Corannulene ethers via ullmann condensation

Article abstract of DOI:10.1021/ol902352k

Penta-aryloxycorannulene derivatives, which were previously considered difficult synthetic targets, are efficiently achieved via the Cu(I)catalyzed Ullmann condensation reaction between 1,3,5,7,9-pentachlorocorannulene and a broad variety of substituted p

Full text of DOI:10.1021/ol902352k

ORGANIC
LETTERS
2009
Vol. 11, No. 22
5146-5149
Corannulene Ethers via Ullmann
Condensation
Renana Gershoni-Poranne,† Doron Pappo,*,† Ephrath Solel,† and Ehud Keinan*,†,‡
Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Technion City,
Haifa 32000, Israel, and Department of Molecular Biology and the Skaggs Institute for
Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road,
La Jolla, California 92037
keinan@technion.ac.il; pappod@technion.ac.il
Received July 26, 2009
ABSTRACT
Penta-aryloxycorannulene derivatives, which were previously considered difficult synthetic targets, are efficiently achieved via the Cu(I)-
catalyzed Ullmann condensation reaction between 1,3,5,7,9-pentachlorocorannulene and a broad variety of substituted phenols. The reaction
proceeds under air and mild conditions that are compatible even with 4-bromophenol. These findings open new avenues for easy preparation
of other symmetrically substituted pentagonal building blocks that can be used for the preparation of new materials and new supramolecular
architectures.
The construction of large molecular and supramolecular
architectures of pentagonal symmetry is a nontrivial task due
to the scarcity of C5-symmetrical organic molecules, unlike
those having C2, C3, C4, and C6 symmetries.1 The few known
pentagonal compounds include mainly conformationally
flexible macrocycles, such as calix[5]arenes,2 calix[5]furans,
calix[5]pyrroles,3 crown ethers, and aza-crown ethers,4 as
well as a few conformationally rigid molecules.5 In contrast,
pentagonal symmetry is quite abundant in the realm of
inorganic materials and metal coordination complexes6 and
in natural biomolecules, such as protein pentameric structures
and DNA.7
This background renders the corannulene molecule,8 which
is characterized by a C5-symmetrical bowl shape and rigid
polycyclic aromatic nature, a unique building block. Periph-
eral functionalization of this molecule can lead to large
molecular9 and supramolecular architectures having 5-fold
symmetry, including quasicrystals,10 discotic liquid crystals,11
chemical capsids,12 pentagonal dendrimers,13,14 single-wall
nanotubes,15 light emitters,16 and helical foldamers.17
† Technion-Israel Institute of Technology.
‡ The Scripps Research Institute.
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10.1021/ol902352k CCC: $40.75
Published on Web 10/20/2009
 2009 American Chemical Society

For example, 12 pentagonal tiles equipped with “sticky
edges” are required to construct a nonprotein molecular
capsid. Such tiles can form a molecular capsule of icosahe-
dral symmetry via self-assembly.12 To meet this synthetic
challenge, we have recently developed a general method for
the cross-coupling of 1,3,5,7,9-pentachlorocorannulene, 1,
with aryl and heteroaryl boronic acids to produce pentaaryl-
corannulenes, 2 (Scheme 1). This approach has also yielded
solubility in most solvents, we envisioned that the corre-
sponding pentaethers, 3-7, would be much more soluble
and easier to manipulate in organic solvents.
An obvious approach to the formation of corannulene
pentaethers was the direct substitution of 1 by alkoxide
nucleophiles. Unfortunately, unlike substitution by thiolate
anions,18 the reaction with phenolate and alkoxide anions,
which are less reactive nucleophiles, requires quite harsh
conditions. For example, sym-pentakis(1,4,7-trioxaoctyl)-
corannulene, which is the only reported pentaalkoxycoran-
nulene thus far, was achieved by heating a solution of 1 with
sodium diethyleneglycolate monomethyl ether at 180 °C for
2 days.18,19 Our efforts to prepare compound 3 from 1 under
similar conditions using 4-methoxyphenol with either NaH
or K2CO3 (DMF, 110 °C) afforded low yields of complex
mixtures of partially substituted corannulene derivatives.
Scheme 1
In principle, the copper-catalyzed arylation of nucleophiles
(Ullmann condensation) could solve this problem because
the method has been widely used for the formation of
C(aryl)-N, C(aryl)-C, and C(aryl)-O bonds.20a Further-
more, the special effect of bidentate N,N- and N,O- ligands
on this reaction, which was discovered by Buchwald, has
extended the synthetic scope and has allowed for substitution
of aryl halides by phenols under mild conditions.20 Unfor-
tunately, the reaction was reported to be limited to aryl
iodides and bromides and did not work well with aryl
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Org. Lett., Vol. 11, No. 22, 2009
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chlorides except for rare cases of highly electron-deficient
substrates.21
rides,21,22 the high efficiency of the coupling between 1 and
various phenols was quite surprising. Furthermore, one would
expect that achieving penta-substitution under mild condi-
tions would become increasingly difficult with the growing
number of electron-donating substituents on the corannulene
core. Increased electron density could diminish the reactivity
of the remaining chloride groups.
Here we report that the synthesis of various pentaaryloxy-
corannulene derivatives can be achieved with high efficiency
via the Cu(I)-catalyzed Ullmann condensation reaction under
mild conditions that are compatible even with 4-chlorophenol
and 4-bromophenol.
A typical procedure for this reaction22 (Scheme 1) involves
mixing 1 (0.1 mmol) in DMF (2 mL) together with the
appropriate phenol (1 mmol, 10 equiv), CuI (0.03 mmol, 6%
per site), 1,10-phenanthroline (0.06 mmol, 12% per site), and
Cs2CO3 (1.2 mmol, 12 equiv). The mixture is stirred at 100
°C for 24-72 h, then cooled to room temperature, diluted
with dichloromethane, and washed with aqueous NaOH, then
with H2SO4, water, and brine. Removal of the solvent affords
an orange-brown solid that can be purified either by
chromatography or by recrystallization. For example, the
reaction with 4-methoxyphenol affords, after purification,
1,3,5,7,9-pentakis(4-methoxyphenoxy)corannulene, 3, in 83%
yield. Considering the five reactive sites on the molecule,
this overall yield reflects over 96% yield per site, which is
quite remarkable for this type of nontrivial coupling. It is
noteworthy that the reaction can be performed under air with
no need for inert atmosphere.
Under these reaction conditions we have prepared a variety
of pentaaryloxycorannulene derivatives, 3-9, in satisfactory
yields (Scheme 1), thus demonstrating the generality of the
reaction with respect to phenols bearing either electron-
withdrawing (CO2Me, CN) or electron-donating (OMe, tert-
Bu) groups. All products are highly soluble in chlorinated
solvents, such as CH2Cl2 and CHCl3 and partially soluble in
other common organic solvents, including toluene, ethyl
acetate, THF, and DMF. Consequently, most of these
polyethers can be conveniently purified by silica-gel chro-
matography and easily characterized by NMR and MS. More
importantly, unlike our previously described pentaarylcoran-
nulenes, 2, which are quite insoluble in most organic
solvents,13 the high solubility and ready availability of the
pentaaryloxycorannulene derivatives render them excellent
building blocks for pentagonal molecular and supramolecular
architectures.
Our counterintuitive observations could be explained by
the unusual reactivity of 1. It has already been reported that
corannulene chlorides are more reactive than regular chlo-
roaromatic compounds with respect to either nucleophilic
substitution or oxidative addition to electron-rich transition
metals.9b This unique reactivity could be explained by partial
bond fixation in corannulene, which endows the aryl chloride
functions in 1 with significant vinyl chloride character.
Indeed, crystallographic data indicate that the rim double
bond in corannulene is significantly shorter (1.38 Å) than
an average aromatic bond (1.40 Å).23
In line with this enhanced reactivity was our observation
that the copper-catalyzed substitution reaction proceeds in
high chemoselectivity with 4-chlorophenol. The product,
1,3,5,7,9-pentakis(4-chlorophenoxy)corannulene, 10, was
obtained in 65% yield without any byproducts from either
homocoupling of 4-chlorophenol or further reactions of 10
(Scheme 2). Even more remarkable was the chemoselectivity
Scheme 2
The new coupling products were found to be stable
molecules that were easily transformed under straightforward
conditions to other useful derivatives in high yields. For
example, treatment of 4 with excess BBr3 (CH2Cl2, rt, 24 h)
afforded 1,3,5,7,9-pentakis(4-hydroxyphenoxy)corannulene,
8, in 77% yield. The pentaester 7 was hydrolyzed (LiOH,
THF-H2O) to give 1,3,5,7,9-pentakis(4-carboxyphenoxy)-
corannulene, 9, in 96% yield.
Of particular interest for synthetic applications is the
remarkable scope of this transformation. Since it is com-
monly known that the copper(I)-catalyzed Ullmann conden-
sation reaction between phenols and aryl halides works well
with aryl iodides and bromides but not with aryl chlo-
observed with 4-bromophenol, which produced 1,3,5,7,9-
pentakis(4-bromophenoxy)corannulene, 11, in 54% yield.
The reaction conditions were found to be compatible with
other sensitive functional groups, such as the free aldehyde
in 4-hydroxybenzaldehyde, leading to 1,3,5,7,9-pentakis(4-
formylphenoxy)corannulene, 12, although in low yields
(Scheme 2). Nevertheless, higher yields of 12 were achieved
by adopting a two-step procedure: first coupling of 1 with
4-(1,3-dioxan-2-yl)phenol to produce 1,3,5,7,9-pentakis[4-
(1,3-dioxan-2-yl)phenoxy]corannulene, 13, and then acid-
catalyzed hydrolysis (TFA, CH2Cl2-H2O, rt, 16 h) to
produce 12 in 63% overall yield from 1.
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5148
Org. Lett., Vol. 11, No. 22, 2009

Figure 1. Structure of corannulene ethers 14-17.
Further synthetic opportunities were explored with more
sterically demanding phenols (Figure 1). However, with the
highly sterically hindered R-naphthol the penta-substituted
product, 14, was obtained in 17% yield along with larger
amounts of the tetrasubstituted product, 1-chloro-3,5,7,9-
tetrakis(1-naphthoxy)corannulene, 15, which was isolated in
25% yield.24 The difficult substitution of the fifth position
under our standard reaction conditions, and even when heated
to 120 °C, can be understood in terms of steric shielding of
the chloride atom in 15 by the two adjacent naphthalene
groups. Coupling of phloroglucinol dimethyl ether with 1
afforded 1,3,5,7,9-pentakis(3,5-dimethoxyphenoxy)corannu-
lene, 16, in 28% yield. Compound 17 was isolated in
relatively low yield (17%) due to partial decomposition upon
purification by silica-gel chromatography.
that were previously considered difficult synthetic targets,
thus setting the stage for the design and preparation of new
materials and new supramolecular architectures on the basis
of pentagonal building blocks. Various relevant applications
are currently being investigated in our laboratories, including
pentagonal discotic liquid crystals,11a pentagonal dendrim-
ers,13 potential binders of fullerenes,19d,25 and molecular
capsules.
Acknowledgment. This study was supported by the Israel
Science Foundation, the German-Israeli Project Cooperation
(DIP), the Institute of Catalysis Science and Technology,
Technion, and the Skaggs Institute for Chemical Biology.
E.K. is the incumbent of the Benno Gitter & Ilana Ben-Ami
Chair of Biotechnology, Technion.
In conclusion, this study has paved the way to a new class
of pentaaryloxycorannulene derivatives, made readily avail-
able in good yields via the Ullmann condensation reaction
between 1 and a broad variety of substituted phenols. The
reaction can be performed under air with a catalyst loading
of 6% per site.
Supporting Information Available: General experimental
procedures for the syntheses of compounds 3-17 and
selected 1H NMR, 13C NMR, and UV spectra of compounds
3-17. This material is available free of charge via the
Internet at http://pubs.acs.org.
The discovery that 1 is a reactive partner in the copper-
catalyzed Ullmann condensation reactions opens new av-
enues for easy preparation of other corannulene derivatives
OL902352K
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(24) While the five identical corannulene protons in 14 resonate at 7.09
ppm, the inequivalent protons in 15 resonate at 7.88, 7.18, 7.16, 7.11, and
7.08 ppm.
Synlett 2004, 173
.
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