Magic ring catenation by olefin metathesis

Article abstract of DOI:10.1021/ol050463f

(Chemical Equation Presented) Olefin metathesis has been employed in the efficient syntheses of a [2]catenane with the temptation being provided by the recognition between a secondary ammonium ion and a crown ether. In one approach, a crown ether precurso

Full text of DOI:10.1021/ol050463f

ORGANIC
LETTERS
2005
Vol. 7, No. 11
2129-2132
Magic Ring Catenation by Olefin
Metathesis
Erin N. Guidry,† Stuart J. Cantrill,‡ J. Fraser Stoddart,*,‡ and Robert H. Grubbs*,†
The Arnold and Mabel Beckman Laboratory of Chemical Synthesis, California Institute
of Technology, Pasadena, California 91125, and California NanoSystems Institute &
Department of Chemistry and Biochemistry, UniVersity of California, Los Angeles,
405 Hilgard AVenue, Los Angeles, California 90095
rhg@caltech.edu; stoddart@chem.ucla.edu
Received March 3, 2005
ABSTRACT
Olefin metathesis has been employed in the efficient syntheses of a [2]catenane with the templation being provided by the recognition between
+
a secondary ammonium ion and a crown ether. In one approach, a crown ether precursor has been clipped around an NH2 center situated
in a macrocyclic ring, yielding the mechanically interlocked compound. In the other approach, the reversible nature of olefin metathesis allows
for a magic ring synthesis to occur wherein two free macrocycles can be employed as the stationary materials, leading to the formation of
the same [2]catenane.
Mechanically interlocked molecules1 such as catenanes and
rotaxanes have long been of interest to chemists because of
their unique molecular structures. Furthermore, recent ad-
vances in the science of nanosystems has revealed that these
molecules not only are aesthetically pleasing curiosities but
also can function as the key components in active molecular
electronic devices where bistable derivatives, for example,
serve as volatile bistable switches in both memory and logic
circuits.2
Although a vast number of syntheses of catenanes and
rotaxanes have appeared in the chemical literature, most of
the strategies employ kinetically controlled covalent bond
formation as the final interlocking step.3 This strategy does
not always result in high yields of mechanically interlocked
compounds because of the irreversible formation of unwanted
noninterlocked byproducts. An alternative strategy, however,
exploits dynamic covalent chemistry,4 an approach that
utilizes reversible reactions in which the product distribution
depends on thermodynamic rather than kinetic control, i.e.,
the yield of a mechanically interlocked compound reflects
its stability relative to those of any other noninterlocked
byproducts with proof-reading and error-checking operating
up until a final equilibrium state is reached. Examples of
(2) (a) Collier, C. P.; Mattersteig, G.; Wong, E. W.; Luo, Y.; Beverly,
K.; Sampaio, J.; Raymo, F. M.; Stoddart, J. F.; Heath, J. R. Science 2000,
289, 1172-1175. (b) Pease, A. R.; Jeppesen, J. O.; Stoddart, J. F.; Luo,
Y.; Collier, C. P.; Heath, J. R. Acc. Chem. Res. 2001, 34, 433-444. (c)
Luo, Y.; Collier, C. P.; Jeppesen, J. O.; Nielsen, K. A.; DeIonno, E.; Ho,
G.; Perkins, J.; Tseng, H.-R.; Yamamoto, T.; Stoddart, J. F.; Heath, J. R.
ChemPhysChem 2002, 3, 519-525. (d) Diehl, M. R.; Steuerman, D.; Tseng,
H.-R.; Vignon, S. A.; Star, A.; Celestre, P. C.; Stoddart, J. F.; Heath, J. R.
ChemPhysChem 2003, 4, 1335-1339. (e) Tseng, H.-R.; Wu, D.; Fang, N.
X.; Zhang, X.; Stoddart, J. F. ChemPhysChem 2004, 5, 111-116. (f)
Steuerman, D. W.; Tseng, H.-R.; Peters, A. J.; Flood, A. H.; Jeppesen, J.
O.; Nielsen, K. A.; Stoddart, J. F.; Heath, J. R. Angew. Chem., Int. Ed.
2004, 43, 6486-6491. (g) Flood, A. H.; Ramirez, R. J. A.; Deng, R. P.;
Muller, W. P.; Goddard, W. A., III; Stoddart, J. F. Aust. J. Chem. 2004,
57, 301-322. (h) Flood, A. H.; Peters, A. J.; Vignon, S. A.; Steuerman, D.
W.; Tseng, H.-R.; Kang, S.; Heath, J. R.; Stoddart, J. F. Chem. Eur. J.
2004, 10, 6558-6564. (i) Flood, A. H.; Stoddart, J. F.; Steuerman, D. W.;
Heath, J. R. Science 2004, 306, 2055-2056. (j) Jang, S. S.; Kim, Y. H.;
Goddard, W. A., III; Flood, A. H.; Laursen, B. W.; Tseng, H.-R.; Stoddart,
J. F.; Jeppesen, J. O.; Choi, J. W.; Steuerman, D. W.; DeIonno, E.; Heath,
J. R. J. Am. Chem. Soc. 2005, 127, 1563-1575.
† California Institute of Technology.
‡ University of California, Los Angeles.
(1) (a) Schill, G. Catenanes, Rotaxanes and Knots; Academic Press: New
York, 1971. (b) Amabilino, D. B.; Stoddart, J. F. Chem. ReV. 1995, 95,
2725-2828. (c) Molecular Catenanes, Rotaxanes and Knots; Sauvage,
J.-P., Dietrich-Buchecker, C., Eds.; Wiley-VCH: Weinheim, 1999.
10.1021/ol050463f CCC: $30.25
© 2005 American Chemical Society
Published on Web 05/06/2005

equilibrium reactions employed as the final bond-forming
step in the synthesis of catenanes and rotaxanes include the
reversible formation of imines,5 disulfides,6 and cyclic
acetals,7 as well as olefin metathesis mediated by functional
group-tolerant ruthenium alkylidene catalysts.8 This proto-
col has been applied successfully in the syntheses of both
[2]catenanes9 and [2]rotaxanes.10 Recently, we have dem-
onstrated11 that the ring closing of certain olefin-containing
polyether substrates around appropriately substituted second-
ary dialkylammonium ions results (Scheme 1) in the revers-
CHPh (1),12 the macrocyclic polyether 2 containing one
olefinic double bond can be induced to undergo a magic ring
synthesis in the presence of the dumbbell compound 3-H‚
+
PF6, wherein the NH2 center acts as the template for the
formation of the [2]rotaxane 4-H‚PF6. Here, we show that
two convenient, high-yielding methods for constructing
[2]rotaxanes can be extended to the template-directed forma-
tion of [2]catenanes by (macrocyclic) polyether/secondary
ammonium ion recognition13 by using a cyclic rather than a
linear template.
The formation of the [2]catenane requires that the diben-
zylammonium-template-containing macrocycle is large enough
to permit catenation by the polyether macrocycle. The 27-
membered macrocyclic template 9-H‚PF6, shown in Scheme
2, was identified as a suitable target for synthesis. As outlined
in this scheme, 4-hydroxybenzaldehyde and 4-cyanophenol
were both alkylated in separate reactions (K2CO3/DMF) with
the mesylated ether 5, prepared in two steps from ethylene
glycol and 5-bromo-1-pentene. The cyano group in the
second alkylation product was reduced to the primary amine
6 using LiAlH4 in THF. Condensation of this amine with
the aldehyde 7, followed by reduction (NaBH4/MeOH),
yielded the macrocyclic precursor 8 after protection of the
secondary amine function with a Boc group. Ring-closing
metathesis (RCM) using the ruthenium catalyst 1 in a
CH2Cl2 solution of 8 yielded the expected protected mac-
rocycle, which was hydrogenated (H2/Pd/C/EtOAc), depro-
tected (TFA/CH2Cl2), and subjected to counterion exchange
(NH4PF6/MeOH) to yield the hexafluorophosphate salt
9-H‚PF6 of the macrocycle.
Scheme 1. Magic Ring Synthesis of a [2]Rotaxane (4-H‚PF6)
Templated by a Linear Ammonium Ion-Containing
Dumbbell-Shaped Component (3-H‚PF6)
Ring-closing of the terminal olefin functions in the acyclic
polyether 10 in the presence of the macrocyclic template
9-H‚PF6 and the catalyst 1 afforded (Scheme 3, lefthand
route) the [2]catenane 11-H‚PF6 in 52-75% isolated yield
ible formation of [2]rotaxanes. Thus, for example, by
employing the ruthenium catalyst (H2IMes)(PCy3)(Cl2)Rud
Scheme 2. Synthesis of the Macrocyclic Template 9-H‚PF6
2130
Org. Lett., Vol. 7, No. 11, 2005

