Synthesis and self-photooxygenation of alkenyl-linked [60]fullerene derivatives. A regioselective ene reaction

Article abstract of DOI:10.1021/ol025690l

(equation presented) Alkenyl-linked C₆₀ derivatives undergo self-photooxygenation regioselectively, by the preferential abstraction of allylic hydrogens on the fullerene side of the double bond.

Full text of DOI:10.1021/ol025690l

ORGANIC
LETTERS
2002
Vol. 4, No. 6
945-948
Synthesis and Self-Photooxygenation of
Alkenyl-Linked [60]Fullerene Derivatives.
A Regioselective Ene Reaction
Nikos Chronakis, Georgios C. Vougioukalakis, and Michael Orfanopoulos*
Department of Chemistry, UniVersity of Crete, 71409 Iraklion, Crete, Greece
orfanop@chemistry.uoc.gr
Received January 2, 2002
ABSTRACT
Alkenyl-linked C derivatives undergo self-photooxygenation regioselectively, by the preferential abstraction of allylic hydrogens on the fullerene
60
side of the double bond.
The photophysical and photochemical properties of the
electron-deficient fullerene C60 has received intensive atten-
tion over the past 10 years.1,2 The triplet excited state of C60
is formed with a quantum yield close to unity,3 and by energy
transfer to molecular oxygen, it produces large quantities of
1O2 (eq 1 ). This useful photochemical property makes C60
This useful observation has been applied successfully in
photosensitized studies of biological systems.7 Only two
reports so far deal with the self-sensitized ene photooxy-
genation of fullerene adducts. For example, Rubin and co-
workers reported8 previously an unexpected regioselectivity
in the self-photooxygenation reaction of several adducts
prepared by [4 + 2] cycloaddition to C60. In particular, while
photooxygenation of 1,2-dimethylcyclohexene affords pre-
ferentially the exo ene product in a 89/11 ratio, the self-
photooxygenation of the corresponding C60-fused cyclohex-
ene derivative 1 showed reverse regioselectivity (Scheme 1).
The rationalization of that result was based mainly on the
favorable electrostatic or electronic interactions between the
negative oxygen of the developing endo-perepoxide inter-
mediate and the electron-deficient C60.
3O2
ISC
9
C60
9
hν8 1C60 8 3C60
8 1O2
(1)
a potent sensitizer for the mild photooxygenation of simple
alkenes and dienes.4 It was also observed that fullerene C60
adducts that bear an oxidizable group are sensitive to oxygen
and light.5 Apparently, a self-sensitized photooxygenation
of these derivatives leads to the formation of a variety of
oxygenated adducts. This is a simple synthetic route for oxo
functionalization of fullerene derivatives with increased
solubility in solvents more polar than toluene or benzene.6
Furthermore, in our previous study on the mechanism of
[2 + 2] functionalization of C60 with butadienes, the
(1) Mattay, J.; Ulmer, L. Sotzmann, A. Photophysics and Photochemistry
of Fullerenes and Fullerene DeriVatiVes; Rumamurthy, V., Schanze, K.
S., Eds. In Molecular and Supramolecular Photochemistry: Marcel
Dekker: New York, 2001.
Scheme 1. Regioselectivity in the Self-Sensitized
Photooxygenation of C60-Fused Cyclohexene Derivative 1
(2) Hirsh, A. The Chemistry of the Fullerenes; Thieme Verlag: Stuttgart,
1994.
(3) Arbogast, J. W.; Darmanyan, A. P.; Foote, C. S.; Rubin, Y.; Diederich,
F. N.; Alvarez, M. M.; Anz, S. J.; Whetten, R. L. J. Phys. Chem. 1991, 95,
11.
(4) (a) Orfanopoulos, M.; Kambourakis, S. Tetrahedron Lett. 1994, 35,
1945. (b) Tokuyama, H.; Nakamura, E. J. Org. Chem. 1994, 59, 1135.
(5) Zhang, X.; Romero, A.; Foote, C. S. J. Am. Chem. Soc. 1993, 115,
11024.
10.1021/ol025690l CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/01/2002

with acetic acid while the color of the reaction mixture
became brown. The solid residue was washed with aceto-
nitrile, and the fullerene products were purified by flash
column chromatography (SiO2, hexane).
Scheme 2. Self-Sensitized Photooxygenation of Cycloadduct 2
The trisubstituted alkene 3, bearing a C60 substituent as
the sensitizer, was prepared from the coupling of 4-bromo-
2-methyl-2-butene with the dianion of C60. The allylic
bromide was used in a 6-fold molar excess, relative to C60,
-
and after protonation of the intermediate RC60 anion and
1
flash column chromatographic purification, H NMR spec-
troscopy revealed the formation of the adducts 3a and 3b in
a 85/15 ratio (Figure 1). These adducts were poorly separated
unsaturated cycloadduct 2 was produced9 (Scheme 2).
Because this adduct bears an oxidizable alkene moiety, it
undergoes facile self-sensitized ene photooxygenation and
produces, after reduction, a mixture of the threo/erythro
allylic alcohols 2a and 2b as the only products.
We report here the preparation and self-photooxygenation
of a series of alkenyl-linked[C60] derivatives that produce a
variety of oxo-functionalized ene products. The reactions are
regioselective and show preferential abstraction of the allylic
hydrogens on the fullerene side of the double bond.
The preparation of the desired C60-substituted alkenes was
2-
achieved by the reaction of the C60 anion with allylic
2-
bromides. It is well-known that the C60 anion, generated
electrochemically10 or chemically,11 can be alkylated by alkyl
halides to give adducts C60R2 in good yields (40-60%).
Kadish and co-workers11b have investigated the mechanism
of this two-step reaction by measuring the rate constants of
each step and comparing them with those for genuine elec-
tron transfer and SN2 reactions. According to the proposed
mechanism, electron transfer from the C602- to the RX gives
the radical pair (C60‚-R‚X-), where the R-X bond is cleaved
upon dissociative electron transfer. Facile radical coupling
in the radical pair gives the intermediate anion RC60-. The
addition of a second alkyl halide R′X to RC60- occurs by a
SN2 pathway to yield the final product R(R′)C60.
2-
In the present study the C60 dianion was prepared
selectively by the reaction of C60 with sodium methylthi-
olate12 (CH3S-Na+) in acetonitrile at room temperature under
an argon atmosphere. In a typical procedure, C60 (40 mg,
0.055 mmol) and a 10-fold molar excess of sodium meth-
ylthiolate salt were mixed in dry acetonitrile (30 mL) under
an argon atmosphere, and the mixture was stirred for 1 h at
2-
Figure 1. Preparation and sensitized self-oxygenation of adduct
3a.
room temperature. After the generation of the C60 (dark
red color) the allylic bromide was added with a syringe until
the color of the solution turned to dark green, which is
characteristic of the RC60- anion. The RC60- was protonated
on a Cosmosil 5C18-MS reverse phase column but could
not be separated by flash column chromatography.
(6) Ruoff, R. S.; Tse, D. S.; Malhotra, R.; Lorents, D. C. J. Phys. Chem.
1993, 97, 3379.
(7) (a) An, Y.-Z.; C.-h. B.; Aderson, J. L.; Sigman, D. S.; Foote, C. S.;
Rubin, Y. Tetrahedron 1996, 89, 5179. (b) Boutorine, A. S.; Tokuyama,
H.; Takasugi, M.; Isobe, H.; Nakamura, E.; Helene, C. Angew. Chem., Int.
Ed. Engl. 1994, 33, 2462.
The formation and characterization of the adduct 3b
confirms the electron-transfer mechanism from the C602- to
the alkyl halide, which was proposed by Kadish and co-
workers. The allylic radical formed when the R-Br bond is
(8) An, Y.-Z.; Viado, A. L.; Arce, M.-J.; Rubin, Y. J. Org. Chem. 1995,
60, 8330.
2-
cleaved upon dissociative electron transfer from C60 is a
hybrid of the resonance structures I and II (Scheme 3).
Coupling of the C60•- with the C1 or the C3 radical center
leads to the formation of 3a and 3b, respectively. The
primary carbon of the delocalized radical (Scheme 3) adds
preferentially to C60•-, most probably for steric reasons. In
(9) Vassilikogiannakis, G.; Chronakis, N.; Orfanopoulos, M. J. Am.
Chem. Soc. 1998, 120, 9911.
(10) Caron, C.; Subramanian, R.; D′Souza, F.; Kim, J.; Kutner, W.; Jones,
M. T.; Kadish, K. M. J. Am. Chem. Soc. 1993, 115, 8505.
(11) (a) Subramanian, R.; Kadish, K. M.; Vijayashree, M. N.; Gao, X.;
Jones, M. T.; Miller, M. D.; Krause, K. L.; Suenobu, T.; Fukuzumi, S. J.
Phys. Chem. 1996, 100, 16327. (b) Fukuzumi, S.; Suenobu, T.; Hirasaka,
T.; Arakawa, R.; Kadish, K. M. J. Am. Chem. Soc. 1998, 120, 9220.
1
the H NMR spectrum of 3 the hydrogen atom connected
946
Org. Lett., Vol. 4, No. 6, 2002

Scheme 3. Resonance Structures of the Allylic Radical
Formed via Dissociative Electron Transfer from C60 to
Scheme 4. Synthesis of Adduct 5a from the Coupling of the
2-
2-
cis-1-Bromo-2-butene with C60
4-Bromo-2-methyl-2-butene
on the fullerene core had a characteristic2 absorption at 6.47
ppm due to the deshielding effect of C60. The UV-vis
absorption spectrum showed a strong absorption at 437 nm
that is characteristic13 of 1,2-adducts of C60. The MALDI-
TOF MS spectrum of 3 showed the molecular ion of C60 at
720, thus indicating the decomposition of 3 under the
spectrometric conditions.
A solution of 3a/3b in toluene was irradiated in the
presence of oxygen with a Variac Eimac 300-W Xenon lamp
as the light source. The self-oxidation reaction was monitored
by HPLC. The complete disappearance of 3a was observed
within 15 min, in contrast with adduct 3b, which was
unreactive even after prolonged irradiation. This result was
not surprising, since it is well-known that terminal alkenes
that lack allylic hydrogens are unreactive to singlet oxygen.14
After reduction with PPh3, the reaction mixture was chro-
matographed on silica gel using a mixture of hexane and
ethyl acetate (4/1) as eluent. The structure of the oxo
functionalized 4a and 4b fullerene adducts were determined
The isomeric products derived from the coupling of the
various allylic bromides and the fullerene dianion are shown
in Scheme 5. According to the resonance structures of the
allylic radical formed upon dissociative electron transfer from
C60 to the allylic bromide, and taking into account the
geometrical isomerization of the allylic radicals,18 the forma-
2-
tion of adducts Xa, Xb, and Xc can be easily explained.
1
The structures of Xa, Xb, and Xc were determined by H
NMR spectroscopy by using homonuclear decoupling ex-
periments. Compounds Xa, Xb, and Xc had similar retention
times on a Cosmosil 5C18-MS reverse phase column and
were isolated as the isomeric mixture by flash column
chromatography (SiO2, hexane).
1
by H NMR spectroscopy. Adduct 4a was formed in 68%
relative yield in favor to 4b by the preferential abstraction
of the allylic hydrogen next to C60. Accounting for the
statistical factor, a single methylene hydrogen of 3a is seven
times more reactive than methyl hydrogens, leading to the
observed regioselectivity. It is worth noting here that although
the hydrogen connected to the fullerene core in substrate 3a
is slightly acidic,15 under the photooxygenation conditions
the material is stable and apart from the ene products 4a
and 4b, no other products were detected.
The self-sensitized photooxygenation of the isomeric
mixture Xa/Xb/Xc was performed in toluene by irradiating
the reaction mixture in the presence of oxygen. Alkenes Xa
were self-oxidized, and after 5-7 h of irradiation a 60-
70% conversion was measured by HPLC. trans-Alkene Xb
showed negligible reactivity19 relative to the cis analogue,
whereas Xc was not photooxidized at all.20 After reduction
with triphenylphosphine, the reaction mixture was chromato-
graphed on silica gel by using chloroform as eluent. The
structures of the isolated oxygenated fullerene adducts Ya
To study further this regioselectivity and obtain more
information about its origin, a series of disubstituted alkenes,
bearing the C60 substituent at one terminal of the double bond
and alkyl substituents of variable sizes at the other, were
prepared. Allylic bromides16 cis-1-bromo-2-butene, cis-1-
bromo-2-pentene, cis-1-bromo-4-phenyl-2-butene, cis-1-
bromo-5-methyl-2-hexene, and cis-1-bromo-5,5-dimethyl-2-
hexene were chosen as the appropriate substrates for the
alkylation of C602-. As an example, the synthesis of the
fullerene adduct 5a, derived from the coupling of the cis-
1-bromo-2-butene17 with C602-, is shown in Scheme 4.
1
and Yb were determined by H NMR spectroscopy. The
results are summarized in Scheme 6.
(16) Bromo-2-methyl-2-butene and cis-1-bromo-2-pentene, 6a, were
prepared from the corresponding allylic alcohols by using Ph3P‚Br2 as the
brominating reagent. cis-1-Bromo-5,5-dimethyl-2-hexene and cis-1-bromo-
5-methyl-2-hexene were synthesized according to the literature: Ando, K.
Tetrahedron Lett. 1995, 36, 4105. cis-1-Bromo-4-phenyl-2-butene was
prepared as follows: Wittig reaction between phenylacetaldehyde and the
stabilized ylide from triphenyl phosphine and bromo-ethylacetate, gave the
corresponding R,â-unsaturated esters as a mixture of two stereoisomers (cis/
trans ) 25/75). The cis ester was separated by flash column chromatography
on silica gel by using hexane as eluent. Reduction with LiAlH4/AlCl3
followed by bromination with Ph3P‚Br2 afforded the desired allylic bromide
in good yield.
(17) cis-1-Bromo-2-butene was obtained from the key intermediate cis-
methyl-2-butenoate: Orfanopoulos, M.; Smonou, I.; Foote, C. S. J. Am.
Chem. Soc. 1990, 112, 3607.
(18) Crawford, R. J.; Hamelin, J.; Strehlke, B. J. Am. Chem. Soc. 1971,
93, 3810.
(12) (a) Subramanian, R.; Boulas, P.; Vijayashree, M. N.; D’Souza, F.;
Jones, M. T.; Kadish, K, M. J. Chem. Soc., Chem. Commun. 1994, 1847.
(b) Allard, E.; Rivie´re, L.; Delaunay, J.; Dubois, D.; Cousseau, J.
Tetrahedron Lett. 1999, 40, 7223.
(13) Smith, A. B., III; Strongin, R. M.; Brard, L.; Furst, G. T.; Romanow,
W. J.; Owens, K. G.; King, R. C. J. Am. Chem. Soc. 1993, 115, 5829.
(14) For recent reviews on singlet oxygen, see: (a) Stratakis, M.;
Orfanopoulos, M. Tetrahedron 2000 56, 1595. (b) Clennan, E. L.
Tetrahedron 2000, 56, 6945.
(19) Singlet oxygen ene reaction with cis-butene proceeds 20 times faster
than that of the trans isomer: see ref 17.
(15) Fagan, P. J.; Krusic, P. J.; Evans, D. H.; Lerke, S. A.; Johnston, E.
J. Am. Chem. Soc. 1992, 114, 9697.
(20) (a) Foote, C. S. Acc. Chem. Res. 1968, 1, 104. (b) Hurst, J. R.;
Wilson, S. L.; Schuster, G. B. J. Am. Chem. Soc. 1982, 104, 2065.
Org. Lett., Vol. 4, No. 6, 2002
947

important role than conjugation with the π system of the
phenyl ring in the transition state of this reaction. As the
size of the R group becomes larger, the regioselectivity
toward the fullerene group decreases. This is demonstrated
with substrate 8a, where the preferential hydrogen abstraction
is slightly higher on the fullerene side. When R is tert-butyl,
9a, competition for the two allylic sides leads to nearly equal
hydrogen abstraction from the two methylene sides. It is
useful to note here that photosensitized ene oxidation of 5,5-
dimethyl-2-cis-hexene14a showed regioselectivity similar with
that of substrate 5a. This comparison might indicate that
unlike the rationalization8 for the regioselectivity of the self-
photooxygenation of C60-fused cyclohexene derivative 1, the
nonbonding steric interactions dictate the regioselectivity.
Electrostatic factors from fullerene group most probably play
a negligible role in the transition state of this reaction.
Examination of the possible transition states TSI and TSII
leading to the minor and major products provides an insight
into this regioselectivity (Scheme 7). In transition state TSII,
Scheme 5. Synthesis of Disubstituted Alkenes Bearing C60 as
the Large Substituent
Scheme 7
The ene reaction of the fullerene C60 substituted alkene
of the general type Xa shows a consistent regioselectivity
for double bond formation closer to the fullerene substituent.
For example, when the R group is hydrogen or methyl, com-
pounds 5a and 6a, the preferential abstraction of hydrogen
adjacent to the fullerene group is greater than 67%. A similar
regioselectivity trend is observed when R is a phenyl group,
substrate 7a. Again the major isomer is the product with the
double bond on the side of the fullerene group. This result
indicates that nonbonding sreric interactions play a more
leading to the major product, the nonbonding interactions
involving the large fullerene moiety are smaller than those
at the transition state TSI leading to the minor product. As
the size of the substituent on both sides of the double bond
become similar, as in compound 9a, the nonbonding interac-
tions in TSI and TSII become isoenergetic, leading to equal
amounts of the two isomeric ene products. This explanation
in terms of nonbonding steric interactions is similar to that
of the ene reaction of singlet oxygen with simple alkenes
and has been discussed extensively.14a It is interesting to note
that the regioselectivity is independent of solvent polarity.
Self-photooxygenation of compound 9a in toluene, 1,2-
dichlorobenzene, and benzonitrile gave similar ratios of the
two ene products (within experimental error).
Scheme 6. Regioselective Ene Photooxygenations of Fullerene
Derivatives Xa
In conclusion, the self-photooxygenation of C60-allyl sub-
stituted cis alkenes ocurrs by the preferential abstraction of
an allylic hydrogen next to the fullerene group. The hydrogen
atom linked to the fullerene frame is unreactive under the
photoogygenation conditions.
Acknowledgment. We thank Greek Secretariat of Re-
search and Technology (PENED 1999) for financial support
and for research fellowship to N.C.
Supporting Information Available: 1H NMR, spectral
data for 3a,b, 4a,b, 5a,c, 6a-c, 7a-c, 8a-c, 9a-c, and 10a,-
10b. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL025690L
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Org. Lett., Vol. 4, No. 6, 2002