Synthesis of C5-symmetric functionalized [60]fullerenes by copper-mediated 5-fold addition of reformatsky reagents

Article abstract of DOI:10.1021/ol702874w

A variety of Reformatsky reagents were added five times to [60]fullerene in good yield in the presence of a stoichiometric amount of a copper(l) complex. The penta-addition products C₆₀(CH₂CO₂R) ₅H (R = Et, t-Bu

Full text of DOI:10.1021/ol702874w

ORGANIC
LETTERS
2008
Vol. 10, No. 4
621-623
Synthesis of C5-Symmetric
Functionalized [60]Fullerenes by
Copper-Mediated 5-Fold Addition of
Reformatsky Reagents
Takahiro Nakae, Yutaka Matsuo,* and Eiichi Nakamura*
Nakamura Functional Carbon Cluster Project, ERATO, Japan Science and Technology
Agency, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
matsuo@chem.s.u-tokyo.ac.jp; nakamura@chem.s.u-tokyo.ac.jp
Received December 4, 2007
ABSTRACT
A variety of Reformatsky reagents were added five times to [60]fullerene in good yield in the presence of a stoichiometric amount of a
copper(I) complex. The penta-addition products C60(CH2CO2R)5H (R Et, t-Bu, CH2CF3, (CH2CH2O)2Et, and CH2CH2CCSiMe3) can then be converted
to the corresponding penta-hapto metal complexes. When the R group is a ( )-menthyl group, the corresponding metal complex comprises
an organometallic complex with a coordination sphere consisting of a homochiral C5-symmetric environment.
)
−
Polyfunctionalized fullerene materials have received much
attention because of various applications in the life and
materials sciences.1 For the synthesis of such materials,
control of regioselectivity when introducing multiple func-
tional groups is a key issue2-5 and may be achieved, for
instance, by the addition of multifunctional tethered reactants6
or by multiple additions of monofunctional reactants.7 Penta-
addition reactions of organocopper reagents that selectively
introduce five organic groups around one pentagon are
interesting examples of the latter category.8 The reaction is
extremely selective and high yielding and can be carried out
readily on a multigram scale. The functional group tolerance
is also quite high as exemplified by the synthesis of C60(C6H4-
CO2Et)5H from the corresponding ethyl 4-magneciobenzoate.8c
One major limitation of this copper route, however, is that
one can introduce aryl, alkenyl, methyl, and silylmethyl
(1) (a) Hirsch, A.; Brettreich, M. Fullerenes: Chemistry and Reactions;
Wiley-VCH: Weinheim 2005. (b) Kadish, K. M.; Ruoff, R. S. Fullerenes:
Chemistry, Physics, and Technology; John Wiley & Sons: New York, 2000.
(c) Hirsch, A. The Chemistry of Fullerenes; Theme: Stuttgart, 1994. (d)
The Chemistry of Fullerenes; Taylor, R., Ed.; World Scientific: River Edge,
NJ, 1995.
(6) (a) Isaacs, L.; Haldimann, R. F.; Diederich, F. Angew. Chem., Int.
Ed. Engl. 1994, 33, 2339-2342. (b) Diederich, F.; Kessinger, R. Acc. Chem.
Res. 1999, 32, 537-545. (c) Nakamura, E.; Isobe, H.; Tokuyama, H.;
Sawamura, M. Chem. Commun. 1996, 1747-1748. (d) Isobe, H.; Tokuyama,
H.; Sawamura, M.; Nakamura, E. J. Org. Chem. 1997, 62, 5034-5041.
(7) (a) Hirsch, A. Top. Curr. Chem. 1999, 199, 1-65. (b) Lamparth, I.;
Maichle-Mo¨ssmer, C.; Hirsch, A. Angew. Chem., Int. Ed. Engl. 1995, 34,
1607-1609. (c) Hirsch, A.; Vostrowsky, O. Eur. J. Org. Chem. 2001, 829-
848. (d) Lamparth, I.; Herzog, A.; Hirsch, A. Tetrahedron 1996, 52, 5065-
5075. (e) Camps, X.; Hirsch, A. J. Chem. Soc., Perkin Trans. 1 1997, 1595-
1596.
