CuI-catalyzed oxidative [3 + 2] reaction of fullerene with amidines or amides using air as the oxidant: Preparation of fulleroimidazole or fullerooxazole derivatives

Article abstract of DOI:10.1021/ol401909z

CuI-catalyzed oxidative reaction of amidines with C₆₀ using air as the oxidant has been exploited for the easy preparation of fulleroimidazole derivatives. Furthermore, this kind of CuI-catalyzed [3 + 2] reaction has also been successfully appl

Full text of DOI:10.1021/ol401909z

ORGANIC
LETTERS
2013
Vol. 15, No. 18
4650–4653
CuI-Catalyzed Oxidative [3 þ 2] Reaction
of Fullerene with Amidines or Amides
Using Air as the Oxidant: Preparation
of Fulleroimidazole or Fullerooxazole
Derivatives
Hai-Tao Yang,* Xi-Chen Liang, Yan-Hong Wang, Yang Yang, Xiao-Qiang Sun,* and
Chun-Bao Miao
School of Petrochemical Engineering, Changzhou University, Changzhou 213164,
P. R. China
yht898@yahoo.com; sunxq@yahoo.com
Received July 8, 2013
ABSTRACT
CuI-catalyzed oxidative reaction of amidines with C60 using air as the oxidant has been exploited for the easy preparation of fulleroimidazole
derivatives. Furthermore, this kind of CuI-catalyzed [3 þ 2] reaction has also been successfully applied in the synthesis of fullerooxazole
derivatives starting from amides for the first time. The substrate scope is broad, and the process is particularly cheap and simple.
A great diversity of modifications of the fullerene spher-
oid has attracted the attention of many researchers, which
allows the design of new promising fullerene-based materi-
als with unique biological and technological properties.
Numerous efforts for chemical modification of fullerenes
have been made over the past two decades, involving
various [2 þ n] (n = 1ꢀ4) cycloadditions, radical addi-
tions, nuclophilic additions, and multiadditions.1 The 1,3-
dipolar cycloaddition reaction is one of the most used
methodologies to construct five-membered ring-fused
[60]fullerene derivatives containing one or two hetero-
atoms. Fulleroisoxazoles and fulleropyrazoles can be easily
prepared from the reaction of C60 with the in situ generated
nitrile oxide and nitrilimine, respectively.2 Generally, most
of the [60]fullerene derivatives possess poorer electron
affinity than the pristine C60 due to the partial loss of
conjugation, which raises the LUMO energy.3 Fulleroimi-
dazoles and fullerooxazoles, as isomers of fulleropyrazoles
and fulleroisoxazoles, proved to have better electron ac-
ceptor character than C60 due to the presence of two
electronegative atoms directly linked to the C60 core, which
is beneficial for the preparation of a wide variety of organic
photovoltaic devices. However, there were only a few
reports on their preparation up to now. Photochemical
reactions of C60 with acylazides4 or rearrangement of the
fulleroaziridines generated from the thermal reactions of
(1) For books, see: (a) Hirsch, A.; Brettreich, M. Fullerenes: Chem-
istry and Reactions; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim,
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Applications; RSC Publishing: Cambridge, U.K., 2007.
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r
10.1021/ol401909z
Published on Web 09/04/2013
2013 American Chemical Society

C60 with azidoformates or hydroxamic acid derivatives5 is
the earlier method to synthesize fullerooxazoles. Recently,
the Gao group reported an electrochemical method for the
preparation of fullerooxazoles through aerobic oxidations
of dianionic C60 in PhCN solution.6 The Wang and
Minakata groups developed a one-step approach starting
Table 1. Screening of the Reaction Conditionsa
from nitriles or amides mediated by Fe(ClO4)3 6H2O7 or
3
t-BuOI,8 respectively. We also developed a PhI(OAc)2/I2-
mediated [3 þ 2] reaction of C60 with amides for the
preparation of fullerooxazoles.9 As for the fulleroimidazoles,
only the Wang group reported their preparation through the
silver carbonate promoted reaction of [60]fullerene with
N-arylbenzamidines.10 Nevertheless, these reactions have
some limitations. The reaction of C60 with acylazides always
produces the azafulleroid as a byproduct. Furthermore, the
azides are classified as highly explosive and toxic. The
electrochemical method always results in some serious side
reactions, which dramatically decreases its practicability.
Wang’s method needs an excessive amount of nitriles up to
100 equiv. Silver carbonate is an expensive reagent, and a
stoichiometric amount is needed. In continuation of our
interest in fullerene chemistry,11 herein, we reported the
CuI-catalyzed oxidative reaction of C60 with amidines or
amides using air as the oxidant for the easy preparation of
fulleroimidazole or fullerooxazole derivatives.
time yield
entry
Cu
ligand
none
[C60/1a/Cu/L] (h)
(%)b
1
CuI
1:3:3:0
10 6 (85)
10 trace
2
CuBr
CuCl
CuCl2
none
none
none
none
1:3:3:0
3
1:3:3:0
10
0
4
1:3:3:0
10 trace
10 trace
10 trace
5
CuBr2
1:3:3:0
6
Cu(OAc)2 H2O none
1:3:3:0
3
7
Cu(OTf)2
CuI
none
1:3:3:0
10
0
8
pyridine
Bpy
1:3:3:3
10 8 (81)
10 13 (77)
10 14 (80)
10 trace
9
CuI
1:3:3:3
10
11
12
13
14c
15
16
CuI
TMDEA
PMDETA
Phen
1:3:3:3
CuI
1:3:3:3
CuI
1:3:3:3
10 37 (75)
10 35 (84)
24 9 (90)
10 27 (79)
10 34 (86)
CuI
Phen
1:3:0.3:0.3
1:3:0.3:0.3
1:2:0.2:0.2
1:2:0.4:0.4
1:2:0.4:0.4
CuI
Phen
CuI
Phen
CuI
Phen
17d CuI
Phen
10
0
Copper-mediated inter- or intramolecular reactions of
β-enamino carbonyl compounds could afford various
azaheterocycles.12 Stimulated by the structural analogy
of amidines with enamine carboxylates, the Chiba group
developed a copper-catalyzed intramolecular aerobic
[3 þ 2]-annulation reaction of N-alkenyl amidines for the
preparation of bi- and tricyclic amidines.13 Most recently,
the Neuville and Chen groups reported the copper-catalyzed
reaction of the amidines with terminal alkynes or nitroalkenes
a All the reactions were carried out with 0.05 mmol of C60, 0.1 mmol
of 1a, and proper additives in 10 mL of chlorobenzene at 130 °C under
air unless specified otherwise. b Isolated yield; the values in parentheses
are based on consumed C60.
c The reaction was operated at 70 °C. d The
reaction was carried out under a nitrogen atmosphere.
for the preparation of polysubstituted imidazoles, respect-
ively.14 Inspired by their results, we envisioned that similar
oxidative processes could occur through Cu(n)-mediated
aerobic reactions of C60 with amidines, which would lead
to the formation of fulleroimidazole derivatives.
(5) (a) Banks, M. R.; Cadogan, J. I. G.; Gosney, I.; Hodgson,
P. K. G.; Langridge-Smith, P. R. R.; Rankin, D. W. H. J. Chem. Soc.,
Chem. Commun. 1994, 1365–1366. (b) Banks, M. R.; Cadogan, J. I. G.;
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(7) Li, F.-B.; Liu, T.-X.; Wang, G.-W. J. Org. Chem. 2008, 73, 6417–
6420.
We began our investigation with the reaction between
60 and N-(p-tolyl)-4-methylbenzamidine (1a) in the pre-
C
sence of different copper reagents (Table 1). The reaction
of C60 with 1a and CuI in a molar ratio of 1:3:3 at 130 °C
for 10 h gave the desired product 2a in 6% yield. Other
copper salts such as CuCl, CuBr, CuCl2, CuBr2, Cu(OAc)2,
and Cu(OTf)2 were not effective in this reaction (entries
2ꢀ7). Next, the reaction of C60 with1aand CuI was carried
out in the presence of different ligands such as pyridine,
TMEDA (N,N,N0,N0-tetramethylethylenediamine), Bpy
(2,20-bipyridine), PMDETA (pentamethyldiethylenetriamine),
and Phen (1,10-phenanthroline) to improve the yield (Table 1,
entries 8ꢀ12). The results showed that 1,10-phenanthroline
(Phen) was the best ligand and afforded 2a in 37% yield.
Reducing the CuI and Phen to catalytic amounts also gave a
good yield of 2a (Table 1, entry 13). When the temperature
was lowered to 70 °C, 2a was obtained in only 9% yield after
24 h (Table 1, entry 14). Further reducing the amount of 1a,
(8) Takeda, Y.; Enokijima, S.; Nagamachi, T.; Nakayama, K.;
Minakata, S. Asian J. Org. Chem. 2013, 2, 91–97.
(9) This work (PhI(OAc)2/I2-Mediated [3
þ
2] Reaction of
[60]Fullerene with Amides for the Preparation of Fullerooxazoles) has
been submitted to Tetrahedron Letters (Revisions being processed).
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2013, 15, 1532–1535.
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Y.; Xi, H.-T.; Meng, Q.; Jiang, Y.; Sun, X.-Q. J. Org. Chem. 2013, 73,
1163–1170. (b) Yang, H.-T.; Tian, Z.-Y.; Ruan, X.-J.; Zhang, M.; Miao,
C.-B.; Sun, X.-Q. Eur. J. Org. Chem. 2012, 4918–4922. (c) (b) Yang,
H.-T.; Ruan, X.-J.; Miao, C.-B.; Sun, X.-Q. Tetrahedron Lett. 2010, 51,
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Y.; Meng, Q.; Sun, X.-Q. Tetrahedron Lett. 2009, 50, 7337–7339.
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D.; Wu, P.; Liu, X.; Chen, Y.-X.; Guo, S.-B.; Chen, W.-X.; Li, J.-G.;
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3679–3682.
Org. Lett., Vol. 15, No. 18, 2013
4651

Table 2. Substrate Scope of Cu-Catalyzed Synthesis of
Fulleroimidazole from C60 and Amidinesa
Scheme 1. CuI-Catalyzed Oxidative Reaction of C60 with
Benzamide
Table 3. Cu-Catalyzed Synthesis of Fullerooxazole from C60
and Amidea
a All the reactions were performed with a molar ratio of C60
/
amidines/CuI/phen = 1:2:0.4:0.4 in 10 mL of chlorobenzene at 130 °C
for 8ꢀ12 h under air. b Isolated yield; the values in parentheses are based
on consumed C60
.
CuI, and Phen to 2, 0.2, and 0.2 equiv led to an obvious
decrease in the yield of 2a (35% to 27%, Table 1, entry 15 vs 13).
Using 2 equiv of 2a and increasing the amount of CuI and
Phen from 0.2 to 0.4 equiv improved the yield to 34%
(Table 1, entry 16). O2 was crucial to the reaction, and no
reaction occurred under a nitrogen atmosphere (Table 1,
entry 17). From the viewpoint of atom economy, the molar
ratio of C60, 1a, CuI, and Phen as 1:2:0.4:0.4 and the temp-
erature of 130 °C in chlorobenzene under air were chosen as
the optimal reaction conditions (Table 1, entry 16).
a All the reactions were performed with a molar ratio of C60/amidine/
CuI/phen = 1:2:0.4:0.4 in 10 mL of chlorobenzene at 130 °C for 6ꢀ10 h
under air.
With the optimum reaction conditions in hand, we next
investigated the substrate scope of the CuI-catalyzed oxi-
dative synthesis of fulleroimidazoles (Table 2). When R1
and R2 are both aryl groups, all of the substrates gave good
yields of 2. The electronic effect of the substituent group on
the phenyl ring has no significant influence on the reaction.
An electron-donating group gave a slightly higher yield.
However, when either R1 or R2 was replaced by an alkyl
group, the reaction failed.
Amides have structure similarity with amidines only
with the change of CdN double bonds to CdO double
bonds (Scheme 1). We were inquisitive about whether the
4652
Org. Lett., Vol. 15, No. 18, 2013

amides could also react with C60 under similar conditions
to produce the fullerooxazoles. Up to now, there were only
a few reports on the synthesis of oxazoles directly from the
reaction of amides with alkenes such as treating 2-chloro-
2-cyclopropylideneacetates with carboxamides under ba-
sic conditions through a domino transformation involving
a Michael addition followed by an intramolecular nucleo-
philic substitution,15 the NIS-mediated reaction of glucal
with amide.16 The Minakata group developed a t-BuOI
mediated reaction of amides with olefins for the prepara-
tion of a variety of oxazoles, and they also applied this
method in the preparation of fullerooxazoles.8,17
Scheme 2. Proposed Reaction Mechanism
Benzamide 3a was chosen to test this possibility. To our
delight, when C60 was treated with benzamide 3a (2 equiv)
in the presence of CuI (0.4 equiv) and Phen (0.4 equiv) in
chlorobenzene at 130 °C for 8 h, the oxidative cycloaddi-
tionproduct, fullerooxazole4a, wasproduced in36% yield
(Scheme 1). It is the first time to realize such a CuI-
catalyzed [3 þ 2] reaction of amides. Inspired by this result,
we next investigated the scope of this Cu-catalyzed oxida-
tive synthesis of fullerooxazoles (Table 3). It could be seen
that the reaction was tolerant to various functional groups.
Aryl amides with either an electron-donating or -with-
drawing group on the phenyl ring gave a good yield of 4.
Heterocyclic amides 3gꢀi also reacted with C60 to give
corresponding fullerooxazoles 4gꢀi. Alkyl amides were
also applicable, and ester or carbamate groups were also
tolerated in this reaction.
All of the known products were confirmed throuth
comparison of their spectral data with those reported in
the literature.7ꢀ10 The identification of new compounds
2aꢀh, 4c, 4h, and 4i was fully confirmed by their MS,
1H NMR, 13C NMR, FTIR, and UVꢀvis spectra
(see Supporting Information).
In view of the reported Cu-catalyzed oxidative reaction
of enamines and amidines,12ꢀ14 a proposed mechanism is
described in Scheme 2. One-electron oxidation of amidine
1 or amide 3 by CuII species (described as [CuII]) generated
from CuI with molecular oxygen18 would provide nitrogen
radical 6, which was captured by C60 to afford fullerene
radical 7. Further reaction of 7 with CuII generated 8. In
path A, 8 could transform to a six-membered ring Cu(III)
intermediate 9, which underwent elimilation of Cu(I) to
generate 2 or 4. In path B, homolytic cleavageofthe NꢀCu
bond and subsequent intramolecular cyclization would
generate 2 or 4.
In summary, CuI-catalyzed oxidative intermolecular re-
action of amidines or amides with C60 using air as an oxidant
has been exploited for the easy preparation of fulleroimida-
zole or fullerooxazole derivatives. The process, which used
copper as the catalyst and air as the co-oxidant, is particu-
larly cheap, simple, and atom efficient. Further investiga-
tions on the Cu-catalyzed oxidative reaction of amides with
alkynes, other olefins, and nitriles are currently underway.
Acknowledgment. We are grateful for the financial
support from the National Natural Science Foundation
of China (21202011) and the Priority Academic Program
Development of Jiangsu Higher Education Institutions.
Supporting Information Available. Experimental pro-
cedures, spectral data of new compounds, and NMR
spectra of the products. This material is available free of
charge via the Internet at http://pubs.acs.org.
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The authors declare no competing financial interest.
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