Co-catalyzed radical cycloaddition of [60]fullerene with active dibromides: Selective synthesis of carbocycle-fused fullerene monoadducts

Article abstract of DOI:10.1021/ol401876n

An efficient and highly selective Co-catalyzed radical cycloaddition of [60]fullerene with active dibromides for the synthesis of three-, five-, six-, and seven-membered carbocycle-fused fullerene monoadducts has been reported. The controlled experiments unambiguously disclosed that the reaction proceeds through the formation of a fullerene monoradical as a key intermediate.

Full text of DOI:10.1021/ol401876n

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Co-Catalyzed Radical Cycloaddition of
[60]Fullerene with Active Dibromides:
Selective Synthesis of Carbocycle-Fused
Fullerene Monoadducts
Shirong Lu,†,§ Weili Si,† Ming Bao,‡ Yoshinori Yamamoto,†,‡ and Tienan Jin*,†
WPI-Advanced Institute for Materials Research (WPI-AIMR), Tohoku University,
Sendai 980-8577, Japan, and State Key Laboratory of Fine Chemicals, Dalian University
of Technology, Dalian 116012, China
tjin@m.tohoku.ac.jp
Received July 4, 2013
ABSTRACT
An efficient and highly selective Co-catalyzed radical cycloaddition of [60]fullerene with active dibromides for the synthesis of three-, five-, six-,
and seven-membered carbocycle-fused fullerene monoadducts has been reported. The controlled experiments unambiguously disclosed that the
reaction proceeds through the formation of a fullerene monoradical as a key intermediate.
Functionalization of fullerene offers much opportunity
for creating diverse fullerene-based materials with potential
applications in biological, materials science, and medicinal
chemistry.1 The fullerene cycloadducts fused by carbo-
cycles, such as tetrahydronaphthalene or cyclopentane,
exhibit high thermostability and have been demonstrated
to serve as durable electron acceptors for high-performance
polymer solar cells,1f,2 as well as photosensitive biochem-
ical probes.1a,3 The thermal DielsꢀAlder reaction of C60
with o-quinodimethane is one of the most employed and
straightforward methods for the construction of tetrahy-
dronaphthalene-fused fullerenes,4 but it usually requires a
high reaction temperature and produces a mixture of
multiadducts with low selectivity for a monoadduct. The
syntheses of cyclopentane-, cyclopentene-, and cyclopen-
tenone-fused fullerenes were also reported,5 which include
thermal [3 þ 2] cycloadditionofmethylenecyclopropanone
and cyclopropenone ketals with C60;5a,b cyclization of a
€
€
(4) (a) Belik, P.; Gugel, A.; Spickermann, J.; Mullen, K. Angew.
Chem., Int. Ed. 1993, 32, 90. (b) Puplovskis, A.; Kacenes, J.; Neilands, O.
Tetrahedron Lett. 1997, 38, 285. (c) Briggs, J. B.; Miller, G. P. C. R.
Chimie 2006, 9, 916. (d) Hudhomme, P. C. R. Chimie 2006, 9, 881.
(5) (a) Prato, M.; Suzuki, T.; Foroudian, H.; Li, Q.; Khemani, K.;
Wudl, F.; Leonetti, J.; Little, R. D.; White, T.; Rickborn, B.; Yamago,
S.; Nakamura, E. J. Am. Chem. Soc. 1993, 115, 1594. (b) Tokuyama, H.;
Nakamura, M.; Nakamura, E. Tetrahedron Lett. 1993, 34, 7429. (c)
† Tohoku University.
‡ Dalian University of Technology.
§ Present address: Shirong Lu, Department of Materials Science and
Engineering, University of California, Los Angeles, California, CA 90024,
USA.
ꢀ
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Allard, E.; Delaunay, J.; Cheng, F.; Cousseau, J.; Orduna, J.; Garın, J.
Org. Lett. 2001, 3, 3503. (d) O’Donovan, B. F.; Hitchcock, P. B.;
Meidine, M. F.; Kroto, H. W.; Taylor, R.; Walton, D. R. M. Chem.
Commun. 1997, 81. (e) Yang, H.-T.; Ren, W.-L.; Miao, C.-B.; Dong, C.-
P.; Yang, Y.; Xi, H.-T.; Meng, Q.; Jiang, Y.; Sun, X.-Q. J. Org. Chem.
(1) For reviews, see: (a) Nakamura, E.; Isobe, H. Acc. Chem. Res.
2003, 36, 807. (b) Martı
Altable, M.; Filippone, S.; Martı
Matsuo, Y.; Nakamura, E. Chem. Rev. 2008, 108, 3016. (e) Giacalone,
F.; Martın, N. Adv. Mater. 2010, 22, 4220. (f) Li, C.-Z.; Yip, H.-L.; Jen,
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2013, 78, 1163. (f) Marco-Martınez, J.; Marcos, V.; Reboredo, S.;
A. K.-Y. J. Mater. Chem. 2012, 22, 4161. (g) Matsuo, Y. Chem. Lett.
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Filippone, S.; Martın, N. Angew. Chem., Int. Ed. 2013, 52, 5115. (g)
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Chem. Soc. 2005, 127, 14182. (h) Wang, G. W.; Chen, X. P.; Cheng,
X. Chem.;Eur. J. 2006, 12, 7246. (i) Li, Y.-J.; Wang, G.-W.; Li, J.-X.;
Liu, Y.-C. New J. Chem. 2004, 28, 1043. (j) Liu, T.-X.; Li, F.-B.; Wang,
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r
10.1021/ol401876n
XXXX American Chemical Society

