Heck reaction on fullerene derivatives

Article abstract of DOI:10.1016/j.tetlet.2008.03.150

The Heck reaction on fullerene-based aryl iodides has been achieved for the first time in good yields by using microwave irradiation.

Full text of DOI:10.1016/j.tetlet.2008.03.150

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3656–3658
Heck reaction on fullerene derivatives
*
´
´
´
Marıa Jose Gomez-Escalonilla, Fernando Langa
Instituto de Nanociencia, Nanotecnologı´a y Materiales Moleculare (INAMOL)s, Universidad de Castilla-La Mancha, 45071 Toledo, Spain
Received 5 March 2008; accepted 28 March 2008
Available online 8 April 2008
Abstract
The Heck reaction on fullerene-based aryl iodides has been achieved for the first time in good yields by using microwave irradiation.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Fullerene; Heck reaction; Microwave
The palladium-catalyzed Heck reaction of olefins with
aryl and vinyl halides is actually a method of broad scope
that has found application throughout organic chemistry
mainly due to its high chemoselectivity and mild reaction
conditions.1 Particularly interesting is the iterative use of
the Heck reaction for the construction of oligomers of p-
phenylenevinylenes (OPVs),2 compounds of great interests
in materials research such as organic light-emitting displays
(OLEDs),3 field-effect transistors (FETs)4 and organic
solar cells.5
Despite the fact that a great deal of attention has been
devoted in recent years to the direct functionalization of
the fullerene cage, examples of reactions in proximity to
the fullerene surface are scarce6 and some functional
groups have proven to be unreactive in proximity to the
C60 cage,7 probably due to the size of the fullerene which
sterically hinders the approach of the reaction components.
In particular, examples of Pd-catalyzed coupling reactions
in fullerene derivatives are almost absent from the litera-
ture and only two results on Sonogashira coupling in com-
pounds containing fullerenes have been previously
reported.8,9 This observation is probably due to the fact
that low-valent complexes of palladium easily undergo
complexation10 with fullerenes; in this respect, a stable pal-
ladium complex between C60 and palladium acetate has
been described;11 in this sense, fullerenes can be considered
a poison for palladium catalysts. As a consequence, only
one example of the application of the Heck reaction on a
fullerene derivative is known,12 but the described yield is
very low (10%).
In this Letter, we report a procedure to perform the
Heck reaction on fullerene derivatives with good yields.
This procedure is based on the use of microwave irradia-
tion as a source of energy13 which has shown to be very
effective in coupling reactions14 as well as in fullerene
chemistry.15
The starting fullerene derivatives 1–3 were prepared
in good yields (39–52%) according to the standard
Me
X
N
CHO
C60
I
Δ
Me
N
+
HN CO2H
Me
-CO2/ -H2O
toluene, reflux
X
X=I,Br
1 (52%), X=I
3 (39%), X=Br
O2N
NH-NH2
NO2
Me
N
I
N
CHO
I
H
C
N
H
N
1. NCS
I
NO2
AcOH
2. C60, Et3N,
r.t, 1 day
2( 41%)
*
Corresponding author. Tel.: +34 902 268 843; fax: +34 902 204 130.
Scheme 1.
E-mail address: FernandoL.Puente@uclm.es (F. Langa).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.150

