AlCl3-catalyzed tandem acetylation of hydroarylated [60]fullerenes

Article abstract of DOI:10.1021/ol801239y

(Chemical Equation Presented) The AlCl₃-catalyzed acetylation of 1,2-hydrophenylated [60]fullerenes, HC₆₀-Ar, proceeded via a sequential manner involving the acetylation at the hydrogenated fullerene carbon, the following intramolecu

Full text of DOI:10.1021/ol801239y

ORGANIC
LETTERS
2008
Vol. 10, No. 15
3335-3338
AlCl3-Catalyzed Tandem Acetylation of
Hydroarylated [60]Fullerenes
Ken Kokubo,* Shinya Tochika, Mai Kato, Yui Sol, and Takumi Oshima
DiVision of Applied Chemistry, Graduate School of Engineering, Osaka UniVersity,
2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
kokubo@chem.eng.osaka-u.ac.jp
Received June 2, 2008
ABSTRACT
The AlCl3-catalyzed acetylation of 1,2-hydrophenylated [60]fullerenes, HC60-Ar, proceeded via a sequential manner involving the acetylation at
the hydrogenated fullerene carbon, the following intramolecular cyclization with the adjacent aryl group, the facile loss of water, and the
second acetylation of the generated indenylidene double bond. However, the similar reaction of the hydrobiphenylated analogue brought
about the normal acetylation at the terminal aromatic ring prior to the same sequential reactions as did hydrophenylated fullerenes.
Chemical modification of fullerenes has attracted significant
attention in view of the biological and electronic applica-
tions.1 Although such modification has been well documented
for nucleophilic additions and cycloadditions like Bingel,
Prato, Diels-Alder, and Huisgen reactions, little is known
on electrophilic addition such as Friedel-Crafts hydroarylation.
In 1991, Olah et al. reported that the AlCl3-catalyzed
Friedel-Crafts reaction of C60 with aromatic compounds
gave a mixture of multihydroarylated fullerenes for which
the detailed structural analysis was not done.2,3 Over 15 years
later, Nakamura et al. and our group independently clarified
the structures of mono-, bis-, and trishydroarylated adducts.4,5
Recently, various types of monohydroarylated fullerenes have
been exclusively synthesized by way of a rhodium-catalyzed
reaction of organoborons,6 and thus the desired functional-
ization of easily accessible hydroarylated fullerenes can be
taken as a new strategy for fullerene modification.
In this paper, we report the AlCl3-catalyzed novel reactions
of monohydroarylated [60]fullerenes with acetyl chloride
depending on the introduced aryl groups, i.e., (1) for HC60-
C6H4R (R ) p-Me, H, p-Cl), the direct acetylation at the
hydrogenated fullerene carbon followed by the intramolecular
cyclization with the adjacent aromatic ring and the loss of
water and the subsequent acetylation of the generated
indenylidene double bond and (2) for R ) p-C6H5, the
preceding normal Friedel-Crafts acetylation at the terminal
p-position and the following tandem acetylation as above (1).
The 1,2-hydrophenylated fullerenes 2a-c (R ) Me, H,
and Cl) at the [6,6]-conjunct bond were prepared by the
modified Olah method5 using 3 equiv of both aromatic
compounds and AlCl3 relative to C60. The reactions were
carried out in o-dichlorobenzene (o-DCB) at 30-60 °C under
argon atmosphere for 30-80 min to give 2a-c in 28-42%
(1) Hirsch, A.; Brettreich, M. Fullerenes; Wiley-VCH: Weinheim, 2005.
(2) 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
(3) Olah, G. A.; Bucsi, I.; Ha, D. S.; Aniszfeld, R.; Lee, C. S.; Prakash,
G. K. S. Fullerene Sci. Technol. 1997, 5, 389
.
.
(4) Iwashita, A.; Matsuo, Y.; Nakamura, E. Angew. Chem., Int. Ed. 2007,
46, 3513
.
(5) Tochika, S.; Kato, M.; Kuang, C.; Kokubo, K.; Oshima, T. Abstracts
(6) Nambo, M.; Noyori, R.; Itami, K. J. Am. Chem. Soc. 2007, 129,
8080.
of the 31st Fullerene-Nanotubes General Symposium 2006, 62
.
10.1021/ol801239y CCC: $40.75
Published on Web 06/27/2008
2008 American Chemical Society

yields. These adducts 2a-c were then treated with 10 equiv
of acetyl chloride in the presence of 10 equiv of AlCl3 in
o-DCB at elevated temperature (60-70 °C) under argon
atmosphere for 0.5-30 h (Scheme 1).
state (Scheme 2). The Z-isomer demonstrated the NOE
correlation between the aryl and the vinyl proton in addition
to the noticeable upfield shift of the relevant aromatic proton
(δ 9.40 f 8.11).
Scheme 2. E-Z Photoisomerization of Cyclized Fullerene 3b
Scheme 1
.
Synthesis of Hydroarylated Fullerenes 2a-c and the
Following AlCl3-Catalyzed Acetylation
To gain some information on the mechanism, we con-
ducted an isotope-labeled experiment using a 13C-labeled
acetyl chloride at the methyl carbon in the reaction with 2b.
A mass spectrum of the 13C-labeled product (E)-3b showed
the increased molecular ion peak by 2 mass numbers (m/z
from 864 to 866), indicating the introduction of two 13C-
labeled carbon atoms into the product (E)-3b. The 1H NMR
spectrum of this product exhibited a typical 13C-1H coupling
for the methyl proton (J ) 127 Hz) and the vinyl proton
(151 Hz). On the basis of these results, a possible mechanism
for the formation of 3b is depicted in Scheme 3. Thus, the
13C-labeled carbons were sequentially incorporated as the
exo-olefinic carbon and the terminal methyl carbon via a
novel tamdem acetylation reaction.9
According to this mechanism, first the AlCl3-catalyzed
direct electrophilic acetylation on the fullerene cage gives
the fullerenyl ketone A, losing a proton. Then, the acid-
catalyzed 5-exo-trig cyclization followed by dehydration
affords fullerenoindenylidene B. The indenylidene B can
undergo the second acetylation at the terminal methylene
carbon to give the ꢀ-acetyl indenylidene 3 with E-form
avoiding the larger steric hindrance with the fullerene surface
than with the aromatic ring. The reaction was accelerated
by introduction of the electron-donating p-substituent in the
order of 2a > 2b > 2c (Scheme 1), implying that the rate-
determining step is the nucleophilic attack of the adjacent
aromatic ring to the carbonyl group in the favorable 5-exo-
trig cyclization.10,11
It is very interesting that these reactions brought about no
FriedelsCrafts acetylation on the introduced phenyl ring but
instead provided ꢀ-acetyl-substituted fullereno-indenylidenes
3a-c in moderate to good yields (53-63% relative to 2
1
used). The H NMR spectrum of 3b indicated the presence
of an o-phenylene bridge (two dd at δ 7.67 and 7.78 and
two d at 8.24 and 9.40) and the acetyl Me (δ 2.53) and the
vinyl H (7.72). It was also confirmed from the 13C NMR (δ
32.4 and 197.2) and LCMS (m/z ) 864) that 3b has the
structure of a ꢀ-acetyl-substituted fullerenoindenylidene with
Cs symmetry.7
On the basis of the differential NOE measurement of 3b,
we attempted to determine the geometry of the olefinic
double bond. However, no recognizable correlation was
observed between the aromatic proton and either the vinyl
or the methyl proton. However, we can suppose its structure
as E-form from the unusual downfield shift of one aromatic
proton (δ 9.40), probably because this proton strongly suffers
the deshielding effect of the conformationally restricted
facing carbonyl group. Another downfield shift for the
o-proton (δ 8.24) may be rationalized by the strong para-
magnetic current due to the underlying pentagon ring.8 This
geometrical assignment was unequivocally confirmed by the
observation of E-Z photoisomerization of (E)-3b by irradia-
tion with a medium-pressure mercury lamp (>300 nm) for
14 h to afford a 6:4 mixture of E and Z at the photostationary
Here, we have a mechanistic question as to why the
hydrophenylated 2b underwent not the usual Friedel-Crafts
acylation but the displacement of the protruding hydrogen
atom by an acetyl group. Two reasons are conceivable: (1)
the acceptor fullerene core considerably reduces the nucleo-
(9) Ho, T.-L. Tandem Organic Reactions; John Wiley & Sons: New
York, 1992.
(7) The Cs symmetry was confirmed by the presence of 28 peaks (2C)
and 2 peaks (1C) for the different sp2 fullerene carbons, consisting with
the 1,2-addition to the [6,6]-bond.
(10) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734.
(11) Such a Lewis acid catalyzed 5-exo-trig cyclization of the phenyl
group to carbonyl function has been reported for electron-deficient ketones
such as 1-trifluoromethyl-3-phenylpropanone: Aubert, C.; Be´gue´, J.-P.;
Bonnet-Delpon, D.; Mesureur, D. J. Chem. Soc., Perkin Trans. 1 1989,
(8) (a) Pasquarello, A.; Schluter, M.; Haddon, R. C. Science 1992, 257,
1660. (b) Prato, M.; Suzuki, T.; Wudl, F.; Lucchini, V.; Maggini, M. J. Am.
Chem. Soc. 1993, 115, 7876.
395
.
3336
Org. Lett., Vol. 10, No. 15, 2008

Scheme 3. Possible Mechanism for AlCl3-Catalyzed Intramolecular Cyclization of Hydrophenylated Fullerene 2 with Acetyl Chloride
philicity of the introduced phenyl group, and (2) fullerenyl
hydrogen is intrinsically active toward the strong electrophile
such as an acyl cation. Therefore, according to above (1),
we felt that the more remote aromatic ring like in the
biphenyl group might allow a possible acylation in the
present reaction conditions. Indeed, a similar reaction of
hydrobiphenylated fullerene 2d provided the expected prod-
uct 4d in 70% yield along with the further acyl-introduced
fullerenyl ketone 5d (corresponding to A) without any
cyclized product (Scheme 4). This finding implies that the
core. The lower-field shift of one of the fullerene sp3 carbons
of 5d (δ 81.9 vs 69.9) is strongly suggestive of the direct
bonding of the acetyl group on the fullerene surface.
Compared to the possible intermediate A, the persistency
of 5d for the 5-exo-trig reaction may be attributed to the
substitution of the p-acetylphenyl group which will signifi-
cantly reduce the nucleophilicity of the parent aromatic ring
as in the case of 2c. However, the prolonged reaction (72 h)
led to the formation of the expected 3d in 60% yield
(Scheme 5).
Scheme 4
.
AlCl3-Catalyzed Acetylation of Hydrobiphenylated
Fullerene 2d with Acetyl Chloride
Scheme 5. AlCl3-Catalyzed Intramolecular Cyclization of
Fullerenyl Ketone 5d with Acetyl Chloride
acceptor fullerene core exerts the appreciable electron
withdrawal on the directly connected aromatic ring.
The structures of 4d and 5d were confirmed by H and
To the best of our knowledge, only two examples have been
so far reported for the synthesis of fullerenyl ketones. Mattay
et al. first synthesized a fullerenyl ketone by photoinduced
electron transfer reaction of C60 with propanal.12 Recently,
Saigo et al. found that the ring-opening reaction of
aminomethano[60]fullerenes gives several fullerenyl ke-
1
13C NMR as well as LCMS with the APPI method.
Especially, the 1H NMR spectrum of compound 5d displayed
the presence of two acetyl groups (δ 2.58 and 2.63) and two
sets of aromatic AB quartet protons. Similar to 2d, the 13C
NMR spectra of 4d and 5d apparently indicate the 1,2-
addition on the [6,6]-bond with Cs symmetry: 28 peaks (2C)
and 2 peaks (1C) for the different sp2 carbons of the fullerene
(12) Siedschalag, C.; Luftman, H.; Wolff, C.; Mattay, J. Tetrahedron
1997, 53, 3587.
Org. Lett., Vol. 10, No. 15, 2008
3337

tones.13 Accordingly, the reaction mechanism for the present
acetyl substitution of fullerenyl hydrogen C-H is quite
interesting since the cage fullerene cannot undergo a SE2
(back) reaction.14 Some other conceivable mechanisms (a-c)
are shown in Scheme 6. Although a SE2′ reaction15 (b) seems
to be possible, the subsequent thermally forbidden 1,3-acyl-
migration is needed. On the other hand, a SE1 mechanism
(a) is likely to occur on the basis of the fact that the fullerene
C-H bond has a relatively high dissociation constant (pKa
) 4.7 for C60H2 and 5.7 for t-BuC60H).16 However, owing
to the acidic nature of the fullerenyl C-H bond, a possible
SEi mechanism17 (c) can not be thoroughly ruled out in the
Scheme 6
. Possible Mechanisms for AlCl3-Catalyzed Direct
Acetylation on the Fullerene Cage with Acetyl Chloridea
-
presence of an acylium cation complex with AlCl4 .
In conclusion, we found two novel acetylation reactions
of monohydroarylated fullerenes with acetyl chloride, such
as a direct acetylation by substitution of hydrogen on the
fullerene moiety and the following tandem acetylation
associated with intramolecular cyclization and loss of water.
Although the mechanism for the first direct acetylation is
still unclear at the present stage, the observed reaction on
the fullerene surface is quite unusual and unique.
a
Only the reaction site is drawn for clarity.
(13) Tada, T.; Ishida, Y.; Saigo, K. Org. Lett. 2007, 9, 2083.
(14) Smith, M. B.; March, J. March’s AdVanced Organic Chemistry,
5th ed.; John Wiley & Sons: New York; Chapter 12, p 760.
(15) Buckle, M. J. C.; Fleming, I.; Gil, S. Tetrahedron Lett. 1992, 33,
4479.
Supporting Information Available: Experimental pro-
cedures and compound data for new compounds (E)-3a-d,
(Z)-3b, 4d, and 5d. This material is available free of charge
via the Internet at http://pubs.acs.org.
(16) Niyazymbetov, M. E.; Evans, D. H.; Lerke, S. A.; Cahill, P. A.;
Henderson, C. C. J. Phys. Chem. 1994, 98, 13093.
(17) (a) Winstein, S.; Traylor, T. G.; Garner, C. S. J. Am. Chem. Soc.
1955, 77, 3741. (b) Abraham, M. H.; Hill, J. A. J. Organomet. Chem. 1967,
7, 11.
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