Reactions of the electrochemically generated dianion of [60]fullerene with bulky secondary alky bromides

Article abstract of DOI:10.1016/j.tetlet.2019.03.019

Reactions of the electrochemically generated dianion of [60]fullerene (C₆₀ ^2?) with bulky secondary alkyl bromides exhibit different reaction behaviors. Reaction of C₆₀ ^2? with diphenylbromomethane gives rise to

Full text of DOI:10.1016/j.tetlet.2019.03.019

Accepted Manuscript
Reactions of the electrochemically generated dianion of [60]fullerene with bul-
ky secondary alky bromides
Kai-Qing Liu, Guan-Wu Wang
PII:
S0040-4039(19)30227-8
https://doi.org/10.1016/j.tetlet.2019.03.019
TETL 50660
DOI:
Reference:
Tetrahedron Letters
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Please cite this article as: Liu, K-Q., Wang, G-W., Reactions of the electrochemically generated dianion of
[60]fullerene with bulky secondary alky bromides, Tetrahedron Letters (2019), doi: https://doi.org/10.1016/j.tetlet.
2019.03.019
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Reactions of the electrochemically generated dianion of
[60]fullerene with bulky secondary alky bromides
Kaiqing Liu and Guan-Wu Wang
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1
Tetrahedron Letters
Reactions of the electrochemically generated dianion of [60]fullerene with bulky
secondary alky bromides
Kai-Qing Liua, and Guan-Wu Wanga,b 
aHefei National Laboratory for Physical Sciences at Microscale, iChEM and Department of Chemistry, University of Science and Technology of China, Hefei
230026, China
bState Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, P. R. China.
ARTICLE INFO
ABSTRACT
2
Article history:
Received
Received in revised form
Accepted
Reactions of the electrochemically generated dianion of [60]fulllerene (C60 −) with bulky
2−
secondary alkyl bromides exhibits different reaction behaviors. Reaction of C60 with
diphenylbromomethane gives rise to C60HR or C60R2 (R = CHPh2) adducts, while reaction of
C60 with diethyl 2-bromomalonate unexpectedly affords methanofullerene C60>CR2 (R =
CO2Et). Plausible reaction mechanisms have been proposed to explain the formation of the
observed products.
2
−
Available online
2019 Elsevier Ltd. All rights reserved.
Keywords:
[60]Fullerene dianion
Electrosynthesis
Bulky electrophile
Alkyl bromide
———
 Corresponding author. Tel.: +86 0551 63607864; E-mail: gwang@mail.ustc.edu.cn