M. J. Go´mez-Escalonilla, F. Langa / Tetrahedron Letters 49 (2008) 3656–3658
3657
Table 1
procedures, by 1,3-dipolar cycloadditions of C60 and
azomethine ylides16,12 (1 and 3) or a nitrile imine17 (2 )
(Scheme 1).
Reaction conditions and yields for reactions between 1 and 3 and acrylates
4a–d under microwave irradiationa
Entry Fullerene aryl
halide
Acrylate
R
Time
(h)
Product Yield
(%)
We subsequently aimed to study the Heck coupling
between the fullerene-based aryl halides (1–3) and different
acrylates 4a–d. Following the optimization studies, the
reactions were carried out with palladium acetate as the
catalyst, tri-o-tolylphosphine as the ligand and triethyl-
amine as the base. The lack of solubility of fullerene in
polar solvents meant that 1,2-dichloroethane and chloro-
benzene were chosen instead of the classical solvents
employed for this kind of reactions (e.g., DMF, NMP)
(Scheme 2).
1
2
3
4
5
6
7
1
1
1
1
2
2
3
4a
4b
4c
4d
4a
4b
4c
4.5
4.5
4.5
4.5
3
5a
5b
5c
5d
6a
6b
5c
44
52
48
34
41
42
5
3
13.5
a
Reactions performed in sealed Pyrex tubes under argon, using 10 mL
of chlorobenzene as solvent. Continuous irradiation (2450 Hz). Power:
300 W.
Initially, the reaction was studied under classical heating
in refluxing chlorobenzene and 1 was converted into 5a in
15% yield after 6 h (massive polymerization of the starting
butyl acrylate was observed and starting compound 1 was
consumed); 2 afforded 6b in 20% yield under the same reac-
tion conditions with acrylate 4b. These low yields move us
to study the reaction by using microwave irradiation as a
source of energy.
Irradiation experiments were conduced in chlorobenz-
ene as solvent; the temperature was kept below 140 °C in
order to prevent (although not avoid) polymerization of
the acrylates18 and irradiation at 300 W was maintained
until the initial fullerene derivative 1 was consumed
(followed by TLC). The same experimental conditions were
used in the rest of the examples and the preparative results
are summarized in Table 1.
Pyrrolidino[60] fullerene-based aryl iodide 1 was con-
verted into the corresponding cinnamic esters 5a–d19 in
34–52% yields by reaction with acrylates 4a–d (reaction
time: 4.5 h at 300 W). Significant differences in yields were
not observed between fullerene-based aryl iodides and
pyrazolino[60] fullerene 2 was converted into 6a–b in 41%
and 42%, respectively, under analogous conditions in a
shorter reaction time (3 h).
the trans isomers were exclusively obtained. The E config-
uration of the double bond was confirmed by a coupling
constant of ca. 16 Hz for the AB system corresponding to
1
the vinyl hydrogens in the H NMR spectrum. The rest
1
of the expected signals were observed as well in the H
NMR spectra. The FTIR of fullerene derivatives showed
the presence of the typical strong band at around
1715 mÀ1 corresponding to the ester group. In addition,
all the structures of fullerene derivatives 5a–d20 and 6a–b
were confirmed by their MALDI-TOF mass spectra, which
showed the expected molecular ions.
It should be commented that the reaction of other
alkenes (styrene or acrolein) with pyrrolidino[60] fullerene
halide 1 did not lead to any identifiable product, with the
fullerene derivative recovered and massive polymerization
of the alkenes observed.
Pressurized microwave reactors have shown significant
advantages in synthesis.21 Indeed, the reaction between 1
and 4a was performed under pressure (300 W, 38 psi,
135 °C) (Fig. 1) in a focused microwave reactor in 1,2-
dichloroethane, a solvent that absorbs microwave irradia-
tion strongly. After 2.5 h, fullerene derivative 1 had been
The structures of all new compounds were fully sup-
1
ported by FTIR, H and 13C NMR spectroscopies. The
regioselectivity of the addition led in all cases to the b-
products. Furthermore, according to the 1H NMR spectra,
300
Power (W)
250
200
150
100
50
R
Me
Me
X
N
N
Temperature (ºC)
Pd(OAc)2, o(tol)3P,
NEt ,
chlorobenzene
3
+
R
4a-d
microwaves
4a:COO(CH2)2OH
4b:COO(CH2)4OH
4c:COOBu
Pressure (psi)
1, X=I
4d:COOCH2CH2N(CH2CH3)2
3, X=Br
5a-d
O2N
R
O2N
I
Pd(OAc)2, o(tol)3P,
NEt ,
N
N
N
N
chlorobenzene
3
0
+
R
microwaves
4a-b
0
2000
4000
6000
8000
4a:COO(CH2)2OH
4b:COO(CH2)4OH
Time (s)
2
6a-b
Fig. 1. Temperature, irradiation power and pressure profile of 6a for
pressurized microwave conditions. (300 W, 38 psi, 135 °C).
Scheme 2.

3658
M. J. Go´mez-Escalonilla, F. Langa / Tetrahedron Letters 49 (2008) 3656–3658
Arvela, R. K., ; Leadbeater, N. E.; Collins, M. J., Jr. Tetrahedron
2005, 61, 9349; (d) Datta, G. K.; von Schenck, H.; Hallberg, A.;
Larhed, M. J. Org. Chem. 2006, 71, 3896; (e) Nilsson, P.; Olofsson,
K.; Larhed, M. Top. Curr. Chem. 2006, 266, 103; (f) Dallinger, D.;
Oliver Kappe, C. Chem. Rev. 2007, 107, 2563.
consumed and, after workup, compound 6a was isolated in
34% yield—lower than that obtained at atmospheric pres-
sure in chlorobenzene.
In conclusion, we have explored the Heck reaction on
fullerene derivatives. Our results demonstrate the feasibility
of introducing an alkene functionality at the periphery of
the C60 cage through the Heck reaction on a fullerene
derivative with an aryl iodide moiety. The efficiency of
controlled microwave irradiation as the energy source to
promote the Heck coupling in fullerene derivatives has
been demonstrated.
14. (a) Kappe, C. O. Angew Chem., Int. Ed. 2004, 43, 6250; (b) de la Hoz,
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A.; Dıaz-Ortiz , A.; Moreno, A. Chem. Soc. Rev. 2005, 34, 164; (c)
Leadbeater, N. E. Chem. Commun. 2005, 2881.
15. (a) de la Cruz, P.; de la Hoz, A.; Langa, F.; Illescas, B.; Martin, N.
Tetrahedron 1997, 86, 2283; (b) Langa, F.; de la Cruz, P.; Espildora,
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E.; Garcia, J. J.; Perez-Rodriguez, M. C.; de la Hoz, H. Carbon 2000,
38, 1641.
16. Maggini, M.; Scorrano, G.; Prato, M. J. Am. Chem. Soc. 1993, 115,
9798.
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17. (a) Langa, F.; de la Cruz, P.; Delgado, J. L.; Gomez-Escalonilla, M.
Acknowledgements
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´
´
J.; Gonzalez-Cortes, A.; de la Hoz, A.; Lopez-Arza, V. New J.
´
Chem. 2002, 26, 76; (b) Espıldora, E.; Delgado, J. L.; de la Cruz, P.;
This work was financially supported by the Ministerio
´
de la Hoz, A.; Lopez-Arza, V.; Langa, F. Tetrahedron 2002, 58,
5821.
´
de Educacion y Ciencia (proyects ‘Consolider Ingenio
18. Najera, C.; Botella, L. Tetrahedron 2005, 61, 9688.
2010’ Project HOPE CSD2007-00007 and the CTQ2006-
06857) and the Junta de Comunidades de Castilla-La Man-
cha (Project PAI-05-068).
19. Typical procedure for palladium-catalyzed coupling reaction under
microwave irradiation of 5b (Table 1, entry 2). A heavy-walled glass
vial (80 mL capacity) was charged under argon with fullerene aryl
halide (1) (1 equiv) in chlorobenzene (10 mL), the corresponding
acrylate (4b) (excess 1650 lL,) triethyl amine (21 lL), palladium
acetate(II) (10 mol % with respect to C60 derivative), tri(o-tolyl)phos-
phine (4 equiv with respect to palladium (II)) were thereafter added.
The vial was then heated to 132 °C by microwave irradiation at 300 W
for 4.5 h. After cooling, the crude reaction mixture was extracted with
CH2Cl2 (50 mL) and washed with water (50 mL). The organic layer
was dried with MgSO4 and the solvent was removed at reduced
pressure. The residue was purified by chromatography using toluene
and CH2Cl2. Centrifuging three times with methanol and once with
n-pentane accomplished further purification of the solid.
20. Selected spectroscopic data for 5b: yield: 52% (as a dark brown solid);
FTIR (KBr) mmax/cmÀ1 2929, 2855, 2781, 2342, 1715, 1634, 1464,
1176, 1036, 984 and 528; 1H NMR (CDCl3) d/ppm 7.85 (2H, d, J
8.5 Hz), 7.68 (1H, B of AB system, d, J 16 Hz), 7.60 (2H, d, J 8.5 Hz),
6.46 (1H, A of AB system, d, J 16 Hz), 5.00 (1H, d, J 9.5 Hz), 4.97
(1H, s), 4.28 (1H, d, J 9.5 Hz), 4.27–4.18 (2H, m), 3.75–3.69 (2H, m),
2.82 (3H, s), 1.86–1.63 (4H, m); 13C NMR (CDCl3) d/ppm 166.8,
153.8, 153.0, 147.3, 147.2, 146.5, 146.3, 146.2, 146.1, 145.9, 145.8,
145.7, 145.5, 145.4, 145.3, 145.2, 145.1, 144.7, 144.5, 144.4, 144.3,
144.1, 143.1, 142.9, 142.7, 142.6, 142.5, 142.2, 142.1, 142.0, 141.9,
141.8, 141.7, 141.5, 140.1, 139.8, 139.5, 136.9, 136.4, 135.9, 135.6,
134.5, 130.7, 130.6, 129.9, 129.8, 128.4, 128.3, 127.9, 120.3, 118.4,
83.2, 69.9, 69.0, 64.3, 62.4, 62.3, 40.0, 29.6, 29.1 and 25.0; UV–vis
(CH2Cl2) kmax (nm) (loge): 227 (4.9), 256 (5.0), 431 (3.5); MALDI-
TOF m/z 995.1833 (M+).
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