FeCl3-mediated cyclization of [60]fullerene with N-benzhydryl sulfonamides under high-speed vibration milling conditions

Article abstract of DOI:10.1021/ol4014602

The FeCl₃-mediated reaction of [60]fullerene with N-benzhydryl sulfonamides afforded C₆₀-fused indane derivatives using the high-speed vibration milling technique. A possible reaction mechanism involving the unprecedented FeCl₃-mediated homolytic C-N bond cleavage of N-benzhydryl sulfonamides is proposed. The electrochemistry of the obtained C₆₀-fused indanes was also investigated.

Full text of DOI:10.1021/ol4014602

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
FeCl3‑Mediated Cyclization of
[60]Fullerene with N‑Benzhydryl
Sulfonamides under High-Speed
Vibration Milling Conditions
Yi-Tan Su† and Guan-Wu Wang*,†,‡
CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical
Sciences at Microscale, 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 May 23, 2013
ABSTRACT
The FeCl3-mediated reaction of [60]fullerene with N-benzhydryl sulfonamides afforded C60-fused indane derivatives using the high-speed
vibration milling technique. A possible reaction mechanism involving the unprecedented FeCl3-mediated homolytic CꢀN bond cleavage of
N-benzhydryl sulfonamides is proposed. The electrochemistry of the obtained C60-fused indanes was also investigated.
Due to the poor solubility of fullerenes in common
organic solvents, the solvent-free mechanochemical reac-
tion has particular significance in the chemical functiona-
lization of fullerenes.1 In 1996, the first mechanochemical
reaction of [60]fullerene (C60) conducted under solvent-
free and high-speed vibration milling (HSVM) conditions
was reported.2 Following that, many types of reactions such
as DielsꢀAlder reactions, 1,3-dipolar cycloadditions, nucleo-
philic additions, and radical reactions have been explored.1
In most cases, these reactions performed under the HSVM
conditions led to higher yields compared to the liquid-phase
counterparts. More importantly, some HSVM-promoted
reactions provide unexpected products that cannot be
generated by liquid-phase reactions. For example, the
HSVM technique has been applied to the reaction of C60
with various potassium salts, alkaline metals, or amines to
give fullerene dimers and trimers,3 which are still elusive by
the common liquid-phase protocols.
On the other hand, Lewis acids have been utilized in
fullerene functionalization. For instance, AlCl3- or FeCl3-
mediated FriedelꢀCrafts-type hydroarylation reactions of
C60,4aꢀf AlCl3-mediated tandem acetylation of 1,2-HC60Ar
with acetyl chloride,4d and FeCl3-mediated synthesis of
fullerenyl esters5 have been reported. Recently we disclosed
(3) Wang, G.-W.; Komatsu, K.; Murata, Y.; Shiro, M. Nature 1997,
387, 583. (b) Komatsu, K.; Wang, G.-W.; Murata, Y.; Tanaka, T.;
Fujiwara, K.; Yamamoto, K.; Saunders, M. J. Org. Chem. 1998, 63,
9358. (c) Komatsu, K.; Fujiwara, K.; Murata, Y. Chem. Commun. 2000,
1583. (d) Komatsu, K.; Fujiwara, K.; Murata, Y. Chem. Lett. 2000,
1016.
(4) (a) Olah, G. A.; Bucsi, I.; Lambert, C.; Aniszfeld, R.; Trivedi,
N. J.; Sensharma, D. K.; Prakash, G. K. S. J. Am. Chem. Soc. 1991, 113,
9387. (b) Olah, G. A.; Bucsi, I.; Ha, D. S.; Aniszfeld, R.; Lee, C. S.;
Prakash, G. K. S. Fullerene Sci. Technol. 1997, 5, 389. (c) Iwashita, A.;
Matsuo, Y.; Nakamura, E. Angew. Chem., Int. Ed. 2007, 46, 3513. (d)
Kokubo, K.; Tochika, S.; Kato, M.; Sol, Y.; Oshima, T. Org. Lett. 2008,
10, 3335. (e) Matsuo, Y.; Zhang, Y.; Soga, I.; Sato, Y.; Nakamura, E.
Tetrahedron Lett. 2011, 52, 2240. (f) Hashiguchi, M.; Watanabe, K.;
Matsuo, Y. Org. Biomol. Chem. 2011, 9, 6417.
† University of Science and Technology of China.
‡ Lanzhou University.
(1) For reviews, see: (a) Wang, G.-W. Fullerene Mechanochemistry.
In Encyclopedia of Nanoscience and Nanotechnology; Nalwa, H. S., Ed.;
American Scientific Publishers: Stevenson Ranch, CA, 2004; p 557. (b)
Komatsu, K. Top Curr. Chem. 2005, 254, 185. (c) Rodrıguez, B.;
´
Bruckmann, A.; Rantanen, T.; Bolm, C. Adv. Synth. Catal. 2007, 349,
2213. (d) Stolle, A.; Szuppa, T.; Leonhardt, S. E. S.; Ondruschka, B.
Chem. Soc. Rev. 2011, 40, 2317. (e) Zhu, S.-E; Li, F.; Wang, G.-W.
Chem. Soc. Rev. 2013, DOI: 10.1039/c3cs35494f.
(2) Wang, G.-W.; Murata, Y.; Komatsu, K.; Wan, T. S. M. Chem.
Commun. 1996, 2059.
r
10.1021/ol4014602
XXXX American Chemical Society

that the addition of AlCl3 to the Mn(OAc)3-mediated reac-
tion of C60 with active methylene compounds substituted
with an aryl or a benzyl group could switch the reaction
pathway and afford aryl-annulated products.6 However, the
Lewis acid mediated reaction of fullerenes under solvent-free
mechanochemical conditions has not been described. Herein,
we report the solvent-free FeCl3-mediated reaction of
C60 with N-benzhydryl sulfonamides under the HSVM
conditions.
Initially, the reaction of C60 with N-benzhydryl 4-toluene-
sulfonamide (1a) was chosen as the model reaction to screen
the reaction conditions. Much to our delight, when a mix-
ture of C60 (0.02 mmol), 1a (2 equiv), and FeCl3 (2 equiv)
was milled under the HSVM conditions for 1 h, C60-fused
indane 2a was obtained in 23% yield (Table 1, entry 1).
Increasing the amount of FeCl3 further to 3 equiv improved
the product yield to 27% (Table 1, entry 2). However,
prolonging the reaction time to 1.5 h was not beneficial
(Table 1, entry 3 vs 2). Efforts to enhance the product
Therefore, the molar ratio of 1:2:3 for the regents C60, 1a,
and FeCl3 and milling time of 1 h were chosen as the
optimized reaction conditions.
With the optimized conditions in hand, a series of
N-benzhydryl sulfonamides were examined to investigate
the scope and limitation of the reaction. Substrates bearing
weak electron-donating (4-Me and 3,4-(Me)2) or electron-
withdrawing (4-Cl and 4-Br) groups on the phenyl ring of
benzhydryl moieties could be employed and afforded the
corresponding products. It should be noted that the re-
gioselectivity was highly dependent on the electronic prop-
erty of the two aryl moieties, and the cyclization occurred
exclusively on the more electron-rich phenyl ring probably
due to the electron-deficient nature of the fullerene moiety.
All substrates gave only one product except for 1b. In
addition, the reaction selectively occurred at the less
hindered position of the phenyl ring (Table 2, entry 3).
Compared with 1d, substrate 1e containing a chloro group
at the ortho position also proceeded well and provided a
comparable product yield (Table 2, entry 5 vs 4). Substrate
1f bearing the electron-deficient chloro group on both
phenyl rings obviously retarded the reaction, giving pro-
duct 2f in only 16% yield (Table 2, entry 6). Replacement
of the Ts group by the less electron-withdrawing methyl-
sulfonyl (Ms) group reduced the reactivity and resulted
in a lower yield (Table 2, entry 8 vs 7). A larger-scale
reaction could be performed by using 50.0 mg of C60 with
the same reagent ratio, albeit at lower efficiency. For
example, the product yield of 2g was decreased from
41% (64% based on consumed C60) with 14.4 mg of C60
for 1 h to 28% (51% based on consumed C60) with 50.0 mg
of C60 for 2 h. The chloro and bromo groups in products
2dꢀg (Table 2, entries 4ꢀ8) may be used as a handle for
further coupling reactions. The methods for the synthesis
of fulleroindanes are still limited.4d,6,7 The synthesis of
fulleroindane 2a was previously reported by us and
required three steps starting from C60.7 Obviously, the
present mechanochemical protocol in only one step is
much more concise and efficient.
yield proved fruitless by replacing FeCl3 with FeCl3 6H2O,
3
Fe(NO3)3, ZnBr2, AlCl3, p-toluenesulfonic acid (PTSA),
Ce(NH4)2(NO3)6 (CAN), or Mn(OAc)3 2H2O (Table 1,
3
Table 1. Screening Conditions for the Reaction of C60 with 1aa
molar
ratiob
time
(h)
yield
(%)c
entry
additive
FeCl3
1
1:2:2
1:2:3
1:2:3
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
1
23 (56)
2
FeCl3
1
27 (66)
3
FeCl3
1.5
1
25 (60)
4
FeCl3 6H2O
trace
3
5
Fe(NO3)3
ZnBr2
AlCl3
1
0
0
0
0
0
0
0
0
6
1
It is intriguing that the reaction of C60 with substrate 1i
did not afford the desired product 2i. Instead, an unex-
pected DielsꢀAlder type product 3 was obtained in 15%
yield (Scheme 1). This method provides a new route to the
construction of C60-fused polycycles.8
7
1
8
PTSA
CAN
1
9
1
10
11d
12e
Mn(OAc)3 2H2O
1
3
FeCl3
FeCl3
12
12
Product 2a is a known compound, and its identity was
confirmed by comparison of its spectral data with those
reported in the literature.7 New compounds 2bꢀg and 3
were unambiguously characterized by HRMS, 1H NMR,
13C NMR, FT-IR, and UVꢀvis spectral data. All MALDI
mass spectra of these products gave the correct molecular
ion peaks. The 13C NMR spectra of 2cꢀg and 3 clearly
exhibited at least 45 peaks in the range of 133ꢀ159 ppm for
the sp2-carbons of the fullerene cage and two peaks in the
68ꢀ76 ppm range for the two sp3-carbons of the fullerene
skeleton, consistent with the C1 symmetry of their
a All reactions were performed under the HSVM conditions for 1 h
and repeated twice. b Molar ratio refers to C60/1a/additive. c Isolated
yield; that in parentheses was based on consumed C60.
d The reaction was
performed in o-dichlorobenzene (2 mL) at 120 °C. e The reaction was
performed in 1,1,2,2-tetrachloroethane (4 mL) at 120 °C.
entries 4ꢀ10). In addition, when the reaction was performed
in o-dichlorobenzene or 1,1,2,2-tetrachloroethane at 120 °C
for 12 h, no desired product was found (Table 1, entries 11
and 12), demonstrating the advantages of the solvent-free
mechanochemical reaction over the liquid-phase reaction.
(7) Su, Y.-T.; Wang, Y.-L.; Wang, G.-W. Chem. Commun. 2012, 48,
(5) Hashiguchi, M.; Obata, N.; Maruyama, M.; Yeo, K. S.; Ueno, T.;
Ikebe, T.; Takahashi, I.; Matsuo, Y. Org. Lett. 2012, 14, 3276.
(6) Liu, T.-X.; Li, F.-B.; Wang, G.-W. Org. Lett. 2011, 13, 6130.
8132.
(8) Eckert, J.-F.; Bourgogne, C.; Nierengarten, J.-F. Chem. Commun.
2002, 712.
B
Org. Lett., Vol. XX, No. XX, XXXX

Table 2. Results for the Reaction of C60 with N-Benzhydryl
Sulfonamides 1aꢀh in the Presence of FeCl3 under the HSVM
Conditionsa
Scheme 1. FeCl3-Promoted Reaction of C60 with N-Benzhydryl
Sulfonamide 1i under HSVM Conditions
molecular structures. It is noteworthy that line broad-
enings for four aryl protons and four aryl carbons were
observedin theNMR spectra offulleroindanes2 except for
2e due to the restricted rotation of the R2-containing
phenyl ring. The broadened peaks became narrower and
well-resolved ones, when 2d, for example, was heated to
70 °C in CHCl2CHCl2/DMSO-d6. A similar phenomenon
for the restricted rotation of the phenyl substituent in
fulleropyrrolidines has been documented.9 In contrast,
the rotation of the aryl ring in 2e is prevented by its
ortho-chloro substituent and, thus, gave well-resolved
NMR peaks at room temperature. The peak numbers
and splitting patternsof the 1H NMR peaks of 2eremained
unchanged, and no coalescence was observed from 12 to
70 °C in CHCl2CHCl2/DMSO-d6, indicating the existence
of only one diastereoisomeric conformer and thus the high
diastereoselectivity of the reaction.9 Their UVꢀvis spectra
displayed characteristic peaks at around 430 nm, which is a
diagnostic absorption for 1,2-adducts of C60.2,3a,3b,6,7
To gain more insight into the reaction mechanism, we
carried out the MALDI-TOF MS analysis of the reaction
mixture of C60, 1g, and FeCl3 under our HSVM conditions
and observed the formation of the benzhydryl dimer 4
(Figure 1). In the absence of C60, dimer 4 was also for-
med by treating 1g with FeCl3. Furthermore, when an
equimolar amount of 2,2,6,6-tetramethylpiperidine-N-oxide
(TEMPO) was added to the reaction system, compound 2g
could not be obtained. These results suggested that
N-benzhydryl radicals were most likely generated from
N-benzhydryl sulfonamides via the FeCl3-meditated CꢀN
bond cleavage under the HSVM conditions. To the best of
our knowledge, the Lewis acid promoted homolytic CꢀN
bond cleavage of N-benzhydryl sulfonamides is unprece-
dented, although the corresonding FeCl3-meditated het-
erolytic CꢀN bond cleavage has been reported.10
On the basis of the above experimental results, a plau-
sible mechanism for the formation of fulleroindanes 2aꢀg
(9) Ajamaa, F.; Duarte, T. M. F.; Bourgogne, C.; Holler, M.; Fowler,
P. W.; Nierengarten, J.-F. Eur. J. Org. Chem. 2005, 3766.
(10) For selected recent examples: (a) Liu, C.-R.; Yang, F.-L.; Jin,
Y.-Z.; Ma, X.-T.; Cheng, D.-J.; Li, N.; Tian, S.-K. Org. Lett. 2010, 12,
3832. (b) Liu, C.-R.; Wang, T.-T.; Qi, Q.-B.; Tian, S.-K. Chem. Commun.
2012, 48, 10913.
a All reactions were performed with 0.02 mmol of C60, 0.04 mmol of 1,
and 0.06 mmol of FeCl3 under the HSVM conditions for 1 h, repeated twice.
b Isolated yield; that in the parentheses was based on consumed C60.c Products
2b and 2b0 could not be separated from each other by preparative HPLC.
Org. Lett., Vol. XX, No. XX, XXXX
C

Table 3. Half-Wave Reduction Potentials (V) of C60, PCBM, 2a,
2cꢀg, and 3a
compd
E1
E2
E3
C60
PCBM
2a
ꢀ1.076
ꢀ1.160
ꢀ1.165
ꢀ1.182
ꢀ1.153
ꢀ1.159
ꢀ1.142
ꢀ1.156
ꢀ1.174
ꢀ1.460
ꢀ1.538
ꢀ1.540
ꢀ1.566
ꢀ1.530
ꢀ1.534
ꢀ1.526
ꢀ1.540
ꢀ1.550
ꢀ1.925
ꢀ2.050
ꢀ2.069
ꢀ2.113
ꢀ2.059
ꢀ2.068
ꢀ2.058
ꢀ2.078
ꢀ2.090
2c
2d
2e
Figure 1. Benzhydryl dimer 4.