Scheme 3. Dynamic Synthesis of a Catenane (11-H‚PF6) by
Two Distinct, Yet Complementary, Routesa
Figure 1. Partial 1H NMR spectra showing the change over time
during the magic ring synthesis of the dynamic [2]catenane
11-H‚PF6. Peak labels are defined in Scheme 3.
of 11-H‚PF6 is observed, by 1H NMR spectroscopy (Figure
1), to occur within a matter of minutes. After only 2 minutes,
1
signals are observed in the H NMR spectrum at δ ∼4.3
+
ppm, corresponding to the NH2 -adjacent methylene protons
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a Either ring-closing (left) or ring-opening-ring-closing (right)
metathesis protocols can be exploited.
as a mixture of (E)- and (Z)-isomers, as confirmed by ESI
mass spectrometry14 and both 1H and 13C NMR spectroscopy.
Hydrogenation (H2/PtO2/THF) of the olefinic double bond
in 11-H‚PF6 results in the formation of a single species,15
the [2]catenane 12-H‚PF6.
To demonstrate further the reversible nature of the olefin
metathesis reaction employed in the synthesis of the dynamic
[2]catenane 11-H‚PF6, the preformed macrocycle 2 was
employed in the corresponding magic ring synthesis. When
the two complementary macrocycles (9-H‚PF6 and 2) are
dissolved in CH2Cl2, catenation of these separate rings is,
in the absence of any other species, not possible. Upon the
addition of a catalytic amount of 1, however, the formation
Org. Lett., Vol. 7, No. 11, 2005
2131

(d′) in an environment where they are encircled by a crown
ether-like macrocycle; two sets of signals are observed,
corresponding to the (E)- and (Z)-isomers of the [2]catenane.
Furthermore, signals corresponding to “free” 9-H‚PF6 (b and
c) are observed to diminish in intensity, while others,
corresponding to the [2]catenane 11-H‚PF6, increase in
intensity over the course of the observation, with equilibrium
(75% interlocked product) being achieved after only 30
minutes. Formation of this interlocked compound presumably
occurs via a process in which (i) the olefin 2 undergoes a
ring-opening metathesis reaction to form a linear oligoether
species, that (ii) subsequently threads through the ammonium
ion-containing macrocycle 9-H‚PF6 to form a [2]pseudoro-
taxane, prior to (iii) a ring-closing metathesis reaction that
stitches the ends of the linear component back together, to
reform a macrocycle with the same constitution as 2 that is
[2]catenane based upon the secondary dialkylammonium
ion/(macrocyclic) polyether recognition system. The syn-
thesis, under thermodynamic control, of interlocked mol-
ecules allows for the efficient and high-yielding construc-
tion of complex molecular architectures. The extension
of this methodology from simple catenanes and rotaxanes
to larger macromolecular systems is currently under inves-
tigation.
Acknowledgment. This work was supported by a re-
search grant from the Office of Naval Research through its
MURI program.
Supporting Information Available: Experimental pro-
cedures and characterization data for compounds 2, 5-8,
and 9-H‚PF6-12-H‚PF6. This material is available free of
charge via the Internet at http://pubs.acs.org.
+
now, however, wrapped around the NH2 center of what
was previously 9-H‚PF6, resulting in the formation of a
[2]catenane, namely, 11-H‚PF6. In essence, catalyst 1 enables
the topological isomerization of two noninterlocked rings into
a catenated architecture, reminiscent of the conjurer’s simple
parlor trick, or, in a more scientific context, the action of
topoisomerases16 on circular double-stranded DNA.
OL050463F
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(14) Peaks at m/z ) 774 and 760 were observed in the mass spectrum
of the [2]catenane 11-H‚PF6. The lower mass peak arises from an impurity
in the dibenzylammonium-based macrocycle 9-H‚PF6, which is formed
during the ring-closing metathesis (RCM) macrocyclization of the diolefin
8. Olefin isomerization prior to the RCM reaction affords a macrocycle
with one methylene deletion, resulting in a 26-membered ring, rather than
the expected 27-membered one.
(15) Further confirmation of the interlocked nature of this [2]catenane
(12-H‚PF6) was obtained following acylation of this compound under basic
conditions. The acylated product, in which the mutual recognition expressed
between the two mechanically interlocked rings has been removed, was
proven to be a single species that had not fallen apart, as evidenced by
both NMR spectroscopy and ESI mass spectrometry; see Supporting
Information.
In conclusion, the use of ruthenium-mediated reversible
alkene metathesis has been applied to the synthesis of a
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