A Janus [2]rotaxane synthesized by using an anion-templated clipping methodology

Article abstract of DOI:10.1002/chem.201101905

Clipping a Janus rotaxane: The synthesis of a novel anion-templated Janus [2]rotaxane species consisting of pyridinium chloride axle and isophthalamide macrocyclic components is reported. This represents a rare example of the synthesis of a Janus [2]rotax

Full text of DOI:10.1002/chem.201101905

DOI: 10.1002/chem.201101905
A Janus [2]Rotaxane Synthesized by Using an Anion-Templated Clipping
Methodology
Nicholas H. Evans and Paul D. Beer*[a]
The construction of interlocked molecules provides the
ambitious supramolecular chemist with a stimulating syn-
thetic challenge.[1] [2]Rotaxanes and [2]catenanes are typi-
cally prepared by use of either cationic[2] or neutral[3] tem-
plation methodologies. In our laboratories we have focused
on an anion-templation strategy[4] that uses appropriately
functionalized components containing pyridinium[4a–f,i] and
triazolium[4g,h] halide salts in combination with isophthala-
mide motifs to facilitate the self-assembly of orthogonal
Figure 1. Schematic representation of the preparation of a pyridinium
chloride/isopthalamide Janus [2]rotaxane.
complexes that upon Grubbsꢀ-catalyzed mediated cycliza-
tion, furnish the desired interlocked species. Meanwhile, a
diverse range of interlocked higher-order molecules have
also been prepared by employing cationic and neutral tem-
plates, including catenanes with up to seven interlocked
rings,[5] trefoil knots,[6] suitanes,[7] and Borromean rings.[8] As
part of our own program of research on anion templation
we have very recently reported the preparation of a “hand-
cuff catenane”.[9]
A Janus [2]rotaxane (or alternatively a [c2]daisy chain)
consists of two interlocked components each of which con-
tains an axle covalently attached to a macrocycle, with the
axle threaded through the other macrocycle of the rotaxane.
Such species have been constructed by cationic and neutral
templation methodologies[10] inspired in part by the possibil-
ity of generating molecules capable of controlled motion of
the macrocycles along the axles of the rotaxane akin to the
contraction and stretching of muscles.[11] Herein we report
the preparation and characterization of the first anion-tem-
plated Janus [2]rotaxane. Importantly, a “clipping” synthetic
Figure 2. Design of RCM precursor 1-Cl.
methodology is used to trap the axle components in the
formed macrocycles, making this a rare example of a Janus
[2]rotaxane prepared in such a fashion (Figure 1).[12]
the macrocyclic precursor consisting of an isophthalamide
motif that will hydrogen bond to the chloride anion leading
to the formation of the prerequisite orthogonal complex.
The isophthalamide group is appended with bis-vinyl arms
to allow RCM and contains hydroquinone units that will
favor p–p stacking with the electron-deficient pyridinium
motif. Finally, a hydrocarbon chain links together the axle
and macrocyclic precursor components.
The design of a precursor able to undergo ring-closing
metathesis (RCM) to form the desired interlocked structure
is depicted in Figure 2. Precursor 1-Cl consists of three
parts. First, a “stoppered” axle component containing the
pyridinium chloride motif that will exist as a strongly associ-
ated ion pair in the CH2Cl2 solvent of the reaction. Second,
The synthesis of precursor 1-Cl is detailed in Scheme 1.
Selective reduction of the 5-nitroisophthalamide compound
2[4c] was achieved by use of SnCl2.[13] The resulting amino
compound 3 was then coupled to the tert-butyloxycarbonyl-
[a] N. H. Evans, Prof. P. D. Beer
Inorganic Chemistry Laboratory, Department of Chemistry
University of Oxford
South Parks Road, Oxford, OX1 3QR (UK)
E-mail: paul.beer@chem.ox.ac.uk
AHCTUNGTRENNUNG
(Boc)-protected aminocarboxylic acid 4[14] using 1-ethyl-3-
(3-dimethylaminopropyl)carbodiimide (EDC) to afford 5.
Boc deprotection by treatment with trifluoroacetic acid
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101905.
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COMMUNICATION
Scheme 1. Preparation of RCM precursor 1-Cl.
(TFA), gave the aliphatic amine 6. This compound was then
coupled to asymmetric stopper 7[15] again using EDC to ach-
ieve amide formation. After silica gel chromatography pu-
rification, pyridine 8 was isolated in 77% yield. Methylation
using MeI, followed by anion exchange (by washing with
NH4Cl solution) afforded precursor 1-Cl in almost quantita-
tive yield from 8.
Precursor compound 1-Cl was dissolved in dry CH2Cl2
and Grubbsꢀ second-generation RCM catalyst (10% by wt)
