Retro-cycloaddition Reaction to Fullerene
SCHEME 1.
[60]fullerenes 1a-e
Retro-cycloaddition Reaction of Isoxazolino-
azolinofullerenes have been readily obtained by addition of
nitrile oxides to [60]fullerene to form stable brown solids in
moderate yields. Starting nitrile oxides are in turn efficiently
prepared by dehydrochlorination of chloroximes, obtained by
chlorination of the respective oximes.5 Despite the huge amount
of work devoted to the preparation of fullerene cycloadducts
and particularly to those obtained by 1,3-dipolar cycloaddition
reactions, much less is known about their chemical and thermal
stability. Thus, we recently reported the thermally induced
transition metal-catalyzed quantitative retro-cycloaddition reac-
tion of pyrrolidino[3,4:1,2]fullerenes and proved its utility as a
new and useful protection-deprotection protocol.6 We recently
showed a similar reaction induced via electrochemical oxidation
of the pyrrolidine adduct.7 In this communication we report that
isoxazolinofullerenes also undergo a retro-cycloaddition thermal
reaction under the same relatively mild experimental conditions
used previously for fulleropyrrolidines to afford pristine fullerenes
efficiently, thus proving that they can also be used as a
protection-deprotection protocol compatible with other cy-
cloadduct derivatives present on the same fullerene sphere,
including fulleropyrrolidines.
In contrast to other pentagonal heterocycles, isoxazolines
undergo a variety of reactions resulting in the ring cleavage.
Opening isoxazolines involves N-O and CdN bond reduction,
and different reagents, such as TiCl3, diisobutyl aluminum
hydride, lithium aluminum hydride, Birch reduction, or hydrogen
and Raney nickel,8-10 have been used to reduce aliphatic and
aromatic isaxazolines. However, the chemical reduction of
isoxazolinofullerenes presents a problem since fullerenes them-
selves are very easy to reduce11 and are likely to be reduced
before the isoxazoline moiety.
at very high temperatures in the range of 280-400 °C.9 Prato
and co-workers reported that treatment of isoxazolinofullerenes
with Mo(CO)6 in refluxing chlorobenzene leads quantitatively
to pristine fullerene and the respective nitrile, resulting from
the further reduction of the nitrile oxide formed in the retro-
cycloaddition process. Similar results were also obtained by
treatment with excess of DIBAL-H in toluene at room temper-
ature.9 In order to determine the scope of the experimental
conditions used for the retro-cycloaddition reactions of fulle-
ropyrrolidines,6 we have applied the same reagents excess of
dipolarophile (maleic anhydride) as well as the use of CuTf2 as
a catalyst to the retro-cycloaddition of isoxazolinofullerenes.
The results obtained show that they efficiently undergo the retro-
cycloaddition process, and that the electronic nature of the
substituent on the isoxazoline ring has a strong influence on
the reaction outcome. Furthermore, these conditions can be also
successfully applied to higher fullerenes (C70) or to remove,
selectively, the isoxazoline ring from the fullerene surface in
the presence of other Bingel-Hirsch1 or Prato3 cycload-
ducts.
Following previously reported standard procedures,4,8 we have
synthesized a series of isoxazolinofullerenes 1a-e (Scheme 1).
The electroreduction of isoxazolines has been used to prepare
precursors for a variety of organic compounds including
aldehydes, alcohols, lactones, amino acids, thiiranes, and
olefins.12,13 Electrochemical reduction or oxidation has never
been used to attempt the retro-cycloaddition reaction of isox-
azolinofullerenes. Therefore, we have carried out controlled
potential electrolysis (CPE) in the present study to investigate
the electrochemical stability of isoxazolinofullerenes.
When these compounds were heated at reflux in o-dichlo-
robenzene (o-DCB) for 24 h, pristine C60 was obtained in a
variable amount (16-55%) together with other unidentified
compounds which were observed by HPLC (entries 1-5, Table
1).
In an attempt to increase the retro-cycloaddition procces, we
carried out the same reactions but in the presence of a big excess
(30 equiv) of a highly efficient dipolarophile, such as maleic
anhydride, according to our previously reported method.6 Under
these conditions, although the yields were improved (25-90%)
and the reactions were significantly more clean (HPLC), the
efficiency of the retro-cycloaddition process was remarkably
lower than that found for the related fulleropyrrolidines.
It is interesting to note, however, that compound 1c bearing
a p-(N,N-dimethylamino)phenyl substituent on the isoxazoline
ring (entry 8, Table 1) showed a remarkable conversion
efficiency (90.2%) in just 12 h, whereas the p-nitrophenyl group
(entry 7, Table 1) showed the lowest (25%) conversion. These
findings clearly suggest the strong impact that the electronic
effect has on the stabilization of the 1,3-dipole resulting from
the retro-cycloaddition process. The negative charge in the 1,3-
dipole should be localized on the more electronegative oxygen
atom, and the positive charge on the benzylic carbon, which is
stabilized by the presence of the strongly electron-releasing N,N-
dimethylamino group (1c) and destabilized by the electron-
withdrawing nitro group (1b). In agreement with these data,
the presence of the ethoxycarbonyl group (1d) or an alkyl
substituent (1e), which do not stabilize the respective 1,3-dipoles,
also led to remarkably low conversion efficiencies (entries 9,
10, Table 1).
Results and Discussion
Although isoxazolinofullerenes have been reported to be resis-
tant to further functionalization, they revert back to [60]fullerene
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W. E.; Ciuofolini, M. A.; Hauge, R. H.; Margrave, J. L.; Wilson, L. J.;
Curl, R. F.; Smalley, R. E. J. Phys. Chem. 1990, 94, 8634.
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