Hexafunctionalized borromeates using olefin cross metathesis

Article abstract of DOI:10.1021/ol070535y

Employing well-established template-directed protocols, which depend upon dynamic covalent, coordinate, and noncovalent chemistry for their efficient outputs, we have synthesized, in a convergent manner, Borromeates composed of three Identical macrocycles

Full text of DOI:10.1021/ol070535y

ORGANIC
LETTERS
2007
Vol. 9, No. 13
2433-2436
Hexafunctionalized Borromeates Using
Olefin Cross Metathesis
Claire R. Yates, Diego Ben´ıtez, Saeed I. Khan, 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
stoddart@chem.ucla.edu
Received March 2, 2007
ABSTRACT
Employing well-established template-directed protocols, which depend upon dynamic covalent, coordinative, and noncovalent chemistry for
their efficient outputs, we have synthesized, in a convergent manner, Borromeates composed of three identical macrocycles which present,
diagonally in pairs, six exo-bidentate bipyridyl ligands and six endo-diiminopyridyl ligands, each carrying either pentenyloxy or p-tolylpentenyloxy
substituents on their 4-positions, to six zinc(II) ions.
The molecular construction of the Borromean Ring (BR)
topology1 has been achieved2 successfully from 18 individual
components under dynamic control that characterizes not
only the noncovalent but also the coordinative3 and covalent
bonds formed in the molecules. This dynamic covalent
chemistry4 (DCC) assembly process is dependent on the
ability of the system to control the placement of 12 organic
ligands around six transition metal (zinc) ions in near
quantitative yields.
orthogonal approaches have been investigated, namely, pre-
assembly modification, which involves6 the incorporation of
the desired functionality on the incipient tridentate ligand,
followed by subsequent assembly of the rings via metal
template-directed synthesis,7 and post-assembly modification,
which first of all involves the synthesis of Borromeates with
pendant reactive groups attached to the incipient tridentate
ligand prior to assembly, then modification of the periphery
via the introduction of a new functional group. The functional
groups that are compatible with pre-assembly modification
of the Borromeate core are more or less limited to groups
This molecular BR topology5 provides a unique sym-
metrical, nanoscale, three-dimensional scaffold onto which
particular structural features can be embedded at will. Two
(5) (a) Siegel, J. S. Science 2004, 304, 1256-1258. (b) Cantrill, S. J.;
Chichak, K. S.; Peters, A. J.; Stoddart, J. F. Acc. Chem. Res. 2005, 38,
1-9.
(6) Chichak, K. S.; Peters, A. J.; Cantrill, S. J.; Stoddart, J. F. J. Org.
Chem. 2005, 70, 7956-7962.
(1) (a) Ruzmaikin, A.; Akhmetiev, P. Phys. Plasmas 1994, 1, 331-336.
(b) Liang, C.; Mislow, K. J. Math. Chem. 1994, 16, 27-35. (c) Cromwell,
P.; Beltrami, E.; Rampichini, M. Math. Intelligencer 1998, 20, 53-62. (d)
Mislow, K. Top. Stereochem. 1999, 22, 1-82.
(2) Chichak, K. S.; Cantrill, S. J.; Pease, A. R.; Chiu, S.-H.; Cave, G.
W. V.; Atwood, J. L.; Stoddart, J. F. Science 2004, 304, 1308-1312.
(3) (a) Hubin, T. J.; Kolchinski, A. G.; Vance, A. L.; Busch, D. L. AdV.
Supramol. Chem. 1999, 5, 237-357. (b) Leigh, D. A.; Lusby, P. J.; Teat,
S. J.; Wilson, A. J.; Wong, J. K. Y. Angew. Chem., Int. Ed. 2001, 40, 1538-
1543. (c) Blanco, M.-J.; Chambron, J.-C.; Jime´nez, M. C.; Sauvage, J.-P.
Top. Stereochem. 2003, 23, 125-173.
(7) (a) Anderson, S.; Sanders, J. K. M. Acc. Chem. Res. 1993, 26, 469-
475. (b) Hoss, R.; Vo¨gtle, F. Angew. Chem., Int. Ed. Engl. 1994, 33, 374-
384. (c) Schneider, J. P.; Kelly, J. W. Chem. ReV. 1995, 95, 2169-2187.
(d) Raymo, F. M.; Stoddart, J. F. Pure Appl. Chem. 1996, 68, 313-322.