2
Tetrahedron Letters
when the reaction temperature was elevated to 30 oC and allowed
Introduction
to react for 3 h (Scheme 1c). The details for monitoring the
reaction mixture at 30 oC by high-performance liquid
chromatography can be found in Figure S1. It should be noted
that no appreciable amount of 1,2- and 1,16-bisadducts could be
identified.
[60]Fullerene (C60) has attracted great attention since it was
discovered in 1985.1 For the wide applications in materials and
biological science, great efforts have been made in the synthesis
of fullerene derivatives.2 Numerous methods have been
established to synthesize functionalized fullerene derivatives.3
2
Among these methods, fullerene dianion C60 −, which can be
generated either chemically or electrochemically, is considered as
an excellent building block in fullerene chemistry.4
2
−
Electrochemical generation of C60 is a preferable way to
accurately realize and control its formation.5
2
−
Alkylation reactions of C60 had been studied extensively in
2
the literature. Previous studies showed that C60 − could react with
alkyl bromides or iodides to generate bisadducts 1,2- and/or 1,4-
2
−
C60R2.4 When C60 reacted with methyl iodide, the least steric
hindered electrophile, the 1,2-bisadduct (1,2-C60Me2) was the
main product along with the 1,4-bisadduct (1,4-C60Me2) as the
2
−
minor product.4a However, when C60 reacted with other steric
bulkier primary halides, the regioselectivity was reversed. That is
to say, 1,4-bisadducts were obtained predominantly or
2
−
exclusively.4b-h Interestingly, it was reported that C60 could
react with the sterically hindered diethyl 2-bromo-2-
methylmalonate, a tertiary alkyl halide, to provide 1,4- and 1,16-
bisadducts C60[-CMe(CO2Et)2]2 in 35% and 7% yields,
respectively.6 We were wondering what would happen if a bulky
2
secondary alkyl halide was utilized to react with C60 −. With this
question in mind and our continuous interest in fullerene
chemistry using fullerene anions as the reactants,7 herein we
2
−
report the reactions of C60
with diphenylbromomethane
(BrCHPh2) and diethyl 2-bromomalonate (BrCH(CO2Et)2) as the
representative bulky secondary alkyl halides.
Scheme 1. Reaction of C602– with BrCHPh2 under different conditions.
Computational studies at the B3LYP/6-31G(d) level were also
performed to give a better understanding of the regioselectivity
for the bisalkylation process.9 Figure 1 shows the partial natural
bond orbital (NBO) charge distribution of the optimized
intermediate C60(CHPh2)−. According to the calculated charge
distribution, C2 (−0.105) of C60(CHPh2)− is the most negatively
charged carbon atom among the nonfunctionalized C60 carbon
atoms, and should be more prone to react with a less steric
hindered electrophile. The less negatively charged carbon atoms
are C4 (−0.080) and C11 (−0.077) followed by C16 (−0.048).
Thus, the most electronegative C2 is preferable for protonation
due to the small size of the proton. The introduction of the
second CHPh2 group at the C2 atom would lead to bisalkylated
1,2-C60(CHPh2)2, while reaction at both C4 and C11 results in
1,4-C60(CHPh2)2. In parallel, the reaction of BrCHPh2 with
C60(CHPh2)− at the C16 atom would provide 1,4-C60(CHPh2)2.
The relative energies of the optimized 1,2-, 1,4- and 1,16-adducts
with two CHPh2 groups were performed and the results are
shown in Figure 1. The calculated energy of 1,4-C60(CHPh2)2 is
lower those of 1,2-C60(CHPh2)2 and 1,16-C60(CHPh2)2 by 11.8
and 10.6 kcal/mol, respectively. These computation results are
consistent with the selective formation of 1,4-C60(CHPh2)2, and
Results and discussion
2
−
We first examined the reaction of C60 with BrCHPh2. A
solution of 14.5 mg (0.02 mmol) of C60 in 15.8 mL of ortho-
dichlorobenzene (ODCB) containing 0.1
M
tetra-n-
butylammonium perchlorate (TBAP) was electroreduced by
controlled potential electrolysis (CPE) at −1.20 V vs SCE under
argon atmosphere at 20 oC. The potentiostat was turned off when
the theoretical number of coulombs required for full conversion
2
−
of C60 into C60 was reached. Then, 24.6 mg (0.10 mmol) of
2
BrCHPh2 was added to the solution of C60 −. The reaction
mixture was allowed to stir for 3 h, and filtered through a silica
gel plug to remove TBAP. Column separation over silica gel
afforded 1,2-dihydrofullerene 2 in a yield of 42% along with 25%
of recovered C60 (Scheme 1a). The yield of 2 could not be further
increased by extending the reaction time to 5 h, and no other
products could be isolated in an amount enough for spectral
characterization. We noted that the color of the reaction mixture
before the filtration through silica gel to remove TBAP was
greenish, indicating that the fullerenyl monoanion C60(CHPh2)−
should exist in the solution and captured a proton during the
filtration through silica gel to provide 2.7e Therefore, an acid was
added to completely protonate the fullerenyl anion before
workup. To our satisfaction, the yield of 2 was increased to 59%
when 1 equiv. of trifluoroacetic acid (TFA) was added to quench
2
can explain the observed regioselectivity of C60 − with BrCHPh2,
which is dominantly governed by the steric hindrance rather than
charge density distribution due to the two bulky CHPh2 addends.
the reaction (Scheme 1b). Compound
2 was previously
According to the experimental and computation results, a
plausible mechanism is outlined in Scheme 2. First, C60 is
synthesized from the monoalkylation of C60H2 with 109 equiv of
BrCHPh2 in the presence of excess tetrabutylammonium
hydroxide (TBAOH) at room temperature.8 In this case, the
formation of bisalkylated product 3 was not observed, consistent
with the fact that we could not isolate compound 3 at ambient
temperature even after prolonged reaction time. To our delight,
the desired product 3 could be selectively obtained in 46 % yield

3
Scheme 2. Proposed reaction mechanism of C602– with diphenylbromomethane.
2
−
We then explored the reaction of C60 with 2 equiv of
BrCH(CO2Et)2, a bulky secondary alkyl bromide with two strong
electron-withdrawing substituents. To our surprise, no expected
1,2- 1,4- or 1,16-bisadduct C60[CH(CO2Et)2]2 was obtained.
Instead, the methanofullerene product 4 was unexpectedly
isolated in 53% yield after reaction for only 10 min (Scheme 3).
The same compound 4 was obtained in 45% yield from the
Bingel reaction of C60 with 1.5 equiv of BrCH(CO2Et)2 in the
presence of 10 equiv of NaH for 6.5 h.10 Intriguingly, the same
11.8 kcal/mol
1,2-bisadduct
0.0 kcal/mol
1,4-bisadduct
10.6 kcal/mol
1,16-bisadduct
2
−
product 4 was also synthesized from the reaction of C60 with
excess amount of dibromomalonate ester Br2C(CO2Et)2, yet in
only 20% yield.11,12 Therefore, our protocol for the synthesis of
methanofullerene 4 has advantages over the previously reported
procedures in term of higher product yield and shorter reaction
time.
Figure 1. NBO charge distribution of the intermediate C60(CHPh2)−, and relative
energies of 1,2-, 1,4- and 1,16-bisadducts at B3LYP/6-31G(d) level.
2
electroreduced to its dianion C60 −. Then a single electron-transfer
2
(SET) process takes place between C60 − and Ph2CHBr and leads
to C60 anion radical (C60−·) and diphenylbromomethanyl radical
·CHPh2.4b Then, the coupling of these two radicals generates the
intermediate C60(CHPh2)−. The C60(CHPh2)− intermediate can
undergo either protonation process to provide hydrofullerene 2 or
an SN2 reaction process with BrCHPh2 at slightly elevated
temperature to afford 1,4-bisadduct 3.
Scheme 3. Reaction of C602– with diethyl 2-bromomalonate.
It is of interest to understand the reaction pathway for the
formation of 4. Although the exact reaction mechanism is not
clear now, we believe that the first step should be an electron-
2
−
−·
transfer from C60
to BrCH(CO2Et)2 to give C60 and
·CH(CO2Et)2 (A) with the removal of Br−, followed by the radical
coupling to afford fullerenyl anion C60[CH(CO2Et)2] (B).4b
−
Owing to the attachment of two strong electron-withdrawing
CO2Et groups to the CHBr moiety, BrCH(CO2Et)2 is a better
electron acceptor than other alkyl bromides such as BrCHPh2 and
may be able to accept an electron from anionic B to generate
·
radical C60[CH(CO2Et)2] (C). The trace amount of O2 existed in
the reaction system may also help to oxidize the anionic B to the
radical C. Radical C prefers to undergo cyclization with the
assistance of hydrogen abstraction by the generated A to provide
the observed methanofullerene 4 (Scheme 4).

4
Tetrahedron Letters
K. M.; Gao, X.; Van Caemelbecke, E.; Hirasaka, T.; Suenobu, T.;
Fukuzumi, S. J. Phys. Chem. A 1998, 102, 3898-3906; (d) Allard,
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Y.; Cousseau, J.; Ordúna, J.; Garín, J. Org. Lett. 2001, 3, 3503-
3506; (f) Allard, E.; Cheng, F.-Y.; Chopin, S.; Delaunay, J.;
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Allard, E.; Delaunay, J.; Cousseau, J. Org. Lett. 2003, 5, 2239-2242;
(h) Zheng, M.; Li, F.-F.; Shi, Z.-J.; Gao, X.; Kadish, K. M. J. Org.
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5.
6.
Echegoyen, L.; Echegoyen, L. E. Acc. Chem. Res. 1998, 31, 593-
601.
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Xiao, Y.; Zhu, S.-E; Liu, D.-J.; Suzuki, M.; Lu, X.; Wang, G.-W.
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G.-W. Chin. J. Chem. 2014, 32, 699-702; (d) Wang, J.-J.; Lin, H.-
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Scheme 4. Plausible reaction mechanism of C602– with diethyl 2-bromomalonate.
In order to provide more evidence for the proposed electron-
transfer process from the anionic B to BrCH(CO2Et)2, we
performed the reaction of radical anion C60−· with BrCH(CO2Et)2.
It turned out that the reaction indeed proceeded and afforded the
same methanofullerene 4 in 51% yield (Scheme 5). It is believed
−·
that C60 can transfer an electron to BrCH(CO2Et)2 to provide
8.
9.
Meier, M. S.; Bergosh, R. G.; Gallagher, M. E.; Spielmann, H. P.;
Wang, Z.-W. J. Org. Chem. 2002, 67, 5946-5952.
Gaussian09 (RevisionB.01), M. J. Frisch, et al., Gaussian Inc.
Wallingford CT, 2010.
C60 and malonate radical A, which combine to form radical C and
subsequent cyclization to provide 4. A long reaction time of 1 h
−·
2
was required for C60 than for with C60 −, probably due to the
stronger electron-donating capability of the latter to
BrCH(CO2Et)2.
10. Bingel, C. Chem. Ber. 1993, 126, 1957-1959.
11. Boulas, P. L.; Zuo, Y.-H.; Echegoyen L. Chem, Commun. 1996,
1547-1548.
12. The methanofullerene 4 was obtained in 53% yield when the
2-
reaction of C60 with Br2C(CO2Et)2 was performed under our
conditions.
Supplementary Material
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.tetlet.
–
Scheme 5. Reaction of C60 · with diethyl 2-bromomalonate.
Conclusion
In summary, the reactions of the electrochemically generated
2
−
C60 with diphenylbromomethane and diethyl 2-bromomalonate
as representative bulky second alkyl bromides have been
investigated. This study shows that different second alkyl
bromides with different electronic properties exhibit different
2
reaction behaviors towards C60 −. Plausible reaction mechanisms
have been proposed to explain the observed formation of
monoalkylation, bisalkylation and cyclopropylation products.
Acknowledgements
We are thankful for financial support from the National Natural
Science Foundation of China (21572211).
References and notes
1.
2.
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2012, 22, 4161-4177.
3.
4.
For selected reviews, see: (a) Thilgen, C.; Diederich, F. Chem. Rev.
2006, 106, 5049-5135; b) Matsuo, Y.; Nakamura, E. Chem. Rev.
2008, 108, 3016-3028; (c) Zhu, S.-E; Li, F.; Wang, G.-W. Chem.
Soc. Rev. 2013, 42, 7535-7570.
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Jones, M. T.; Kadish, K. M. J. Am. Chem. Soc. 1993, 115, 8505-
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5
Highlights
2
−
 Reaction of the electrogenerated C60 with
bulky second alkyl bromides
 Different alkyl bromides exhibiting different
2
−
reaction behaviors toward C60
 Reaction of C60 − with BrCHPh2 affording 1,2-
2
C60HR or 1,4-C602R2 (R = CHPh2)
−
 Reaction of C60 with BrCH(CO2Et)2 giving
methanofullerene C60>CR2 (R = CO2Et)