C-pentyltetra(3-pyridyl)cavitand: A versatile building block for the directed assembly of hydrogen-bonded heterodimeric capsules

Article abstract of DOI:10.1021/ol060922s

Hydrogen-bond-directed assembly of heterodimeric cavitand-based capsules is of considerable interest. Herein, we report the synthesis and single-crystal X-ray structure determination of a pyridyl-functionalized cavitand that contains suitable hydrogen-bond acceptor moieties for the construction of asymmetric cavitand-based capsules.

Full text of DOI:10.1021/ol060922s

ORGANIC
LETTERS
2006
Vol. 8, No. 12
2607-2610
C-Pentyltetra(3-pyridyl)cavitand: A
Versatile Building Block for the Directed
Assembly of Hydrogen-Bonded
Heterodimeric Capsules
Christer B. Aakero1y,* Nate Schultheiss, and John Desper
Department of Chemistry, Kansas State UniVersity, Manhattan, Kansas 66503
aakeroy@ksu.edu
Received April 16, 2006
ABSTRACT
Hydrogen-bond-directed assembly of heterodimeric cavitand-based capsules is of considerable interest. Herein, we report the synthesis and
single-crystal X-ray structure determination of a pyridyl-functionalized cavitand that contains suitable hydrogen-bond acceptor moieties for
the construction of asymmetric cavitand-based capsules.
The deliberate and predesigned assembly of individual
molecular entities into larger well-defined cavities with acces-
sible space is an area of considerable fundamental scientific
interest.1 It has been shown that encapsulation of guest
molecules within a rigid interior framework can produce
nanosized reaction vessels and containers that exhibit drasti-
cally different behavior from bulk-phase environments,
leading to successful stabilization of highly reactive inter-
mediates2 and enhanced chemical reaction rates.3
employed as synthetic tools for the construction of homo-
meric cages.5
To expand the library of readily accessible and versatile
building blocks for both organic and metal-containing
capsules, we report the synthesis, characterization, and single-
crystal X-ray structure determinations of a C-pentyltetra(3-
pyridyl)cavitand and its tetrabromo precursor.
The synthesis of precursor 1 was achieved in good yields,
following previously reported procedures.6 Crystals suitable
for single-crystal X-ray crystallography of 1 were grown by
slow evaporation of an acetonitrile solution at room tem-
perature over 24 h. The structure determination of 1, Figure
1, shows that one guest molecule of acetonitrile is positioned
at the “lower rim” of the cavitand, surrounded by the “pentyl
feet”.7
During the past few years, a variety of homomeric capsules
have been constructed from resorcinarene-based cavitands
and metal ions, primarily cis-capped palladium(II) or plati-
num(II) ions.4 In addition, silver(I) ions have also been
(1) (a) Fujita, M.; Tominaga, M.; Hori, A.; Therrien, B. Acc. Chem. Res.
2005, 38, 369. (b) Fiedler, D.; Leung, D. H.; Bergman, R. G.; Raymond,
K. N. Acc. Chem. Res. 2005, 38, 351. (c) Seibel, S. R.; Stang, P. J. Acc.
Chem. Res. 2002, 35, 972. (d) Caulder, D. L.; Raymond, K. N. Acc. Chem.
Res. 1999, 32, 975.
(2) (a) Korner, S. K.; Tucci, F. C.; Rudkevich, D. M.; Heinz, T.; Rebek,
J., Jr. Chem.-Eur. J. 2000, 6, 187. (b) Kusukawa, T.; Fujita, M. J. Am.
Chem. Soc. 1999, 121, 1397. (c) Ziegler, M.; Brumaghim, J. L.; Raymond,
K. N. Angew. Chem., Int. Ed. 2000, 39, 4119.
(3) (a) Purse, B. W.; Ballester, P.; Rebek. J., Jr. J. Am. Chem. Soc. 2003,
125, 14682. (b) Yoshizawa, M.; Takeyama, T.; Okano, T.; Fujita, M. J.
Am. Chem. Soc. 2003, 125, 3242. (c) Fiedler, D.; Bergman, R. G.; Raymond,
K. N. Angew. Chem., Int. Ed. 2004, 43, 6748.
(4) (a) Kobayashi, K.; Yamada, Y.; Masamichi, Y.; Sei, Y.; Yamaguchi,
K. J. Am. Chem. Soc. 2004, 126, 13896. (b) Yamanaka, M.; Yamada, Y.;
Sei, Y.; Yamaguchi, K.; Kobayashi, K. J. Am. Chem. Soc. 2006, 128, 1531.
(c) Pinalli, R.; Cristini, V.; Sottili, V.; Geremia, S.; Campagnolo, M.;
Caneschi, A.; Dalcanale, E. J. Am. Chem. Soc. 2004, 126, 6516.
(5) (a) Haino, T.; Kobayashi, M.; Chikaraishi, M.; Fukazawa, Y. Chem.
Commum. 2005, 2321. (b) Haino, T.; Kobayashi, M.; Fukazawa, Y. Chem.-
Eur. J. 2006, 12, 3310.
(6) (a) Aoyama, Y.; Tanaka, Y.; Sugahara, S. J. Am. Chem. Soc. 1989,
111, 2167. (b) Bryant, J. A.; Blanda, M. T.; Vincenti, M.; Cram, D. J. J.
Am. Chem. Soc. 1991, 113, 2167.
10.1021/ol060922s CCC: $33.50
© 2006 American Chemical Society
Published on Web 05/19/2006

Figure 1. Molecular structure and thermal ellipsoids (50%
probability level) of the tetrabromo cavitand in the crystal structure
of 1‚acetonitrile.
Figure 3. Neighboring cavitands linked through short Br‚‚‚Br
interactions in cavitand 1‚acetonitrile.
The cavitands are organized into one-dimensional strands
as a result of the interaction between one of the pentyl feet
and the upper rim of a neighboring cavitand (Figure 2).
arranged into one-dimensional strands where one of the
pentyl feet is dipping into the upper rim of a neighboring
cavitand (Figure 4).
Figure 2. Packing of cavitand 1‚acetonitrile. The hydrogen atoms
have been removed, except on the acetonitrile solvent molecules,
for clarity.8
Figure 4. Packing of cavitand 1‚dichloromethane. The hydrogen
atoms have been omitted, except from the dichloromethane solvent
molecules, for clarity.
Cavitands in neighboring strands are arranged in antipar-
allel dimers organized via a pair of very short and symmetry-
related Br‚‚‚Br interactions (3.470 Å, Figure 3).
One of the “feet” of the cavitand in 1‚CH2Cl2 does display
a gauche conformation; although unusual, such configura-
tions are not rare,10 and it is difficult to point directly to
what may cause this geometry. The crystallographic screw
axis is essentially perpendicular to the two 1D strands shown
If 1 is recrystallized from dichloromethane, however,9 a
cavitate-type structure is formed where the guest molecule
resides outside of the host cavitand framework. However,
regardless of the location of the guest, neighboring hosts are
(9) Crystal data for 1‚dichloromethane: C52H60Br4O8‚CH2Cl2, M )
1217.57 amu, monoclinic, P2(1), a ) 10.4432(15) Å, b ) 15.049(2) Å, c
) 16.320(2) Å, R ) γ ) 90°, â ) 97.977(3)°, V ) 2540.0(6) Å3, Z ) 2,
Dc ) 1.592 g cm-3, µ(Mo KR) ) 3.328 mm-1, crystal size 0.22 × 0.19 ×
0.02 mm. Data were collected at 100 K on a Bruker SMART 1000
diffractometer using Mo KR radiation. A total of 22 914 reflections (2.39°
< θ < 30.09°) were processed, of which 7209 were unique and significant
with I > 2σ(I). Structure solution and refinement were carried out using
SHELXS-97 and SHELXL-97. Rint ) 0.735. Final residuals for I > 2σ(I)
were R1 ) 0.0447 and 0.0674 (GOF ) 0.735).
(7) Crystal data for 1‚acetonitrile: C52H60Br4O8‚C2H3N, M ) 1173.69
amu, triclinic, P1h, a ) 10.7767(7) Å, b ) 11.6740(7) Å, c ) 20.8192 Å,
R ) 80.392(4), â ) 97.977(3)°, γ ) 76.503(3)°, V ) 2510.8(3) Å3, Z ) 2,
Dc ) 1.552 g cm-3, µ(Mo KR) ) 3.261 mm-1, crystal size 0.30 × 0.25 ×
0.20 mm. Data were collected at 173 K on a Bruker SMART 1000
diffractometer using Mo KR radiation. A total of 18 907 reflections (1.82°
< θ < 28.28°) were processed, of which 9466 were unique and significant
with I > 2σ(I). Structure solution and refinement were carried out using
SHELXS-97 and SHELXL-97. Rint ) 0.0287. Final residuals for I > 2σ(I)
were R1 ) 0.0330 and 0.0877 (GOF ) 1.097).
(10) See CSD ref codes, e.g., FEBVUE, FESMEW, FEXFIY, LIFNUJ,
and TUTYEM.
(8) Images created using mercury 1.4.1.
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Org. Lett., Vol. 8, No. 12, 2006

in Figure 4, which means that the cavitands are not all
pointing in the same direction.
Two symmetry-related pairs of Br‚‚‚Br interactions, 3.349
and 3.676 Å, respectively, also play an important role in
positioning adjacent cavitands into an extended up-and-down
arrangement (running parallel with a) (Figure 5).
Figure 6. Thermal ellipsoid plot (50% probability level) of py-
cavitand 2‚acetonitrile.
determination of 2, Figure 6, shows one py-cavitand and three
acetonitrile molecules, although the asymmetric unit contains
only one-half cavitand and three-halves solvent molecules.
Cavitand 2 was also crystallized from methanol by slow
evaporation at room temperature over 36 h.15 The asymmetric
unit contains two py-cavitands and seven methanol solvent
molecules (Figure 7).
Figure 5. Adjacent hosts in cavitand 1‚dichloromethane linked
via multiple Br‚‚‚Br interactions.
The desired pyridyl-functionalized cavitand was synthe-
sized by a palladium-catalyzed Suzuki-Miyaura cross-
coupling reaction11 of cavitand 1 and excess 3-pyridyl
boronic acid12 under a basic media (Scheme 1). The target
Scheme 1. Synthesis of C-Pentyltetra(3-pyridyl)cavitand (2)
compound was purified by silica gel column chromatography
and recrystallized from acetonitrile yielding ∼87% of pure
py-cavitand 2.
It should be noted that cavitands similar to 2, C-heptyltetra-
(3-pyridyl)- and C-phenylethyltetra(3-pyridyl)cavitands, have
been reported in the literature;13 however, overall yields of
these cavitands were 23% and 20%, respectively. In those
cases, the synthesis was achieved by converting a tetrabromo
cavitand to the desired tetraboronic acid followed by reaction
with 3-bromopyridine.
Good quality crystals of the C-pentyltetra(3-pyridyl)-
cavitand were obtained by slow evaporation at room tem-
perature of an acetonitrile solution of 2.14 The structure
Figure 7. (a) Thermal ellipsoid plots (50% probability level) of
the two independent py-cavitands in the crystal structure of
2‚methanol. The seven methanol solvent molecules have been
omitted for clarity. (b) Asymmetric unit of 2‚methanol with the
hydrogen atoms removed, except on the methanol solvent mol-
ecules, for clarity. The pyridyl nitrogen atoms are represented as
light-blue spheres.
(11) (a) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11,
513. (b) Suzuki, A. J. Organomet. Chem. 1999, 576, 147 and references
therein.
(12) Li, W.; Nelson, D. P.; Jensen, M. S.; Hoerrner, R. S.; Cai, D.; Larsen,
R. D.; Reider, P. J. J. Org. Chem. 2002, 67, 5394.
(13) Kobayashi, K.; Ishii, K.; Sakamoto, S.; Shirasaka, T.; Yamaguchi,
K. J. Am. Chem. Soc. 2003, 125, 10615.
The improved synthetic route presented herein means that
the py-decorated cavitand 2 is readily available in large
Org. Lett., Vol. 8, No. 12, 2006
2609

quantities which offers new opportunities for preparing
heterodimeric capsules using: (1) complementary hydro-
gen-bond functionalities on different host molecules and
(2) transition metals as tools for the assembly of homo-
meric capsules. It is also noteworthy that intermolecular
halogen‚‚‚halogen interactions can play important roles in
organizing relatively large molecules such as the tetrabromo-
substituted host presented herein.
the rim display orientations that may result in polymeric
networks instead of the desired discrete heterodimeric
capsules. However, heterotopic assembly can be achieved
under suitable reaction conditions,13,16 and thus, the py-
cavitand 2 presented provides more opportunities for the
construction of asymmetric dimeric capsules that contain two
different guests.
Acknowledgment. We are grateful for the financial
support from NSF (CHE-0316479) and Dr. Doug Powell
(University of Oklahoma) for the single-crystal data collec-
tion on C-pentyltetra(3-pyridyl)cavitand-acetonitrile and
C-pentyltetra(3-pyridyl)cavitand-methanol.
The noncovalent assembly of heterodimeric capsules may
be somewhat hampered because the four nitrogen atoms on
(14) Crystal data for 2‚acetonitrile: C72H76N4O8‚3C2H3N, M ) 1248.53
amu, tetragonal, P4(3)2(1)2, a ) b ) 18.3708(7) Å, c ) 19.8745(15) Å, R
) γ ) â ) 90°, V ) 6707.4(6) Å3, Z ) 4, Dc ) 1.236 g cm-3, µ(Mo KR)
) 0.080 mm-1, crystal size 0.24 × 0.10 × 0.10 mm. Data were collected
at 100 K on a Bruker SMART APEX 1000 diffractometer using Mo KR
radiation. A total of 30 563 reflections (1.87° < θ < 28.31°) were processed,
of which 3614 were unique and significant with I > 2σ(I). Structure solution
and refinement were carried out using SHELXS-97 and SHELXL-97.17 Rint
) 0.0582. Final residuals for I > 2σ(I) were R1 ) 0.0514 and 0.1353 (GOF
) 1.059).
Supporting Information Available: Detailed experi-
mental procedures and characterization of compounds 1 and
2. This material is available free of charge via the Internet
at http://pubs.acs.org.
(15) Crystal data for 2‚methanol: 2C72H76N4O8‚7CH3OH , M ) 2475.03
amu, monoclinic, P2(1)/n, a ) 23.3560(16) Å, b ) 22.1519(16) Å, c )
25.5165(16) Å, R ) γ ) 90°, â ) 93.302(4)°, V ) 13164.5(15) Å3, Z )
4, Dc ) 1.249 g cm-3, µ(Mo KR) ) 0.084 mm-1, crystal size 0.45 × 0.25
× 0.10 mm. Data were collected at 153 K on a Bruker SMART APEX
1000 diffractometer using Mo KR radiation. A total of 59 710 reflections
(1.23° < θ < 26.48°) were processed, of which 8691 were unique and
significant with I > 2σ(I). Structure solution and refinement were carried
out using SHELXS-97 and SHELXL-97. Rint ) 0.1700. Final residuals for
I > 2σ(I) were R1 ) 0.0929 and 0.2680 (GOF ) 0.957).
OL060922S
(16) (a) Kobayashi, K.; Ishii, K.; Yamanaka, M. Chem.-Eur. J. 2005,
11, 4725. (b) Higler, I.; Grave, L.; Breuning, E.; Verboom, W.; De Jong,
F.; Fyles, T. M.; Reinholdt, D. N. Eur. J. Org. Chem. 2000, 1727.
(17) Sheldrick, G. M. SHELXS-97, Program for solution of crystal
structures; University of Go¨ttingen, Germany, 1997. Sheldrick, G. M.
SHELXL-97, Program for refinement of crystal structures; University of
Go¨ttingen, Germany, 1997.
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