Versatile launch pad for facile functionalization of cavitands

Article abstract of DOI:10.1002/ejoc.201101036

Suzuki-Miyaura cross-coupling reactions have been utilized for the derivatization of the upper-rim of cavitands, but unfortunately, only a relatively small number of suitable, inexpensive boronic acids are available. Herein, we report the synthesis and st

Full text of DOI:10.1002/ejoc.201101036

FULL PAPER
DOI: 10.1002/ejoc.201101036
Versatile Launch Pad for Facile Functionalization of Cavitands
Christer B. Aakeröy,*[a] Prashant D. Chopade,[a] Nate Schultheiss,[a] and John Desper[a]
Keywords: Cavitands / Molecular devices / Cross-coupling / Boron / Supramolecular chemistry
Suzuki–Miyaura cross-coupling reactions have been utilized
for the derivatization of the upper-rim of cavitands, but un-
fortunately, only a relatively small number of suitable, inex-
pensive boronic acids are available. Herein, we report the
synthesis and structure determination of a tetraboronic pin-
acolyl ester functionalized cavitand, which has been success-
fully employed in high-yielding coupling reactions with
iodoarenes covering a range of functional groups, thereby
demonstrating the versatility and chemoselectivity of this
platform.
coupling of a substituted (e.g., pyridyl, benzonitrile, or
methoxyphenyl) arylboronic acid or ester with a tetrahalo-
genated (I or Br) cavitand. The only reported exception in-
volved coupling of a tetraboronic acid cavitand to 3-bromo-
pyridine, albeit in low yields (ca. 20%).[7l]
Introduction
Carbon–carbon bond formation, utilizing a palladium cata-
lyst, is a well-known and versatile synthetic process in or-
ganic chemistry.[1] More specifically, the Suzuki–Miyaura
reaction, where a palladium species catalyzes the coupling
of organic halides or triflates with organoboronic acids or
esters, is arguably one of the most useful and important of
such reactions.[2,3] There are several reasons for its diversity
and wide acceptance: (1) It is tolerable to a large variety of
electron-donating and electron-withdrawing functional
groups. (2) It utilizes mild reaction conditions (i.e., 25–
70 °C), low catalyst loading, and dried solvents are not nec-
essary. (3) Many boronic acids/esters are stable over long
periods of time.[3] In short, this reaction is highly efficient
and, consequently, has been employed extensively in the
synthesis of natural products,[4] potential drug candidates,[5]
and a range of functional materials.[6]
The limited range of functional groups that has been suc-
cessfully appended to cavitands can be attributed in part to
the fact that a relatively small number of suitable, inexpen-
sive boronic acids and esters are commercially available for
cross-coupling. Moreover, arylboronic acids are often syn-
thesized by low-temperature transmetalation reactions and
can be difficult to isolate. In addition, effective coupling
of tetrahalogenated cavitands to arylboronic acid or esters
demands careful and time-consuming optimization of reac-
tion conditions (e.g., change of base, catalyst, ligand, etc.)
depending on the type of arylboronic acid or ester used.[7]
Sometimes, coupling reactions with tetrahalogenated cavit-
ands yields multisubstituted and multi-“protio”-cavitands
as byproducts, causing tedious chromatographic separa-
tions and very low yields.[8]
Within the last few years, the Suzuki–Miyaura reaction
has also been utilized in the synthesis of functionalized res-
orcinarene-based cavitand receptor molecules[7] by cross-
Scheme 1. Synthetic route to tetraboronic pinacolyl ester cavitand 2. Reagents and conditions: (a) nBuLi, THF, –78 °C; (b) B(OMe)3,
–78 °C to r.t.; (c) H+/H2O; (d) pinacol, MgSO4, DCM.
Against this background, we sought to design a more
[a] Department of Chemistry, Kansas State University
stable (compared to its boronic acid counterpart) tetra-
boronic ester cavitand counterpart,[9] and herein, we present
a facile synthetic procedure for the construction of
tetraboronic pinacolyl ester functionalized cavitand 2
Manhattan, KS 66503, USA
Fax: +1-785-532-6666
E-mail: aakeroy@ksu.edu
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101036.