(e) Templated Organic Synthesis; Diederich, F., Stang, P. J., Eds.; Wiley-
VCH: Weinheim, Germany, 1999. (f) Stoddart, J. F.; Tseng, H.-R. Proc.
Natl. Acad. Sci. U.S.A. 2002, 99, 4797-4800. (g) Busch, D. H. Top. Curr.
Chem. 2005, 249, 1-65. (h) Northrop, B. H.; Arico´, F.; Tangchaivang, N.;
Badjic´, J. D.; Stoddart, J. F. Org. Lett. 2006, 8, 3899-3902.
(4) Rowan, S. J.; Cantrill, S. J.; Cousins, G. R. L.; Sanders, J. K. M.;
Stoddart, J. F. Angew. Chem., Int. Ed. 2002, 41, 898-952.
10.1021/ol070535y CCC: $37.00
© 2007 American Chemical Society
Published on Web 05/22/2007

(e.g., olefinic) that do not alter significantly the solubility
or interfere with the reactivity of the components.6 Herein,
we show (1) that both pentenyloxy and p-tolylpentenyloxy
groups can be incorporated into the convergent synthesis of
a Borromeate core, and (2) that modification of a hexaolefinic
Borromeate using olefin cross metathesis8 (OXM) as a means
of introducing divergently six pendant groups onto the
outside of the Borromeate core is inefficient when compared
to Borromeates formed in a convergent manner.
was conveniently oxidized to the O-DFP building block in
91% yield, employing Swern conditions.13 See Supporting
Information.
The hexaolefinic Borromeate BRO6•12TFA (TFA )
trifluoroacetate) was assembled utilizing the diaminobipy-
ridine (DAB) component, along with O-DFP building block
employing the self-assembly conditions developed previ-
1
ously.2 The reaction was followed (Figure 1) by H NMR
spectroscopy.
Olefin metathesis has been developed into a powerful
synthetic tool for carbon-carbon bond-forming transforma-
tions, important in the fields of synthetic chemistry spanning
from natural products9 to commercial polymeric materials.10
Since the discovery of functional group tolerant and highly
active catalysts by Grubbs,11 the design of new systems has
focused on optimizing products for specific applications.12
Given the wide applicability and reasonable selectivity of
ruthenium-catalyzed olefin metathesis, we envisage that it
can be used to attach virtually any olefinic substrate to a
pre-assembled olefin-functionalized Borromeate core. In this
manner, we can functionalize the 2,6-diformylpyridine (DFP)
building block with a terminal olefin at its 4-position (O-
DFP) without affecting the solubility or reactivity of the
initially employed2 unsubstituted DFP precursor. Since the
olefinic functionality is completely inert during the self-
assembly process, it does not interfere with the DCC.3
Scheme 1. Synthesis of the O-DFP Building Block
Figure 1. Partial 1H NMR spectrum (600 MHz) recorded in
CD3OD of BRO6•12TFA.
The target BRO6•12TFA was obtained in 85% yield and
was fully characterized by 1H NMR spectroscopy and mass
1
spectrometry. The H NMR spectra (600 MHz, CD3OD)
reveal the appearance of a new resonance at δ ) 8.8 ppm
for the imine protons that corresponds to the formation of
12 imine bonds. All of the resonances observed were in
agreement with those reported2,6,14 previously for other
Borromeates. High-resolution electrospray ionization mass
spectrometry (HR-ESI MS) revealed peaks at m/z 1632.9560
(10) (a) Woodson, C. S., Jr.; Grubbs, R. H. U.S. Patent No. 5,939,504,
August 17, 1999. (b) Woodson, C. S., Jr.; Grubbs, R. H. Patent No.
6,310,121 B1, October 30, 2001.
(11) (a) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2039-2041. (b) Welhelm, T. E.; Belderrain,
T. R.; Brown, S. N.; Grubbs, R. H. Organometallics 1997, 16, 3867-3869.
(c) Scholl, M.; Ding, S.; Lee, C. W. ; Grubbs, R. H. Org. Lett. 1999, 1,
953-956. (d) Bielawski, C. W.; Grubbs, R. H. Angew. Chem., Int. Ed.
2000, 39, 2903-2906. (e) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.;
Wilhelm, T. E.; Scholl, M.; Choi, T.-L.; Ding, S.; Day, M. W.; Grubbs, R.
