A double ring-closing olefin metathesis approach to [3]catenanes

Article abstract of DOI:10.1016/j.tetlet.2008.03.012

A [3]catenane with peripheral olefinic macrocycles was conveniently synthesized via a double ring-closing olefin metathesis. Highlights of this work include the synthesis of a 65-membered macrocycle featuring two phenanthroline ligands, a Cu(I)-templated synthesis of a [3]pseudorotaxane, and the key double ring-closing olefin metathesis to afford the desired [3]catenane in 71% yield.

Full text of DOI:10.1016/j.tetlet.2008.03.012

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2946–2950
A double ring-closing olefin metathesis approach to [3]catenanes
Manav Gupta, Songsu Kang, Michael F. Mayer *
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, USA
Received 26 February 2008; revised 4 March 2008; accepted 4 March 2008
Available online 8 March 2008
Abstract
A [3]catenane with peripheral olefinic macrocycles was conveniently synthesized via a double ring-closing olefin metathesis. Highlights
of this work include the synthesis of a 65-membered macrocycle featuring two phenanthroline ligands, a Cu(I)-templated synthesis of a
[3]pseudorotaxane, and the key double ring-closing olefin metathesis to afford the desired [3]catenane in 71% yield.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Catenane; Macrocycle; Pseudorotaxane; Ring-closing metathesis
Catenanes and rotaxanes have long been of interest to
chemists due, in part, to the various unique chemical and
physical consequences of the fact that these types of com-
pounds are composed of interlocking, but otherwise
unbound, molecular-level species.1 Over the last few dec-
ades, improved syntheses of interlocked structures based
upon templation, molecular recognition, and host–guest
interactions have finally allowed this field of study within
supramolecular chemistry an opportunity to thrive.2 More
specifically, recent syntheses of [2]catenanes based upon
supramolecular pre-organization in tandem with ring-clos-
ing olefin metathesis have been particularly fruitful, even
allowing some of these methods to become preparatively
useful.3
Beyond [2]catenanes, the synthesis of higher order
[n]catenanes is significantly more challenging for a variety
of reasons including the requirement for the central macro-
cycles to be doubly threaded. Nevertheless, several groups
have achieved spectacular syntheses of [3], [4], and [5]caten-
anes.4 In our own efforts to access polycatenanes and other
polymers with interlocked components, we have developed
a need for [3]catenanes that specifically feature peripheral
macrocycles with olefin functionality. Our approach to
[3]catenanes consists of a double clipping of two peripheral
macrocycles onto a central macrocycle.5 While a couple
groups have accessed [3]catenanes in low yields via double
olefin cross metatheses of [2]pseudorotaxanes, herein we
describe a relatively high yielding synthesis of a [3]catenane
via a related double ring-closing olefin metathesis of a
[3]pseudorotaxane. Scheme 1 illustrates a pictorial repre-
sentation of our complementary approach to [3]catenanes.
Our synthesis began with diol 1 which was prepared in
three steps (61% overall yield) from 1,10-phenanthroline
as described in the literature.6 In Scheme 2, diol 1 was trea-
ted with allyl bromide to afford both the monoallylic spe-
cies 2 and the diallylic species 6 in 67% and 15% yields,
respectively. Two equivalents of monoallylic 2 were teth-
ered in a diesterification reaction with isophthaloyl dichlo-
ride to provide diester 3 in 66% yield. Ring-closing olefin
metathesis of diester 3 (5 mM) with 10 mol % Grubbs’
2nd generation pre-catalyst7 afforded the olefinic macro-
cycle 4 in 85% yield. The internal olefin of macrocycle 4
was reduced upon treatment with 10 mass% palladium/
carbon to provide macrocycle 5 in 91% isolated yield.
Macrocycle 5 possesses several useful structural features
for [3]catenane synthesis. Most prominently 5 is large
enough (65-membered ring) and it incorporates two
phenanthroline ligands, inwardly directed, to enable a
copper(I)-assisted double threading to access a [3]pseudo-
rotaxane. Macrocycle 5 has one rigid aromatic tether
*
Corresponding author. Tel.: +1 806 742 0019; fax: +1 806 742 1289.
E-mail address: mf.mayer@ttu.edu (M. F. Mayer).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.012

M. Gupta et al. / Tetrahedron Letters 49 (2008) 2946–2950
2947
+ 2
+
2
- 2
- 2
Scheme 1. Schematic representation of the [3]catenane synthesis.
N
N
N
N
N
N
Cl
Cl
Br
O
O
O
O
O
O
O
O
O
O
O
NaH, DMF, 80 ˚C
67%
Proton sponge,
THF, 66%
O
O
O
O
O
O
O
O
OH
HO
HO
1
2
O
O
O
O
O
O
O
O
O
O
O
O
O
O
1) 10 mol% Grubbs' catalyst
DCM, 85%
N
N
N
N
N
N
2) 10 mass% Pd/C
THF, H2, 91%
3
O
O
O
O
O
O
5
Scheme 2. Synthesis of macrocycle 5.
between the two 2,9-diaryl-1,10-phenanthroline moieties
such that the two phenanthroline groups of 5 are unlikely
to collapse, intramolecularly, onto a single copper(I) ion
in a stable tetrahedral arrangement. Furthermore, the
diethyleneglycol tethers between the 2,9-diaryl-1,10-phen-
anthrolines and the isophthaloyl group are short enough
to prevent the phenanthrolines from twisting outward, thus
precluding the formation of stable supramolecular oligo-
mers in the presence of copper(I). Additionally, the more
flexible fully aliphatic polyether linker between the two
O
O
O
O
O
O
O
O
N
N
O
O
O
O
O
O
PF6
PF6
N
N
Cu
N
N
N
[Cu(CH3CN)4]PF6
92%
Cu
N
+
5
O
O
O
O
N
N
O
O
O
O
O
O
O
O
O
O
O
O
O
O
7
6
O
O
O
O
O
O
O
O
O
O
O
O
O
O
N
N
N
N
N
1) 10 mol% Grubbs' catalyst, DCM, 71%
2) aq. KCN, CH3CN, 92%
N
N
N
O
O
O
O
O
O
O
O
O
O
O
O
9
Scheme 3. Synthesis of [3]catenane 9.

2948
M. Gupta et al. / Tetrahedron Letters 49 (2008) 2946–2950
2,9-diaryl-1,10-phenanthrolines functions as a solubilizing
group for the compound in organic solvents. In compari-
son, a known, more symmetrical, bisphenanthroline
macrocycle, similar to 5, but with two aromatic linkers,
was found to be poorly soluble in organic solvents.8
To access [3]catenane 9, macrocycle 5 was briefly stirred
with 2 equiv of copper(I), to form the Cu2Á5 complex, and
then treated with 2 equiv of diallyl 6 to provide the stable
[3]pseudorotaxane 7 in 92% yield after column chromato-
graphy, Scheme 3. A minor byproduct, CuÁ62, was easily
1
separable by column chromatography. A sharp H NMR
spectrum of 7 demonstrated formation of the tethered bis-
phenanthroline copper complexes from the characteristic
upfield shift of the signals due to the 2,9-aryl substituents
of the phenanthroline ligands.9 The [3]pseudorotaxane 7
was also clearly inferred by MALDI-TOF-mass spectro-
metry from the distribution of peaks of the components
of 7 as shown in Figure 1. Figure 1 shows that under the
conditions of the MALDI-TOF-MS experiment, complex
7 undergoes some scrambling, for example to yield CuÁ62,
which was not present in the purified sample of 7 (the Rf
values of 7 and CuÁ62 differ greatly).
Fig. 2. MALDI-TOF-MS of 8. Peak assignments (m/z): 2722.7, [8ÀPF6]+;
1922.2, [8À2PF6ÀCuÀ(6–CH2@CH2)]+; 1289.9, [8À2PF6]2+; 595.2, [(6–
CH2@CH2)+H]+.
MALDI-TOF mass spectrum of 8 was simplified; no
scrambling of the macrocyclic components was observed
as would be expected for a covalently interlocked structure.
Lastly, the intermediate copper-complexed [3]catenane 8
was demetallated under mild conditions by the treatment
with aq KCN in acetonitrile to provide the colorless,
metal-free, and charge-neutral [3]catenane 9 in 92% yield,
Scheme 3. The removal of copper was confirmed in the
1H NMR spectrum by a return downfield shift of two diag-
nostic signals due to the 2,9-aryl substituents of the
phenanthroline ligands from d 6.03 and d 7.29 to d 7.10
and d 8.40, respectively.9 The MALDI-TOF mass spectrum
of 9, Figure 3, was simplified in comparison to the spec-
trum for 8 due to 9 being a neutral compound. Figure 3
shows three peaks in the mass spectrum that straightfor-
wardly correspond to [3]catenane 9 (base peak, 2450.8)
and two fragments. The two fragment peaks at 1859 and
595 are attributable to the [2]catenane and the smaller,
peripheral (cleaved) macrocycle, respectively. Interestingly,
under these MS experimental conditions, it appears that
The [3]pseudorotaxane 7 was treated with 10 mol %
Grubbs’ 2nd generation pre-catalyst to perform the key
double ring-closing olefin metathesis wherein two new 32-
membered macrocycles were formed. Copper-complexed
[3]catenane 8 was isolated in 71% yield (Scheme 3). The
relatively high yield further demonstrates the remarkable
nature of the bisphenanthroline–copper complex as an
efficient pre-organizational element for the macrocyclic
ring-closing olefin metathesis reaction.3j The 1H NMR
spectrum of the isolated product was consistent with the
formation of the [3]catenane complex as judged by the dis-
appearance of the signals due to the terminal olefin at
5.2 ppm and the appearance of a slightly broad signal at
6 ppm for the newly formed internal olefin.9 MALDI-
TOF-MS also clearly supported the formation of the
[3]catenane structure (Fig. 2). As compared to 7, the
Fig. 1. MALDI-TOF-MS of 7. Peak assignments (m/z): 2779.5, [7ÀPF6]+;
1950.7, [7À6ÀCuÀ2PF6]+; 1330, [7À2(6)ÀCuÀ2PF6]+; 1319.9,
[7À2PF6]2+; 1306.1, [2(6)+Cu]+; 623.6, [6+H]+.
Fig. 3. MALDI-TOF-MS of 9. Peak assignments (m/z): 2450.8, [9+H]+;
1859.6, [9À(6–CH2@CH2)+H]+; 595.1, [(6–CH2@CH2)+H]+.

M. Gupta et al. / Tetrahedron Letters 49 (2008) 2946–2950
2949
fragmentary ring-opening occurs only within one of the
smaller, peripheral macrocycles (derived from 6) rather
than from within the larger, central macrocycle. In general,
the observation of a molecular ion, along with further
peaks due to loss of rings from the parent catenane,
without observation of peaks due to species of intermedi-
ary mass, is characteristic of mass spectra of catenanes.4k
Several unique byproducts that feature inter-threaded
components could have arisen during the key double
ring-closing metathesis, structures A–C in Figure 4.
Byproduct A was anticipated as a result of a single tem-
plated intramolecular cross metathesis reaction between
the diallyl 6 components of [3]pseudorotaxane 7. However,
we did not observe formation of such a species as deter-
mined by 1H NMR spectroscopy (no terminal olefins)
and MALDI-TOF-MS (no mass fragment at m/z = 2748,
1277, or 1214 corresponding to [7–CH2@CH2–PF6]+,
[CuÁ62–CH2@CH2]+, and [62–CH2@CH2+H]+, respec-
tively). Two additional byproducts of interest could have
arisen during the double ring-closing olefin metathesis of
[3]pseudorotaxane 7. A templated double cross-metathesis
between two separate molecules of 6 (within 7) could have
occurred in two specific ways: that is, (1) to provide the
simple ring-in-ring product B (not interlocked), and (2) to
provide the racemic doubly interlocked [2]catenane prod-
uct C. Neither of these byproducts were formed. Byproduct
B was ruled out since demetallation released all noninter-
locked components of 9 and no peak for the cyclic cross
metathesis dimer of 6 (m/z: 1186 corresponding to [62-
2(CH2@CH2)+H]+) was observed in the MALDI-TOF
mass spectrum of the crude product. Byproduct C was
ruled out since, under the MALDI-TOF-MS experimental
conditions, we observed all species that are possible by a
single fragmentary ring-opening of macrocycles containing
an olefin. As can be seen in Figure 3, we did not observe a
peak (again, m/z of 1186) for the cyclic cross metathesis
dimer of 6 as would be expected if the doubly interlocked
[2]catenane had been formed.
In summary, the strategy presented here establishes a
reasonably efficient approach to a [3]catenane via a double
intramolecular ring-closing olefin metathesis reaction
within a [3]pseudorotaxane. The yield of the one-pot,
double ring-closing metathesis (71%) that creates the
copper-complexed [3]catenane is among the highest
reported yields to date for any process that creates a
[3]catenane that consists of rings of all covalently bonded
atoms.11 The overall synthetic strategy is modular with
respect to the template elements that enable the preorga-
nized synthesis of the interlocked species as well as to the
nature of the linkers between these elements. Upon modifi-
cation or adoption of iterative sequences, this strategy may
allow access to more elaborate interlocked oligomeric
species and networks.
Acknowledgments
We thank the donors of the American Chemical Society
Petroleum Research Fund (Grant No. 42943) and the
Texas Advanced Research Program of the Texas Higher
Education Coordinating Board under grant no. 003644-
0013-2006 for financial support for this project. MG
thanks the Graduate School of Texas Tech University for
a research assistantship. We thank Mr. Furong Sun at
the Mass Spectrometry Laboratory of the University of
Illinois at Urbana-Champaign for mass spectrometry
analysis of all new compounds.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2008.
03.012.
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´
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ˇ
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