(2) (a) Wang, G.-W.; Murata, Y.; Komatsu, K.; Wan, T. S. M. Chem.
Commun. 1996, 2059-2060. (b) Allard, E.; Delaunay, J.; Cousseau, J. Org.
Lett. 2003, 5, 2239-2242. (c) Wang, Z.; Meier, M. S. J. Org. Chem. 2003,
68, 3043-3048.
(3) Wang, G.-W.; Zhang, T.-H.; Cheng, X.; Wang, F. Org. Biomol. Chem.
2004, 2, 1160-1163.
(4) Allard, E.; Rivie`re, L.; Delaunay, J.; Dubois, D.; Cousseau, J.
Tetrahedron Lett. 1999, 40, 7223-7226.
(8) (a) Sawamura, M.; Iikura, H.; Nakamura, E. J. Am. Chem. Soc. 1996,
118, 12850-12851. (b) Matsuo, Y.; Muramatsu, A.; Tahara, K.; Koide,
M.; Nakamura, E. Org. Synth. 2006, 83, 80-87. (c) Zhong, Y.-W.; Matsuo,
Y.; Nakamura, E. Org. Lett. 2006, 8, 1463-1466.
(5) Zhang, T.-H.; Wang, G.-W.; Lu, P.; Li, Y.-J.; Peng, R.-F.; Liu, Y.-
C.; Murata, Y.; Komatsu, K. Org. Biomol. Chem. 2004, 2, 1698-1702.
10.1021/ol702874w CCC: $40.75
© 2008 American Chemical Society
Published on Web 01/23/2008

groups, but not alkyl groups, probably because the interme-
diary alkylcopper reagents decompose via â-elimination.
Here, we report that Reformatsky reagents9 undergo penta-
addition to [60]fullerene in the presence of a stoichiometric
amount of a copper(I) catalyst to produce C60(CH2CO2R)5H
(1) (eq 1). The product 1 is not exactly the desired penta-
by filtration and to use excess Reformatsky reagent. [60]-
Fullerene in 1,2-dichlorobenzene was added at once at 25
°C, and the mixture was stirred for 4 h at 25 °C. After acidic
workup and filtration through a pad of silica gel, we obtained
the pentafunctionalized [60]fullerene, for instance, C60(CH2-
CO2Et)5H (1a) in 92% yield with 88% purity (HPLC) (Table
1, entry 1). For reasons yet unknown, the products prepared
Table 1. Copper-Mediated Penta-addition of Reformatsky
Reagent to [60]Fullerenea
yieldb purityc
entry
BrCH2CO2R (2)
BrCH2CO2Et (2a)
product
(%)
(%)
alkylated fullerene but can serve as its surrogate because one
can install various alkyl groups and functional groups via
the ester linkage without imposing steric effects on the central
cyclopentadiene moiety. The utility of the products is
illustrated by the smooth conversion of 1 to the C5-symmetric
iron and ruthenium complexes 4 and 5 (Scheme 1). The
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
92 (40)d
91
89
19d
30d
91
29d
31d
88
86
86
BrCH2CO2(1-hexyl) (2b)
BrCH2CO2CH2C6H5 (2c)
BrCH2CO2(tert-butyl) (2d)
BrCH2CO2(1-adamantyl) (2e)
BrCH2CO2CH2CF3 (2f)
BrCH2CO(OCH2CH2)3H (2g)
BrCH2CO2CH2CH2CCSiMe3
(2h)
80
1g
1h
Scheme 1. Derivatization of Pentafunctionalized Fullerene 1
into Methylated Compound 3 and Metal Complexes 4 and 5
9
BrCH2CO2[(-)-menthyl)] (2i)
1i
92
84
a The syntheses were carried out according the typical procedure
described in footnote 10. Details are reported in the Supporting Information.
b Unless otherwise noted, the yields are determined for the crude product
on which the purity was assessed by HPLC. c Purity was determined by
HPLC area ratio measured at 350 nm. d Yield of isolated product after
purification by silica gel chromatography and preparative HPLC.
by this method were much more susceptible to air oxidation
than any other similar compounds we have previously
synthesized.8 Thus, we could isolate pure samples of 1 in
40-50% isolated yield after careful chromatographic puri-
fication out of the crude product of 88% purity.