added. Notably, precipitation was observed within minutes.
After stirring for 16 h, the crude reaction mixture was sub-
jected to silica gel preparatory TLC in an attempt to sepa-
rate the different species present (Scheme 2).
within the interlocked structure (Figure 3). The alkene reso-
nance j is not observed in the spectrum of the rotaxane,
while multiplet i has become a broad singlet confirming cyc-
lization has occurred. The internal pyridinium cavity proton
c has shifted upfield, while internal isophthalamide cavity
proton f has moved substantially downfield implying the ex-
istence of competitive hydrogen bonding to the chloride
anion.[16] Crucially, there is an upfield shift and splitting of
hydroquinone protons g and h that is consistent with inter-
calation of the electron-poor pyridinium motif between the
electron-rich hydroquinones. The interpenetrated nature of
the species is further corroborated by evidence from 2D
ROESY NMR spectroscopy where through-space correla-
tions are observed between the hydroquinone and alkene
protons (g, h, and i) and protons associated with the pyridi-
nium axle component (a to d) (Figure 4).
Proof that the isolated product was indeed the Janus ro-
taxane 9-(Cl)2 rather than the [1]rotaxane 10-Cl was provid-
ed by positive electrospray mass spectrometry.[17] A peak at
m/z 1367.74 with Dm/z=0.5 is consistent with the doubly
charged organic fragment 92+ (Figure 5).
[1]Rotaxane 10-Cl was also formed in the RCM reaction,
and was found in the more polar band on the prep TLC
plate at an Rf identical to that of the precursor 1-Cl. Indeed,
this band was found to contain [1]rotaxane 10-Cl, its un-
Two distinct bands were observed on the TLC plate. Once
developed, the band with the higher Rf value proved to con-
tain material insoluble in common organic solvents, with
partial solubility being achieved in 4:1 CDCl3/CD3OD. Sub-
sequent replating allowed pure Janus [2]rotaxane 9-(Cl)2 to
be isolated in a yield of 8%. This low yield is attributed in
part due to the low solubility of the compound.
Janus rotaxane 9-(Cl)2 was characterized by 1H and
13C NMR spectroscopy and high-resolution electrospray
1
mass spectrometry. The H NMR spectrum of 9-(Cl)2 (in 4:1
CDCl3/CD3OD) compared to that of precursor 1-Cl pro-
vides evidence of the supramolecular interactions present
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P. D. Beer and N. H. Evans
Scheme 2. Summary of products for RCM reaction of 1-Cl.
Figure 4. Section of 1H ROESY NMR spectrum of Janus [2]rotaxane 9-
(Cl)2 (solvent: 4:1 CDCl3/CD3OD, T=293 K). For atom labels see
Figure 2.
threaded isomer 11-Cl and trace amounts of unreacted start-
ing material 1-Cl. Despite repeated attempts, in our hands,
it proved impossible to separate these components.
To test whether the formation of the Janus [2]rotaxane
was chloride anion-templated, the non-coordinating hexa-
fluorophosphate salt of 1-PF6 was prepared and submitted
to the same RCM conditions as 1-Cl. In this case, no precip-
1
itation of material was observed, however a H NMR spec-
trum of the crude reaction mixture recorded after 16 h re-
vealed that cyclization had occurred. Attempted purification
by silica gel preparative TLC proved exceedingly difficult
due to the generation of multiple poorly separated bands on
Figure 3. 1H NMR spectra of a) RCM precursor 1-Cl and b) Janus [2]ro-
taxane 9-(Cl)2 (solvent: 4:1 CDCl3/CD3OD, T=293 K). For atom labels
see Figure 2.
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Anion-Templated Synthesis of a Janus [2]Rotaxane
COMMUNICATION
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MS evidence, the threaded [1]rotaxane 10-PF6, but isolated
in low yield due to the very challenging purification (see the
Supporting Information).
In summary, the first anion-templated Janus [2]rotaxane
has been prepared consisting of pyridinium chloride axle
and isophthalamide macrocyclic components. Its synthesis
by a Grubbsꢀ-catalyzed RCM clipping reaction is an unusual
method to use for the construction of a Janus rotaxane. The
synthesis of further “higher-order” interlocked molecules by
anion-templation strategies are continuing in our laborato-
ries
Acknowledgements
N.H.E. wishes to thank the EPSRC for a DTA studentship and Laura
Hancock (University of Oxford) for useful discussions about the prepara-
tions of compounds 3 and 7.
Keywords: anions · rotaxanes · supramolecular chemistry ·
template synthesis
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Received: June 21, 2011
Published online: August 18, 2011
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Chem. Eur. J. 2011, 17, 10542 – 10546