5H, tosyl-H + Hb), 2.53-2.63
(m, 2H, Hl), 2.83-3.26 (m, 12H, Hc+e+g+C), 3.40-3.53 (m, 4H, Hh+n),
3.79-3.90 (m, 6H, Ha+F), 4.74 (d, J ) 13.9, 2H, HC’), 6.28 (d, J )
7.6, 2H, Hd+f), 6.42-6.57 (m, 8H, HD+E), 6.66-6.71 (m, 4H, stopper-
H), 6.88 (d, J ) 7.3, 1H, Hk), 7.02-7.15 (m, 19H, stopper-H + tosyl-H
+ Hi), 7.18-7.26 (m, 12H, stopper-H), 7.80-7.86 (m, 5H, tosyl-H +
Acknowledgment. This work was financed by the EU project
SingleMotor-FLIN and the EPSRC. We also thank the Ramsay
Memorial Trust (J.D.C.), EPSRC (D.A.L.), Royal Society
(P.J.L.), Deutscher Akademischer Austausch Dienst (C.P.), and
the Swiss National Science Foundation (L.-E.P.-A.) for their
generous support through various fellowship schemes.
Supporting Information Available: Experimental procedures
and spectroscopic data for all new compounds, details of the
model heterocycle exchange experiments, the protonation/
deprotonation-driven shuttling experiments, and full crystal-
lographic details of L1Pd(2,6-dipropylPy) and L1Pd(2,6-
dipropylDMAP). This material is available free of charge via
the Internet at http://pubs.acs.org.
Hj+B), 8.06-8.10 (m, 1H, HA), 14.00 (br, 1H, DMAP-H).
Preparation of DMAP-L2Pd Wia Translational Isomerization of
Py-L2Pd: Rotaxane Py-L2Pd was heated to 110 °C in DMF-d7 (1 g)
JA076570H
9
15090 J. AM. CHEM. SOC. VOL. 129, NO. 48, 2007