2f
2g
3
Scheme 2. Proposed Reaction Mechanism for the Formation of
Fulleroindanes 2aꢀg
a Versus ferrocene/ferrocenium. Experimental conditions: 1 mM of
compound and 0.1 M of n-Bu4NClO4 in anhydrous o-dichlorobenzene;
reference electrode: SCE; working electrode: Pt; auxiliary electrode: Pt
wire; scanning rate: 20 mV sꢀ1
.
(ꢀ1.174 V) are even more cathodically shifted relative to
PCBM (ꢀ1.160 V). Since the LUMO levels of fullerene
compounds are estimated by their onset reduction poten-
tials (LUMO = ꢀ(E1 þ 4.8) eV).12 The high LUMO levels
of fulleroindanes 2 and 3 imply a potential application as
acceptors in organic photovoltaic devices.13
In summary, we have disclosed that the solvent-free
FeCl3-mediated reaction of C60 with N-benzhydryl sulfo-
namides under high-speed vibration milling conditions af-
fords the scarce C60-fused indanes, which cannot be obtained
in the liquid-phase counterparts. The intriguing formation of
fulleroindane derivatives is believed to proceed via a se-
quence that includes the unprecedented FeCl3-mediated
homolytic CꢀN bond cleavage of N-benzhydryl sulfona-
mides, radical addition to C60, intramolecular radical annu-
lation, and oxidation. The fulleroindane derivatives may be
utilized in solar cells.
is outlined in Scheme 2. Initially benzhydryl radicals A are
generated from N-benzhydryl sulfonamides 1 through the
FeCl3-mediated homolytic CꢀN bond cleavage. Addition
of radicals A to C60 provides fullerenyl radicals B, which
can undergo intramolecular cyclization to give radicals C.
Due to the electron deficiency of fullerenyl radicals B, the
cyclization selectively occurred on the more electron-rich
phenyl ring. Oxidation of radicals C by the Fe3þ species
results in aryl cations D.11 Loss of Hþ from cations D leads
to the formation of C60-fused indanes 2. Although the
reaction most likely proceeds in a radical process via the
homolytic CꢀN bond cleavage, the alternative pathway via a
sequence of heterolytic CꢀN bond cleavage followed by
addition of the formed carbocation to C60 and final intra-
molecular FriedelꢀCrafts arylation cannot be completely
excluded and may operate simultaneously.
Table 3 summarizes the half-wave reduction potentials
of C60, PCBM, 2a, 2cꢀg, and 3. It can be seen that the first
reduction potentials (E1) of fulleroindanes 2 and polycycle
3 are 66ꢀ106 mV more negative than that of C60. Notably,
most of them were comparable to that of PCBM. Further-
more, the onset reduction potential of 2c (ꢀ1.182 V) and 3
Acknowledgment. We are grateful for financial support
from the National Natural Science Foundation of China
(21132007, 91021004), Specialized Research Fund for the
Doctoral Program of Higher Education (20123402130011),
and National Basic Research Program of China (2011-
CB921402).
Supporting Information Available. Experimental pro-
cedures, spectral data, NMR spectra, MS of reaction
mixtures, and voltammograms. This material is available
free of charge via the Internet at http://pubs.acs.org.
(12) Matsuo, Y.; Iwashita, A.; Abe, Y.; Li, C. Z.; Matsuo, K.;
Hashiguchi, M.; Nakamura, E. J. Am. Chem. Soc. 2008, 130, 15429.
(13) For a recent review, see: Li, C.-Z.; Yip, H.-L.; Jen, A. K.-Y.
J. Mater. Chem. 2012, 22, 4161.
(11) For a recent example, see: Wei, W.-T.; Zhou, M.-B.; Fan, J.-H.;
Liu, W.; Song, R.-J.; Liu, Y.; Hu, M.; Xie, P.; Li, J.-H. Angew. Chem.,
Int. Ed. 2013, 52, 3638.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX