Synthesis of disubstituted [60]fullerene-fused lactones: Ferric perchlorate-promoted reaction of [60]fullerene with malonate esters

Article abstract of DOI:10.1021/ol102056k

The ferric perchlorate-mediated reaction of [60]fullerene with substituted malonate esters in the presence of acetic anhydride afforded the rare disubstituted [60]fullerene-fused lactones. A possible reaction mechanism is proposed.

Full text of DOI:10.1021/ol102056k

ORGANIC
LETTERS
2010
Vol. 12, No. 21
4896-4899
Synthesis of Disubstituted
[60]Fullerene-Fused Lactones: Ferric
Perchlorate-Promoted Reaction of
[60]Fullerene with Malonate Esters
Fa-Bao Li,† Xun You,† and Guan-Wu Wang*,†,‡
Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory
of Soft Matter Chemistry, and Department of Chemistry, UniVersity of Science and
Technology of China, Hefei, Anhui 230026, P. R. China, and State Key Laboratory of
Applied Organic Chemistry, Lanzhou UniVersity, Lanzhou, Gansu 730000, P. R. China
gwang@ustc.edu.cn
Received August 30, 2010
ABSTRACT
The ferric perchlorate-mediated reaction of [60]fullerene with substituted malonate esters in the presence of acetic anhydride afforded the rare
disubstituted [60]fullerene-fused lactones. A possible reaction mechanism is proposed.
Although a large variety of reactions for the functional-
ization of fullerenes have been explored over the past 20
years,1 the metal salt-mediated reactions of [60]fullerene
(C60) are relatively underdeveloped. Recently, our group
has been interested in reactions of C60 mediated by metal
salts such as Mn(OAc)3,2,3 Cu(OAc)2,3c Pb(OAc)4,3h
Up to now, only a few papers described the lactonization
reactions of C60.3g-i,6,7 Foote et al. reported the synthesis of
two C60-fused γ-lactones by the [2 + 2] cycloaddition of
C60 with diethylaminopropyne/ketene acetal, subsequent ring
opening by acid hydrolysis, and final oxidative cyclization
in the presence of charcoal.6 We disclosed the preparation
of four C60-fused δ-lactones through the reaction of C60 with
anthranilic acids and isoamyl nitrite in the presence of
triethylamine.7 We previously revealed the facile one-step
reaction of C60 with carboxylic acids, or with carboxylic
5
Pd(OAc)2,4 and Fe(ClO4)3 to obtain a variety of novel
compounds with desired moieties.
† University of Science and Technology of China.
‡ Lanzhou University.
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10.1021/ol102056k  2010 American Chemical Society
Published on Web 09/29/2010

anhydrides, or with malonic acids in the presence of
Mn(OAc)3 to afford three C60-fused γ-lactones.3g Recently,
we further extended the Mn(OAc)3-promoted reaction of C60
with various carboxylic acids in the presence of 4-dimethyl-
aminopyridine to afford a series of C60-fused γ-lactone
derivatives.3h,i Unfortunately, nearly all of the reported C60-
fused γ-lactones are monosubstituted lactones. Only one
disubstituted C60-fused γ-lactone was reported, and it was
formed from the Mn(OAc)3-mediated reaction of C60 with
isobutyric acid.3h However, the concurrent formation of a
fullerenyl ester byproduct originated from the facile genera-
tion of a secondary radical via decarboxylation from isobu-
tyric acid was unavoidable. The isolated yield (17%) of the
unsymmetrical fullerenyl ester was even higher than that
(10%) of the desired C60-fused γ-lactone under the employed
standard conditions.3h
Scheme 1. Mn(OAc)3-Mediated Reaction of C60 with 1a
Affording C60-Fused 2a, 1,4-Adduct 3a, and 1,16-Adduct 4a
It seems that the synthesis of disubstituted C60-fused
γ-lactones from carboxylic acids in high yields is quite
challenging. This obstacle prompted us to develop an
alternative efficient protocol to obtain the scarce disubstituted
C60-fused γ-lactones. In continuation of our interest in
Fe(ClO4)3-mediated reactions of C60,5 herein we describe the
successful synthesis of disubstituted C60-fused γ-lactones
through the reaction of C60 with substituted malonate esters
in the presence of Fe(ClO4)3 and acetic anhydride.
the selectivity. The reaction conditions were screened for
the model reaction of C60 with 1a mediated by Fe(ClO4)3
(Table 1). The reaction of C60 with 1a, Fe(ClO4)3·xH2O
Table 1. Optimization of Reaction Conditions for the Fe(ClO4)3
Reaction of C60 with 1a
We previously reported that the Mn(OAc)3-mediated
reaction of C60 with dialkyl malonates, i.e., CH2(CO2Me)2
and CH2(CO2Et)2, in refluxing chlorobenzene afforded the
singly bonded fullerene dimers [(RO2C)2CH]C60-
C60[CH(CO2R)2] and 1,4-adducts C60[CH(CO2R)2]2, while
the corresponding reaction with BrCH(CO2Et)2 generated a
1,4-adduct and a 1,16-adduct of C60.3a In contrast, the
Mn(OAc)3-promoted reaction of C60 with substituted mal-
onate esters in refluxing toluene gave the benzyl-substituted
unsymmetrical 1,4-adducts of C60.3b In all of the aforemen-
tioned reactions, no C60-fused lactones could be identified.3a,b
More recently, we attempted the Mn(OAc)3-mediated reac-
tion of C60 with diethyl methylmalonate (1a) in an alternative
solvent to avoid the participation of toluene. Interestingly,
we obtained disubstituted C60-fused γ-lactone 2a besides 1,4-
adduct 3a and 1,16-adduct 4a as the major products along
with other byproducts from the reaction of C60 with diethyl
methylmalonate (1a) and Mn(OAc)3 in a molar ratio of 1:2:2
in o-dichlorobenzene (ODCB) at 140 °C and under nitrogen
atmosphere (Scheme 1).8
reaction
reaction yield of recovered
entry molar ratioa temp (°C) time (min) 2a (%)b C60 (%)
1
2
3
4
5
6
7
8
9
1:2:2:20
1:2:2:20
1:2:2:20
1:2:2:10
1:2:2:30
1:2:2:20
1:2:2:0
25
40
60
60
60
80
60
60
60
300
120
20
16
17
26
20
25
34
9
81
80
58
62
26
38
89
75
42
60
20
20
120
160
10
1:2:2:0c d
13
20
,
1:2:2:20d e
,
a Molar ratio refers to C60:1a:FEP:Ac2O. b Isolated yield. c The reaction
was conducted by the dissolution of Fe(ClO4)3·xH2O (FEP) in 1a (direct
dissolution method). d An unknown product having a polarity similar to
C60 was observed besides the desired fullerene lactone. e AcOH was used
instead of Ac2O.
It should be emphasized that the protection of a nitrogen
atmosphere proved to be crucial for the successful synthesis
of C60-fused lactone 2a as well as 1,4-adduct 3a and 1,16-
adduct 4a, with either little or no products being obtained
in air. Nevertheless, the poor yield and selectivity for the
formation of lactone 2a led us to explore other reaction
conditions to selectively obtain the rare disubstituted C60-
fused lactone. To our great satisfaction, we found that
Fe(ClO4)3 in place of Mn(OAc)3 could dramatically improve
(FEP), and Ac2O in a molar ratio of 1:2:2:20 gave lactone
2a in 16% yield at ambient temperature (entry 1, Table 1).
Raising the temperature to 60 °C enhanced the yield to 26%
(entry 3, Table 1). Increasing or decreasing the amount of
Ac2O lowered the product yield (entries 4-5 vs entry 3,
Table 1). The isolated yield could be further improved to
34% at the expense of recovered C60 by increasing the
reaction temperature to 80 °C (entry 6, Table 1). The absence
of Ac2O deteriorated the yield significantly (entries 7-8 vs
entry 3, Table 1). Replacing Ac2O with AcOH gave inferior
result too (entry 9 vs entry 3, Table 1). The role played by
Ac2O is not clear, yet it is known in the literature that Ac2O
is beneficial to Fe(ClO4)3-mediated radical reactions.9b Thus,
(8) After we had completed our work, the synthesis of 3a and 4a from
2-
the reaction of C60 with diethyl 2-bromo-2-methylmalonate appeared:
Kokubo, K.; Arastoo, R. S.; Oshima, T.; Wang, C.-C.; Gao, Y.; Wang,
H.-L.; Geng, H.; Chiang, L. Y. J. Org. Chem. 2010, 75, 4574.
Org. Lett., Vol. 12, No. 21, 2010
4897

the molar ratio of 1:2:2:20 for the reagents C60, 1a,
Fe(ClO4)3·xH2O, and Ac2O and the reaction temperature of
80 °C were chosen as the optimized reaction conditions.
Similar optimized reaction conditions could be successfully
extended to the Fe(ClO4)3-mediated reaction of C60 with other
substituted malonate esters such as diethyl ethylmalonate
(1b), diethyl benzylmalonate (1c), diethyl phenylmalonate
(1d), diethyl bromomalonate (1e), and triethyl methanetri-
carboxylate (1f). Table 2 lists the reaction conditions and
presence of Ac2O to produce lactone 2e with the retention
of the bromo substituent. Ethoxycarbonyl-substituted mal-
onate ester 1f was the least reactive among the investigated
substituted malonate esters and required a higher reaction
temperature (110 °C). It is noteworthy that acetic anhydride
played a crucial role for the successful synthesis of C60-fused
lactones, with low and/or poor selectivity being obtained in
its absence. Surprisingly, the Fe(ClO4)3-mediated reaction
of C60 with diethyl malonate, the unsubstituted malonate
ester, at 80 °C for 7 min failed to give the desired C60-fused
lactone, instead affording at least four unidentified products.
The structures of disubstituted C60-fused lactones 2a-f
were fully characterized by HRMS, 1H NMR, 13C NMR, FT-
IR, and UV-vis spectra. In the 1H NMR spectra of lactones
2a-f, the two methylene protons in the ethoxy group were
nonequivalent and split as two double quartets due to the
adjacent chiral center. In their 13C NMR spectra, the chemical
shifts for the lactone and ester carbons appeared at
166.49-173.56 and 162.91-169.69 ppm, and the two sp3-
carbons of the C60 skeleton were located at 95.57-96.43 and
68.41-72.40 ppm, close to those of reported C60-fused
lactone derivatives in the previous literature.3g-i,6,7 There
were at least 46 peaks in the 134-152 ppm region for the
58 sp2-carbons of the C60 moiety for lactones 2a-e,
consistent with the C1 symmetry of their molecular structures.
In contrast, only 26 lines in the 136-149 ppm region could
be found for lactone 2f, agreeing well with its Cs symmetry.
The IR spectra of 2a-f showed absorptions at 1786-1798
and 1730-1760 cm-1 due to the lactone and ester groups.
Their UV-vis spectra exhibited a peak at 415-419 nm,
which is a characteristic absorption for the 1,2-adducts of
C60 with the oxygen atom directly attached to the fullerene
skeleton.3g-i,6,7
Table 2. Reaction Temperatures, Molar Ratios, Reaction Times,
and Yields of C60-Fused Lactones 2a-fa
Even though the exact pathway is not quite clear for the
formation of disubstituted C60-fused lactones 2, a possible
reaction mechanism is proposed and shown in Scheme 2.
a All reactions were carried out with a molar ratio of C60:1:Fe(ClO4)3·xH2O:
Ac2O ) 1:2:2:20 in o-dichlorobenzene under nitrogen atmosphere unless
indicated otherwise. b Isolated yield; that in parentheses was based on
Scheme 2
.
Proposed Reaction Mechanism for the Formation of
c
consumed C60. C60:1d:Fe(ClO4)3·xH2O:Ac2O ) 1:2:2:50.
Lactones 2
yields for the Fe(ClO4)3-mediated reaction of C60 with
malonate esters 1a-f in the presence of Ac2O, affording the
scarce disubstituted C60-fused lactones 2a-f. It should be
pointed out that no 1,4-adduct, 1,16-adduct, and single-
bonded dimeric adduct of C60 could be identified from these
reactions under our optimized conditions.
As can be seen from Table 2, all examined malonate esters
1a-f could be utilized to prepare disubstituted C60-fused
lactones 2a-f in 12-37% yields (53-71% based on
consumed C60). Alkyl-substituted malonate esters 1a-c at
80 °C afforded good isolated yields (27-37%) for monoad-
ducts 2a-c. Interestingly, phenyl-substituted malonate ester
1d was very reactive (reaction temperature at 0 °C) yet gave
lower yield due to its tendency to form some byproducts.
Diethyl bromomalonate, which has been widely used in the
Bingel reaction, could react with C60 and Fe(ClO4)3 in the
Substituted malonate ester reacts with Fe(ClO4)3 to generate
radical A accompanied with the formation of Fe(ClO4)2 and
HClO4.9 Addition of radical A to C60 produces fullerenyl
4898
Org. Lett., Vol. 12, No. 21, 2010

radical B, which undergoes intramolecular cyclization to give
radical C. Oxidation of radical C by another molecule of
Fe(ClO4)3 leads to cation D along with counteranion ClO4
fused lactones. The synthesized disubstituted C60-fused
lactones have lactone and ester moieties, which can be
further manipulated to make other fullerene derivatives
including hydrofullerenes, fullerene hemiacetals, fullerene
hemiketals, and fullerenols.3g,10 A plausible reaction mech-
anism for the formation of lactones 2 is proposed. The present
study hints that the metal salts have significant effects on
the outcome of the reactions of C60, and it is worthwhile to
further explore their application in fullerene chemistry and
organic synthesis in general.
-
and Fe(ClO4)2. The addition of H2O, originated from hydrated
water in Fe(ClO4)3·xH2O or concomitant water in the system,
to cation D with the loss of H+ results in E. Elimination of
EtOH from intermediate E catalyzed by H+ affords C60-fused
lactone 2. The failure to obtain the expected C60-fused lactone
from the reaction with diethyl malonate might be due to
undesired pathways such as the deprotonation of intermediate
cation D and hydrogen atom abstraction from E by the ferric
ion.
In summary, the reaction of C60 with a substituted
malonate ester promoted by Mn(OAc)3 afforded only a
small amount of the desired disubstituted C60-fused lactone
along with the 1,4- and 1,16-adducts bearing two malonyl
groups as the major products. However, the scarce
disubstituted C60-fused lactones could be selectively
synthesized by simply changing the promoter from
Mn(OAc)3 to Fe(ClO4)3, indicating that Fe(ClO4)3 altered
the reaction pathway in favor of the formation of the C60-
Acknowledgment. The authors are grateful for the finan-
cial support from the National Natural Science Foundation
of China (No. 20972145), the Specialized Research Fund
for the Doctoral Program of Higher Education (No.
200803580019), and the National Basic Research Program
of China (2006CB922003).
Supporting Information Available: Experimental pro-
cedures, spectral data, and NMR spectra of 2a-f, 3a, and
4a. This material is available free of charge via the Internet
at http://pubs.acs.org.
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OL102056K
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