Sequential fullerenylation of bis-malonates-efficient access to oligoclusters with different fullerene building blocks

Article abstract of DOI:10.1002/ejoc.201300122

A method for the sequential fullerenylation of bis-malonates with parent C₆₀ and C_2v-symmetric pentakis-adducts is reported. This approach relies on the finding that (a) chloromalonates can be used for the nucleophilic cyclopropanation of [6,6] double bonds of C₆₀, and (b) chloromalonates, in contrast to bromomalonates, do not undergo base-catalyzed halogen exchange reactions. For the proof of concept, we synthesized a heptafullerene by using a divergent approach based on a fullerene hexakis-adduct with six bis-malonate addends in octahedral positions, each of which is suitable for an additional cyclopropanation of a fullerene building block. A sequence for the selective fullerenylation of bis-malonates with C₆₀ and its exohedral C_2v-symmetric pentakis-adducts has been developed. This method enables the straightforward synthesis of highly functional fullerene derivatives such as the heptafullerene 1.

Full text of DOI:10.1002/ejoc.201300122

FULL PAPER
DOI: 10.1002/ejoc.201300122
Sequential Fullerenylation of Bis-malonates – Efficient Access to Oligoclusters
with Different Fullerene Building Blocks
[a]
[a]
[a]
Lennard K. Wasserthal, Andreas Kratzer, and Andreas Hirsch*
Keywords: Fullerenes / Protecting groups / Cyclopropanation
A method for the sequential fullerenylation of bis-malonates
with parent C60 and C2v-symmetric pentakis-adducts is re-
ported. This approach relies on the finding that (a) chlor-
omalonates can be used for the nucleophilic cyclopropan-
ation of [6,6] double bonds of C60, and (b) chloromalonates, in
contrast to bromomalonates, do not undergo base-catalyzed
halogen exchange reactions. For the proof of concept, we
synthesized a heptafullerene by using a divergent approach
based on a fullerene hexakis-adduct with six bis-malonate
addends in octahedral positions, each of which is suitable for
an additional cyclopropanation of a fullerene building block.
Introduction
and controlled addition of one malonate followed by the
other to the corresponding fullerene building blocks. The
The nucleophilic cyclopropanation of fullerenes was
originally described by Bingel and belongs to the most im-
portant transformations in fullerene chemistry.[ In such a
reaction, 1,3-dicarbonyl compounds, in most cases malon-
ates, are first transformed into the corresponding mono-
bromides or monoiodides and then added to a [6,6] double
bond of the fullerene, promoted by deprotonation of the
1]
acidic H atom located at C-2. Monohalides can be either
used directly or prepared in situ.[
2–4]
For the highly regio-
selective oligoaddition of malonates to C60 to form bis-,
tris-, and tetrakismalonates with a stereochemically defined
addition pattern, we have developed the addition chemistry
of cyclo-[n]-malonates, in which several malonates (e.g., 2–
4
) are linked together with alkano bridges to form a macro-
[
5]
cycle. On the other hand, these cyclo-[n]-malonates offer
the opportunity to successively bind several fullerene build-
ing blocks of different natures, for example, with variations
of the exohedral functionalities, the degree of addition, and
the addition pattern. In this manner, a modular system of
highly functional macromolecules with tunable properties
would become available. Nierengarten and co-workers
undertook different approaches for the controlled construc-
tion of multifullerene dendrimers,[ which relied on asym-
metric coupling reactions of fullerene adducts and led to
further reactive sites in the linker. However, the attempt to
build unsymmetric structures by using the same reaction on
either end of the linker, as we want to, requires a selective
6]
[
a] Department of Chemistry and Pharmacy, Interdisciplinary
Center of Molecular Materials (ICMM), Friedrich-Alexander-
Universität Erlangen-Nürnberg,
Henkestrasse 42, 91054 Erlangen, Germany
Fax: +49-9131-852-6864
E-mail: andreas.hirsch@fau.de
Homepage: http://www.chemie.uni-erlangen.de/hirsch/
index.html
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300122.
Scheme 1.Sequential fullerenylation of cyclo-[2]-malonates with
two different fullerene adducts.
Eur. J. Org. Chem. 2013, 2355–2361
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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L. K. Wasserthal, A. Kratzer, A. Hirsch
FULL PAPER
sequential functionalization of macrocyclic bis-malonates scrambling reactions and b) further investigations of the
with two different fullerene building blocks is exemplified mechanisms of cylopropanation chemistry. Moreover, sys-
in Scheme 1.
tematic studies that reveal the role of X in the malonates
The obvious way to realize such an approach would be depicted in Scheme 1 are required.
to monobrominate the bis-malonate on one side, fullerenyl-
In this paper, we report on the successful avoidance of
ate it by letting only the brominated side react, monobrom- halogen scrambling reactions by introducing the use of
inate the second malonate site, and finally perform the re- chloromalonates as addends, and we exemplify highly selec-
maining fullerenylation with another building block. How- tive and sequential fullerenylation of bis-malonates with the
ever, in preliminary experiments, we realized that a con- divergent synthesis of the heptafullerene 1 (Figure 1).
trolled sequential addition cannot be accomplished, pre-
sumably because of scrambling of the Br atom between
both malonate sites. Recently, we have also shown that, very
Results and Discussion
unexpectedly, bis(bromo)malonates are also able to cyclo-
To systematically address the question of Br scrambling
propanate fullerenes and we have provided an explanation mentioned above, we treated diethyl 2-bromomalonate (2)
for this observation.[ These developments and the chal- in the presence of cyclo-[2]-octylmalonate (3) with diazabi-
lenge of gaining control over the step-by-step fullerenyl- cycloundecene (DBU) in the absence of C . These are typi-
7]
60
ation of oligomalonates require a) methods that increase cal conditions for the cyclopropanation of fullerenes
[
1,2]
the selectivity of the sequential addition by eliminating (Scheme 2).
Figure 1. Intended heptafullerene target molecule 1 as proof of applicability.
Scheme 2. Observed bromine exchange reactions between 2 and 3.
356
2
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Eur. J. Org. Chem. 2013, 2355–2361

Sequential Fullerenylation of Bis-malonates
We observed the formation of the monobrominated cy- ing reaction of C60 with diethyl-2-bromomalonate, in which
[
2]
clo-[2]-octylmalonate 4 and diethyl malonate 5, which are in 9 was obtained in 45% yield.
equilibrium with the starting material. Clearly, Br exchange As an alternative approach would have been to find a
reactions take place. Interestingly, the exclusive treatment protecting group for the malonates, we examined whether
of 2 with DBU led to the formation of tetraethyltetra- the tropylium cation was suitable as a protecting group
carboxyethene (6, Scheme 3). As a consequence, bromo- (Scheme 5) that would allow access to oligomeric malonates
malonates are indeed not suitable for a selective step-by- with just one binding site for nucleophilic cyclopropan-
step functionalization sequence of oligomalonates, as these ation. The reaction of tropylium tetrafluoroborate with a
side reactions will also occur in the presence of C60 under malonic ester successfully yields the malonates 10 and 11,
the usual cyclopropanation reaction conditions.
in which one C–H-acidic hydrogen is substituted by the tro-
pylium ion. Deprotection of 10 with HBr (48% in ace-
tic acid), diluted in dichloromethane, was achieved in one
hour. As expected, the protected diethylmalonate 10 did not
undergo a nucleophilic cyclopropanation reaction with C .
60
However, if unprotected malonates were present, the cyclo-
heptatriene group decomposed to unidentified compounds,
1
which showed H NMR signals in the aromatic region, so
this method was unsuitable for this purpose.
Scheme 3. Observed side reactions during the treatment of bromo-
and chloromalonates 2 and 7 with DBU.
It is reasonable to assume that these side reactions in-
volve nucleophilic substitutions at the bromine atoms at-
tached to C2 atoms of the malonate. The corresponding
nucleophiles are the malonate anions formed after depro-
tonation with DBU. Nucleophilic substitution of bromine
atoms is a common phenomenon.[
2,8,9,10]
As nucleophilic
[
8]
substitutions of chlorine atoms are much more difficult,
we then investigated whether there is also scrambling if
chloro- instead of bromomalonates are used. In the analo-
gous control experiment as that depicted in Scheme 2 but
with diethyl 2-chloromalonate (7) instead of its brominated
counterpart, we observed no Cl exchange. This positive re-
sult suggested that monochlorinated oligomalonates should
Scheme 5. Formation of the tropylium derivative 11 and deprotec-
be able to undergo selective monofullerenylation. However, tion of the tropylium derivative 10.
first we had to test whether cyclopropanation of C60 with
chloromalonates is possible at all. Although chloromalon-
Thus, we relied on the preactivation of the malonates
[
11]
ates have been used for S 2Ј reactions on fullerenes,
no with chlorine atoms. For proof of principle, we investigated
N
nucleophilic cyclopropanation reactions have been de- the sequential synthesis of the heptafullerene 1, which is
scribed. The test reaction we employed was performed with similar to one that we synthesized recently by following a
[
12]
7
and DBU as base (Scheme 4).
less efficient route. In our old pathway, fullerene-contain-
The targeted monoadduct 9 was formed and, hence, ing addends were added to a blank center. The necessary
chloromalonates can be used as precursor addends for the templating significantly impeded the reaction, and ad-
nucleophilic cyclopropanations of fullerenes. The isolated ditions at the wrong positions made the use of HPLC neces-
yield of 15%, however, is lower than that of the correspond- sary to remove side-products. In contrast, in our new ap-
Scheme 4. Cyclopropanation of C60 with 7.
Eur. J. Org. Chem. 2013, 2355–2361
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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L. K. Wasserthal, A. Kratzer, A. Hirsch
FULL PAPER
Scheme 6. Synthesis of the hexakis-adduct 13.
Scheme 7. Divergent synthesis of the heptafullerene 1.
proach depicted in Schemes 6 and 7, the octahedral ad- amount of chloroform solvent was kept as low as possible.
dition pattern of the central fullerene core is completed be- To separate the product from the starting material, column
fore the terminal fullerenes are connected in the final step. chromatography of the crude product in dichloromethane
For this purpose, we first had to synthesize the monochlori- was performed. Efficient separation required the use of rela-
nated cyclo-[2]-octylmalonate 12 (Scheme 6), which was ac- tively dilute solutions of the product mixtures. A large
complished by heating 3 to reflux in the presence of a stoi- amount of starting material could be recovered. Sub-
chiometric amount of sulfuryl dichloride for 12 h. The sequently, a 25-fold excess of addend 12 was allowed to re-
2358
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Sequential Fullerenylation of Bis-malonates
act with C by templating with 9,10-dimethylanthracene used for the nucleophilic cyclopropanation of [6,6] double
6
0
[
13]
(DMA).
The highest yields (3.3%) of the T -symmetric bonds of C60 and b) chloromalonates, in contrast to bromo-
h
hexakis-adduct 13 were obtained with toluene as solvent malonates, do not undergo base-catalyzed halogen-ex-
and DBU as a base. Purification was performed by column change reactions. For the proof of concept, we synthesized
chromatography on 15 micron silica with toluene/ethyl acet- the heptafullerene 1 by using a divergent approach based
ate (4:1) as eluent. The expected hexakisaddition was con- on the hexakis-adduct 13 with six bis-malonate addends in
1
3
firmed by mass spectrometry. In the C NMR spectrum, octahedral positions, each of which is suitable for an ad-
the T -symmetric addition pattern was obvious by the ditional cyclopropanation of a fullerene building block. The
h
matching number of signals for the depicted symmetry, es- method for the sequential and orthogonal oligofunctional-
2
pecially the two characteristic signals for the sp C atoms ization of oligomalonates bears many possibilities for the
of the fullerene core at δ = 145.8 and 141.0 ppm[ and the design of highly functional oligofullerene architectures with
14]
[
14]
two carbonyl signals at δ =166.48 and 163.84 ppm.
tunable properties. The systematic exploration of these op-
The final step was the conversion of the hexakis-adduct portunities is currently underway in our laboratories.
13 to the target molecule 1 (Scheme 7) with the terminating
building blocks 14. Compound 14 represents a [5.0]-penta-
Experimental Section
kis-adduct of C , for which we recently disclosed an ef-
6
0
General Remarks and Chemicals: Chemicals were purchased from
commercial sources and were used without further purification (un-
less otherwise stated). C60 was purchased from IoLiTec Nanomat-
erials. Solvents were distilled before use; solvents that generated
acid had K CO in the distillation flask. For reactions with fuller-
2 3
enes, HPLC grade solvents were used. The dichloromethane used
ficient access based on the photocleavage of one reversibly
binding addend of the corresponding [5:1]-isoxazoline pre-
[
15,16]
cursor.
The coupling of 14 to 13 was performed in tol-
uene by the stoichiometric addition of 13, tetrabromo-
methane, tert-butylimino-tri(pyrrolidino)phosphorane (P -
1
[
17]
tBu),
and a slight excess of addend 14. Although both
for the synthesis of 3 was dried by distillation from lithium alumi-
num hydride. TLC: Merck TLC silica gel 60 F254, KMnO (1%
4
fullerene-containing components readily precipitate under
these conditions, the reaction was left for one month. Sub- solution in 1% aqueous KOH) was used to develop the plates.
sequently, dichloromethane was added to redissolve the rea- Flash chromatography: Interchim puriFlash 430 instrument,
gents. The addition of an excess of tetrabromomethane, SIHC-JP 15 μm 40 g column, substances purified portionwise. UV/
Vis spectroscopy: Varian Cary 5000 spectrophotometer, CH
2 2
Cl
phosphazene base, and some amount of the addend 14 in
three portions over one month gave the seven-membered
fullerene adduct 1 in 43% isolated yield.
The straightforward workup of the reaction mixture and
the purification of 1 was accomplished by plug filtration.
For this purpose, the plug was packed with a toluene/ethyl
acetate mixture (6:1), and the free pentakis-adduct was
solvent, absorption maxima given in nm, extinction coefficients
–
1
–1
given in m cm . IR spectroscopy: attenuated total reflectance
ATR), Bruker FTIR Tensor 27 instrument. Abbreviations: w
(
weak, m medium, s strong. NMR spectroscopy: Bruker Avance 400
or Avance 300 spectrometer. Field strengths are given as the reso-
nance frequency of the respective nucleus. The chemical shifts are
given in ppm relative to tetramethylsilane (TMS). Abbreviations: s
eluted. Subsequently, the product was eluted with a toluene/ singlet, d doublet, t triplet, q quartet, m multiplet, br. broad. Spec-
ethyl acetate (2:1) mixture. Distinct product signals were tra were recorded at room temperature. MALDI MS: Shimadzu
observed in both ESI (four charges) and MALDI (one Axima Confidence instrument (TOF). ESI MS: Bruker Daltronics
micrOTOF (TOF) instrument. Matrices: (E)-2-(3-(4-(tert-butyl)-
phenyl)-2-methylallylidene)malononitrile (dctb), 3,5-dimethoxy-4-
hydroxycinnamic acid (sin).
Cyclo-[2]-octylmalonate (3): The procedure in ref.[5] was improved
as follows: 1,8-octanediol (8 g, 54.7 mmol, 1 equiv.) and pyridine
charge) MS, but no signals for incompletely reacted starting
2
13
materials were observed. The characteristic sp C60
C
[
14]
NMR signals
were found at δ = 145.8, 145.7, 141.0,
141.1 ppm. The absence of unidentified signals in the re-
gions around δ = 45 and slightly less than 30 ppm, which
would be characteristic of unattached malonates, corrobo-
rates the complete substitution. Thus, we can conclude that,
as incompletely substituted molecules such as penta- or
hexafullerenes would have been difficult to separate owing
to their similar polarity and solubility, the conversion to 1
(
8.66 g, 8.81 mL, 54.7 mmol, 1 equiv.) were dissolved in anhydrous
dichloromethane (4 L), and malonyl dichloride (7.71 g, 5.32 mL,
4.7 mmol, 1.3 equiv.) was dissolved in dry dichloromethane and
5
added portionwise over 4 d. The solution was stirred for 2 d and
then concentrated to 600 mL. Ethyl acetate (67 mL) was added,
and the mixture was plug-filtered through silica (6ϫ12 cm plug).
was exhaustive and no such lower clusters exist in the reac- The solvent was removed, and the mixture was chromatographi-
tion mixture. The UV/Vis spectrum of the product shows cally purified (SiO , dichloromethane/ethyl acetate, 19:1, diluted, at
2
1
a pattern characteristic of hexakis-adducts, especially the least 1.5 L bed volume), yield up to 2.7 g (23%). H NMR
3
absorptions at 316 and 334 nm,[ which is further evidence
14]
(400 MHz, CDCl ): δ = 4.11 (t, J
H,H 2
= 6.7 Hz, 8 H, CH O), 3.33
3
(
s, 4 H, COOCH
CH CH CH CH
66.4 (4 C, C=O), 65.4 (4 C, CH
4 C, CH CH O), 28.4 [4 C, CH (CH
ppm. IR (ATR, diamond): ν˜ = 2960 (w), 2922 (m), 2855 (m), 1740
2
COO), 1.60 (m, 4 H, CH
2
CH
O) ppm. C NMR (100.5 MHz, CDCl
O), 42.1 (COOCH COO), 29.2
O], 25.8 [4 C, C(CH O]
2
O), 1.3 (m, 16 H,
that the fullerenes are attached in a symmetric pattern.
1
3
2
2
2
2
3
): δ =
1
(
2
2
2
2
2
2
)
2
2 3
)
Conclusions
(
(
s), 1478, 1389, 1326 (s), 1254 (s), 1217 (s), 1138 (s), 1064 (w), 1028
m), 1003 (m), 892 (m), 724 (m) cm . MS (MALDI, dhb): m/z =
ylation of bis-malonates with different fullerenes. This ap- 429 [M + H] , 451 [M + Na] . C H (300.53): calcd. C 61.66, H
We have developed a concept for the sequential fulleren-
–1
+
+
2
2
36
proach relies on the finding that a) chloromalonates can be 8.47; found C 60.93, H 8.35.
Eur. J. Org. Chem. 2013, 2355–2361
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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L. K. Wasserthal, A. Kratzer, A. Hirsch
FULL PAPER
Cation Exchange Experiment Resulting in Bis-malonate 4 and Di-
added and the mixture was stirred for 12 h. The mixture was fil-
ethyl Malonate 5: Diethyl bromomalonate (47.573 mg, 33.9 μL,
tered and purified by column chromatography (SiO
2
, CH
): δ = 6.68 (m, 2 H,
.199 mmol, 1 equiv.) were dissolved in toluene (5 mL). DBU CHCHCH=CHCH=CH), 6.24 (2 H, CHCHCH=CH), 5.36 (2 H,
2 2
Cl ),
1
0
0
.199 mmol, 1 equiv.) and cyclo-[2]-octylmalonate (2, 85 mg, yield 70% H NMR (400 MHz, CDCl
3
3
3
(
30.3 mg, 29.7 mL, 0.199 mmol, 1 equiv.) was added, and the mix-
CHCHCH=CH), 4.21 (q, JH,H = 7 Hz, 4 H, CH
2
O), 3.65 [d, JH,H
], 1.27
) ppm. C NMR (100.5 MHz,
): δ = 168.1 (2 C, C=O), 130.9 (2 C, CHCHCH=CH), 126.6
): δ = 4.83 (s, 1 H, CHBr), 4.35–4.08 (m, (2 C, CHCHCH=CHCH=CH), 122.3 (2 C, CHCHCH=CH), 61.4
O), 3.34 [s, 2 H, CH(C=O) ], 1.6 (m, 8 H, CH CH O), (2 C, CH O), 52.7 [2 C, CHCH(C=O) ], 38.25 [2 C, CHCH-
.3 (m, 16 H, CH CH CH CH ], 14.1 (2 C, CH ) ppm. HRMS (ESI, CH Cl /MeCN/tolu-
O) ppm. 13C NMR (75.4 MHz, (C=O)
): δ = 166.5 [2 C, CH (C=O) ene): calcd. for 18NaO
[M + Na]+ 273.10973; found
7.2, 65.5 (4 C, CH O), 43.2 (1 C, CHBr), 42.2 [1 C, CH ], 273.10998. IR (ATR, diamond): ν˜ = 2983 (m), 2939 (w), 2906 (w),
9.3, 29.2 [4 C, CH CH O], 28.5, 28.4 (4 C, CH CH CH
5.7 (4 C, CH CH CH CH
C NMR (100.5 MHz, CDCl
ture was stirred for 2.5 h. Acetic acid (100 μL) was added, and the
resulting solution was purified by column chromatography (SiO
dichloromethane), yield 13 mg, 12.8%. Brominated malonate 4: H
NMR (300 MHz, CDCl
8
1
= 10 Hz, 1 H, CHCH(C=O) ], 2.73 [m, 1 H, CHCH(C=O)
2
2
3
13
2
,
(t,
JH,H = 7.0 Hz, 6 H, CH
3
1
CDCl
3
3
H, CH
2
2
2
2
2
2
2
2
2
2
2
3
2
2
CDCl
3
2
2
], 164.5 [2 C, CHBr(C=O)
2
],
C
14
H
4
6
2
2
2
2
(C=O)
2
2
2
2
2
2
O), 25.8, 1728 (s), 1464 (w), 1446 (w), 1369 (w), 1299 (m), 1258 (m), 1229
2
2
2
2
O) ppm. Data for diethyl malonate 5:
): δ = 166.6, 61.5, 41.7, 14.0 ppm.
(m), 1151 (s), 1131 (w), 1096 (w), 1028 (s), 860 (m), 744 (w), 701
1
3
–1
3
(s), 593 (m) cm .
Cation Exchange Experiment Resulting in Bis-malonate 4 and Com-
pound 6: Diethyl bromomalonate (476 mg, 339 μL, 1.99 mmol,
Tropylium-Protected Bismalonate 11: Tropylium hexafluorophos-
phate (138 mg, 0.583 mmol, 1 equiv.) was suspended in dichloro-
methane (4 mL). Cyclo-[2]-octylmalonate (3, 250 mg, 0.583 mmol,
1 equiv.) and DBU (88.8 mg, 87 μL, 1 equiv.) were added, and the
1
1
1
1
1
0 equiv.), diethyl malonate (5, 319 mg, 302 μL, 1.99 mmol,
equiv.), and cyclo-[2]-octylmalonate (3, 85 mg, 0.199 mmol,
equiv.) were dissolved in toluene (5 mL). DBU (303 mg, 297 mL, mixture was stirred for 48 h. The mixture was purified by column
.99 mmol, 10 equiv.) was added, and the mixture was stirred for
2 h. Acetic acid (0.5 mL) was added, and the resulting solution
chromatography (SiO
2
, CH
NMR (400 MHz, CDCl
CHCHCH=CHCH=CH), 6.23 (2 H, CHCHCH=CH), 5.26 (2 H,
CHCHCH=CH) 4.18 (4 H, CHCHC=OOCH ), 4.12 (4 H,
CH C=OOCH ), 4.02 (4 H, CHCHC=OOCH ), 3.61 [d, 1 H,
CHCH(C=O) ], 3.34 [2 H, CH (C=O) ] 2.7 (1 H, CHCH(C=O) ),
1.61 (8 H, CH CH O), 1.29 (16 H, CH
NMR (75.4 MHz, CDCl ): δ = [ppm] = 168.1 (2 C, C=O), 166.4
2
Cl
2
), yield 37%. R
f
(CH
2
Cl
2
) = 0.45.
1
H
3
): 6.64 (m,
δ
=
2
H,
2
was plug-filtered twice (SiO , dichloromethane/ethyl acetate, 1:1
and then SiO , dichloromethane, 6 bed volumes dichloromethane/
2
2
ethyl acetate, 1:1). The resultant product was purified by column
chromatography (dichloromethane/ethyl acetate, 19:1). In the frac-
2
2
2
2
2
2
2
1
3
tion with R
f
= 0.11 in dichloromethane, 18 mg of the monobromin-
2
2
2
CH
2
CH
2
CH
2
O) ppm.
C
ated cyclic compound was obtained. Furthermore, tetraethyltetra-
3
carboxyethene (6, at least 60 mg) and tetraethyl 1,1,2,2-ethanetetra-
carboxylate were also found. Data for brominated malonate 4:
(2 C, C=O), 130.9 (2 C, CHCHCH=CH) 125.6 (2 C,
CHCHCH=CHCH=CH) 122.4 (2 C, CHCHCH=CH), 65.43,
1
H NMR (300 MHz, CDCl
O), 3.34 [s, 2 H, CH(C=O)
.3 (m, 16 H, CH CH CH CH
O) ppm. 13C NMR (75.4 MHz, (OCH
): δ = 166.5 [2 C, CH (C=O)
O), 43.2 (1 C, CHBr), 42.2 [1 C, CH
3
): δ = 4.83 (s, 1 H, CHBr), 4.35.4.08 65.36 (4 C, CO), 52.71 [(C=O)
], 1.6 (m, 8 H, CH CH O), [(C=O) CHCH] 29.2 (OCH CH
CH CH CH ) ppm. MS (MALDI): m/z = 523 [M –
4H + Li] , 554 [M – 4H + K] . MS (MALDI, sin): m/z = 544 [M –
2
CHCH], 42.1 [(C=O)
2
CH
2
], 38.0
(m, 8 H, CH
2
2
2
2
2
2
2
), 28.4 (OCH CH
2
2
CH
2
), 25.8
1
2
2
2
2
2
2
2
2
+
+
CDCl
3
2
2
], 164.5 [2 C, CHBr(C=O)
2
],
], 2H + Na] . HRMS (ESI, CH
+
6
2
2
7.2, 65.5 (4 C, CH
9.3, 29.2 (4 C, CH
5.7 (4 C, CH CH
2
2
(C=O)
2
2
Cl
2
/MeCN/MeOH): calcd. for
+
2
CH
2
O), 28.5, 28.4 (4 C, CH
CH
2
CH
2
CH
2
O), 25.8,
29 8
C H42NaO [M + Na] 541.2771; found 541.27851. IR (ATR, dia-
1
2
2
CH
2
2
O) ppm. Data for 6: H NMR
mond): ν˜ = 3022 (w), 2956 (w), 2927 (s), 2853 (m), 1740 (s), 1726
(s), 1476 (w), 1392 (w), 1321 (m), 1262 (m), 1215 (m), 1164 (m),
3
(
(
300 MHz, CDCl
t,
3
): δ = 4.29 (q, JH,H = 7.2 Hz, 8 H, CH
H,H = 7.2 Hz, 12 H, CH
): δ = 162.3 (4 C, C=O), 135.3 (2 C, C=C), 62.6 (4 C, CH
3.8 (4 C, CH ) ppm. Data for tetraethyl 1,1,2,2-ethanetetracarb-
oxylate 8: H NMR (400 MHz, CDCl ): δ = 4.24–4.12 (m, 8 H,
2
O), 1.29
3
) ppm. 13C NMR (75.4 MHz, 1137 (m), 1063 (w), 1026 (w), 999 (m), 977 (w), 734 (s), 698 (s)
J
3
–
1
CDCl
1
3
2
O),
cm .
3
1
Cleavage of Tropylium-Protected Diethyl Malonate 10: Tropylium-
protected diethyl malonate 10 (50 mg, 0.2 mmol) was dissolved in
anhydrous dichloromethane (10 mL). HBr (2 mL) was added, and
the mixture was stirred for 1 h at room temperature. Water (10 mL)
was added. The phases were separated, and the organic phase was
3
3
CH
2
O), 4.09 (s, 2 H, CH-CH), 1.24 (t, JH,H = 7 Hz, CH
3
) ppm.
): δ = 167.0 (4 C, C=O), 62.0 (4 C,
], 13.9 (4 C, CH ) ppm.
/MeCN/MeOH): calcd. for
M + H]+ 319.13874; found 319.13946; calcd. for C14
13
C NMR (100.5 MHz, CDCl
3
CH
2
O), 51.4 [2 C, (C=O)
Cl
2
CHCH(C=O)
2
3
HRMS (ESI, CH
2
2
C
14
H
23
O
8
stirred over NaHCO
vent, diethyl malonate was obtained without traces of 10, yield
9%.
3
(5 g). After filtration and removal of the sol-
[
[
H22NaO
8
M + Na]+ 341.12069; found 341.12146;
3
Monoadduct 9: Diethyl chloromalonate (45.5 mg, 37.8 μL,
.236 μmol, 1.13 equiv.) and C60 (170 mg, 236 μmol, 1.13 equiv.)
were dissolved in toluene (75 mL). DBU (31.7 mg, 31.1 μL,
Monochlorinated Bis-malonate 12: To cyclo-[2]-octylmalonate (3,
.17 g, 7.40 mmol, 1 equiv.) suspended in chloroform (4.4 mL) was
added sulfuryl dichloride (1 g, 0.5985 mL, 7.40 mmol, 1 equiv.),
and the mixture was heated to 70 °C for 24 h. The resultant mixture
was diluted with dichloromethane (200 mL) and chromatographi-
0
3
0
2
.209 μmol, 1 equiv.) was added, and the mixture was stirred for
1 h. The mixture was plug-filtered (SiO , toluene) and purified by
, toluene). R = 0.726, yield 28 mg
15% based on DBU). Product 9 was verified by NMR spec-
troscopy and HRMS. HRMS (ESI, CH Cl /MeCN/toluene): calcd.
[M] 878.05846; found 878.05829.
2
column chromatography (SiO
(
2
f
cally purified very slowly over a 200 mL bed-volume plug (SiO
CH Cl ). Unreacted starting material can be recovered by washing
the plug with dichloromethane/ethyl acetate, 1:1, yield 1.233 g
36%, 70% based on recovered starting material). R = 0.155 (prod-
uct). Impurities: R = 0.352 (both sides monochlorinated), 0.2535
(one side dichlorinated). H NMR (300 MHz, CDCl
(1 H, CHCl), 4.2 (2m, 4 H, CH OC=OCHCl), 4.12 (t, 4 H, CH
C=OCH ), 3.33 [s, 2 H, CH (C=O) ], 1.63 (m, 8 H, CH CH
2
,
2
2
2
2
+
10 4
for C67H O
(
f
Tropylium-Protected Diethyl Malonate 10: Tropylium tetrafluo-
roborate (293 mg, 1.24 mmol, 1 equiv.) was suspended in dichloro-
methane (5 mL). Diethyl malonate 5 (200 mg, 210 μL, 1.24 mmol,
f
1
3
): δ = 4.84
O-
O),
2
2
1
equiv.) and DBU (88.8 mg, 192 μL, 1.24 mmol, 1 equiv.) were
2
2
2
2
2
2360
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2355–2361

Sequential Fullerenylation of Bis-malonates
1
.32 (16 H, CH
CDCl ): δ = 166.4, 164.3 (4 C, C=O), 67.11, 65.4 (4 C, CH
5.8 (1 C, CHCl), 42.1 [1 C, C(C=O)CH
2
CH
2
CH
2
CH
2
O) ppm. 13C NMR (75.4 MHz, CH
O), ppm. MS (MALDI, dctb): m/z = 12330 [M – 2H] . HRMS (ESI,
2 2 2 2 2 2 2 3
CH CH O), 26.0, (24 C, CH CH CH CH O) 14.0 (60 C, CH )
+
3
2
1
3
5
CH
CH
2
], 29.21, 29.18 (4 C, CH
3
CN/MeOH/ HCOOH): calcd. for C758
C
8
H
492Na
4
O
168 [M +
4
+
2
CH
CH
2
O), 28.4, 28.3 (4 C, CH
CH CH
[M + Na] 485.19127; found 485.19089. IR (ATR, (s), 1216 (s), 1079 (m), 1043 (m), 1018 (m), 857 (w), 715 (m) cm .
2
CH
2
CH
2
O), 25.8, 25.7 (4 C,
4Na] 3106.74488 found; 3106.75364. IR (ATR, diamond): ν˜ =
2
2
2
2
O) ppm. HRMS (ESI, MeCN/MeOH): calcd. for 2980 (m), 2934 (m), 2857 (m), 1742 (s), 1464 (w), 1368 (w), 1262
+
–1
C
22
H35ClNaO
8
–
1
–1
diamond): ν˜ = 2935 (s), 2856 (m), 1735 (s), 1469 (m), 1318 (s), 1306
2 2
UV/Vis (CH Cl ): λ (ε, m cm ) = 246 (418000), 274 (415000), 282
–1
(s), 1282 (s), 1202 (m), 1164 (m), 1147 (m), 1000 (m) cm .
(403000), 316 (333000), 334 (290000), 380 (71000) nm.
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectra of compounds 1, 4, 10, 11, 12, 13, ESI-MS,
MALDI MS and UV/Vis data of 1.
Hexakis-adduct 13: Malonate 12 (400 mg, 864 umol, 25 equiv.),
9
,10-dimethylanthracene (70 mg, 414 umol, 12 equiv.), and C60
24 mg, 34.6 umol, 1 equiv.) were dissolved in toluene (12 mL) and
stirred for 3 h. DBU (63.1 mg, 62.0 μL, 414 umol, 12 equiv.) was
added, and the mixture was stirred for 5 d. Further DBU (15.8 mg, Acknowledgments
5.5 μL, 104 umol, 3 equiv.) was added, and the mixture was stirred
for an additional 3 d. Ethyl acetate (4 mL) was added, and the mix-
ture was plug-filtered (SiO , toluene/ethyl acetate, 4:1). The solvent
was removed, and the crude mixture was purified twice by flash
chromatography (SiO , toluene/ethyl acetate, 4:1; the second time
on 15 μ grain size SiO and very slowly), yield 16 mg, (13.7% based
on fullerene, 3.3% based on malonate). 1H NMR (400 MHz,
CDCl ): 4.22 (24 H, 60C=OOCH
=OOCH ), 3.4 [12 H, CH (C=O) ], 1.75–1.6 (48 H,
CH O), 1.567 (128 H, CH CH CH CH
): δ = 166.5 [12 C, CH
(
1
This work was supported by the Deutsche Forschungsgemeinschaft
(DFG) (SFB 953 – Synthetic Carbon Allotropes and Hi-468/13-4).
2
2
[
[
1] C. Bingel, Chem. Ber. 1993, 126, 1957–1959.
2] X. Camps, A. Hirsch, J. Chem. Soc. Perkin Trans. 1 1997,
1595–1596.
2
3
δ
=
C
2
), 4.13 (24 H, [3] W. H. Hunter, D. E. Edgar, J. Am. Chem. Soc. 1932, 54, 2025–
CH
2
2
2
2
2028.
) ppm. 1 C NMR
3
[4] J.-F. Nierengarten, V. Gramlich, F. Cardullo, F. Diederich, An-
gew. Chem. 1996, 108, 2242; Angew. Chem. Int. Ed. Engl. 1996,
35, 2101–2103.
CH
2
2
2
2
2
2
CH
(C=O)
2
2
(100.5 MHz, CDCl
3
2
], 163.8 [12 C,
2
3
C60=C(C=O)
2
], 145.8, 141.0 (48 C, C60 sp ), 69.1 (12 C, C60 sp ),
), 65.6 (12 C, H CC=OOCH ), 45.3
], 42.3 [6 C, H C(C=O) ], 29.4 (24 C,
O), 28.6, 28.5 (24 C, CH CH CH O), 25.9 (24 C,
CH CH O) ppm. MS (MALDI, sin): m/z 3302
[
5] U. Reuther, T. Brandmüller, W. Donaubauer, F. Hampel, A.
Hirsch, Chem. Eur. J. 2002, 8, 2261–2273.
67.0 (12 C, C60=CC=OOCH
2
2
2
[6 C, C60=C(C=O)
2
2
2
[6] a) J. Iehl, R. P. de Freitas, J.-F. Nierengarten, Tetrahedron Lett.
CH
CH
2
CH
CH
+
2
2
2
2
2008, 49, 4063–4066; b) D. Felder, H. Nierengarten, J.-P. Gis-
2
2
2
+
2
=
selbrecht, C. Boudon, E. Leize, J.-F. Nicoud, M. Gross, A. V.
Dorsselaer, J.-F. Nierengarten, New J. Chem. 2000, 24, 687–
695.
+
+
[M
Na] , 3303 [M + Na] , 3304 [M + 2H + Na] , 3305
+
+
[
M + 3H + Na] , 3305 [M + 4H + Na] . HRMS (ESI, MeCN/
48 [M + 2H + 2Na]2 1662.67328;
+
[7] F. Hörmann, A. Hirsch, Chem. Eur. J. 2013, 19, 3188–3197.
MeOH): calcd. for C192
H
204Na
2
O
[
[
[
[
8] G. Wittig, H. Witt, Ber. Dtsch. Chem. Ges. 1941, 74, 1474–
491.
9] A. A. Neverov, R. S. Brown, J. Org. Chem. 1998, 63, 5977–
982.
10] N. Liu, J. B. Werness, I. A. Guzei, W. Tang, Tetrahedron 2011,
7, 4385–4390.
found 1662.67012. IR (ATR, diamond): ν˜ = 2929 (s), 2856 (m),
1
1
1
2
3
732 (s), 1465 (w), 1387 (w), 1260 (m), 1212 (s), 1158 (w), 1081 (w),
019 (m), 802 (m), 715 (w) cm . UV/Vis (CH Cl ): λ (ε, m cm )
2 2
45 (87000), 271 (66000), 282 (71000), 317 (45000), 335 (36000),
81 (5000) nm.
–1
–1
–1
5
6
11] A. D. Darwish, I. V. Kuvytchko, X.-W. Wei, O. V. Boltalina,
Heptafullerene 1: Hexakis-adduct 13 (31 mg, 9.452 mmol, 1 equiv.)
was dissolved in toluene (3 mL). A solution of pentakis-adduct 14
I. V. Gol’dt, J. M. Street, R. Taylor, J. Chem. Soc. Perkin Trans.
2
2002, 1118–1121.
(
114 mg, 75.618 mmol, 8 equiv.) in toluene (5 mL) was added. The
starting materials precipitated. Solutions of CBr (18.8 mg,
-tBu (13.3 mg, 14.4 μL, 56.7 mmol,
equiv.) were added, and the mixture was stirred for 22 d. Dichlo-
[12] P. Witte, F. Hörmann, A. Hirsch, Chem. Eur. J. 2009, 15, 7423–
4
7433.
5
6
6.7 mmol, 6 equiv.) and P
1
[13] I. Lamparth, C. Maichle-Mössmer, A. Hirsch, Angew. Chem.
1
995, 107, 1755–1757; Angew. Chem. Int. Ed. Engl. 1995, 34,
1
607–1609.
romethane was added until the precipitate dissolved, and further
pentakis-adduct 14 (21 mg, 14 mmol, 1.5 equiv.), CBr (31 mg,
-tBu (22.2 mg, 24 μL, 94.5 mmol,
0 equiv.) were added portionwise over 2 weeks, and the mixture
[14] a) A. Hirsch, I. Lamparth, T. Grösser, J. Am. Chem. Soc. 1994,
4
1
16, 9385–9386; b) M. Braun, U. Hartnagel, E. Ravanelli, B.
94.5 mmol, 10 equiv.), and P
1
Schade, C. Böttcher, O. Vostrowsky, A. Hirsch, Eur. J. Org.
Chem. 2004, 9, 1983–2001.
1
was stirred for another 2 weeks. Ethyl acetate (5 mL) was added,
and the mixture was plug-filtered (SiO , toluene/ethyl acetate, 4:1).
The solvent was evaporated, and the mixture was purified by col-
umn chromatography (SiO , toluene/ethyl acetate, 6:1; toluene/
[15] F. Hörmann, W. Donaubauer, F. Hampel, A. Hirsch, Chem.
Eur. J. 2012, 18, 3329–3337.
2
[16] F. Langa, P. de la Cruz, E. Espıldora, A. Gonzalez-Cortes, A.
de la Hoz, V. Lopez-Arza, J. Org. Chem. 2000, 65, 8675–8684,
method A. However, 1,2,4-trimethylbenzene was used as sol-
vent, and the reaction conditions were 12 h at 0 °C instead of
microwave irradiation.
2
1
3
ethyl acetate, 2:1). H NMR (400 MHz, CDCl
7.0 Hz, 120 H, CH CH O), 4.22 (m, 48 H, CH
48 H, CH CH O), 1.36 ppm (96 H, CH
H,H = 7.0 Hz, 180 H, CH ) ppm. C NMR
): δ = 163.81, 163.78, 163.75 (84 C, C=O),
45.8, 145.7, 141.1, 141.0 (336 C, C60 sp ), 69.09, 69.05, 69.01, 67.0
84 C, C60 sp ), 62.8 (84 C, H
C, C(C=O) ], 29.46, (24 C, CH
3
): δ = 4.30 (q, JH,H
CH O), 1.70 ppm
CH CH CH O),
=
(
3
2
2
2
2
2
2
2
2
2
[
17] R. Schwesinger, C. Hasenfratz, H. Schlemper, L. Walz, E.-M.
3
13
1.30 ppm (t,
J
3
Peters, K. Peters, H. G. von Schnering, Angew. Chem. 1993,
(
1
(
100.5 MHz, CDCl
3
1
05, 1420–1422; Angew. Chem. Int. Ed. Engl. 1993, 32, 1361–
2
1363.
3
2
CO), 45.31,45.29, 45.27, 45.24 [42
CH CH O), 28.48, (24 C,
Received: January 25, 2013
Published Online: March 7, 2013
2
2
2
2
Eur. J. Org. Chem. 2013, 2355–2361
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2361