Palladium-catalysed heteroannulation of [60]fullerene with N-benzyl sulfonamides and subsequent functionalisation

Article abstract of DOI:10.1039/c2cc33923d

The palladium-catalysed heteroannulation of [60]fullerene with various N-benzyl sulfonamides via C-H bond activation affords [60]fullerene-fused tetrahydroisoquinolines. In the presence of a Bronsted acid [60]fullerene-fused tetrahydroisoquinolines are transformed to [60]fullerene-fused indanes, in which the sulfonamide group can be removed or replaced with an aryl group.

Full text of DOI:10.1039/c2cc33923d

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COMMUNICATION
Palladium-catalysed heteroannulation of [60]fullerene with N-benzyl
sulfonamides and subsequent functionalisationwzy
Yi-Tan Su,a You-Liang Wanga and Guan-Wu Wang*ab
Received 31st May 2012, Accepted 22nd June 2012
DOI: 10.1039/c2cc33923d
The palladium-catalysed heteroannulation of [60]fullerene with
various N-benzyl sulfonamides via C–H bond activation affords
[60]fullerene-fused tetrahydroisoquinolines. In the presence of a
Brønsted acid [60]fullerene-fused tetrahydroisoquinolines are trans-
formed to [60]fullerene-fused indanes, in which the sulfonamide
group can be removed or replaced with an aryl group.
Pd-catalysed heteroannulation of C60 with N-benzyl sulfonamides.
Intriguingly, the obtained C60-fused tetrahydroisoquinolines have
been transformed to C60-fused indanes through a Brønsted acid-
promoted rearrangement. Furthermore, the sulfonamide group in
C60-fused indanes can be removed or replaced with an aryl group.
Initially, we chose the Pd-catalysed reaction of C60 with
N-benzyl-4-toluenesulfonamide (1a) as the model reaction
for our optimization study. When a mixture of C60 (36.0 mg,
0.05 mmol), 1a (5 equiv.) and Pd(OAc)2 (10 mol%) in
O-dichlorobenzene (4 mL) was heated at 100 1C for 2 h, only
a trace amount of the product was identified (Table 1, entry 1).
p-Toluenesulfonic acid (PTSA) was found to be beneficial to the
C–H activation reaction of C60.4a After addition of 2 equiv. of
PTSA, C60-fused tetrahydroisoquinoline 2a was obtained in 13%
yield (Table 1, entry 2). In contrast to the previously reported
Pd-catalysed reaction of C60 with N-benzyl benzamides,4b
A vast number of chemical reactions have been discovered to
functionalise fullerenes since the 1990s.1 Among them transition-
metal-mediated or -catalysed reactions of fullerenes have attracted
significant attention.2 Palladium-catalysed reactions of [60]fullerene
(C60) have also been disclosed.3,4 However, functionalisation of C60
via a C–H bond activation strategy is underdeveloped and limited
to the Pd-catalysed reactions of C60 with anilides,4a benzamides4b
and arlysulfonic acids.4c It was reported that the amide-directed
ortho C–H bond activation occurred selectively at the benzamide
phenyl ring rather than at the phenyl ring of the N-benzyl moiety
for the Pd-catalysed reaction of C60 with N-benzyl benzamides.4b
In continuation of our interest in Pd-catalysed C–H activation
reactions4,5 and in efforts to extend N-benzyl benzamides4b to
other substrates, we have found that the usage of N-benzyl
sulfonamides changes the site selectivity of the ortho C–H
activation to the phenyl ring of the N-benzyl moiety (Fig. 1).
Herein, we report this new finding and its application to
the synthesis of C60-fused tetrahydroisoquinolines from the
Table 1 Screening the Pd-catalysed reaction of C60 and N-benzyl-4-
toluenesulfonamidea
Entry Acid
Oxidant
Solvent (mL)
Yieldb (%)
1
2
3
4
None K2S2O8
PTSA K2S2O8
ODCB (4)
ODCB (4)
ODCB (4)
ODCB (4)
ODCB (4)
ODCB (4)
ODCB (4)
ODCB (4)
Trace
13 (81)
4 (44)
Trace
4 (49)
29 (47)
28 (58)
6 (40)
7 (78)
3 (38)
3 (38)
12 (63)
CSA
K2S2O8
PWA K2S2O8
TFA K2S2O8
TFA K2S2O8
MesSA K2S2O8
MesSA Oxone
5
6c
7
Fig. 1 Different site selectivity for the Pd-catalysed C–H bond activation
of N-benzyl benzamides and N-benzyl sulfonamides.
8
9
MesSA Cu(OAc)2ꢀH2O ODCB (4)
a 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. E-mail: gwang@ustc.edu.cn;
Fax: +86 551 3607864; Tel: +86 551 3607864
10
11
12d
13
14
15
MesSA AgOAc
MesSA BQ
ODCB (4)
ODCB (4)
ODCB (4)
ODCB(4)/DMSO (0.5) NR
ODCB(4)/CH3CN (0.5) NR
ODCB(4)/dioxane (0.5) NR
MesSA K2S2O8
MesSA K2S2O8
MesSA K2S2O8
MesSA K2S2O8
b State Key Laboratory of Applied Organic Chemistry,
Lanzhou University, Lanzhou, Gansu 730000, P. R. China
w Dedicated to Professor Koichi Komatsu on the occasion of his 70th
birthday.
a
Unless indicated otherwise, all reactions were performed in the
indicated solvent at 100 1C for 2 h, molar ratio of C60/1a/Pd(OAc)2/
oxidant/acid = 1/5/0.1/5/2. Isolated yield. Values in parentheses are
b
z This article is part of the ChemComm ‘Aromaticity’ web themed
c
. 0.5 mL of TFA was used. Molar ratio of
d
issue.
based on consumed C60
C60/1a/Pd(OAc)2/oxidant/acid = 1/3/0.1/3/2. Ts = 4-toluenesulfonyl,
ODCB = O-dichlorobenzene, DMSO = dimethyl sulfoxide.
y Electronic supplementary information (ESI) available: Experimental
procedures for the synthesis, spectral data and NMR spectra of
compounds 2a–2h, 3a–3h and 4a–4c. See DOI: 10.1039/c2cc33923d
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun.

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replacing the amide group with the sulfonamide group switches
the C–H bond activation selectivity to the benzylamine moiety.
The use of camphorsulfonic acid (CSA), 12-phosphotungstic
acid (PWA) or trifluoroacetic acid (TFA) in place of PTSA led
to obvious decrease in the product yield of 2a (Table 1, entries
3–5). To our delight, if TFA was employed as the cosolvent, a
yield of 29% (47% based on the consumed C60) was obtained
(Table 1, entry 6). In addition, mesitylenesulfonic acid dihydrate
(MesSA) was superior to TFA in terms of both the amount of
the used acid and product yield based on consumed C60 (58% vs.
47%) (Table 1, entry 7 vs. entry 6). After the acid was selected,
several other oxidants including oxone, Cu(OAc)2ꢀH2O,
AgOAc and p-benzoquinone (BQ) were explored, and
K2S2O8 was found to be the best oxidant for the reaction
(Table 1, entries 8–11 vs. entry 7). Decreasing the amount of 1a
and K2S2O8 reduced the product yield to 12% (Table 1,
entry 12 vs. entry 7). Disappointingly, no reaction occurred
when CH3CN, DMSO and 1,4-dioxane were employed as
cosolvents (Table 1, entries 13–15).
Scheme 1 Proposed mechanism for the formation of C60-fused
tetrahydroisoquinolines.
attached to the nitrogen atom such as benzenesulfonyl (Bs)
(1f), 4-chlorobenzenesulfonyl (Cs) (1g), and methanesulfonyl
(Ms) (1h) worked well and gave the corresponding products 2f,
2g and 2h in 22–31% yields (Table 2, entries 6–8).
The exact pathway leading to 2 is unknown now. On the
basis of the suggested mechanisms in the literature,4,5 a proposed
mechanism is shown in Scheme 1. Palladation of N-benzyl
sulfonamides 1 with Pd(OAc)2 produces intermediate A, followed
by insertion of C60 to generate intermediate B. Similar processes
have been suggested previously.4a,b Subsequent reductive
elimination produces C60-fused tetrahydroisoquinolines 2
and Pd(0). The latter is oxidized to Pd(II) by K2S2O8 to
complete the catalytic cycle.
With the optimal conditions (Table 1, entry 7) in hand, the
substrate scope and limitation were investigated by employing
a wide array of N-benzyl sulfonamides. The reaction conditions,
product yields along with recovered C60 are shown in Table 2.
Substrates bearing electron-withdrawing group (4-Cl) and electron-
donating groups (4-Me, 4-MeO, 3,4-(Me)2) on the benzylamine
moiety were all tolerated. Substrates 1b and 1c gave products 2b and
2c in 22% and 30% yields, respectively (Table 2, entries 2 and 3).
Under the employed standard conditions, substrate 1d tended to
generate more byproducts, thus the reaction temperature and the
amount of MesSA were lowered, and the desired product could be
obtained in 17% yield (Table 2, entry 4). The corresponding
product of N-(3,4-dimethylbenzyl)-4-toluenesulfonamide 1e
was regioselectively formed in 33% yield due to steric hindrance
(Table 2, entry 5). On the other hand, different functional groups
Intriguingly, we found that treatment of 2a with 3 equiv. of
MesSA afforded a rearrangement product, i.e., C60-fused
indane 3a, in 70% yield (Table 3, entry 1). Until now, the
access to C60-fused indane derivatives is limited.6 We thus
extended this conversion to other fullerotetrahydroisoquino-
lines 2b–2h. Substrates bearing both electron-withdrawing
group (2b) and electron-donating groups (2c–2e) on the benzyl-
amine moiety could furnish the rearrangement products in
acceptable yields (62% for 3b, 65% for 3c, 48% for 3d and
67% for 3e) (Table 3, entries 2–5). On the other hand, substrates
containing different sulfonamide groups such as BsNH (2f),
Table
2
Pd-catalysed heteroannulation of C60 with N-benzyl
sulfonamidesa
Table
3 Conversion of fullerotetrahydroisoquinolines 2a–2h to
fulleroindanes 3a–3h promoted by MesSAa
Time Yieldb Recovered
(h) (%) C60 (%)
Entry Product R1, R2, R3
1
2
2a
2b
R1 = Ts, R2 = R3 = H 2.0
28 (58) 52
22 (57) 61
R1 = Ts, R2 = H,
R3 = Cl
3.5
1.5
6.0
3
2c
2d
R1 = Ts, R2 = H,
R3 = Me
30 (63) 52
17 (61) 72
Time Yieldb Recovered 2
Entry 3 R1, R2, R3
(h)
(%)
(%)
4c
R1 = Ts, R2 = H,
R3 = MeO
1
2
3
4
5
6
7
8
3a R1 = Ts, R2 = R3 = H
9
70 (77)
9
R1 = Ts, R2 = R3 = Me 1.5
R1 = Bs, R2 = R3 = H 2.0
R1 = Cs, R2 = R3 = H 2.5
R1 = Ms, R2 = R3 = H 3.0
33 (63) 47
31 (56) 45
23 (54) 59
22 (47) 53
3b R1 = Ts, R2 = H, R3 = Cl 14
62 (70) 11
65 (81) 20
48 (72) 33
5
6
7
8
2e
2f
2g
2h
3c R1 = Ts, R2 = H, R3 = Me
4
3d R1 = Ts, R2 = H, R3 = MeO 10
3e R1 = Ts, R2 = R3 = Me
3f R1 = Bs, R2 = R3 = H
3g R1 = Cs, R2 = R3 = H
3h R1 = Ms, R2 = R3 = H
2.5 67 (88) 22
a
8
9
6
72 (77) 7
74 (84) 14
58 (69) 16
Unless indicated otherwise, all reactions were performed in ODCB at
100 1C, molar ratio of C60/2/Pd(OAc)2/K2S2O8/MesSA = 1/5/0.1/5/2.
b
Isolated yield. Values in parentheses are based on consumed C60
.
c
a
The reaction was performed in ODCB at 80 1C, molar ratio of C60
/
All the reactions were performed in ODCB at 100 1C, molar ratio of
b
3/MesSA = 1/3. Isolated yield. Values in parentheses are based on
2d/Pd(OAc)2/K2S2O8/MesSA = 1/5/0.2/5/1. Bs = benzenesulfonyl,
Cs = 4-chlorobenzenesulfonyl, Ms = methanesulfonyl.
consumed material.
c
Chem. Commun.
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In summary, we have discovered an effective way for the
synthesis of C60-fused tetrahydroisoquinolines via Pd-catalysed
heteroannulation of C60 with N-benzyl sulfonamides via C–H
bond activation. Intriguingly, change of the directing group
from the amide group to the sulfonamide group switches the
C–H activation selectivity to the benzylamine moiety. A novel
rearrangement of C60-fused tetrahydroisoquinolines in the
presence of mesitylenesulfonic acid dihydrate has been found
to give C60-fused indanes, in which the sulfonamide group can
be replaced with an aryl group in the presence of FeCl3/arene
or removed by FeCl3/Et3SiH.
We are grateful for financial support from the National
Natural Science Foundation of China (21132007, 20972145) and
National Basic Research Program of China (2011CB921402).
Scheme 2 Proposed mechanism for conversion of C60-fused tetrahydro-
isoquinolines 2 to C60-fused indanes 3.
Notes and reference
1 For selected reviews, see: (a) A. Hirsch, Synthesis, 1995, 895; (b) C.
Thilgen and F. Diederich, Chem. Rev., 2006, 106, 5049; (c) F. Giacalone
and N. Martın, Chem. Rev., 2006, 106, 5136; (d) M. Murata, Y. Murata
and K. Komatsu, Chem. Commun., 2008, 6083.
2 For reviews, see: (a) G.-W. Wang and F.-B. Li, J. Nanosci. Nano-
technol., 2007, 7, 1162; (b) Y. Matsuo and E. Nakamura, Chem. Rev.,
2008, 108, 3016; (c) G.-W. Wang and F.-B. Li, Curr. Org. Chem.,
2012, 16, 1109. For recent selected papers, see: (d) M. D. Tzirakis and
M. Orfanopoulos, Angew. Chem., Int. Ed., 2010, 49, 5891; (e) Z. Xiao,
Y. Matsuo and E. Nakamura, J. Am. Chem. Soc., 2010, 132, 12234;
(f) M. Nambo, Y. Segawa and K. Itami, J. Am. Chem. Soc., 2011,
133, 2402; (g) E. E. Maroto, A. de Cozar, S. Filippone, A. Martın-
Domenech, M. Suarez, F. P. Cossıo and N. Martın, Angew. Chem.,
Int. Ed., 2011, 50, 6060; (h) S. Lu, T. Jin, E. Kwon, M. Bao and
Y. Yamamoto, Angew. Chem., Int. Ed., 2012, 51, 802; (i) F.-B. Li,
T.-X. Liu and G.-W. Wang, Org. Lett., 2012, 14, 1800.
3 (a) L.-L. Shiu, T.-I. Lin, S.-M. Peng, G.-R. Her, D.-D. Ju,
S.-K. Lin, J.-H. Hwang, C.-Y. Mon and T.-Y. Luh, J. Chem.
Soc., Chem. Commun., 1994, 647; (b) C. K. F. Shen, K.-M. Chien,
T.-Y. Liu, T.-I. Lin, G.-R. Her and T.-Y. Luh, Tetrahedron Lett.,
1995, 36, 5383; (c) H. Inoue, H. Yamaguchi, T. Suzuki, T. Akasaka
and S. Murata, Synlett, 2000, 1178; (d) S. Mori, M. Nambo,
L.-C. Chi, J. Bouffard and K. Itami, Org. Lett., 2008, 10, 4609;
(e) M. Nambo and K. Itami, Chem.–Eur. J., 2009, 15, 4760;
(f) B. Zhu and G.-W. Wang, J. Org. Chem., 2009, 74, 4426;
(g) M. Nambo, A. Wakamiya, S. Yamaguchi and K. Itami,
J. Am. Chem. Soc., 2009, 131, 15112.
4 (a) B. Zhu and G.-W. Wang, Org. Lett., 2009, 11, 4334;
(b) S.-C. Chuang, V. Rajeshkumar, C.-A. Cheng, J.-C. Deng and
G.-W. Wang, J. Org. Chem., 2011, 76, 1599; (c) F. Li, T.-X. Liu and
G.-W. Wang, Org. Lett., 2012, 14, 2176.
5 (a) G.-W. Wang, T.-T. Yuan and X.-L. Wu, J. Org. Chem., 2008,
73, 4717; (b) G.-W. Wang and T.-T. Yuan, J. Org. Chem., 2010,
75, 476; (c) G.-W. Wang, T.-T. Yuan and D.-D. Li, Angew. Chem.,
Int. Ed., 2011, 50, 1380; (d) D.-D. Li, T.-T. Yuan and G.-W. Wang,
Chem. Commun., 2011, 47, 12789; (e) D.-D. Li, T.-T. Yuan and
G.-W. Wang, J. Org. Chem., 2012, 77, 3341.
Scheme 3 Transformation of fulleroindane 3a.
CsNH (2g), and MsNH (2h) worked well and gave products
3f–3h in 58–74% yields (Table 3, entries 6–8). This appealing
reaction might proceed via protonation to generate ammonium
intermediate C, subsequent ring opening to afford fullerenyl
cation D,2f and final ring closure with the assistance of mesitylene-
sulfonate ions (MesSꢁ) to produce 3 (Scheme 2).
These fulleroindanes could be synthetic precursors for
further transformation via C–N bond cleavage, as shown in
Scheme 3 with 3a as an example. The Friedel–Crafts type
reactions of 3a with benzene and mesitylene were successfully
achieved when a mixture of ODCB and ArH (v/v = 3/1)
was used in the presence of FeCl3 at 130 1C for 1 h. The rare
C60-fused indane derivatives 4a and 4b were obtained in 68%
and 82% yields, respectively. Treatment of compound 3a with
FeCl3 and Et3SiH at 130 1C for 12 h produced the simplest
C60-fused indane 4c in 70% yield.
6 (a) M. Saunders, H. A. Jimenez-Vazquez, R. J. Cross, E. Billups,
C. Gesenberg and D. J. McCord, Tetrahedron Lett., 1994, 35, 3869;
(b) K. Kokubo, S. Tochika, M. Kato, Y. Sol and T. Oshima,
Org. Lett., 2008, 10, 3335; (c) T.-X. Liu, F.-B. Li and
G.-W. Wang, Org. Lett., 2011, 13, 6130.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun.