Synthesis of [60]fullerene-fused sultones via sulfonic acid group-directed c-h bond activation

Article abstract of DOI:10.1021/ol3007452

Functionalization with the sulfonic acid group as the directing group in a C-H activation reaction has been revealed for the first time. [60]Fullerene has been employed in the unprecedented palladium-catalyzed C-H activation reaction of arylsulfonic acids to afford [60]fullerene-fused sultones.

Full text of DOI:10.1021/ol3007452

ORGANIC
LETTERS
2012
Vol. 14, No. 8
2176–2179
Synthesis of [60]Fullerene-Fused
Sultones via Sulfonic Acid Group-Directed
CÀH Bond Activation
Fei Li,† Tong-Xin Liu,† 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 March 22, 2012
ABSTRACT
Functionalization with the sulfonic acid group as the directing group in a CÀH activation reaction has been revealed for the first time. [60]Fullerene
has been employed in the unprecedented palladium-catalyzed CÀH activation reaction of arylsulfonic acids to afford [60]fullerene-fused sultones.
Transition-metal-mediated or -catalyzed reactions of
fullerenes have provided useful methods for the prepara-
tion of a wide range of functionalized fullerene deriva-
tives.1 Our previous workin this direction hasbeenfocused
on the free-radical reactions of [60]fullerene (C60), which
On the other hand, CÀH bond activation has emerged
as one of the most important methodologies to construct
CÀC and CÀX (X = heteroatom) bonds in organic
synthesis.5 A directing group is usually required to achieve
high regioselectivity. A diverse range of directing groups,
such as amides, anilides, pyridines, oxime ethers, quino-
lines, oxazolines, and amines, have been reported for CÀH
activationreactions.5 However, only one type of acids, that
is, carboxylic acid, has been exploited to direct CÀH bond
activations, and CÀH halogenation, arylation, alkylation,
olefination, hydroxylation, and carboxylation reactions
was mainly promoted by Mn(OAc)3 and Fe(ClO4)3.3
2
Recently, we have developed the Pd-catalyzed reactions
of C60 and obtained novel C60-fused indoline and isoqui-
nolinone derivatives in a highly regioselective manner.4
† University of Science and Technology of China
‡ Lanzhou University
(1) For recent selected examples, see: (a) Nambo, M.; Noyori, R.;
(4) (a) Zhu, B.; Wang, G.-W. J. Org. Chem. 2009, 74, 4426. (b) Zhu,
B.; Wang, G.-W. Org. Lett. 2009, 11, 4334. (c) Chuang, S.-C.; Rajesh-
kumar, V.; Cheng, C.-A.; Deng, J.-C.; Wang, G.-W. J. Org. Chem. 2011,
76, 1599.
Itami, K. J. Am. Chem. Soc. 2007, 129, 8080. (b) Filippone, S.; Maroto,
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n-Domenech, A.; Suarez, M.; Martı
E. E.; Martı
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1, 578. (c) Tzirakis, M. D.; Orfanopoulos, M. J. Am. Chem. Soc. 2009,
131, 4063. (d) Nambo, M.; Wakamiya, A.; Yamaguchi, S.; Itami, K.
J. Am. Chem. Soc. 2009, 131, 15112. (e) Tzirakis, M. D.; Orfanopoulos,
M. Angew. Chem., Int. Ed. 2010, 49, 5891. (f) Xiao, Z.; Matsuo, Y.;
Nakamura, E. J. Am. Chem. Soc. 2010, 132, 12234. (g) Nambo, M.;
Segawa, Y.; Itami, K. J. Am. Chem. Soc. 2011, 133, 2402. (h) Maroto,
(5) For selected reviews on CÀH activations, see: (a) Chen, X.; Engle,
K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48, 5094.
(b) Xu, L.-M.; Li, B.-J.; Yang, Z.; Shi, Z.-J. Chem. Soc. Rev. 2010, 39,
712. (c) Sehnal, P.; Taylor, R. J. K.; Fairlamb, I. J. S. Chem. Rev. 2010,
110, 824. (d) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147.
(e) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215.
(e) Ackermann, L. Chem. Rev. 2011, 111, 1315. (f) Wencel-Delord, J.;
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E. E.; de Cozar, A.; Filippone, S.; Martı
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Cossıo, F. P.; Martın, N. Angew. Chem., Int. Ed. 2011, 50, 6060. (i) Lu,
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Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740.
S.; Jin, T.; Bao, M.; Yamamoto J. Am. Chem. Soc. 2011, 133, 12842.
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(2) Liu, T.-X.; Li, F.-B.; Wang, G.-W. Org. Lett. 2011, 13, 6130 and
references cited therein.
(6) For a review, see: Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q.
Acc. Chem. Res. 2012, DOI: 10.1021/ar200185g.
(7) (a) Wang, G.-W.; Yuan, T.-T.; Wu, X.-L. J. Org. Chem. 2008, 73,
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1800 and references cited therein.
r
10.1021/ol3007452
Published on Web 04/10/2012
2012 American Chemical Society

have been successfully realized.6 Our interest in CÀH
activation reactions4b,c,7 prompted us to explore another
type of organic acids for directing CÀH functionalization.
p-Toluenesulfonic acid (TsOH) has been added frequently
to promote Pd-catalyzed CÀH activation reactions by
increasing the electrophilicity of the Pd(II) center.4b,8 Pd-
(OTs)2 has also been employed asthe palladium source in a
few CÀH activation reactions.8b,9 Just like carboxylic
acids, it is possible that arylsulfonic acids can be functio-
nalized via sulfonic acid group-directed CÀH activation.
However, suchTsOHderivativeshavenotbeenreported in
all the aforementioned cases.4b,8,9 The electron-deficient
aryl ring of arylsulfonic acids is less prone to the CÀH
activation step compared to that of aryl carboxylic acids.
We have addressed this challenge, and herein report the
synthesis of sultones by Pd-catalyzed reaction of arylsul-
fonic acids with C60 via unprecedented sulfonic acid group-
directed CÀH bond activation.
thus inhibiting the catalytic reaction.4b With K2S2O8 as the
oxidant, various Pd catalysts were screened (Table 1, en-
tries 13À16). It was found that Pd(TFA)2 gave comparable
yield to that of Pd(OAc)2 (Table 1, entry 13 vs entry 1),
while PdCl2, Pd(PPh3)2Cl2, and Pd(PPh3)4 exhibited
slightly lower yields (Table 1, entries 14À16 vs entry 1).
A control experiment showed that the absence of a palla-
dium catalyst under otherwise identical conditions did not
produce any 2a (Table 1, entry 17). With economic con-
siderations, the optimized reaction conditions were thus
chosen as follows: Pd(OAc)2 and K2S2O8 as the catalyst
and oxidant, respectively, in ODCB/CH3CN = 8:1 at
140 °C for 24 h.
Table 1. Screening the Reaction Conditions for the
Pd-Catalyzed Reaction of C60 with 1aa
The readily available TsOH (1a) was chosen as a model
substrate. Our initial attempts to olefinate TsOH failed
with both acrylate esters and styrene under conditions
previously employed for aromatic carboxylic acids10 or
other combinations of Pd(OAc)2, oxidants, and solvents.
Gratifyingly, when C60 was utilized, TsOH could be
functionalized to give C60-fused sultone derivative 2a. This
sultone construction via Pd-catalyzed sp2 CÀH activation
of arylsulfonic acids has no precedent in the literature.
This reaction of C60 (36.0 mg, 0.05 mmol) with TsOH
(3 equiv) was screened in the presence of different palladium
catalysts (10 mol %), oxidants (3 equiv), and solvents. The
results are summarized in Table 1. Because of the poor
solubility of TsOH in ODCB, a mixture of ODCB (4 mL)
and CH3CN (0.5 mL) was first usedas the solvent to afford
product 2a in 30% yield (73% based on consumed C60)
when the reaction was catalyzed with Pd(OAc)2 (Table 1,
entry 1). However, the absence of CH3CN as the cosolvent
lowered the yield to 11% (Table 1, entry 2). Replacing
CH3CN with DMSO and DMF generated only a trace
amount of the desired product (Table 1, entries 3 and 4).
Further examination of other oxidants, including Cu-
(OAc)2, Cu(OTf)2, AgOAc, Ag2O, Ag2CO3, oxone, BQ,
and PhI(OAc)2, proved that K2S2O8 was the best for this
reaction with Pd(OAc)2 as the catalyst and provided the
highest product yield (Table 1, entry 1 vs entries 5À12).
Similar superior performance of CH3CN and K2S2O8 was
also observed previously for the Pd-catalyzed reaction of
C60 with anilides via CÀH bond activation.4b The exact
reason is unknown now, although the inefficiency of
DMSO and DMF compared to CH3CN might be due to
their stronger coordination to the palladium species and
yield of
entry
catalyst
oxidant
solvent (mL)
2a (%)b
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(TFA)2
PdCl2
K2S2O8
K2S2O8
K2S2O8
K2S2O8
ODCB/CH3CN (4:0.5) 30 (73)
2
ODCB (4)
11 (61)
trace
3
ODCB/DMF (4:0.5)
4
ODCB/DMSO (4:0.5) trace
5
Cu(OAc)2 ODCB/CH3CN (4:0.5) 6 (33)
Cu(OTf)2 ODCB/CH3CN (4:0.5) 5 (25)
6
7
AgOAc
Ag2O
Ag2CO3
oxone
BQ
ODCB/CH3CN (4:0.5) 11 (31)
ODCB/CH3CN (4:0.5) trace
ODCB/CH3CN (4:0.5) trace
ODCB/CH3CN (4:0.5) 10 (27)
ODCB/CH3CN (4:0.5) trace
8
9
10
11
12
13
14
15
16
17
PhI(OAc)2 ODCB/CH3CN (4:0.5) 18 (41)
K2S2O8
K2S2O8
ODCB/CH3CN (4:0.5) 31 (72)
ODCB/CH3CN (4:0.5) 24 (80)
ODCB/CH3CN (4:0.5) 27 (77)
ODCB/CH3CN (4:0.5) 26 (79)
ODCB/CH3CN (4:0.5) 0 (0)
PdCl2(PPh3)2 K2S2O8
Pd(PPh3)4
K2S2O8
K2S2O8
a All reactions were carried out with C60 (36.0 mg, 0.05 mmol),
catalyst (0.005 mmol), TsOH (28.5 mg, 0.15 mmol), and oxidant
(0.15 mmol) in the indicated solvent at 140 °C for 24 h in air. b Isolated
yield. Values in parentheses were based on consumed C60
.
The scope of this annulation reaction was investi-
gated next by exploring different arylsulfonic acids. As
shown in Table 2, a variety of arylsulfonic acids reacted
efficiently to afford the desired C60-fused sultones in
synthetically valuable yields. Arylsulfonic acids with both
electron-donating (Table 2, entries 1, 3, and 5) and elec-
tron-withdrawing (Table 2, entry 4) substituents on the
phenyl ring could be smoothly transformed into the de-
sired products in 18À30% yields (60À81% based on
consumed C60). β-Naphthylsulfonic acid (1f) could also
be employed and furnished sultone 2f in 22% yield (69%
based on consumed C60). In principle, two isomers could
(8) For selected examples, see: (a) Boele, M. D. K.; van Strijdonck, G.
P. F; de Vries, A. H. M.; Kamer, P. C. J.; de Vries, J. G.; Leeuwen, P. W.
N. M. J. Am. Chem. Soc. 2002, 124, 1586. (b) Houlden, C. E.; Bailey,
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C. D.; Ford, J. G.; Gagne, M. R.; Lloyd-Jones, G. C.; Booker-Milburn,
K. I. J. Am. Chem. Soc. 2008, 130, 10066. (c) Giri, R.; Lam, J. K.; Yu,
J.-Q. J. Am. Chem. Soc. 2010, 132, 686.
(9) Ng, K.-H.; Chan, A. S. C.; Yu, W.-Y. J. Am. Chem. Soc. 2010,
132, 12862.
(10) Miura, M.; Tsuda, T.; Satoh, T.; Pivsa-Art, S.; Nomura, M.
J. Org. Chem. 1998, 63, 5211.
Org. Lett., Vol. 14, No. 8, 2012
2177

regioisomers from bisadducts and multiadducts when
overreacted.
Table 2. Results for the Pd-Catalyzed Reaction of C60 with
Arylsulfonic Acids 1aÀfa
The structures of C60-fused sultones 2aÀf were fully
1
characterized by HRMS, H NMR, 13C NMR, FT-IR,
and UVÀvis spectroscopy. The high-resolution mass spec-
tra of 2aÀf displayed the correct molecular ion peaks. The
1H NMR spectra of 2aÀf showed all expected signals, with
one less aromatic proton than the starting material 1aÀf
due to the removal of one proton during the CÀH activa-
tion process. In the 13C NMR spectra of 2aÀf, there were
29À30 peaks including two half-intensity ones in the
134.60À153.19 ppm region for the 58 sp2-carbons of the
C60 moiety, consistent with their Cs symmetry. The two
sp3-carbons of the C60 skeleton were located at 97.56À
98.25 ppm and 59.91À60.38 ppm, close to those of the
previously reported C60-fused lactone derivatives.11 It
should be pointed out that the very low solubility of 2c
prevented us from obtaining its 13C NMR spectrum with
good signal/noise ratio. The IR spectra of 2aÀf showed
two strong absorptions at 1370À1377 and 1190À1200 cmÀ1
due to the sultone group. Their UVÀvis spectra exhibited a
peak at 421À422 nm, which is a characteristic absorption
for the 1,2-adducts of C60.2À4,11
Sultones exhibit biological activities12 and are syntheti-
cally valuable heterocycles that can react with a variety of
compoundstoaffordotheruseful products.13 Itisexpected
that our C60-fused sultones can be further elaborated to
produce functionalized fullerenes. Indeed, we successfully
achieved the ring-opening of C60-fused sultone 2a by
treating with excess BF3 OEt2 in ODCB at 150 °C and
obtained arylsulfonic ester-substituted hydrofullerene 3 in
3
86% yield (Scheme 1). To the best of our knowledge, the
unusual ring-opening of a sultone by BF3 OEt2 is also
3
unprecedented. Hydrofullerene 3 was likely formed via the
BF3-mediated cleavage of diethyl ether followed by hy-
dride transfer (see the Supporitng Information).14 The
acidic hydrogen attached to the fullerene skeleton in
hydrofullerene 3 could be easily deprotonated with KOtBu
in THF at room temperature.15 The color of the solution
changed immediatelyfrombrowntodark green, indicating
the formation of a monoanion C60RÀ. Further nucleophi-
lic substitution reaction of the in situgenerated C60RÀ with
CH3I gave 1,4-bisadduct 4 in 82% yield (Scheme 1).16
When the monoanion C60RÀ was treated with I2, the singly
bonded dimer 5 existed as a mixture of racemic and meso
isomers and was formed in 91% yield by coupling of the
monomer radicals C60R•,17 which were produced by one-
electron oxidation of C60RÀ with I2 (Scheme 1).16
a Unless otherwise specified, all reactions were performed with C60
(36.0 mg, 0.05 mmol), 1 (0.15 mmol), K2S2O8 (40.5 mg, 0.15 mmol), and
Pd(OAc)2 (1.1 mg, 0.005 mmol) in ODCB (4 mL)/CH3CN (0.5 mL) at
140 °C for 24 h. b Isolated yield by column chromatography. Values
in parentheses were based on consumed C60.
c Substrate 1c (30.9 mg,
0.15 mmol) was first dissolved in acetonitrile (0.5 mL) and then added
to the ODCB (4 mL) solution of C60 (36.0 mg, 0.05 mmol), Pd(OAc)2
(2.2 mg, 0.01 mmol), and K2S2O8 (40.5 mg, 0.15 mmol).
be produced for the reaction with both 1e and 1f. The
regioselective formation of 2e and 2f may be governed by
steric factors.4,7 It should be pointed out that the 18À30%
yields (60À81% based on consumed C60) of 2aÀf are
comparable with the reported yields for most other
monoadducts2À4,11 in fullerene chemistry, as C60 has 30
reactive CdC bonds and tended to give a mixture of
(12) (a) Meschkat, E.; Barratt, M. D.; Lepoittevin, J.-P. Chem. Res.
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Toxicol. 2001, 14, 110. (b) Perez-Perez, M.-J.; Balzarini, J.; Hosoya, M.;
Clercq, E. D.; Camarasa, M. J. Bioorg. Med. Chem. Lett. 1992, 2, 647.
(13) For a review on sultone chemistry, see: Metz, P. J. Prakt. Chem.
1998, 340, 1.
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33, 5045. (b) Smith, C. L. Organometallics 1995, 14, 3098.
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(17) (a) Wang, G.-W.; Wang, C.-Z.; Zhu, S.-E; Murata, Y. Chem.
Commun. 2011, 6111. (b) Wang, G.-W.; Wang, C.-Z.; Zou, J.-P. J. Org.
Chem. 2011, 76, 6088.
(11) For C60-fused lactones, see: (a) Bernstein, R.; Foote, C. S.
Tetrahedron Lett. 1998, 39, 7051. (b) Wang, G.-W.; Li, F.-B.; Zhang,
T.-H. Org. Lett. 2006, 8, 1355. (c) Wang, G.-W.; Zhu, B. Chem.
Commun. 2009, 1769. (d) Li, F.-B.; Liu, T.-X.; Huang, Y.-S.; Wang,
G.-W. J. Org. Chem. 2009, 74, 7743. (e) Li, F.-B.; Zhu, S.-E; Wang,
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Org. Lett. 2010, 12, 4896.
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Org. Lett., Vol. 14, No. 8, 2012

Scheme 1. Ring-Opening and Further Functionalization of
Sultone 2a
Scheme 2. Kinetic Isotope Effect Study for the Formation of
Sultone 2a
In summary, we have addressed the challenge of using
the sulfonic acid group for directing CÀH activation
reactions for the first time. C60 could be successfully
utilized in the Pd-catalyzed CÀH activation of arylsulfonic
acids leading to C60-fused sultones, albeit the attempts to
olefinate TsOH with acrylates and styrenes failed. The
present reaction involves the cleavage of CÀH and OÀH
bonds as well as the formation of CÀC and CÀO bonds.
The unprecedented ring-opening of C60-fused sultones was
To gain insight into the reaction mechanism for the forma-
tion of sultones 2, we performed a kinetic isotope effect (KIE)
study. Experiments revealed that the Pd-catalyzed reaction of
C60 with 1.5 equiv of 1a and 1.5 equiv of 1a-d4 exhibited a
primary kinetic isotope effect kH/kD = 4.3 (Scheme 2).
During our work, Bedford et al. reported the Pd-catalyzed
ortho-selective halogenation of anilides in the presence of
TsOH, and identified that the orthopalladated species of
TsOH was actually the catalyst.18 Nevertheless, the pallada-
cyclic complex was fragile and underwent rapid loss of
TsOH.18 Therefore, the CÀH functionalization of arylsulfo-
nic acids is viewed to be extremely difficult. Although the
exact reaction mechanism for the formation of 2 is currently
unknown, the reaction is believed to proceed through the
sulfonic acid group-directed ortho sp2 CÀH bond activation
to afford the same palladacycles,18 which undergo subse-
quent cyclization with C60 to eventually afford sultones 2.
achieved by heating with BF3 OEt2, and could be further
functionalized to 1,4-adduct and singly bonded fullerene
dimer.
3
Acknowledgment. The authors are grateful for financial
support from the National Natural Science Foundation of
China (21132007, 20972145) and National Basic Research
Program of China (2011CB921402).
Supporting Information Available. Experimental pro-
1
cedures, characterization data, and the H NMR and
13C NMR spectra of products 2aÀf, 3À5. This material
is available free of charge via the Internet at http://pubs.
acs.org.
(18) Bedford, R. B.; Haddow, M. F.; Mitchell, C. J.; Webster, R. L.
Angew. Chem., Int. Ed. 2011, 50, 5524.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 8, 2012
2179