H. J. Am. Chem. Soc. 2003, 125, 2546-2558.
The synthesis of the O-DFP building block was achieved
as outlined in Scheme 1, starting with the alkylation of
dimethylchelidamate (1) with 5-bromo-1-pentene to afford
2 in 85% yield. Subsequent reduction of 2 with sodium
borohydride yielded (97%) the corresponding diol 3, which
(12) Love, A. J.; Sanford, M. S.; Day, M. W.; Grubbs, R. H. J. Am.
Chem. Soc. 2003, 125, 10103-10109.
(8) (a) Grubbs, R. H. Handbook of Metathesis; Wiley-VCH: Weinheim,
Germany, 2003. (b) Grubbs, R. H. Tetrahedron 2004, 60, 7117-7140. (c)
Grubbs, R. H. Angew. Chem., Int. Ed. 2006, 45, 3760-3765.
(9) (a) Kodota, I.; Takamura, H.; Sato, K.; Ohno, A.; Matusuda, K.;
Yamamoto, Y. J. Am. Chem. Soc. 2003, 125, 46-47. (b) Nicola, T.; Brenner,
M.; Donsbach, K.; Kreye, P. Org. Process Res. DeV. 2005, 9, 513-515.
(13) (a) Mancuso, A. J.; Huang, S.-L.; Swern, D. J. Org. Chem. 1978,
43, 2480-2482. (b) Hicks, R. G.; Koivisto, B. D.; Lemaire, M. T. Org.
Lett. 2004, 6, 1887-1890.
(14) (a) Chichak, K. S.; Cantrill, S. J.; Stoddart, J. F. Chem. Commun.
2005, 3391-3393. (b) Peters, A. J.; Chichak, K. S.; Cantrill, S. J.; Stoddart,
J. F. Chem. Commun. 2005, 3394-3396.
2434
Org. Lett., Vol. 9, No. 13, 2007

for [BRO6•12TFA-3TFA]3+, 1196.7330 for [BRO6•12TFA-
4TFA]4+, and 934.6344 for [BRO6•12TFA-5TFA]5+.
Single colorless crystals15 of BRO6•12TFA, suitable for
X-ray crystallography,16 were obtained by vapor diffusion
of Et2O into a methanolic solution of the compound. The
solid-state structure revealed (Figure 2a) that all three
macrocycles of the hexaolefinic Borromeate adopt chairlike
conformations, as in the structure of the parent Borromeates.2
In the case of the hexaolefinic Borromeate, we expected the
rings to adopt S6 symmetry. However, even though the same
chairlike conformations are evident and the rings are pseudo-
S6 with respect to the core, the overall symmetry is reduced
to Ci as a consequence of the relative orientations of the
olefinic tails. Similar observations have been made17 in the
case of some chiral Borromeates, where the symmetry is also
reduced to being C1. The olefinic tails on two of the
macrocycles are pointing in the same direction, whereas, on
the third macrocycle, the olefinic tails are pointing in the
opposite direction, indicating that there is a center of
inversion in the structure (Figure 2a and b). Moreover,
beyond the molecule, the packing diagrams (Figure 2c and
d) show that these olefinic tails orientate themselves so that
they occupy alternating hydrophobic solvent channels through-
out the crystal lattice.
For comparative purposes (pre- versus post-assembly), the
hexa-p-tolylpentenyloxyBorromeateBRS6•12TFAwasassem-
bled utilizing the DAB component, along with S-DFP (see
Supporting Information) as a building block employing the
identical self-assembly conditions used for BRO6•12TFA.
For each of the precursors (4, 5, and S-DFP, see Supporting
Information), the E-isomer was the major product isolated,
resulting from the OXM of 4-methylstyrene with 5-bromo-1-
pentene18 to afford 1-((E)-5-bromopent-1-enyl)-4-methylben-
zene (4), which was in agreement with extensive studies under-
taken by Grubbs and co-workers.18 The target BRS6•12TFA
(Figure 3) was obtained in 83% yield and was characterized
fully by 1H NMR spectroscopy and mass spectrometry. The
1H NMR spectra (600 MHz, CD3OD) revealed the appear-
ance of new resonances at (1) δ ) 8.7 ppm for the imine
Figure 2. Different structural and superstructural representations
of the BRO612+ dodecacation(s) in the solid state, as deduced from
X-ray crystallography carried out on a single crystal of BRO6•12TFA;
(a) tubular representation viewed down the S6 axis, revealing the
low symmetry (Ci) resulting from the opposite orientations in two
of the terminal olefin tails; (b) space-filling representation of a,
showing the cavity with a diameter of 2.08 Å; (c) space-filling
12+
representation of the packing of BRO6
dodecacations viewed
down the a-axis, revealing alternating hydrophobic solvent channels
12+
occupied by the olefinic tails; and (d) stack of three BRO6
dodecacations present in superstructural columns that run through
the crystal lattice in the a direction. The distance within the columns
12+
between the centers of repeating BRO6
dodecacations is 18.7
Å.
protons and corresponds to the formation of 12 imine bonds,
(2) δ ) 7.18 and 7.02 ppm for the p-tolylpentenyloxy protons
and δ ) 2.19 ppm for the protons of the aromatic methyl
group. The fact that two signals are observed for Hn δ )
6.24 (J ) 14 Hz) and 5.45 ppm tells us that the p-
tolylpentenyloxy substituents adopt both E and Z configura-
tions. HR-ESI MS revealed peaks at m/z 1813.6404 for
[BRS6•12TFA-3TFA]3+ and 1331.9202 for [BRS6•12TFA-
4TFA]4+.
The hexaolefinic Borromeates were modified in a post-
assembly fashion with styrenic substrates employing ruthe-
nium-based catalysts19 in an attempt to afford exclusively
hexasubstituted Borromeates. See Supporting Information.
BRO6•12TFA was subjected to OXM with 4-methylstyrene
in CH2Cl2 in the presence of the Grubbs second-generation
catalyst20 employing18 a large excess (10 equiv per olefin)
of the styrenic substrate. HR-ESI MS (Figure 4) was
employed to determine the efficacy of the OXM reactions.
Reactions of this type would be expected to yield a statistical
(15) Empirical formula [(C72H62N10O6)3(ZnCF3CO2)6] 2[Zn(CF3CO2)4],
M ) 5580.68, triclinic, space group P1h; a ) 18.668(7), b ) 20.237(8), c
) 20.728(8) Å; R ) 84.727(6), â ) 75.374(6), γ ) 74.548(5)°, V ) 7301-
(5) Å3, Z ) 1, Fc ) 1.357 g cm-3, µ(Mo KR) ) 0.750 mm-1, F(000) )
3034, T ) 100 K; colorless platelets, 0.20 × 0.10 × 0.10 mm3, 69 506
independent observed reflections, F2 using SHELXTL software package,
1724 parameters, R1/wR2 [I > 2σ(I)] ) 0.116/0.2943. A single colorless
crystal was attached with oil to a thin glass fiber. Solvent loss was
immediately evident as soon as the crystal was removed from the mother
liquor, which caused some disorder in embedded solvents. One of the long
olefinic chains and a free TFA anion were also disordered, and their
geometries were constrained. Beside the disordered atoms and solvent
molecules, the rest of the structure was refined anisotropically.
(16) Crystals were analyzed with a Bruker Smart 1000 CCD-based
diffractometer. Narrow-frame integration used the Bruker SAINT program
system. Crystallographic data (excluding structure factors) for the structure
of the hexaolefinic Borromeate reported in this communication have been
deposited with the Cambridge Crystallographic Data Centre as a supple-
mentary publication no. CCDC-638763. Copies of the data can be obtained
free of charge on application to CCDC, 12 Union Road, Cambridge CB2
1EK, U.K. (fax (+44)1223-336-033; e-mail deposit@ccdc.cam.ac.uk).
(17) Pentecost, C. D.; Peters, A. J.; Chichak, K. S.; Cave, G. W. V.;
Cantrill, S. J.; Stoddart, J. F. Angew. Chem., Int. Ed. 2006, 45, 4099-
4104.
(18) Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H. J.
Am. Chem. Soc. 2003, 125, 11360-11370.
Org. Lett., Vol. 9, No. 13, 2007
2435

Figure 3. Partial 1H NMR spectra (600 MHz) recorded in
CD3OD of a mixture of isomers of BRS6•12TFA where some of
the p-tolylpentenyloxy substituents adopt an E configuration and
others a Z configuration. Primed letters relate to this stereohetero-
genicity.
Figure 4. HR-ESI MS of BRO6•12TFA following OXM with
4-methylstyrene employing the Grubbs second-generation catalyst.
appeared to be no evident peaks that corresponded to
unreacted BRO6•12TFA or complete OXM functionalization
to afford BRS6•12TFA.22
distribution21 of cross-metathesis products. The HR-ESI MS
revealed key peaks at m/z 1022.4319 for [BRO1S5•12TFA-
5TFA]5+, 950.3944 for [BRO5S1•12TFA-5TFA]5+, 833.1957
for [BRO1S5•12TFA-6TFA]6+,788.1723for [BRO4S2•12TFA-
6TFA]6+, and 646.5716 for [BRO5S1•12TFA-7TFA]7+.
From an analysis of HR-ESI MS data obtained, it is
evident that the dominant product of the OXM reactions is
one that results from five cross metatheses and that there
The efficient convergent formation of both hexaolefinic
and hexa-p-tolylpentenyloxy Borromeates has been de-
scribed. This introduction of a further level of sophistication
structure-wise into the metal-containing BRs opens up the
ability to create new Borromeates and BR compounds. The
making of hexasubstituted Borromeates divergently is still
an open challenge, as demonstrated by the application of
ruthenium-catalyzed OXM to a pre-assembled hexaolefinic
Borromeate core.
(19) For previous examples of ruthenium-catalyzed metathesis reactions
involving mechanically interlocked compounds, see: (a) Dietrich-Buchecker,
C.; Rapenne, G. N.; Sauvage, J.-P. Chem. Commun. 1997, 2053-2054. (b)
Mohr, B.; Weck, M.; Sauvage, J.-P.; Grubbs, R. H. Angew. Chem., Int. Ed.
Engl. 1997, 36, 1308-1310. (c) Hamilton, D. G.; Sanders, J. K. M. Chem.
Commun. 1998, 1749-1750. (d) Hamilton, D. G.; Feeder, N.; Teat, S. J.;
Sanders, J. K. M. New J. Chem. 1998, 22, 1019-1021. (e) Dietrich-
Buchecker, C.; Rapenne, G. N.; Sauvage, J.-P. J. Am. Chem. Soc. 1999,
121, 994-1001. (f) Dietrich-Buchecker, C.; Sauvage, J.-P. Chem. Commun.
1999, 615-616. (g) Kidd, T. J.; Leigh, D. A.; Wilson, A. J. J. Am. Chem.
Soc. 1999, 121, 1599-1600. (h) Leigh, D. A.; Lusby, P. J.; Teat, S. J.;
Wilson, A. J.; Wong, J. K. Y. Angew. Chem., Int. Ed. 2001, 40, 1538-
1543. (i) Collin, J. P.; Laemmel, A. C.; Sauvage, J.-P. New J. Chem. 2001,
25, 22-24. (j) Raehm, L.; Hamilton, D. G.; Sanders, J. K. M. Synlett 2002,
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Org. Lett. 2003, 5, 1907-1910. (l) Kaiser, G.; Jarrosson, T.; Otto, S.; Ng,
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Sanders, J. K. M.; Stoddart, J. F. J. Am. Chem. Soc. 2004, 126, 9884-
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N.; Cantrill, S. J.; Stoddart, J. F,; Grubbs, R. H. Org. Lett. 2005, 7, 2129-
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Acknowledgment. We thank the National Science Foun-
dation (NSF) for supporting this research.
Supporting Information Available: Synthetic procedures
for the synthesis of O-DFP, BRO6•12TFA, S-DFP, BRS6•
12TFA and OXM reactions, mass spectrometric and room
temperature 1H and 13C NMR spectroscopic data, as well as
the distance and angle measurements associated with all
noncovalent and metal bonding interactions present in the
BRO6•12TFA. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL070535Y
(20) Chatterjee, A. K.; Toste, F. D.; Choi, T.-L.; Grubbs, R. H. AdV.
Synth. Catal. 2002, 344, 634-637.
(21) BROnSm will be used to indicate the number of successful OXM
reactions, where O ) olefin, S ) styrene, n ) number of unreacted olefin
tethers, and m ) number of styrene residues.
(22) Given that the product distribution observed in the HR-ESI MS is
highly skewed toward lower molecular weight compounds, we believe that,
even though we could not positively identify a peak for BRS6, it does not
eliminate the real possibility of it being present in a considerable amount
in the product mixture.
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Org. Lett., Vol. 9, No. 13, 2007