Coupling of alkylarene and pentamethyl[60]fullerene by iridium-catalyzed benzylic C-H bond activation

Article abstract of DOI:10.1246/cl.2006.858

Heating of C₆₀Me₅Br in toluene in the presence of an iridium catalyst and triethylamine results in benzylation of the fullerene core to yield C₆₀Me₅CH₂C₆H₅. The reaction is general for various alkylarenes, and probably takes place via iridium-catalyzed activation of a benzylic C-H bond. Copyright

Full text of DOI:10.1246/cl.2006.858

858
Chemistry Letters Vol.35, No.8 (2006)
Coupling of Alkylarene and Pentamethyl[60]fullerene
by Iridium-catalyzed Benzylic C–H Bond Activation
Yutaka Matsuo,1 Akihiko Iwashita,2 and Eiichi NakamuraÃ1;2
1Nakamura Functional Carbon Cluster Project, ERATO, Japan Science and Technology Agency
2Department of Chemistry, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033
(Received May 22, 2006; CL-060598; E-mail: nakamura@chem.s.u-tokyo.ac.jp)
R
Br
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Heating of C60Me5Br in toluene in the presence of an iridi-
um catalyst and triethylamine results in benzylation of the full-
erene core to yield C60Me5CH2C6H5. The reaction is general
for various alkylarenes, and probably takes place via iridium-
catalyzed activation of a benzylic C–H bond.
Me
Me
Me
[IrCl(coe)2]2
(0.1 equiv.)
+
Et3N (1 equiv.)
toluene
80 °C, 2.5 h
1
2: R = Bn, 41%
3, 43%
Scheme 1.
Among popular topics of metal-catalyzed C–H bond activa-
tion,1 selective activation of one type of C–H bond over the oth-
ers is a relatively unexplored field of research. For instance, con-
version of an aromatic C–H bond into a C–C bond2 is a ubiqui-
tous reaction, but selective activation of a benzylic C–H bond in
an alkylarene compound in preference to other aromatic C–H
bonds in the same molecule is not an easy task.3 It is partly
due to a thermodynamic reason: The C–H bond activation of
the methyl group of toluene is a process usually thermodynami-
cally less favored than the aryl C–H bond activation at the meta-
and para-position.4 To achieve the selectivity, ideas of utilizing
steric effects to direct the catalyst toward activation of the meth-
yl group of toluene have been examined successfully,5 but the
extension of such approaches beyond toluene remains yet to
be investigated. Herein, we report alkylation of the cyclopenta-
diene moiety of pentamethyl[60]fullerene, C60Me5H,6 with an
alkylarene in the presence of an iridium catalyst. This transfor-
mation allows introduction of a variety of (alkyl)(aryl)methyl
groups to the carbon atom surrounded by the five methyl groups.
The method is complementary to previously reported methods of
alkylation of C60Me5H in that it allows introduction of a second-
ary benzylic group to the hindered position of the molecule.7
The new reaction was discovered in the course of attempted
synthesis of iridium–fullerene complexes. The first synthetic
approach to Ir(ꢀ5-C60Me5)(CO)2 relying on the reaction of
an anion, K(C60Me5), with [IrCl(CO)2]2 took place smoothly
to give the iridium–fullerene complex.8 A polarity-reversed
approach relying on the reaction of bromo(pentamethyl)[60]-
fullerene, C60Me5Br (1)9 with one equivalence of [IrCl(coe)2]2
(coe = cyclooctene) in toluene at 25 ꢀC for 120 h unexpectedly
gave benzyl(pentamethyl)[60]fullerene, C60Me5(CH2Ph) (2) in
33% yield (100% conversion of 1). Clearly, a C–H bond activa-
tion of the solvent molecule took place.10 The reaction afforded
C60Me5H (3, 50%) and several oxidized products such as
C60Me5O3H11 as by-products. We found that the reaction of 1
with 10 mol % of [IrCl(coe)2]2 in the presence of triethylamine
(1 equiv.) in toluene at 80 ꢀC for 2.5 h afforded 2 and 3 in 41
and 43% yield, respectively (Scheme 1 and Table 1, Entry 1).
Other bases were examined without success: e.g., pyridine and
1,8-diazabicyclo[5.4.0]undec-7-ene. No such benzylation reac-
tion was found in the same reaction of the more sterically hin-
dered molecule, C60Ph5H.
(a)
(b)
C8
C7
C2
C3
C4
C1
C5
C6
Figure 1. Crystal structure of 2. (a) ORTEP drawing with
30% probability level ellipsoids. (b) Space-filling models
˚
from top and side view. Selected bond length (A) and angles
(ꢀ): C1–C2 = 1.522(11), C2–C3 = 1.357(11), C3–C4 =
1.494(10), C4–C5 = 1.366(12), C5–C1 = 1.529(12), C1–
C7 = 1.592(12), C7–C8 = 1.511(13); C6–C1–C7 = 107.2(7),
C1–C7–C8 = 117.0(7).
HR-MS as well as X-ray crystallographic analysis.12 The 1H
and 13C NMR spectra exhibited signals characteristic of the Cs
symmetric structure. The ORTEP drawing and CPK models
are shown in Figure 1. Bond lengths of the top pentagon (C1
to C5) are in good agreement with an ordinary cyclopentadiene
structure. The bond distance between C1 and C7 (1.592(12) A)
is considerably longer than an ordinary C(sp3)–C(sp3) bond
˚
(1.54 A), likely due to steric hindrance.
As summarized in Table 1, a variety of arenes bearing alkyl
or substituted alkyl side chains (used as a solvent) have been
found to take part in the reaction albeit in poor to moderate yield.
The major product besides the desired one was the reduction
product 3. When mesitylene was used as a solvent, 3,5-dimethyl-
benzyl adduct of fullerene was obtained (Entry 2). The use of
ethylbenzene as a solvent resulted in introduction of a 1-phenyl-
ethyl group (C60Me5(CHMePh)) (Entry 3). The C–H bond
activation approach is a synthetically useful reaction, since the
synthesis of this compound by the conventional method by
using C60Me5K and an adequate halide is not a synthetically
viable reaction.
˚
4-Methoxytoluene and benzyl methyl ether are more reac-
tive than toluene and smoothly afforded the benzyl activation
The benzylated product 2 was characterized by NMR and
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.8 (2006)
859
Table 1. Iridium-catalyzed alkylation of C60Me5H with alkyl-
arenesa
Cl
L
L
Br
Ir(III)
Ir(I)
Me
Me
Me
[IrCl(coe)2]2
Me
Me
Me
Me
Me
Me
Entry
1
Solvent
R
Time/h
2.5
Yield/%b
41
Me
[IrCl(coe)2]2
1
CH3
− Ir(III)
C−H Bond
Activation
Oxidative Addition
base
Coordinately
Unsaturated
Complex
H
H
Br
L
L
2
3
4
5
6
7
8
1.5
2
37
32c
40c
13
36
19
25
Ir(III)
Ir(III)
L = Cyclooctene
= vacant site
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
1
2
1.5
3.5
1
"Ir(I)HL"
Oxidative Addition
Reductive Elimination
OMe
OMe
Scheme 2.
MeO
MeO
cyclopentadienyl moiety of C60Me5. This reaction is a rare
example of transition metal-mediated catalytic chemical modifi-
cation of fullerenes,13 and will serve to expand the molecular
library of functionalized fullerenes.
OMe
MeO
We thank Prof. Fumitoshi Kakiuchi in Keio University for
fruitful discussion. This study was partially supported by a grant
from the 21st Century COE Program for Frontiers in Fundamen-
tal Chemistry.
6
Br
2.5
References and Notes
Br
1
2
3
4
Activation of Unreactive Bonds and Organic Synthesis, ed.
by S. Murai, Springer, Berlin, 1999.
S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani,
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Feher, J. Am. Chem. Soc. 1984, 106, 1650. c) P. Burger,
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1996, 118, 12850.
aA solution of 1, [IrCl(coe)2]2 (0.1 mol %), and Et3N (1.0 equiv.)
in an alkylarene (3.8 mM solution) was heated under argon at
b
1
c
80 ꢀC. Determined by H NMR. Isolated yield.
products (Entries 4 and 6). 2-Methoxytoluene was much less re-
active probably due to the steric effect of the flanking methoxy
group (Entry 5). In all three cases, we did not observe products
due to methoxy-group activation. Similarly, sterically hindered
1-methylnaphthalene reacted rather slowly (Entry 7). 4-Bromo-
toluene gave C60Me5(CH2C6H4Br) in 25% yield (Entry 8).
The bromo group did not affect the reaction rate and the yield
(cf. Entry 1). We did not detect any products due to the reaction
of the bromine atom. The bromo product offers possibilities of
further elaboration of the product.
A possible catalytic pathway is discussed below (Scheme 2).
The iridium(I) cyclooctene complex undergoes oxidative addi-
tion to the fullerene–bromine bond to form an Ir(III)–fullerene
intermediate. A second molecule of the iridium(I) complex re-
duces the intermediate to generate a coordinatively unsaturated
Ir(I)-intermediate. It reacts with the C–H bond of toluene to give
an Ir(III)C60Me5–benzyl complex. Reductive elimination pro-
duces the alkylated product 2 and an Ir(I) complex, which then
reacts with 1 to generate a bromo–hydro Ir(III)-complex. Reduc-
tion of this complex by triethylamine regenerates the coordina-
tively unsaturated complex. A possibility of intervention of radi-
cal intermediates cannot be discounted.
5
6
7
8
9
R. Hamasaki, Y. Matsuo, E. Nakamura, Chem. Lett. 2004,
33, 328.
Y. Matsuo, A. Iwashita, E. Nakamura, Organometallics
2005, 24, 89.
Procedure for synthesis of 1 will be described elsewhere.
10 We confirmed that 2 was obtained by the reaction of
KC60Me5 with benzyl bromide.
11 a) H. Al-Matar, P. B. Hitchcock, A. G. Avent, R. Taylor,
Chem. Commun. 2000, 1071. b) H. Al-Matar, A. K.
Abdul-Sada, A. G. Avent, P. W. Fowler, P. B. Hitchcock,
K. M. Rogers, R. Taylor, J. Chem. Soc., Perkin Trans. 2
2002, 53.
In summary, we found an interesting instance of the chemo-
selective control of C–H bond activation, where the alkyl side
chain of alkylarene compounds is selectively alkylated by the
12 CCDC No. 609651.
13 G. P. Miller, M. C. Tetreau, Org. Lett. 2000, 2, 3091.
Published on the web (Advance View) July 1, 2006; doi:10.1246/cl.2006.858