One-pot regioselective synthesis and X-ray crystal structure of a stable [60]fullerene trisadduct with the eedge,eface,trans-1 addition pattern

Article abstract of DOI:10.1039/c1cc15596b

The Bingel functionalisation of C₆₀ with a structurally novel tether equipped with three reactive malonate groups afforded a C _2v-symmetrical e_edge,e_face,trans-1 trisadduct in a complete regioselective manner an

Full text of DOI:10.1039/c1cc15596b

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COMMUNICATION
One-pot regioselective synthesis and X-ray crystal structure of a stable
[60]fullerene trisadduct with the eedge,eface,trans-1 addition patternw
Maria Riala, Marios S. Markoulides, Eleni E. Moushi and Nikos Chronakis*
Received 9th September 2011, Accepted 22nd September 2011
DOI: 10.1039/c1cc15596b
The Bingel functionalisation of C60 with a structurally novel
tether equipped with three reactive malonate groups afforded a
C2v-symmetrical eedge,eface,trans-1 trisadduct in a complete
regioselective manner and in an excellent yield of 65%. The
[60]fullerene trisadduct showed pronounced ability to crystallise
and gave X-ray quality single crystals for analysis.
The regioselective functionalisation of the most abundant fullerene,
the Ih-symmetrical [60]fullerene, has led to tremendous research
activity focused on the development of methods able to control
bis- to hexa-additions at specific double bonds.1 The tether-directed
remote functionalisation method2 is a sophisticated and powerful
approach which has been applied successfully for the regioselective
Scheme 1 Synthesis of the topological isomers of the e,e,trans-1
functionalisation of C60. To access three-dimensional fullerene
trisadduct of C60 by (a) Diederich8 and (b) Rubin.10
architectures, absolute control of the regioselectivity of tris-
additions on the spherical fullerene carbon network is needed,
has been reported before but required multiple synthetic steps
and chromatographic separations. Specifically, Diederich et al.8
since compared with bis-additions on C60 the number of the
possible trisadducts is dramatically increasing. As such, the design
developed a reversible tether-directed remote functionalisation
of appropriate tethers becomes a more demanding task. The
strategy which yielded the
eedge,eface,trans-1 trisadduct
synthesis of trisadducts of C60 by stepwise Bingel nucleophilic
cyclopropanations followed by separation with the aid of prepara-
tive HPLC was firstly reported by Hirsch et al.3 More recently,
tethered reagents equipped with the reactive malonate groups were
successfully employed to afford mainly C3-symmetrical trisadducts
which were isolated by simple column chromatography.4
[Scheme 1(a)]. In the first step, the e,e,trans-1 was prepared by
functionalising C60 via a Bingel and a double Diels–Alder
reaction with an appropriate tether. The formed trisadduct is
sensitive to singlet oxygen (1O2) photo-oxidation of the cyclo-
hexene moieties and thus, unstable when exposed to light and air.
Two of the three remaining equatorial double bonds were then
cyclopropanated by malonate esters, the cyclohexene rings were
removed following a protocol based on their reactivity with 1O2
Among the 46 possible trisadducts of C60 (excluding the
ones having a cis-1 position relationship), we targeted the
e,e,trans-1 for the following reasons: (a) this addition pattern
cannot be accessed by stepwise Bingel cyclopropanations on
C60,5 (b) the e,e,trans-1 trisadduct is a synthetically valuable
precursor for the synthesis of mixed [3 : 3] hexakisadducts6
with different types of addends located at octahedral sites. By
varying the nature or the hydrophobic/hydrophilic character
of the different organic addends, globular dendrimers, lipo-
fullerenes and novel functional materials were synthesized and
studied,7 and (c) the synthesis of the e,e,trans-1 trisadduct of C60
and finally, a transesterification reaction furnished the eedge
face,trans-1 topological isomer.9
Rubin and Qian10 followed a different approach by synthesizing
,
e
a trans-1 bisadduct of C60 via a double Diels–Alder reaction
using a tethered bisdiene [Scheme 1(b)]. Sequential bromomalonate
addition on the three reactive equatorial double bonds of C60
followed by removal of the masking tether afforded the
e
face,eedge,trans-1 topological isomer.9 In both examples, the
tethers served as protecting groups assisting the regioselective
stepwise addition of the malonates at the remaining equatorial
bonds of C60.
Department of Chemistry, University of Cyprus, P. O. Box 20537,
1678 Nicosia, Cyprus. E-mail: nchronak@ucy.ac.cy;
Fax: +357 22892801; Tel: +357 22892781
w Electronic supplementary information (ESI) available: Experimental
section and spectroscopic data. CCDC 843535 and 843536. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c1cc15596b
To the best of our knowledge, a one-pot synthesis of a stable
e,e,trans-1 trisadduct of C60 via a three-fold Bingel reaction
has not been reported in the literature. With this in mind, we
designed the structurally new tether 8 (Scheme 2) bearing three
malonate groups incorporated in a well preorganised molecular
c
11948 Chem. Commun., 2011, 47, 11948–11950
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Scheme 2 Synthesis of tethers 7 and 8. (i) Methyl malonyl chloride, DCM, pyridine, 0 1C for 2 h then rt for 12 h, 99%. (ii) Malonyl dichloride,
DCM, pyridine, 0 1C for 2 h then rt for 12 h, 50%.
system comprised of two crown ether type macrocycles.
Additionally, to test the regioselectivity of bis-additions
on C60, the corresponding bismalonate tether 7 was designed
featuring the same structural characteristics with tether 8. The
synthesis of tethers 7 and 8 is described in Scheme 2
(for experimental details and characterisation data see ESIw).
2-Bromoethanol was protected as a TBDMS ether and subjected
to a two-fold Williamson etherification with 3,5-dihydroxy-
benzyl alcohol to afford the benzyl alcohol 2. Protection of the
hydroxyl group with DHP followed by the selective deprotection
of the silyl ethers furnished diol 4 in good yield. To incorporate
the malonate moiety in a macrocycle we attempted the cyclisation
of diol 4 with malonyl dichloride under high dilution
conditions.11 In the absence of alkali metal cations, as templates,
the desired cyclised product 5 was not detected in the reaction
mixture. Consequently, we tested the esterification reaction by
using Li+, Na+ and K+ as templates, in the form of their
Scheme 3 Synthesis of the equatorial bisadduct 9 and the eedge
,
eface,trans-1 trisadduct 10.
LiBF4, NaBF4, KPF6 and KBF4 salts. The highest yield of the
12
product (7%) was obtained when KBF4 was used, while
NaBF4 and KPF6 led to the formation of 5 in about 5%
isolated yield. The utilisation of the LiBF4 salt furnished 5 in
only 1% isolated yield. Worthy of note was that despite using
the templated synthesis, the employment of high dilution
conditions was necessary. In the next step, 5 was deprotected
under mild acidic conditions to afford successfully the benzylic
alcohol 6 which is the key intermediate to access the designed
tethers. In separate experiments, methyl malonyl chloride and
malonyl dichloride were reacted with 6, in DCM solvent
and using pyridine as a base. Tethers 7 and 8 were isolated by
flash column chromatography and their structures were
unambiguously assigned by 1H and 13C NMR spectroscopy
and by mass spectrometry (see ESIw).
and fully characterised. The obtained spectroscopic data
(see ESIw) were in full agreement with the equatorial addition
pattern and unambiguously supported the Cs-symmetrical structure
of 9 which was isolated in 68% yield.
In the next step, the one-pot, three-fold Bingel cyclopropanation
of C60 with the tether 8 was investigated. The reaction was carried
out in a mixture of toluene/DCM as a solvent, in the presence of I2
and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (Scheme 3). TLC
monitoring revealed the formation of a single fullerene adduct
which was isolated by flash column chromatography (SiO2,
toluene/EtOAc, 7 : 3). The MALDI-TOF mass spectra (negative
mode) of the purified product showed the [M + 2K]À molecular
ion at 1453.0534 m/z confirming that the three-fold Bingel
cyclopropanation of C60 was successful and led to the formation
of a trisadduct. Its UV-VIS spectrum was identical with the one
reported by Diederich et al.,8 thus supporting the eedge,eface,trans-1
addition pattern for trisadduct 10.
The remote functionalisation of C60 with tether 7 was
performed under the Bingel experimental conditions, in a
toluene/DCM solvent mixture. The use of DCM was necessary
as 7 is not soluble in pure toluene. Tether 7 reacted cleanly with
C60 to afford completely regioselectively the equatorial bisadduct
Furthermore, in the 13C NMR spectrum of 10 (Fig. 1), 14
signals for the sp2 carbons of the fullerene skeleton were
9 (Scheme 3) that was purified by flash column chromatography
c
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Chem. Commun., 2011, 47, 11948–11950 11949

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and the fullerene skeleton, equipped with oxygen atoms and
aromatic rings. Furthermore, the designed tethers enhance the
crystallisability of fullerene adducts and this might be useful
for the functionalisation of higher fullerenes where the assignment
of the addition patterns is difficult by NMR spectroscopy.
To the best of our knowledge, there is no X-ray crystal
structure of a C60 bisadduct with the equatorial addition
pattern, while one crystal structure of a C60 trisadduct synthesised
by a stepwise Diels–Alder cycloaddition of 9,10-dimethylanthracene
with C60 has been reported in the literature.13
This work was financially supported by the Cyprus
Research Promotion Foundation (Grant NEKYP/0308/02).
We also thank Mr Vasilios Sordakis for performing preliminary
experiments on the synthesis of tethers 7 and 8.
Fig. 1 13C NMR spectra (125 MHz, C2D4Cl2) of the eedge
face,trans-1 trisadduct 10 in the region 139–166 ppm.
,
e
observed in the region between 139 and 148 ppm clearly
indicating a C2v-symmetrical structure. This was further
confirmed by the presence of two signals at 161.98, 164.77 ppm
corresponding to the carbonyl carbons, one signal for the meta
aromatic carbons at 160.15 ppm, three distinct peaks at 68.53,
70.66 and 72.27 ppm characteristic for the fullerene sp3
carbons and two absorptions at 46.73 and 53.27 ppm attributed
to the bridgehead sp3 carbon atoms (for detailed spectroscopic
data see ESIw). Finally, trisadduct 10 was isolated in an
excellent yield of 65% which demonstrated the perfect match
of tether 8 with the targeted e,e,trans-1 addition pattern of C60.
Bisadduct 9 and trisadduct 10 showed pronounced ability to
crystallise and dark brown single crystals were easily obtained
by slow diffusion of pentane into their DCM solutions. The
crystal structures of 9 and 10 (Fig. 2) provided the ultimate
support for their addition patterns which are in full agreement
with those determined by the spectroscopic data.
Notes and references
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and Reactions, Wiley-VCH, Weinheim, 2005; (b) C. Thilgen,
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(c) C. Thilgen and F. Diederich, C. R. Chim., 2006, 9, 868;
(d) C. Thilgen and F. Diederich, Chem. Rev., 2006, 106, 5049.
2 L. Isaacs, R. F. Haldimann and F. Diederich, Angew. Chem., Int.
Ed. Engl., 1994, 33, 2339.
3 A. Hirsch, I. Lamparth and H. R. Karfunkel, Angew. Chem., Int.
Ed. Engl., 1994, 33, 437.
4 (a) G. Rapenne, J. Crassous, A. Collet, L. Echegoyen and
F. Diederich, Chem. Commun., 1999, 1121; (b) N. Chronakis and
A. Hirsch, Chem. Commun., 2005, 3709; (c) F. Beuerle,
N. Chronakis and A. Hirsch, Chem. Commun., 2005, 3676;
(d) F. Beuerle and A. Hirsch, Chem.–Eur. J., 2009, 15, 7434;
´ ´
(e) D. Gonzalez-Rodrıguez, E. Carbonell, D. M. Guldi and
T. Torres, Angew. Chem., 2009, 121, 8176; (f) A. Kraszewska,
P. Rivera-Fuentes, G. Rapenne, J. Crassous, A. G. Petrovic,
J. L. Alonso-Gomez, E. Huerta, F. Diederich and C. Thilgen,
´
Eur. J. Org. Chem., 2010, 4402.
5 F. Djojo, A. Hirsch and S. Grimme, Eur. J. Org. Chem., 1999, 3027.
6 A. Hirsch and O. Vostrowsky, Eur. J. Org. Chem., 2001, 829.
7 For some examples see: (a) M. Hetzer, S. Bayerl, X. Camps,
O. Vostrowsky, A. Hirsch and T. M. Bayerl, Adv. Mater., 1997,
The unit cells of adducts 9 and 10 contain one and two
molecules, respectively, and both crystallise with the inclusion
of DCM molecules. Close contacts between neighbouring fullerene
9, 913; (b) X. Camps, H. Schonberger and A. Hirsch, Chem.–Eur.
¨
molecules
(CC60Á Á ÁO–C,
CC60Á Á ÁOQC,
CC60Á Á ÁCAr
,
J., 1997, 3, 561; (c) M. Hetzer, H. Clausen-Schaumann, S. Bayerl,
T. M. Bayerl, X. Camps, O. Vostrowsky and A. Hirsch, Angew.
Chem., Int. Ed., 1999, 38, 1962; (d) X. Camps, E. Dietel, A. Hirsch,
CC60ÁÁÁCAr, CÁÁÁO–C, CÁÁÁOQC) in the range of 3.05–3.40 A
as well as between solvent molecules and fullerene adducts
(ClÁÁÁOQC, ClÁÁÁO–C, ClÁÁÁCAr, ClÁÁÁCC60) in the range of
S. Pyo, L. Echegoyen, S. Hackbarth and B. Roder, Chem.–Eur. J.,
¨
1999, 5, 2362; (e) A. Herzog, A. Hirsch and O. Vostrowsky, Eur. J.
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and A. Hirsch, Eur. J. Org. Chem., 2000, 1051; (g) M. Braun,
3.12–3.42
A were observed in both crystal structures
(see ESIw).
U. Hartnagel, E. Ravanelli, B. Schade, C. Bottcher, O. Vostrowsky
¨
In conclusion, tethers 7 and 8 showed excellent behaviour in
the regioselective Bingel functionalisation of C60 and gave the
equatorial bisadduct 9 and the eedge,eface,trans-1 trisadduct 10,
respectively, regioselectively and in excellent yields. These
fullerene derivatives represent new molecular structures due
to the three-dimensional cavities that form between the tether
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9 In the eedge,eface,trans-1 topological isomer the two trans-1 cyclo-
propanated bonds of C60 see the face of the central one. In the
eface,eedge,trans-1, the trans-1 bonds see the edges of the central one.
10 (a) W. Qian and Y. Rubin, Angew. Chem., Int. Ed., 1999, 38, 2356;
(b) W. Qian and Y. Rubin, Angew. Chem., Int. Ed., 2000, 39, 3133.
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¨
A. Hirsch, Chem.–Eur. J., 2002, 8, 2261; (b) N. Chronakis,
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¨
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12 W. Jiang and C. A. Schalley, Beilstein J. Org. Chem., 2010, 6, DOI:
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Fig. 2 X-Ray crystal structures of the equatorial bisadduct 9 (left)
and the eedge,eface,trans-1 trisadduct 10 (right).
13 A. Duarte-Ruiz, K. Wurst and B. Krautler, Helv. Chim. Acta,
2008, 91, 1401.
¨
c
11950 Chem. Commun., 2011, 47, 11948–11950
This journal is The Royal Society of Chemistry 2011