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C. B. Aakeröy, P. D. Chopade, N. Schultheiss, J. Desper
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(Scheme 1) and demonstrate that it can be coupled success-
fully to a variety of iodoarenes under Suzuki–Miyaura con-
ditions. Thus, this new tetraboronic pinacolyl ester cavitand
represents a versatile and efficient synthetic platform that
can provide a gateway to the successful and facile prepara-
tion of a much wider selection of chemically and structur-
ally functionalized cavitands of interest to a broad range of
synthetic and materials chemists.
Results and Discussion
The synthesis of 2 was achieved in 50% yield by follow-
ing a modified procedure.[10] It should be noted that in the
reported case, the goal was to only convert two of the four
bromine atoms into the pinacolyl boronate derivative. In
our case, C-pentyltetrabromo cavitand[11] 1 (carefully dried
by using Sherburn’s procedure[12]) was allowed to react with
n-butyllithium (4.6 equiv.) at –78 °C for 0.5 h, resulting in a
fourfold lithium–halogen exchange. To this was added tri-
methoxyborane (6 equiv.), and the reaction was allowed to
reach room temperature after 0.5 h. The mixture was acidi-
Figure 1. Side view of the host–guest complex in the crystal struc-
ture of 2. The disordered atoms around one boronic pinacolyl ester
and the exterior solvent molecule have been omitted for clarity.
Boron atoms are shown as light-pink spheres and the interior hex-
ane molecule is shown in orange.[16]
fied with hydrochloric acid, producing the tetraboronic acid the “leg” of one cavitand is inserted into the cavity of a
cavitand, which was then converted into the desired tetra- neighboring host molecule.[14] This type of interaction has
boronic pinacolyl ester cavitand 2 by addition of an excess recently been used for designing supramolecular polymers
amount of pinacol and magnesium sulfate (Scheme 1). Puri- having cavity-bearing moieties.[15] All four pinacolyl ester
fication was carried out by dissolving the reaction mixture groups are oriented perpendicularly with respect to the
in dichloromethane and adding an excess amount of acet- phenyl group to which they are connected, presumably due
one, resulting in the formation of a white precipitate.
to oxygen–oxygen repulsion between neighboring bridging
Crystals of 2, suitable for single-crystal X-ray diffraction, ether groups.
were grown from a saturated hexanes/dichloromethane
In order to successfully couple 2 to different representa-
solution by slow evaporation at room temperature over tive haloarenes, we had to identify the optimum reaction
3 d.[13] Structure determination of 2 shows one tetraboronic conditions that result in versatile and facile tetrafunction-
pinacolyl ester cavitand and two molecules of hexane in the alization on the upper-rim of the cavitand. Our choice of
asymmetric unit (Figure 1).
suitable haloarenes was based on two criteria: (1) the
Furthermore, one hexane molecule resides within the up- haloarenes should represent different classes of functional
per-cavity, whereas a second solvent molecule resides out- groups to establish the versatility of this system and (2) the
side the cavitand, filling space within the crystalline lattice. end product, the resulting tetrafunctionalized cavitand,
The presence of an alkyl group inside the cavity is akin to should have obvious applications and utility in host–guest
what has been observed in other cavitand structures, where chemistry.
Scheme 2. Synthetic route to tetraboronic pinacolyl ester cavitand 2. Reagents and conditions: (a) Pd2(dba)3, Ag2CO3, PPh3, THF, r.t.,
dark, 72 h.
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Versatile Launch Pad for Facile Functionalization of Cavitands
We chose 4-iodoanisole as a representative of arenes tion of a variety of homo- and heterocavitand metal
bearing an electron-donating group. The targeted product, cages.[7d,20] Using the coupling protocol outlined for the
tetra-4-methoxyphenyl cavitand, is – upon deprotection – synthesis of 3, we were successful in tetracoupling 4-iodo-
an important precursor for the construction of heteromeric benzonitrile to precursor 2 (Scheme 2, 4).
capsules.[17] Consequently, 2 was allowed to react at room
Cavitands bearing heterocyclic moieties on the upper-rim
temperature with 4-iodoanisole (5 equiv.), Pd2(dba)3 as a are of great interest in the assembly of noncovalent cap-
catalyst, Ag2CO3 as a base, and PPh3 as a ligand in THF sules,[17] as multidentate ligands for coordination complex-
(18 m) to give the tetra-4-methoxyphenyl cavitand es,[7d] and as well in systematic co-crystal studies.[14,21] We
(Scheme 2, 3).[18,19]
therefore treated 2 with 4-iodopyridine to yield the desired
1
The H NMR spectrum of 3 clearly shows that only the tetrapyridyl cavitand 5 (Scheme 2).
desired tetra-4-methoxyphenyl cavitand product is formed
Finally, we wanted to determine if this platform could
with no unreacted starting material present (Figure 2).
display chemoselective coupling to arenes bearing both
iodo and bromo substituents. We chose 3-bromo-5-iodo-
pyridine as a representative substrate because the desired
tetrafunctionalized product would have active nitrogen
atoms capable of forming coordination cages with metals
and could be used to assemble noncovalent capsules (bulky
bromide group at the 3-position should aid pyridyl nitrogen
atoms to orient upward, facilitating capsule formation).
Using our coupling protocol with 2 and 3-bromo-5-iodo-
pyridine, we achieved complete selective cross-coupling at
the iodo substituent, and no reaction was observed with the
bromo functional group, yielding desired tetra(3-bromo-
pyridyl)cavitand 6 (Scheme 2).
Conclusions
Figure 2. Partial 1H NMR spectrum (CDCl3) of cavitand 3 (δ =
3.8 to 8 ppm region). Magnified region shown for corresponding
bridging protons of 3.
We have described the design, synthesis, and structural
characterization of a tetraboronic pinacolyl ester cavitand
that can be prepared in good yields. High-yielding Suzuki–
Miyaura coupling reactions of 2 to iodoarenes covering a
range of functional groups shows the robustness and versa-
tility of this tetraboronic ester cavitand, making it a “launch
pad” for the synthesis of many new cavitands in a facile
manner. The presented coupling protocol of 2 has many
advantages compared to conventional routes, such as no
byproduct formation, no need of tedious chromatographic
separation, and highly improved economical efficiency due
to the need of fewer equivalents of inexpensive iodoarenes
compared to their expensive boronic acid/ester counterparts
(which also need to be used in 8–10-fold excess). It is also
notable that so far no examples of cavitand cross-coupling
with successful chemoselectivity have been reported, which
opens new avenues for designing and synthesizing macro-
cycles. The depth and electronic nature of the interior of
the cavitand can be readily altered through the suitable
choice of haloarene, and new molecular capsules can also
be envisioned in a straightforward manner.
Furthermore, we have characterized product 3 by high-
resolution TOF (time of flight) mass spectrometry (Fig-
ure 3), and we only observed the molecular ion peaks corre-
sponding to the desired product.
Figure 3. High-resolution TOF mass spectrum of 3 showing molec-
ular ion peaks corresponding to [M + H]+ (m/z = 1241.6) and [M
+ NH4]+ (m/z = 1258.6).
Experimental Section
C-Pentyltetraboronic Acid Dipinacolyl Ester (2): C-Pentyltetra-
bromocavitand 1 (1.00 g, 0.883 mmol) was dissolved in dry tetra-
hydrofuran (10 mL), and then the solution was evaporated and
dried at 100 °C (0.1 Torr) for 2 h under an argon atmosphere. This
procedure was repeated twice. The resulting cavitand was dissolved
Our next goal was to couple 2 to an iodoarene bearing
an electron-withdrawing group. We chose 4-iodobenzo-
nitrile as a haloarene because the target product, tetra-4-
cyanophenyl cavitand 4, can be employed in the construc- in dry tetrahydrofuran (70 mL) and cooled to –78 °C (dry ice/acet-
Eur. J. Org. Chem. 2011, 6789–6793
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C. B. Aakeröy, P. D. Chopade, N. Schultheiss, J. Desper
FULL PAPER
one bath) under a dinitrogen atmosphere. To this solution was
added n-butyllithium (1.6 m in hexanes, 2.54 mL, 4.06 mmol) drop-
wise over 10 min, and the mixture was stirred for an additional 0.5
(m, 24 H), 0.97 (t, J = 8 Hz, 12 H) ppm. 13C NMR (400 MHz,
CDCl3): δ = 152.25, 138.59, 131.70, 130.80, 127.69, 120.86, 118.52,
111.27, 100.43, 37.06, 31.98, 27.59, 22.67, 14.12 ppm. IR: ν = 2925,
˜
h. Trimethoxyborane (0.60 mL, 5.3 mmol) was added dropwise 2226, 1608, 1447, 1157, 1082, 971, 839, 805, 740, 692 cm–1. MS
over 10 min, and the resulting solution was stirred at –78 °C for
0.5 h, at which time the dry ice/acetone bath was removed, and the
reaction mixture was allowed to reach room temperature. Upon
reaching room temperature, the mixture was quenched with a 1 m
hydrochloric acid solution (100 mL) and stirred for 0.5 h. The mix-
ture was extracted with dichloromethane (3ϫ100 mL), and the or-
ganic portions were collected and dried with magnesium sulfate.
The solvent was removed under reduced pressure, and the resulting
residue was dissolved in dichloromethane (100 mL). Excess
amounts of pinacol (750 mg, 6.30 mmol) and magnesium sulfate
(2.25 g) were added to the mixture, which was stirred for 12 h and
then filtered and dried via a rotary evaporator. The residue was
dissolved in dichloromethane and added to a beaker of acetone,
which was left on the rotary evaporator until the dichloromethane
was completely removed; precipitation of the product was induced
by using acetone and the product was filtered off resulting in pure
product 1 (570 mg, 50%). The product can be recrystallized from
dichloromethane/ethyl acetate/hexane (1:1:1). M.p. Ͼ280 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.10 (s, 4 H), 5.59 (d, J = 6.8 Hz, 4
H), 4.75 (t, J = 7.2 Hz, 4 H), 4.54 (d, J = 7.6 Hz, 4 H), 2.17–2.15
(m, 8 H), 1.40–1.29 (m, 72 H), 0.90–0.88 (m, 12 H) ppm. 13C NMR
(200 MHz, CDCl3): δ = 157.72, 137.77, 122.37, 99.42, 83.53, 36.11,
(ESI-TOF): m/z = 1265.5 [M + CH2O2 – H]+.
5: This compound was synthesized by using the general coupling
procedure with 4-iodopyridine as iodoarene. The crude product
was purified by column chromatography (100 g of silica; ethyl acet-
ate/ethanol, 1:1 + 3% triethylamine) to give 5 (63 mg, 74%). M.p.
1
Ͼ280 °C. H NMR (400 MHz, CDCl3): δ = 8.59 (d, J = 6.0 Hz, 8
H), 7.37 (s, 4 H), 6.98 (d, J = 6 Hz, 8 H), 5.29 (d, J = 6 Hz, 4 H),
4.84 (t, J = 8 Hz, 4 H), 4.23 (d, J = 8.0 Hz, 4 H), 2.34 (m, 8 H),
1.46 (m, 24 H), 0.96 (t, J = 7 Hz, 12 H) ppm. 13C NMR (400 MHz,
CDCl3): δ = 152.17, 149.46, 142.02, 138.00, 126.83, 124.91, 120.85,
100.39, 43.23, 37.01, 31.99, 30.24, 27.58, 22.68, 14.14 ppm. IR: ν =
˜
2929, 2859, 1583, 1450, 1408, 1160, 1084, 975, 716 cm–1. MS (ESI-
TOF): m/z = 1125.5 [M + H]+.
6: This compound was synthesized by using the general coupling
procedure with 3-bromo-5-iodopyridine as iodoarene. The crude
product was purified by column chromatography (100 g of silica;
ethyl acetate/ethanol, 8:2) to give 6 (84 mg, 77%). M.p. Ͼ280 °C.
1H NMR (400 MHz, CDCl3): δ = 8.59 (d, J = 2.0 Hz, 4 H), 8.14
(s, 4 H), 7.62 (t, J = 2 Hz, 4 H), 7.37 (s, 4 H), 5.38 (d, J = 8 Hz, 4
H), 4.83 (t, J = 8 Hz, 4 H), 4.21 (d, J = 4.0 Hz, 4 H), 2.34 (m, 8
H), 1.46 (m, 24 H), 0.96 (t, J = 6 Hz, 12 H) ppm. 13C NMR
(400 MHz, CDCl3): δ = 152.53, 149.59, 147.88, 140.28, 138.56,
130.93, 124.48, 121.05, 37.03, 31.97, 30.21, 27.57, 22.67, 14.12 ppm.
31.91, 30.89, 29.88, 27.54, 24.70, 22.65, 14.02 ppm. IR: ν = 2977,
˜
2931, 1705, 1592, 1442, 1358, 1316, 1145, 978, 851, 582 cm–1. MS
(MALDI-TOF/TOF): m/z = 1343.75 [2 + Na]+. C76H108B4O16
(1320.91): calcd. C 69.11, H 8.24; found C 69.24 H 8.44.
IR: ν = 2921, 2850, 1583, 1459, 1400, 1299, 1259, 1177, 1080, 1013,
˜
970, 732 cm–1. MS (ESI-TOF): m/z = 1441.3 [M + H]+.
Supporting Information (see footnote on the first page of this arti-
cle): Detailed experimental procedures and characterization of
compounds 2–5 along with crystallographic data for 2 (CCDC-
647956 contains the supplementary crystallographic data for this
paper; these data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif).
General Procedure for the Coupling Reaction: An oven-dried round-
bottom flask was placed under an argon atmosphere and charged
with 1 (100 mg; 75.7 μmol), iodoarene (378 μmol, 5 mol equiv.), sil-
ver carbonate (608 μmol, 8.0 mol equiv.), tris(dibenzylideneacet-
one)dipalladium(0) (36 μmol, 0.12 mol equiv.), and triphenylphos-
phane (151 μmol, 2 mol equiv.). The flask was evacuated and re-
filled with dinitrogen three times then dry tetrahydrofuran (5 mL)
was added. The reaction mixture was stirred at room temperature
in the dark for 72 h then filtered through a short plug of Celite,
washed with chloroform (3ϫ), and the solvent was evaporated to
afford the crude product, which was purified by column
chromatography (SiO2).
Acknowledgments
We are grateful for the financial support of the National Science
Foundation (NSF) (CHE-0957607) and the Johnson Center of Ba-
sic Cancer Research.
3: This compound was synthesized by using the general coupling
procedure with 4-iodoanisole as iodoarene. The crude product was
purified by column chromatography (100 g of silica; hexane/ethyl
acetate, 10:0 Ǟ 8:2) to give 3 (73 mg, 78%). M.p. Ͼ280 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.32 (s, 4 H), 6.76 (d, J = 8 Hz, 8
H), 6.59 (d, J = 8 Hz, 8 H), 5.03 (d, J = 4 Hz, 4 H), 4.88 (t, J =
8 Hz, 4 H), 4.10 (d, J = 4 Hz, 4 H),3.00 (br. s, 8 H), 2.40–2.33 (m,
8 H), 1.50–1.38 (m, 24 H), 0.97 (t, J = 8 Hz, 12 H) ppm. 13C NMR
(400 MHz, CDCl3): δ = 158.26, 152.84, 138.46, 130.90, 129.73,
125.84, 119.48, 113.15, 99.88, 75.03, 37.12, 32.03, 27.63, 24.81,
[1] a) J. Tsuji, Palladium Reagents and Catalysts, New Perspectives
for the 21st Century, Wiley, 2004; b) J. Tsuji, Transition Metal
Reagents and Catalysts: Innovations in Organic Synthesis,
Wiley, 2002; c) J. J. Li, G. W. Gribble, Palladium in Heterocyclic
Chemistry: A Guide for the Synthetic Chemist, Pergamon, 2000;
d) J. C. Fiaud, J.-L. Malleron, J. Y. Legros, Handbook of Palla-
dium-Catalyzed Organic Reactions, Academic Press, 1997; e) A.
Suzuki, Metal-Catalyzed Cross-Coupling Reactions (Eds.: F.
Diederich, P. J. Stang), Wiley-VCH, Weinheim, Germany, 1998,
ch. 2.
22.71, 14.17 ppm. IR: ν = 3403, 2927, 1611, 1514, 1447, 1244, 1156,
˜
1110, 1018, 973, 949, 827, 805, 673 cm–1. MS (ESI-TOF): m/z =
[2] a) J.-P. Corbet, G. Mignani, Chem. Rev. 2006, 106, 2651; b) L.
1241.6 [M + H]+, 1258.6 [M + NH4]+.
Lin, J. Liebscher, Chem. Rev. 2007, 1, 133.
[3] F.-X. Felpin, T. Ayad, S. Mitra, Eur. J. Org. Chem. 2006, 2679.
[4] a) N. K. Garg, R. Sarpong, B. Stoltz, J. Am. Chem. Soc. 2002,
124, 13179; b) C.-G. Yang, G. Liu, B. Jiang, J. Org. Chem.
2002, 67, 9392; c) D. J. Yoo, Y. H. Jeon, D. W. Kim, G. S. Han,
S. Shim, Bull. Korean Chem. Soc. 1995, 16, 1212; d) K. Jones,
M. Keenan, F. Hibert, Synlett 1996, 509; e) D. L. Boger, S. H.
Miyazaki, S. H. Kim, J. H. Wu, S. L. Castle, O. Loiseleur, Q.
Jin, J. Am. Chem. Soc. 1999, 121, 10004.
4: This compound was synthesized by using the general coupling
procedure with 4-iodobenzonitrile as iodoarene. The crude product
was purified by column chromatography (100 g of silica; chloro-
1
form/ethyl acetate, 8:2) to give 4 (69 mg, 75%). M.p. Ͼ280 °C. H
NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 8 Hz 8 H), 7.38 (s, 4
H), 7.17 (d, J = 8 Hz, 8 H), 5.25 (d, J = 8 Hz, 4 H), 4.83 (t, J =
8 Hz, 4 H), 4.20 (d, J = 4 Hz, 4 H), 2.40–2.33 (m, 8 H), 1.50–1.38
6792
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Versatile Launch Pad for Facile Functionalization of Cavitands
[5] a) C.-Y. Chen, P. Dagneau, E. J. J. Grabowski, R. Oballa, P.
O’Shea, P. Prasit, J. Robichaud, R. Tillyer, X. Wang, J. Org.
Chem. 2003, 68, 2633; b) Y. Urawa, H. Naka, M. Miyazawa,
S. Souda, K. Ogura, J. Organomet. Chem. 2002, 653, 269; c)
G. B. Smith, G. C. Dezeny, D. L. Hughes, A. O. King, T. R.
Verhoeven, J. Org. Chem. 1994, 59, 8151.
Sheldrick, SHELXL-97, Program for Refinement of Crystal
Structures, University of Göttingen, Germany, 1997. Crystal
data for 2: C76H108O16B4·2C6H14, M = 1493.21 amu, mono-
clinic, P21/n, a = 15.0290(12) Å, b = 21.2864(17) Å, c =
28.579(2) Å,
α
=
Z
90°, 102.322(5)°,
β
=
γ
=
90°,
V
=
=
8932.2(13) Å3,
=
4, Dc =
1.110 gcm–3, μ(Mo-Kα)
[6] a) Z. Bo, A. Schafer, P. Franke, A. D. Schluter, Org. Lett. 2000,
2, 1645; b) T. Hadizad, J. Zhang, Z. Y. Wang, T. C. Gorjanc,
C. Py, Org. Lett. 2005, 7, 795; c) Y. Jiang, J.-Y. Wang, Y. Ma,
Y.-X. Cui, Q.-F. Zhou, J. Pei, Org. Lett. 2006, 8, 4287.
[7] a) C. B. Aakeröy, N. Schultheiss, J. Desper, Org. Lett. 2006, 8,
2607; b) C. B. Aakeröy, P. D. Chopade, Org. Lett. 2011, 13, 1;
c) M. Yamanaka, K. Ishii, Y. Yamada, K. Kobayashi, J. Org.
Chem. 2006, 71, 8800; d) K. Kobayashi, Y. Yamada, M. Yam-
anaka, Y. Sei, K. Yamaguchi, J. Am. Chem. Soc. 2004, 126,
13896; e) T. Haino, M. Kobayashi, M. Chikaraishi, Y. Fukaz-
awa, Chem. Commun. 2005, 2321; f) C. von dem Bussche-
Hünnefeld, R. C. Helgeson, D. Bühring, C. B. Knobler, D. J.
Cram, Croat. Chem. Acta 1996, 68, 447; g) S. Ma, D. M. Rud-
kevich, J. Rebek Jr., J. Am. Chem. Soc. 1998, 120, 4977; h) D. J.
Sinclair, M. S. Sherburn, J. Org. Chem. 2005, 70, 3730; i) O.
Hass, A. Schierholt, M. Jordan, A. Lützen, Synthesis 2006, 3,
519; j) C. Ihm, K. Paek, Tetrahedron Lett. 2007, 48, 3263; k)
L. Sebo, F. Diederich, V. Gramlich, Helv. Chim. Acta 2000, 83,
93; for tetraboronic acid cavitand coupling, see: l) K. Kobaya-
shi, K. Ishii, S. Sakamoto, T. Shirasaka, K. Yamaguchi, J. Am.
Chem. Soc. 2003, 125, 10615.
[8] C. B. Aakeröy, P. D. Chopade, A. Rajbanshi, N. Schultheiss,
unpublished results.
[9] a) J. Spencer, C. B. Baltus, H. Patel, N. J. Press, S. K. Callear,
L. Male, S. J. Coles, ACS Comb. Sci. 2011, 13, 24; b) D. G.
Hall, Boronic Acids-Preparation, Applications in Organic Syn-
thesis and Medicine (Ed.: D. G. Hall), Wiley-VCH, Weinheim,
Germany, 2005, pp. 1–99.
[10] H. Jude, D. J. Sinclair, N. Das, M. S. Sherburn, P. J. Stang, J.
Org. Chem. 2006, 71, 4155.
[11] a) Y. Aoyama, Y. Tanaka, S. Sugahara, J. Am. Chem. Soc.
1989, 111, 2167; b) J. A. Bryant, M. T. Blanda, M. Vincenti,
D. J. Cram, J. Am. Chem. Soc. 1991, 113, 2167.
0.074 mm–1, crystal size 0.40ϫ0.35ϫ0.10 mm. Data were col-
lected at 173 K with a Bruker SMART 1000 diffractometer
using Mo-Kα radiation. A total of 64051 reflections (1.20 Ͻ θ
Ͻ 27.53°) were processed, of which 20283 were independent
and 7465 were observed with I Ͼ 2σ(I). Structure solution and
refinement were carried out using SHELXS-97 and SHELXL-
97. Rint = 0.0970. Final residuals for I Ͼ 2σ(I) was R1 = 0.3080
(GOF = 0.953).
[14]
[15]
C. B. Aakeröy, N. Schultheiss, J. Desper, CrystEngComm 2006,
8, 502.
Z. Zhang, Y. Luo, J. Chen, S. Dong, Y. Yu, Z. Ma, F. Huang,
Angew. Chem. Int. Ed. 2011, 50, 1397.
Images created using Mercury 2.4.
Cavitands with different “feet” than what has been reported in
the current manuscript can be found in the following refer-
ences: a) K. Kobayashi, R. Kitagawa, Y. Yamada, M. Yam-
anaka, T. Suematsu, Y. Sei, K. Yamaguchi, J. Org. Chem. 2007,
72, 3242; b) H. Kitagawa, Y. Kobori, M. Yamanaka, K. Yoza,
K. Kobayashi, Proc. Natl. Acad. Sci. USA 2009, 106, 10444.
[16]
[17]
[18] From the 1H NMR spectrum and low-resolution mass spec-
trum of the crude product, only tetrafunctionalized cavitand as
a product was observed. Silver carbonate as a base is necessary
for optimum yield.
[19] Reaction conditions were modified from those reported for the
coupling reaction that was done on a monoboronic ester cavit-
and with different iodoarenes: T. V. Nguyen, D. V. Sinclair,
A. C. Willis, M. S. Sherburn, Chem. Eur. J. 2009, 15, 5892.
[20] a) L. Pirondini, F. Bertolini, B. Cantadori, F. Ugozzoli, C.
Massera, E. Dalcanale, Proc. Natl. Acad. Sci. USA 2002, 99,
4911; b) N. Cuminetti, M. H. K. Ebbing, P. Prados, J. Men-
doza, E. Dalcanale, Tetrahedron Lett. 2001, 42, 527.
[21] C. B. Aakeröy, N. Schultheiss, J. Desper, CrystEngComm 2007,
9, 211.
[12] E. S. Barrett, J. L. Irwin, P. Turner, M. S. Sherburn, J. Org.
Chem. 2001, 66, 8227.
[13] G. M. Sheldrick, SHELXS-97, Program for Solution of Crystal
Structures, University of Göttingen, Germany, 1997. G. M.
Received: July 15, 2011
Published Online: September 23, 2011
Eur. J. Org. Chem. 2011, 6789–6793
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6793