Efficient templated synthesis of donor - Acceptor rotaxanes using click chemistry

Article abstract of DOI:10.1021/ja063127i

The mild reaction conditions, remarkable functional group compatibility, and complete regioselectivity of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition ("click chemistry") between organic azides and terminal alkynes have led to a threading-followed-b

Full text of DOI:10.1021/ja063127i

Published on Web 07/25/2006
Efficient Templated Synthesis of Donor-Acceptor Rotaxanes Using Click
Chemistry
William R. Dichtel,†,‡ Ognjen Sˇ . Miljanic´,† Jason M. Spruell,† James R. Heath,*,‡ and
J. Fraser Stoddart*,†
California NanoSystems Institute and Department of Chemistry and Biochemistry, UniVersity of California, Los
Angeles, 405 Hilgard AVenue, Los Angeles, California 90095, and DiVision of Chemisty and Chemical Engineering,
California Institute of Technology, 1200 East California BouleVard, Pasadena, California 91125
Received May 4, 2006; E-mail: heath@caltech.edu; stoddart@chem.ucla.edu
Scheme 1
The discovery of highly efficient synthetic strategies for making
electrochemically switchable, mechanically interlocked compounds
will facilitate their continued development as components in
molecular electronic devices1 (MEDs) and nanoelectromechanical
systems2 (NEMS). Traditionally, such compounds, incorporating
cyclobis(paraquat-p-phenylene) (CBPQT4+) as the π-accepting ring
component, have been synthesized3 by “clipping” a partially formed
CBPQT4+ ring (Figure 1a) around a dumbbell or ring containing
π-electron-rich recognition sites. Although this synthetic strategy
has found wide application,4 the moderate yield typical of the
CBPQT4+ clipping reaction limits its practical value to the
preparation of [2]rotaxanes and [2]catenanes. Herein, we describe
an alternative synthetic approach (Figure 1b,c) to donor-acceptor
rotaxanessincluding previously inaccessible [3]- and [4]rotaxanes.
Their synthesis relies upon the efficient stoppering of their
pseudorotaxane precursors.
Motivated by the use of click chemistry5 in the synthesis of a
variety of functional materials,6-8 including an example9 in which
the Cu catalyst templates rotaxane formation, we reasoned that
donor-acceptor rotaxanes might be obtained by attaching alkyne-
terminated stoppers to CBPQT4+ pseudorotaxanes using the Cu-
(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (“click” chemistry).
The click reaction has been noted for its high regioselectivity,5-8
tolerance of sensitive functional groups, mild reaction conditions,10
and excellent yields. The click reaction occurs at room temperature
(and below), requiring only the addition of catalytic amounts of
CuSO4 and ascorbic acid, all conditions which are ideal for strong
binding of CBPQT4+ to a wide variety of thread molecules
containing π-donors.
This threading-followed-by-stoppering approach is complemen-
tary to clipping and has a number of advantages. Because the
recognition elements are fully formed from the outset of the
reaction, templation utilizes the full thermodynamic binding of
CBPQT4+ to the guest of interest. The click methodology is also
much more convergent: relatively simple, modular rotaxane
components are synthesized in parallel, and the mechanically
interlocked structure is assembled in the final step of the reaction
protocol. The general synthetic strategy (Scheme 1) involves the
mixing of CBPQT‚4PF6 in DMF at -10 °C, with a 1,5-
dioxynaphthalene (DNP) derivative 1 carrying azide-terminated
Figure 1. Graphical representations of different strategies employed in the
glycol chains. Under these conditions, the equilibrium lies pre-
dominantly in favor of the [2]pseudorotaxane [1 ⊂ CBPQT4+]‚
4PF6. A propargyl ether-functionalized stopper 2 is then added to
the reaction mixture along with CuSO4‚5H2O and ascorbic acid.
Following these mild reaction conditions, the [2]rotaxane 3‚4PF6
was isolated in 82% yield. Formation of the dumbbell was not
observed by thin layer chromatography.
template-directed syntheses of donor-acceptor rotaxanes: (a) clipping of
a macrocycle around a dumbbell; (b) double stoppering of a pseudorotaxane
to form a [2]rotaxane (Scheme 1); and (c) attachment of two semirotaxanes
onto a bifunctional stopper to form a [3]rotaxane (Scheme 2). An analogous
approach to a [4]rotaxane is depicted in Scheme 3.
† CNSI/UCLA.
‡ California Institute of Technology.
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C O M M U N I C A T I O N S
Scheme 2
Figure 2. Partial 1H NMR spectra (500 MHz, CD3COCD3) of 8‚12PF6
recorded at different temperatures. Several diagnostic peaks are labeled,
including the signals for the CBPQT4+ R and â protons, and resonances
for two of the three DNP protons. Slow rotation of the bipyridinium and
p-phenylene units in the CBPQT4+ rings is reflected in their broad proton
resonances at 298 K. At lower temperatures, these rotations are slowed
even further until the signals become clearly resolved. The signals for the
CBPQT4+ R and â protons coalesce into single, albeit broad, peaks at higher
temperatures.
Scheme 3
Encouraged by this successful proof of concept, we decided to
apply this methodology to the synthesis of [3]rotaxanes. Doubly
bistable [3]rotaxanes incorporating tethered CBPQT4+ rings have
been used as redox-driven molecular muscles.11 Although actuation
was achieved, clipping two CBPQT4+ rings around the synthetically
valuable palindromic dumbbell gave the desired [3]rotaxane in only
9% yield. Using the click methodology, a similar (albeit simplified)
palindromic [3]rotaxane was synthesized from relatively simple
precursors CBPQT‚4PF6, the stoppered DNP azide 4, and bis-
(propargyl ether) 5 in 79% isolated yield.12
The comparative efficiency of the click methodology is empha-
sized by the synthesis (Scheme 3) of the branched [4]rotaxane 8‚
12PF6 in 72% isolated yield after reacting 4 with tris-1,3,5(4′-
ethynylphenyl)benzene13 7 in the presence of CBPQT‚4PF6. A
clipping approach is expected to provide this [4]rotaxane in very
low (<3%) yield.
1
The partial H NMR spectra (Figure 2) of 8‚12PF6 reflect its
3-fold symmetry. The resonances for the DNP protons, which are
shielded and resonate at δ ) 6.49 (H-2/6), 6.22 (H-3/7), and 2.75
(H-4/8, not shown) ppm, are typical for rotaxanes containing
CBPQT4+ and DNP residues. At +25 °C, rotations of the
bipyridinium units and p-phenylene ring systems in the CBPQT4+
rings are slow on the 1H NMR time scale, resulting in broadening
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C O M M U N I C A T I O N S
of the signals for the CBPQT4+ protons. The spectrum becomes
much simpler as the signals for these protons coalesce at higher
temperatures. At lower temperatures, the exchange processes
between all of the relevant protons slow yet further, allowing for
resolution of nonequivalent proton signals. Throughout the tem-
perature range investigated, the triazole resonance remains a sharp
singlet near δ ) 8.60 ppm, a reasonable value for triazole protons.
This observation suggests that the triazole does not compete with
DNP to bind with the CBPQT4+ ringsa hypothesis we are currently
investigating more thoroughly.
During this preliminary research, it has become apparent that,
as a result of using click chemistry as the covalent modification
step in rotaxane synthesis, it not only renders the simple donor-
acceptor [2]- and [3]rotaxanes (Schemes 1 and 2) much more
accessible but it also provides the opportunity to prepare respectable
quantities of more exotic mechanically interlocked compounds, such
as the branched [4]rotaxane (Scheme 3). The synthesis and
applications of these new materials to MEDs and NEMS will now
become part of the ongoing research efforts in our laboratories.
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Acknowledgment. The collaboration was supported by the
Microelectronics Advanced Research Corporation (MARCO, J.F.S.)
and its Focus Centers on Functional Engineered NanoArchitectonics
(FENA) and Materials Structures and Devices, the Moletronics
Program of the Defense Advanced Research Projects Agency
(DARPA, J.F.S. and J.R.H.), and the Center for Nanoscale
Innovation for Defense (CNID, J.F.S.). J.M.S. gratefully acknowl-
edges the NSF for a Graduate Research Fellowship.
Supporting Information Available: Experimental details, spectral
characterization data of all new compounds (PDF), and complete refs
1a,e and 11. This material is available free of charge via the Internet
at http://pubs.acs.org.
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