Other examples of the synthesis of the penta-adducts 1b-h
from the corresponding R-bromo acetates 2b-h are shown
in Table 1 (entries 2-8). The reactions of the Reformatsky
reagents bearing 1-alkyl, benzyl, and tert-alkyl groups
(entries 1-5) also proceeded smoothly (the lower yields in
entries 4 and 5 are because of the oxidative loss of the
product during purification). We examined the esters bearing
fluorinated and polyoxo groups (entries 6 and 7), and these
products showed higher solubility than the compounds in
entries 1-5. The trifluoroethyl ester 2f was soluble in
methanol and acetone, which are generally not good solvents
for organofullerenes. The polyether derivative 2g was an oily
material at room temperature and is highly soluble in various
introduction of five equivalents of a chiral group as R groups
(e.g., five (-)-menthyl groups) provides chiral C5-symmetric
molecules that belong to a rarely investigated class of chiral
molecules.
Reformatsky reagent BrZnCH2CO2Et was prepared in THF
from metallic zinc powder (Kanto Chemical) and a bro-
moacetic acid ester and then allowed to react with 1 equiv
of CuBr‚SMe2 in a mixture of THF and N,N′-dimethyl-2-
imidazolidinone. To obtain the cleanest possible product, it
is essential to remove the unreacted zinc powder completely
(10) A typical procedure for preparation of 1a: To a THF (10 mL)
suspension of CuBr‚SMe2 (308 mg, 1.50 mmol) and N,N′-dimethyl-2-
imidazolidinone (0.16 mL, 1.5 mmol) was added dropwise a THF solution
of BrZnCH2CO2Et (0.7 M, 2.1 mL, 1.5 mmol) at 25 °C under an argon
atmosphere. After the copper/zinc mixture was stirred for 10 min, a 1,2-
dichlorobenzene (5 mL) solution of C60 (72 mg, 0.10 mmol) was added at
once. The reaction mixture was stirred at 25 °C for 4 h and then quenched
with saturated aqueous ammonium chloride solution (0.1 mL). The resulting
mixture was diluted with degassed toluene (10 mL) and ethyl acetate (10
mL) and quickly filtered through a pad of silica gel to remove insoluble
materials. The solution was quickly concentrated under reduced pressure,
and was diluted with degassed methanol (100 mL). The resulting precipitate
was collected and dried in vacuo to obtain 1a (107 mg, 92% yield, purity
88% as determined by HPLC area).
(9) (a) Knochel, P.; Leuser, H.; Gong, L.-Z.; Perrone, S.; Kneisel, F. F.
In Handbook of Functionalized Organometallics; Knochel, P., Ed.; Wiley-
VCH: Weinheim, 2005; Vol. 1, pp 251-346. (b) Knochel, P. In Science
of Synthesis; O’Neil, I. A., Ed.; Georg Thime Verlag: Stuttgart, 2004; Vol.
3, pp 5-90. (c) Ocampo, R.; Dolbier, W. R., Jr. Tetrahedron 2004, 60,
9325-9374.
622
Org. Lett., Vol. 10, No. 4, 2008

common organic solvents, such as acetone and THF. A
silylalkynyl group was found to survive the reaction condi-
tions (entry 8). A rather bulky (-)-menthyl ester moiety
could also be introduced smoothly (Table 1, entry 9).
The cyclopentadienyl moiety in compound 1a can be
methylated11 or converted to the corresponding bucky-
ferrocene 4a12 and buckyruthenocene 5a.13 (Scheme 1).
The chirality of the (-)-menthol moieties in 1i provides
an interesting opportunity to create a chiral C5-symmetric
environment around a metal atom. Thus, the penta-adduct
1i was converted into the ferrocene compound (4i) in 28%
yield. The 1H and 13C NMR data for 4i indicated a
C5-symmetric structure, indicating either free rotation of the
menthyl group on the NMR time scale or that all menthyl
groups are oriented in the same conformation making a C5-
symmetric chiral structure. The CD spectrum of 4i exhibited
a strong negative Cotton effect at 273 nm (Figure S2,
Supporting Information). Chiral C5 symmetric compounds
have found use in biological applications,14 and the prepara-
tion of 4i suggests the utility of C5 chirality in catalysis15
and materials chemistry.
1
The structures were analyzed by H, 13C NMR, IR, and
HRMS and, for 4a, also by X-ray crystallographic analysis
(Figure 1).
In conclusion, we have shown that a variety of alkyl groups
and functional groups can be introduced to a fullerene core
with the aid of the Reformatsky reagent in the presence of
a copper complex. It is possible that zinc to copper
transmetalation is involved as the first step of the reaction16
and, if so, that the subsequent reactions follow a pathway
similar to those in the penta-addition of the organocopper
reagent based on Grignard reagents.8 Ester linkage has served
as a useful tool for construction of fullerene molecular array
such as donor-acceptor hybrid molecules.17 We expect that
the flexibility of the present Reformatsky approach will allow
us to synthesize a wide variety of functional fullerene
derivatives thus far unavailable by other methods. The utility
of the chiral C5-symmetric organometallic compounds is of
considerable interest and will be investigated in the near
future.
Figure 1. Molecular structure of 4a (a) ORTEP drawing. (b) Top
view of a CPK model. (c) Side view of a CPK model.
Acknowledgment. We thank Dr. S. Fukuzawa (Depart-
ment of Chemistry, the University of Tokyo) for his help of
CD spectrum measurement and MEXT for partial support
of the work (KAKENHI for E.N., No. 18105004).
Complex 4a underwent reversible one-electron oxidation
and one-electron reduction (E1/2ox ) 0.38 and E1/2red ) -1.48
V vs Fc/Fc+) (Figure S1, Supporting Information). The
oxidation potential was higher than that of pentamethyl-
buckyferrocene Fe(C60Me5)Cp (E1/2ox ) 0.22 V vs Fc/Fc+),12
and it is consistent with the electron-withdrawing effects of
the five esters through the fullerene cage (note that the ester
group and the fullerene conjugation system are not directly
conjugated).
Supporting Information Available: Experimental pro-
cedures, spectroscopic data for all new compounds, and CIF
file for 4a. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL702874W
(11) Hamasaki, R.; Matsuo, Y.; Nakamura, E. Chem. Lett. 2004, 33,
328-329.
(12) Sawamura, M.; Kuninobu, Y.; Toganoh, M.; Matsuo, Y.; Yamanaka,
M.; Nakamura, E. J. Am. Chem. Soc. 2002, 124, 9354-9355.
(13) Matsuo, Y.; Kuninobu, Y.; Ito, S.; Nakamura, E. Chem. Lett. 2004,
33, 68-69.
(14) Isobe, H.; Cho, K.; Solin, N.; Werz, D. B.; Seeberger, P. H.;
Nakamura, E. Org. Lett. 2007, 9, 4611-4614.
(15) Kagan, H. B. Ann. N. Y. Acad. Sci. 1980, 333, 1-15.
(16) Kuwajima, I.; Doi, Y. Tetrahedron Lett. 1972, 13, 1163-1166.
(17) Guldi, D. M.; Aminur Rahman, G. M.; Sgobba, V.; Ehli, C. Chem.
Soc. ReV. 2006, 35, 471-487.
Org. Lett., Vol. 10, No. 4, 2008
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