dianion with 1,3-dihalalkanes;5c phosphine- or
fullerene 2a was obtained in 57% yield (Table 1, entry 1).
Among the other ligands, such as BINAP, dppb, and dppf
that were tested, the use of dppf obviously increased the
yield of 2a up to a 67% isolated yield (entries 2ꢀ4). The
reaction did not proceed without the cobalt catalyst or
Mn reductant (entries 5ꢀ6). It is interesting to note that,
although we assumed that the H2O additive should be a
proton source for the formation of the hydroalkylated
fullerenes in the previous Co-catalyzed hydroalkylation of
2ꢀ
C60
DMAP-mediated or -catalyzed cycloaddition of C60 with
electron-deficient alkynes, alkenes, and allenes;5dꢀf photo-
cycloaddition of dienyl cyclopropanes with C60;5g and Mn-
mediated radical cycloaddition of C60 with R-aryl active
methylenes.5h However, a flexible and practical method
that can construct carbocycle-fused fullerenes with various
sizes is still rarely reported. It has been proven that func-
tionalization of fullerenes catalyzed by transition-metal
catalysts exhibits high efficiency and selectivity under mild
reaction conditions as well as high compatibility with a wide
range of functional groups.6 However, to the best of our
knowledge, the transition-metal-catalyzed cycloaddition of
C
60 (Scheme 1),6j the water additive is also indispensable
for the success of the present cycloaddition (entry 7). We
found that upon the addition of H2O to the CoCl2dppf
complex in ODCB, the color of the mixture was changed to
an orange solution, while CoCl2dppf in ODCB showed a
dark green suspension (Figure S1). Although the exact
structure of the cobalt complex formed from the reaction
of CoCl2dppf with water is yet to be verified, we thought
that the cobalt hydrate complex formed in situ should be the
actually active catalytic species. As byproducts, a very small
amount of biscycloadducts was produced together with the
recovered C60. The high selectivity of the monocycloadduct
should be attributed to the mild reaction conditions.
C60 for the preparation of those carbocycle-fused fullerenes
has never been reported to date.
Recently, we have developed a novel cobalt-catalyzed
radical hydroalkylation of C60 with various activated alkyl
bromides, such as benzyl bromide and allyl bromide, pro-
ducing the corresponding hydrofullerenes in good to high
yields with high monoselectivity.6j Herein, we report a new
and efficient Co-catalyzed radical carbocyclization of C60
with various active dibromides, which produced the [3 þ 2],
[4 þ 2], [5 þ 2], and [2 þ 1] fullerene cycloadducts in good to
high yields and high monoadduct selectivity at rt (eq 1).
Table 2. Co-Catalyzed [4 þ 2] Cycloaddition for Synthesis of
Fullerene-Fused Tetrahydronaphthalenesa
Table 1. Optimization of Reaction Conditionsa
catalyst
yield of 2a
recovered
entry
(10 mol %)
(%)b
C
60 (%)b
1
CoCl2dppe
CoCl2dppb
CoCl2BINAP
CoCl2dppf
none
57
34
34
68
5
2
53
3
25
4
70 (67)
5
0
0
0
91
94
95
6c
7d
CoCl2dppf
CoCl2dppf
a Reaction conditions: A 1,2-dichlorobenzene (ODCB, 4 mL) solu-
tion of CoCl2dppf (10 mol %), Mn (3 equiv), C60 (21.6 mg), H2O
(9 equiv), and dibromide 1 (1.5 equiv) under an Ar atmosphere was
stirred at rt. b Isolated yield.
a Reaction conditions: A 1,2-dichlorobenzene (ODCB, 4 mL) solu-
tion of catalyst (10 mol %), Mn (3 equiv), C60 (21.6 mg), H2O (9 equiv),
and 1a (1.5 equiv, 0.045 mmol) under an Ar atmosphere was stirred at rt
for 44 h. b HPLC yield using C70 as an internal standard. Isolated yield is
shown in parentheses. c Without Mn additive. d Without water additive.
Under the optimized conditions, the scope of the Co-
catalyzed cycloaddition of C60 with various active dibro-
mides was examined. All the reactions were monitored by
HPLC. The corresponding products 2 and the recovered
C60 were isolated using HPLC. The results of a [4 þ 2]
cycloaddition of the substituted 1,2-bis(bromomethyl)-
benzenes with C60 are shown in Table 2. Dibromides 1
having a bromo- (1b), ester- (1c), and cyano-group (1d) on
Initially, we tested the reaction of C60 with 1,2-bis-
(bromomethyl)benzene (1a) under the monoalkylation
conditions by using CoCl2(dppe) (10 mol %) as the
catalyst, a Mn reductant (3 equiv), and a H2O additive (9
equiv) at rt under an Ar atmosphere in 1,2-dichloroben-
zene (ODCB),6j and the corresponding dihydronaphthyl
B
Org. Lett., Vol. XX, No. XX, XXXX

the benzene ring produced the corresponding C60-
fused tetrahydronaphthalenes 2bꢀd in good yields with
excellent monocycloaddition selectivity (entries 1ꢀ3 and
HPLC spectra in the Supporting Information).2a 2,3-Bis-
(bromomethyl)naphthalene 1e is also an active dibromide
source, affording the corresponding monocycloadduct
2e in 56% yield (entry 4). The cycloaddition also showed
good compatibilities with dibromides 1f and 1g having a
substituent at the β-position, furnishing the corresponding
products 2f and 2g in 60% and 44% yields, respectively
(entries 5 and 6). It was noted that the indene monoadduct
2g has been demonstrated as an efficient electron acceptor
for polymer solar cells.2b
Although 1,3-dibromo-1,3-diphenylpropane 1k showed
relatively low activity, we were able to obtain the corre-
sponding diphenyl-substituted cyclopenta-fused fullerene
monoadduct 2k in moderate yield with a mixture of cis and
trans isomers.
Scheme 1. Co-Catalyzed [3 þ 2] Cycloaddition for Synthesis of
The reaction was further extended to the construction of
the seven- and three-membered carbocycles. For example,
1,8-bis(bromomethyl)naphthalene (1l) underwent the [5 þ 2]
cycloaddtion with C60 to afford the seven-membered carbo-
cycle-fused fullerene cycloadduct 2l in 40% yield (eq 2).
Moreover, the [2 þ 1] cycloaddition of 1-(dibromomethyl)-
3-fluorobenzene (1m) with C60 under the standard condi-
tions gave the corresponding phenylmethanofullerene 2m
in moderate yield (eq 3). Unfortunately, the [2 þ 2]
cycloaddition of C60 with active dibromides such as ethyl
2,3-dibromo-3-phenylpropionate or meso-1,2-dibromo-
1,2-diphenylethane did not proceed at all under the standard
conditions. It should be noted that the unactive aliphatic
dibromides such as 1,4-dibromobutane and 1,3-dibromo-
propane were totally inactive for the present cycloaddition.
The present cobalt catalysis was successfully applied to
the construction of a crown ether appended fullerene,
which has potential application in supramolecular assem-
blies, ion sensors, and fluorescence devices.7 For example,
under the standard conditions, the [4 þ 2] cycloaddition of
Cyclopenta-Fused Fullerenes under Standard Conditions
a A mixture of two products.
We also examined the [3 þ 2] cycloaddition of C60
with allylic dibromides for the construction of the fullerene-
fused five-membered carbocycles. As shown in Scheme 1,
the reaction of 3-bromo-2-(bromomethyl)prop-1-ene 1h
with C60 gave the corresponding cyclopenta-fused fullerene
monoadduct 2h in 63% yield, while the reaction of
(3-bromo-2-(bromomethyl)prop-1-en-1-yl)benzene 1i with
C60 with 1,2-bis(bromomethyl)benzene derivative 1n bear-
ing a crown ether moiety afforded the fullerene-bound
crown ether 2n in 73% yield (eq 4). This reaction also
provided an interesting opportunity for the synthesis of the
potentially useful fullerene dimer containing two fullerene
units bridged through an electroactive spacer.8 The reac-
tion of C60 with 1,2,3,4-tetrakis(bromomethyl)benzene 1o
(0.8 equiv) produced fullerene dimer 2o in 38% yield (eq 5).
C60 produced the corresponding cycloadducts as a mixture
of two regioisomers 2i and 2i0 in 69% total yield due to the
allylic migration. Similarly, 1-bromo-2-(bromomethyl)-1H-
indene 1j also exhibited high activity, which afforded a
mixture of two indene derivatives 2j and 2j0 in 53% yield.
(6) For selected transition-metal-catalyzed functionalization of full-
erenes, see: (a) Becker, L.; Evans, T. P.; Bada, J. L. J. Org. Chem. 1993,
58, 7630. (b) Martın, N.; Altable, M.; Filippone, S.; Martın-Domenech,
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n-Domenech, A.; Suarez, M.; Martın, N. Nat.
´ ´
To gain further insight into the reaction details, we carried
out the following control reactions as shown in Scheme 2.
Although our previous Co-catalyzed monofunctionalization
of C60 showed that the water additive was a hydrogen source
for the formation of the monosubstituted hydrofullerenes,6j
ꢀ
Chem. Soc. 2010, 132, 12234. (i) Maroto, E. E.; De Cozar, A.; Filippone,
S.; Martın-Domenech, A.; Suarez, M.; Cossıo, F. P.; Martın, N. Angew.
´
´
´
Chem., Int. Ed. 2011, 50, 6060. (j) Lu, S.; Jin, T.; Bao, M.; Yamamoto, Y.
J. Am. Chem. Soc. 2011, 133, 12842. (k) Lu, S.; Jin, T.; Kwon, E.; Bao,
M.; Yamamoto, Y. Angew. Chem., Int. Ed. 2012, 51, 802.
Org. Lett., Vol. XX, No. XX, XXXX
C

affords biradical C5g together with a Co(II) complex.
Intramolecular radical coupling in biradical C produces
the corresponding cycloadduct 2a along with the Co(0)
catalyst upon treatment with the Mn reductant. The
reactivity differences among the tested cobalt catalysts
having varied ligands and the significant effect of the water
additive in Table 1 indicate the interaction between the
formed radical intermediates and cobalt complexes,10
which may influence the reaction efficiency and selectivity.
Scheme 2. Control Experiments under Standard Conditions for
Formation of Cycloadduct 2a
a A mixture of meso and racemic isomers.
Scheme 3. Proposed Reaction Mechanism
we noticed that water was also indispensable for the present
cycloaddition. This result led us to examine the reaction
pathway from the hydrofullerene to cycloadduct. However,
when hydrofullerene 3a was treated with the standard con-
ditions, the corresponding cycloadduct 2a was obtained only
in 26% yield and most of 3a was decomposed, which is
inconsistent with the result obtained from Table 1, entry 4.
We further tested the cycloaddition using the single-
bonded fullerene dimer 4a as a substrate to investigate
the involvement of the fullerene monoradical intermediate
A (Scheme 3), because it was well demonstrated that the
single-bonded fullerene dimers dissociate to the stable mono-
radicals in solution.6k,9 Treatment of 4a with the standard
Co-catalyzed cycloaddition conditions produced the corre-
sponding cycloadduct 2a in 98% yield. These experimental
results clearly indicate that the reaction might proceed pre-
dominantly through the formation of a fullerene radical
intermediate followed by the intramolecular cycloaddtion
without formation of the hydrofullerene.
In summary, we have developed a new, efficient, and
general method for the construction of carbocyle-fused
fullerenes with various sizes via Co-catalyzed carbocy-
cloaddition of C60 with active dibromides. Various carbo-
cycle-fused fullerenes possessing 3-, 5-, 6-, and 7-membered
rings were obtained in good to high yields with high mono-
adduct selectivity under very mild conditions. The use of a
cobalt catalyst combined with a Mn reductant and water
additive in argon is crucial for the selective implementation
of the present cycloaddition efficiently. The results clearly
indicate that the corresponding products were formed
through the radical intermediates rather than the two-step
process through the formation of hydrofullerene products.
Investigation on further catalytic and selective synthesis of
the fullerene biscycloadducts or multicycloadducts, and
application to the electronic devices are in progress.
On the basis of these experimental observations, the
reaction mechanism is proposed as shown in Scheme 3.
Initially, the Co(II) complex activated by water is reduced
to the electron-rich Co(0) species by a Mn reductant.6j A
single electron transfer (SET) from the Co(0) complex to
an alkyl bromide in dibromide 1a forms benzyl radical B
along with a Co(I) complex.6j,10 Addition of radical B to
C60 generates the delocalized fullerene monoradical A, in
which a SET from Co(I) to the remaining alkyl bromide
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Acknowledgment. This work was supported by a Scien-
tific Research (B) from Japan Society for Promotion of
Science (JSPS) (No. 25288043), a Grant-in-Aid for Scientific
Research on Innovative Areas “Organic Synthesis Based on
Reaction Integration. Development of New Methods and
Creation of New Substances” from the MEXT (Japan), and
World Premier International Research Center Initiative
(WPI), MEXT (Japan).
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Supporting Information Available. Experimental pro-
cedures and characterization data. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX