Highly regioselective transformation of out/out-equatorial bis(formylmethano)[60]fullerenes: Construction of dissymmetric [60]fullerene-centered triads

Article abstract of DOI:10.1021/jo060110+

Three kinds of out/out-equatorial bis(formylmethano)[60]fullerenes (1b-d) were obtained by the tether-directed bifunctionalization of [60]fullerene with bis(α-formylsulfonium ylide)s. The condensation of aromatic amines with 1b-d proceeded with an unexpec

Full text of DOI:10.1021/jo060110+

Highly Regioselective Transformation of out/out-equatorial
Bis(formylmethano)[60]fullerenes: Construction of Dissymmetric
[60]Fullerene-Centered Triads
Hiroshi Ito, Yasuhiro Ishida, and Kazuhiko Saigo*
Department of Chemistry and Biotechnology, Graduate School of Engineering, The UniVersity of Tokyo,
Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
saigo@chiral.t.u-tokyo.ac.jp
ReceiVed January 19, 2006
Three kinds of out/out-equatorial bis(formylmethano)[60]fullerenes (1b-d) were obtained by the tether-
directed bifunctionalization of [60]fullerene with bis(R-formylsulfonium ylide)s. The condensation of
aromatic amines with 1b-d proceeded with an unexpectedly high regioselectivity to give one of two
possible regioisomers of mono-imines as the main products (the ratio of the regioisomers, up to 97:3).
By the transformation of the remaining formyl group in the mono-imines thus obtained, the corresponding
dissymmetric bis-imines were efficiently synthesized.
Introduction
functional molecules with a fascinating structure.4 To date,
however, there has been no report on the selective transfor-
mation of only one of two identical addends in bifunction-
alized C60s; this attempt has been regarded hardly possible,
because the two addends are considered to be chemically
equivalent and because their transformations might be antici-
pated to proceed essentially without influence with each other.
Thus, the selective mono-transformation of two identical ad-
dends in bifunctionalized C60s still remains as a challenging
and unsettled target, even though the selective mono-transfor-
mation would give anisotropic C60 derivatives with significant
value from the viewpoints of synthetic chemistry and materials
chemistry.
For the construction of novel [60]fullerenes (C60)-containing
functional materials, bifunctionalized C60s have been recognized
as one of the most fundamental and useful components.1 Since
the development of an elegant and versatile method for the
preparation of regio- and stereo-controlled bifunctionalized C60s,
the so-called tether-directed bifunctionalization, by Diederich
et al., access to these attractive compounds have became easier;
C60 derivatives with a diversity of addition patterns and
functional groups have been able to be efficiently synthesized.2,3
Furthermore, several successful examples have been reported
for the transformation of both addends to other functional
groups, which are applicable to the construction of C60-based
To achieve the first selective mono-transformation of two
identical addends in bifunctionalized C60, we focused on the
regio- and stereochemistries of bifunctionalized C60s. For a
(1) Kadish, K. M.; Ruo, R. S. Fullerenes: Chemistry, Physics, and
Technology; Wiley-Interscience: New York, 2000.
(2) (a) Nierengarten, J.-F.; Gramlich, V.; Cardullo, D.-C. F.; Diederich,
F. Angew. Chem., Int. Ed. Engl. 1996, 35, 2101-2103. (b) Nierengarten,
J.-F.; Habicher, T.; Kessinger, R.; Cardullo, F.; Diederich, F.; Gramlich,
V.; Gisselbrecht, J. P.; Boudon, C.; Gross, M. HelV. Chim. Acta 1997, 80,
2238-2276.
(4) (a) Taki, M.; Takigami, S.; Watanabe, Y.; Nakamura, Y.; Nishimura,
J. Polym. J. 1997, 29, 1020-1022. (b) Kessinger, R.; Thilgen, C.; Mordasini,
T.; Diederich, F. HelV. Chim. Acta 2000, 83, 3069-3096. (c) Hino, T.;
Hamada, M.; Kinbara, K.; Saigo, K. Chem. Lett. 2002, 728-729. (d)
Nierengarten, J.-F. New J. Chem. 2004, 28, 1177-1191.
(3) Diederich, F.; Kessinger, R. Acc. Chem. Res. 1999, 32, 537-545.
10.1021/jo060110+ CCC: $33.50 © 2006 American Chemical Society
Published on Web 05/24/2006
J. Org. Chem. 2006, 71, 4759-4765
4759

Ito et al.
TABLE 1. Synthesis of Bis(formylmethano)[60]fullerenes
bifunctionalized C60 with dissymmetric addends, 22 isomers are
theoretically driven on the basis of eight possible addition
patterns and three relative orientations of the functional groups
(in/in and in/out diastereoisomers for the trans-1 bisadduct; in/
in, in/out, and out/out diastereoisomers for the trans-2, trans-
3, trans-4, cis-3, cis-2, and cis-1 bisadducts; in/out and out/out
diastereoisomers for the equatorial bisadduct).5-7 Only in the
case of the equatorial addition pattern among the eight addition
patterns, two [6,6]-bonds undergoing addition reactions are not
equivalent to each other. Therefore, two functional groups in
the in/in- and in/out-equatorial bisadducts should be theoretically
unequivalent, and the two addends might show different
reactivity toward properly selected reagents, reflecting the subtle
but certain structural difference between them. On the other
hand, unequivalent circumstance around two addends in a
bifunctionalized C60 is able to arise from another reason; in the
cases of the in/out isomers of the trans-2, trans-3, trans-4,
cis-3, cis-2, and cis-1 bisadducts, two addends are also un-
equivalent because of their relative orientation.7 Although all
of the eight isomers are candidates for substrates in the present
study on the selective mono-transformation of bifunctionalized
C60s, the in/out isomers are generally obtained in very poor
yields by a tandem bifunctionalization7 and are hardly pre-
pared by a tether-directed bifunctionalization.6 Considering these
aspects, an out/out-equatorial bisadduct is a sole bisadduct,
which satisfies criteria; its synthetic accessibility and the un-
equivalence of two addends at the same time.
entry
ylide
n
cis-2
cis-3
equatorial
trans-4
1
2
3
4
2a
2b
2c
2d
0
1
2
3
trace
n.d.a
n.d.a
n.d.a
17%
9%
9%
6%
n.d.a
30%
23%
22%
n.d.a
trace
trace
3%
a Not detected.
imines.7,8 (ii) A synthetic method for the preparation of bis-
(formylmethano)C60s by using tethered bis(R-formylsulfonium
ylide)s has already been established by our group, in which the
proper choice of the tether moiety connecting the two sulfonium
ylide moieties led to the efficient formation of the out/out-
equatorial bisadducts.9
In this study, we first succeeded in the mono-transformation
of two identical addends in a bifunctionalized C60 with an
excellent regioselectivity by using an out/out-equatorial bis-
(formylmethano)C60, which was obtained by a tether-directed
method. In addition, by transforming the two functional groups
stepwise, a set of C60-centered triads with a dissymmetric
structure were efficiently synthesized.
Results and Discussion
Design and Synthesis of the out/out-equatorial Bis-
(formylmethano)C60s 1b-d. Among out/out-equatorial bisad-
ducts possessing transformable functional groups, we selected
out/out-equatorial bis(formylmethano)C60s (1) as the substrates
in this study on the basis of the following findings: (i) The
formyl groups could be introduced to a C60 core without any
protecting groups and yet possessed sufficient reactivity to be
transformed into various functional groups, such as acetals,
imines, alkenes, alcohols, etc. For example, we have reported
that the condensation of a formyl group on the methano-bridge
carbon of methanoC60s with aromatic amines proceeded ef-
ficiently under mild conditions to give the corresponding
According to the method we have developed,9 a series of
bis(R-formylsulfonium ylide)s (2a-d) were prepared, of which
the linkers connecting the aromatic core and the sulfonium ylide
moieties were ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl,
and pentane-1,5-diyl groups, respectively.10 By using 2a-d for
the biscyclopropanation reaction of C60, the corresponding bis-
(formylmethano)C60s were obtained as mixtures of two or three
regioisomers. All of the isomers were successfully isolated by
preparative TLC, and their structural assignment was carried
1
out on the basis of H and 13C NMR and UV-vis spectros-
(5) (a) Hirsh, A.; Lamparth, I.; Karfunkel, H. R. Angew. Chem., Int. Ed.
Engl. 1994, 33, 437-438. (b) Schick, G.; Hirsh, A.; Mauser, H.; Clark, T.
Chem. Eur. J. 1996, 2, 935-943. (c) Lu, Q.; Schuster, D. I.; Wilson, S. R.
J. Org. Chem. 1996, 61, 4764-4768. (d) Nakamura, Y.; O-kawa, K.;
Matsumoto, M.; Nishimura, J. Tetrahedron 2000, 56, 5429-5434. (e)
Nakamura, Y.; Takano, N.; Nishimura, T.; Yashima, E.; Sato, M.; Kudo,
T.; Nishimura, J. Org. Lett. 2001, 3, 1193-1196.
copy (Table 1). Although the reaction of 2a did not give the
out/out-equatorial bisadduct 1a at all (entry 1), the other
out/out-equatorial bisadducts 1b-d were obtained as the main
products, respectively (entries 2-4).10 This observation indicates
that the tether moiety in 1b was minimum in length as the tether
to connect the two methano-bridge carbons of an equatorial
bisadduct. This assumption is further supported by the notable
(6) For selected examples of the formation of in/out C60 bisadducts by
the tether-directed method, see: (a) Taki, M.; Sugita, S.; Nakamura, Y.;
Kasashima, E.; Yashima, E.; Okamoto, Y.; Nishimura, J. J. Am. Chem.
Soc. 1997, 119, 926-932. (b) Reference 2a. (c) Nakamura, Y.; O-kawa,
K.; Nishimura, J. Bull. Chem. Soc. Jpn. 2003, 76, 865. (d) Nakamura Y.;
Suzuki, M.; Imai, Y.; Nishimura, J. Org. Lett. 2004, 6, 2797-2799. (e)
Sergeyev, S.; Schar, M.; Seiler, P.; Lukoyanova, O.; Echegoyen, L.;
Diederich, F. Chem. Eur. J. 2005, 11, 2284-2294.
1
signal broadening of the H NMR spectrum of 1b: in the
(8) Hamada, M.; Hino, T.; Kinbara, K.; Saigo, K. Tetrahedron Lett. 2001,
42, 5069-5071.
(9) Ito, H.; Ishida, Y.; Saigo, K. Tetrahedron Lett. 2006, 47, 3095-
(7) Ito, H.; Ishida, Y.; Saigo, K. Tetrahedron Lett. 2005, 46, 8757-
8760.
3098.
(10) See Supporting Information.
4760 J. Org. Chem., Vol. 71, No. 13, 2006

Construction of Dissymmetric [60]Fullerene-Centered Triads
TABLE 2. Assignment of 13C NMR Signals Attributable to the
Methano-bridge Carbons in the equatorial
Bis(formylmethano)[60]fullerenes 1b-f
spectrum of 1d with relatively long linkers, only a set of sharp
peaks were observed for all of the protons, whereas signals in
the spectrum of 1c were observed as partially broadened peaks.
On the other hand, 1b with the shortest linkers gave a spectrum
with significantly broadened peaks, most likely due to the
constrained structure of the tether part, of which the mobility
δ/ppm (orientation)
[1,2]
[18,36]
1b (equatorial, out/out)
1c (equatorial, out/out)
1d (equatorial, out/out)
1e (equatorial, out/out)
1f (equatorial, in/out)
52.66 (out)
52.10 (out)
52.30 (out)
52.29 (out)
52.95 (in)
50.38 (out)
49.78 (out)
50.13 (out)
49.78 (out)
49.97 (out)
1
was considered to be comparable to the H NMR time scale.
Assignment of 13C NMR Signals of Formyl Groups in out/
out-equatorial Bis(formylmethano)C60s 1b-d. As a probe to
detect the transformation of the formyl groups in the out/out-
equatorial bis(formylmethano)C60s 1b-d, we focused on the
13C NMR signals of the methano-bridge carbons. In the 13C
NMR spectra, equatorial biscyclopropanated C60s usually give
two signals around 50 ppm assignable to two methano-bridge
carbons embedded in the [6,6]-junctions at the [1,2] and
[18,36] positions,11 which are suitable for monitoring the
conversion of the formyl groups. Unfortunately, however,
analytical methods for the assignment of these two signals have
participate, we selected the imine formation with an aro-
matic amine promoted by a TiCl4/1,4-diazabicyclo[2,2,2]octane
(DABCO) system, owing to its mild reaction conditions, high
efficiency, and irreversibility.13
Quite interestingly, the mono-imination of 1b proceeded
efficiently with an unexpectedly high regioselectivity. For
example, when the condensation of 1b with aniline (1.0 equiv)
was conducted in CH2Cl2 in the presence of TiCl4 (25 equiv)/
DABCO (234 equiv) and the resultant mixture was subjected
to GPC separation, a mixture of the mono-imines 3b(R1 ) Phe)
and 3b′(R2 ) Phe), the bis-imine 4b(R1, R2 ) Phe), and
unreacted 1b were obtained in 73%, 15%, and 12% yields,
been despairingly limited to date. As far as we know, only 13
C
NMR 2D INADEQUATE is a practical method, which still has
some problems in convenience and generality.12
On the other hand, we have reported the synthesis and charac-
terization of the out/out and in/out isomers of an equatorial bis-
(formylmethano)C60 having no tether moiety (1e and 1f,
respectively), which were prepared by a tandem C60 bifunc-
tionalization, followed by chromatographic separation.7 The
diastereoisomers 1e and 1f might be useful as references for
the NMR signal assignment of the addends at the [1,2] and
[18,36] positions.
1
respectively. The H and 13C NMR analyses of the mixture of
mono-imines 3b(R1 ) Phe) and 3b′(R2 ) Phe) revealed that
one of the two regioisomers was predominantly generated with
a surprisingly high selectivity (major:minor ) 95:5). Moreover,
the peak integral of the 13C NMR signal at around 52 ppm was
obviously small compared with the signal at around 50 ppm.
On the basis of these observations, we could unequivocally
conclude that the [1,2]-CHO group was selectively converted
to an imino group (Table 3, entry 1). From the ratio of the
products, the rate constant ratio was calculated to be k[1,2]:k[18,36]
) 9:1. Worth noting is the fact that the isolated yield of the
mono-iminated species (73%) was much higher than the
theoretical yield of 50%, calculated on the assumption that the
two formyl groups have an identical reactivity. The high yield
of the mono-imines thus observed is in good agreement with
the finding that the reaction of the [1,2]-CHO was nine times
faster than that of the [18,36]-CHO, and clearly shows the
advantage of this reaction for a practical application. The highly
regioselective reaction thus we found was most likely kinetically
controlled, because under the conditions we adopted, the
condensation of a primary amine with an aldehyde generally
proceeds in an irreversible manner.13b,14
In the case of the in/out-equatorial isomer 1f, the formyl
group on the [18,36] methano-bridge carbon taking an out-
orientation ([18,36]-CHO) should be more reactive than that of
the other formyl group on the [1,2] methano-bridge carbon
taking an in-orientation ([1,2]-CHO), upon comparing the steric
congestion around these two formyl groups. When the conden-
sation of the formyl groups in 1f with an equimolar amount of
aniline was conducted, the carbon signal of the methano-bridge
carbon at a higher magnetic field decreased preferentially. It
means that the more reactive formyl group locates on the
[18,36] methano-bridge carbon in the case of 1f and that the
methano-bridge carbon appears at a higher magnetic field.
Moreover, our preliminary study revealed that the chemical
shifts of the 13C signals of the addends in bifunctionalized C60s
are little affected by their orientation (in or out) but are
determined by their positions. With these facts in mind, we
attempted the assignment of the 13C NMR signals of the
methano-bridge carbons in 1b-d. All of the equatorial bisad-
ducts 1b-f showed two signals at around 52 and 50 ppm. On
the basis of the universal relationship between the position of
an addend and its chemical shift mentioned above, the signals
observed at around 52 and 50 ppm were assigned to the [1,2]
and [18,36] methano-bridge carbons, respectively (Table 2).
Regioselective Condensation of the out/out-equatorial Bis-
(formylmethano)C60s equatorial-1b-d with Aniline. Three
kinds of out/out-equatorial bis(formylmethano)C60s (1b-d) with
a well-defined structure were successfully prepared. Then, we
attempted the selective transformation of one of the two formyl
groups. Among various reactions in which formyl groups can
In the mono-imination of bis(formylmethano)C60s with
longer tether moiety, 1c and 1d, regioselective reactions again
occurred. The 13C NMR monitorings revealed the preferential
consumption of the [1,2]-CHO to the [18,36]-CHO in both cases.
Compared with the reaction of 1b, these two reactions resulted
in a lower selectivity (Table 3, entries 2 and 3, 3c(R1 ) Phe):
3c′(R2 ) Phe) ) 60:40, 3d(R1 ) Phe):3d′(R2 ) Phe) ) 62:
38). In addition, the isolated yields of the mono-iminated
compounds were notably lower than that of the reaction of 1b
(34% and 39% yields, respectively). Such decrease in chemical
(13) Higuchi, M.; Kimoto, A.; Shiki, S.; Yamamoto, K. J. Org. Chem.
2000, 65, 5680-5684. (b) Higuchi, M.; Shiki, S.; Yamamoto, K. Org. Lett.
2000, 2, 3079-3082.
(14) Inconsistent with general cases using TiCl4/DABCO, an irreversible
nature of the imination reaction was proved in our system, by using other
substrates; in the transformation of the remaining formyl group of 3b with
an aromatic amine other than that used for the first imination, the products
due to the scrambling of the amino groups were not observed.
(11) For the numbering system of the carbon atoms in C60, see: Taylor,
R. J. Chem. Soc., Perkin Trans. 2 1993, 813-824.
(12) Ball, G. E.; Burley, G. A.; Chaker, L.; Hawkins, B. C.; Williams,
J. R.; Keller, P. A.; Pyne, S. G. J. Org. Chem. 2005, 70, 8572-8574.
J. Org. Chem, Vol. 71, No. 13, 2006 4761

Ito et al.
TABLE 3. Regioselective Mono-imination of the out/out-equatorial Bis(formylmethano)[60]fullerenes 1b-d with Aromatic Amines
1
a Total yield of a mixture of the regioisomers 3 and 3′. Ratio of the regioisomers was determined by H NMR.
yield is reasonably elucidated by the difference in regioselec-
tivity rather than by the difference in efficiency between the
reactions; in the case of a reaction with a low selectivity, the
formation of the undesired bis-imine 4b-d(R1, R2 ) Phe) is
inevitable, which significantly reduces the yields of mono-
imines. In fact, the conversion of aniline was not so different
between the three reactions, which could be roughly estimated
by the equation conversionaniline ) yieldmono-imine + 2(yieldbis-imine).
Thus, the highly regioselective mono-transformation of a
bifunctionalized C60 was accomplished by using 1b. As far as
we know, the reaction demonstrated here is the first example
of a synthetic method to easily access regio- and diastereoregu-
lated bifunctionalized C60s having different functional groups.
As the origin of the difference in reactivity between two
formyl groups, which are apparently equivalent to each other,
the following two factors might be possible: the difference in
electronic state and that in steric hindrance. To clarify the reason,
a control experiment was conducted by using an analogous
out/out-equatorial bisadduct (1e) lacking a tether moiety. In the
mono-imination of 1e, almost the same amounts of the mono-
imines 3e(R1 ) Phe) and 3e′(R2 ) Phe) were generated.
Therefore, the main reason of the moderate to excellent
regioselectivity, observed in the reactions of 1b-d, is concluded
to be the difference in steric congestion arising from the relative
orientation of the tether moiety and the two formyl groups, rather
than the difference in inherent reactivity.
To obtain more detailed information about the contribution
of the tether part to the regioselective transformation, the
molecular modeling of 1b was carried out. A PM3 calculation
showed that the [1,2]-CHO in 1b is oriented to the direction
opposite to the tether part (Figure 1a, top view), whereas the
[18,36]-CHO is located in a sterically hindered environment
surrounded by the propane-1,3-diyl chain and the phenylene
core, which would disturb the nucleophilic attack of an amine
(Figure 1a, side view). Such a characteristic structure around
the [18,36]-CHO was most likely due to the highly constrained
conformation of the tether part of 1b. On the other hand, the
molecular modelings of 1c and 1d revealed that such sterically
congested conformations around the [18,36]-CHO were again
unavoidable (Figure 1b and c, side view). However, owing to
4762 J. Org. Chem., Vol. 71, No. 13, 2006

Construction of Dissymmetric [60]Fullerene-Centered Triads
compared with those of the other amines (entry 9). Thus, the
regioselective imination was found to be generally applicable
to various aromatic amines to afford dissymmetrically bifunc-
tionalized C60 derivatives efficiently. In all cases of the imina-
tions, in which various aromatic amines were employed, two
regioisomers of the mono-imines 3b and 3b′ had quite similar
polarity, so that we could not separate them by chromatography.
However, the major isomers 3b were adequately enriched in
all cases (3b:3b′ ) 89:11-97:3), which enabled us to assign
the NMR signals of the major isomers (see Experimental
Section).
Construction of C60-Centered Dissymmetric Dye Triads.
The success in the mono-transformation of two addends in bis-
(formylmethano)C60s prompted us to apply the reaction to the
construction of dissymmetric triads containing a C60 core at the
center by the transformation of the remaining formyl group in
order to demonstrate an example for the full utility of the
regiocontrolled mono-imination. Although formyl groups are
potentially converted into various functional groups, we selected
a dissymmetric bis-imination; two different amines were used
for the first and second iminations. When 4-methoxyaniline and
1-pyrenamine are used as the amino parts for the bis-imimation
of 1b, a pair of triads, 4b(R1 ) p-MPhe, R2 ) 1-Pyn) and 4b(R1
) 1-Pyn, R2 ) p-MPhe), are possible, taking into account the
dissymmetric structure of 1b. By repetitively conducting two
mono-iminations in a proper order, either of the two triads
should be prepared. For example, the condensation of the mono-
imine 3b(R1 ) p-MPhe), prepared by the reaction of 4-meth-
oxyaniline with 1b as described above, with 1-pyrenamine under
conditions similar to those of the mono-imination of 1b,
followed by GPC separation, gave a fraction containing
compound(s) with a m/z value of 1267.27, which is consistent
with the value expected for the dissymmetric bis-imines 4b(R1
) p-MPhe, R2 ) 1-Pyn) and 4b(R1 ) 1-Pyn, R2 ) p-MPhe)
(69%). The solid mass obtained upon concentrating the fraction
FIGURE 1. PM3-optimized structures of the out/out-equatorial bis-
(formylmethano)C60s: (a) 1b, (b) 1c, and (c) 1d.
the relatively long oligomethylene chains, the degree of “shield-
ing” for the [18,36]-CHO would be reduced, compared with
that of 1b.
Regioselective Condensation of out/out-equatorial Bis-
(formylmethano)C60 1b with Various Aromatic Amines. To
clarify the scope of the present regioselective mono-imination,
various aromatic amines were employed for the condensation
with 1b. The reactions of 1b with the aniline derivatives (Table
3, entries 4-6), possessing an electron-donating (p-DAPhe-NH2
and p-MPhe-NH2) or -withdrawing (p-NPhe-NH2) substituent
at the 4-position, proceeded very smoothly to give the corre-
sponding mono-imines in good yields (55-59%) with an
excellent regioselectivity (3b:3b′ ) 93:7-96:4). The results
suggested that the introduction of an electron-withdrawing group
brought a favorable effect on the regioselectivity, whereas an
electron-donating group had an opposite effect; this tendency
is in good agreement with the relative nucleophilicity of these
aniline derivatives. In addition, 1-pyrenamine (1-Pyn-NH2),
which possesses a highly expanded π-conjugation system, was
found to be applicable to this reaction to give a mixture of the
corresponding mono-imines in satisfactory yield with a suffi-
cient regioselectivity (entry 7). Interestingly, the condensation
of 1b with 4-(10,15,20-triphenylporphyrin-5-yl)phenylamine
(TPP-NH2) gave the corresponding mono-imine in the highest
yield with the best regioselectivity among the reactions exam-
ined (entry 8). Considering the peculiar properties of the por-
phyrin and C60 units, the cooperation of these units,15 and the
potential of further derivertization of the remaining formyl
group, the resultant mono-imine is expected to be an attractive
component for the construction of C60-containing dye arrays.16
Moreover, the condensation with the heteroaromatic amine,
4-pyridinamine (4-Pyd-NH2), could also be conducted, although
the yield and regioselectivity were lowered to some extent
1
exhibited a quite simple H NMR spectrum with one set of
signals, indicating that the solid mass consisted of one species.
Because the products due to the scrambling of the amino groups,
such as 4b(R1, R2 ) p-MPhe) and 4b(R1, R2 ) 1-Pyn), were
hardly detectable through the reaction, the main product was
undoubtedly concluded to be the target bis-imine 4b(R1
)
p-MPhe, R2 ) 1-Pyn) (Scheme 1, left).17 This observation
strongly support the mechanism that this imination reaction is
an irreversible process, which is one of the main reasons for
the regioselectivity observed in the mono-imination of 1b.13b
By conducting two mono-iminations in a reverse order, the other
triad 4b(R1 ) 1-Pyn, R2 ) p-MPhe) was successfully prepared;
the condensation of 1b with with 1-pyrenamine selectively
afforded the mono-imine 3b(R1 ) 1-Pyn) (59% yield), which
was easily converted to the dissymmetric bis-imine 4b(R1 )
1-Pyn, R2 ) p-MPhe) (75%) by a similar procedure (Scheme
1, right).17 Worth noting is the surprisingly high total yields
for the synthesis of the two triads, despite their dissymmetric
structure.
(15) For selected examples of C60-porphyrin hybrids, see: (a) Imahori,
H.; Hagiwara, K.; Aoki, M.; Akiyama, T.; Taniguchi, S.; Okada, T.;
Shirakawa, M.; Sakata, Y. J. Am. Chem. Soc. 1996, 118, 11771-11782.
(b) Dietel, E.; Hirsch, A.; Eichhorn, E.; Rieker, A.; Hackbarth, S.; Roder,
B. Chem. Commun. 1998, 1981-1982. (c) Tashiro, K.; Aida, T.; Zheng, J.
Y.; Kinbara, K.; Saigo, K.; Sakamoto, S.; Yamaguchi, K. J. Am. Chem.
Soc. 1999, 121, 9477-9478.
(16) Luo, C.; Guldi, D. M.; Imahori, H.; Tamaki, K.; Sakata, K. J. Am.
Chem. Soc. 2000, 122, 6535-6551. Imahori, H.; Guldi, D. M.; Tamaki,
K.; Yoshida, Y.; Luo, C. P.; Sakata, Y.; Fukuzumi, S. J. Am. Chem. Soc.
2001, 123, 6617-6628. Herranz, M. A.; Illescas, B.; Martin, N.; Luo, C.
P.; Guldi, D. M. J. Org. Chem. 2000, 65, 5728-5738.
(17) For the synthesis of dissymmetric bis-imines 4b(R1 ) p-MPhe, R2
) 1-Pyn) and 4b(R1 ) 1-Pyn, R2 ) p-MPhe), mixtures of regioisomers 3b
and 3b′ (3b(R1 ) p-MPhe):3b′(R2 ) p-MPhe) ) 95:5 for 4b(R1 ) p-MPhe,
R2 ) 1-Pyn), and 3b(R1 ) 1-Pyr):3b′(R2 ) 1-Pyr) ) 95:5 for 4b(R1
)
1-Pyn. R2 ) p-MPhe)) as the starting materials. As a result, the resultant
bis-imines were also the mixture of regioisomers. Fortunately, the two
regioisomers 4b(R1 ) p-MPhe, R2 ) 1-Pyn) and 4b(R1 ) 1-Pyn, R2
)
p-MPhe) could by separated from each other by HPLC. See Experimental
Section.
J. Org. Chem, Vol. 71, No. 13, 2006 4763

Ito et al.
SCHEME 1. Synthesis of [60]Fullerene-Centered
Dissymmetric Triads 4b(R1 ) p-MPhe, R2 ) 1-Pyn) and
4b(R1 ) 1-Pyn, R2 ) p-MPhe)a
FIGURE 2. UV-vis Spectra of [60]Fullerene-Centered Dissymmetric
Triads 4b(R1 ) p-MPhe, R2 ) 1-Pyn) and 4b(R1 ) 1-Pyn, R2
p-MPhe) in CHCl3.
)
applicable to various aromatic amines. Furthermore, C60-cen-
tered triads with a sequence-controlled structure were efficiently
synthesized by applying this reaction. The synthetic method
developed here would provide reliable routes to access dissym-
metrically functionalized C60 derivatives, which are expected
to expand the scope of C60-containing molecular devises.
Experimental Section
Mono-imination of 1b with Aromatic Amines. Typical Pro-
cedure. To a CH2Cl2 solution (15 mL) of 1b (15.0 mg, 15.6 µmol)
and 1,8-diazabicyclo[2,2,2]octane (DABCO) (409 mg, 3.65 mmol)
were successively added a CH2Cl2 solution of aniline (0.21 M, 73
µL, 15.6 µmol) and TiCl4 (74 mg, 390 µmol). After being stirred
overnight at room temperature, the mixture was subjected to a short
alumina column chromatography eluted by CH2Cl2. The resultant
solution was concentrated under reduced pressure, and the resultant
residue was subjected to preparative GPC to give a mixture of
mono-imines 3b(R1 ) Phe) and 3b′(R2 ) Phe) (11.8 mg, 11.4 µmol,
73%), bis-imine 4b(R1, R2 ) Phe) (2.6 mg, 2.3 µmol, 15%), and
unreacted 1b (1.8 mg, 1.9 µmol, 12%).
a Reagents and conditions: (1) TiCl4 (25 equiv), DABCO (234 equiv),
4-methoxyaniline (1.0 equiv), CHCl2, rt. (ii) TiCl4 (25 equiv), DABCO
(234 equiv), 1-pyrenamine (1.0 equiv), CH2Cl2, rt.
3b(R1 ) Phe): a mixture with 3b′(R2 ) Phe) (3b(R1 ) Phe):
1
3b′(R2 ) Phe) ) 95:5). H NMR (CDCl3) δ 2.0-3.5 (m, 12H),
6.7-6.9 (m, 2H), 7.1-7.2 (m, 1H), 7.2-7.3 (m, 4H), 7.46 (t, J )
7.8 Hz, 2H), 8.69 (s, 1H), 10.51 (s, 1H); 13C NMR (CDCl3) δ 24.34,
25.45, 26.14, 29.69, 34.83, 36.11, 50.04, 50.20, 74.69, 75.84,
120.85, 126.40, 129.32, 129.77, 130.68, 137.63, 138.24, 138.63,
139.05, 139.84, 140.13, 140.47, 141.21, 141.71, 141.97, 142.05,
143.01, 143.09, 143.30, 143.63, 143.73, 143.73, 143.82, 143.91,
143.98, 144.05, 144.25, 144.29, 144.51, 144.54, 144.60, 144.64,
144.82, 144.85, 144.97, 145.29, 145.33, 145.67, 145.74, 145.83,
146.04, 146.18, 146.28, 146.36, 146.40, 146.52, 146.78, 147.18,
147.27, 148.08, 148.68, 151.39, 159.30, 195.44; MALDI-TOF-MS
(dithranol) for [M + H]+ C82H24NO calcd 1038.19, found 1038.18.
3b(R1 ) p-DAPhe): a mixture with 3b′(R2 ) p-DAPhe) (3b(R1
Quite interestingly, in HPLC analyses, the elution times of
two triads thus obtained were significantly different (column,
Merck LiChroCART Si60; eluent, toluene; retention time for
4b(R1 ) p-MPhe, R2 ) 1-Pyn), 9.7 min; retention time for
4b(R1 ) 1-Pyn, R2 ) p-MPhe), 10.7 min). Furthermore, the
two triads exhibited UV-vis spectra distinguishable from each
other (Figure 2). These observations imply the difference in
physical properties between 4b(R1 ) p-MPhe, R2 ) 1-Pyn) and
4b(R1 ) 1-Pyn, R2 ) p-MPhe).
Conclusion
1
) p-DAPhe):3b′(R2 ) p-DAPhe) ) 93:7). H NMR (CDCl3) δ
2.0-3.5 (m, 12H), 3.01 (s, 6H), 6.8-7.3 (m, 4H), 6.80 (d, J ) 8.1
Hz, 2H), 7.28 (d, J ) 8.1 Hz, 2H), 8.73 (s, 1H), 10.51 (s, 1H);
MALDI-TOF-MS (dithranol) for [M + H]+ C84H29N2O calcd
1081.23, found 1080.15.
We first demonstrated the selective transformation of one of
two addends in bifunctionalized C60s by using three kinds of
out/out-equatorial bis(formylmethano)C60s (1b-d). The con-
densation of the formyl groups in 1b with aniline proceeded
predominantly at the [1,2] position to give the corresponding
mono-iminated product with an unexpectedly high regioselec-
tivity. The regioselective imination was found to be generally
3b(R1 ) p-MPhe): a mixture with 3b′(R2 ) p-MPhe) (3b(R1 )
1
p-MPhe):3b′(R2 ) p-MPhe) ) 95:5). H NMR (CDCl3) δ 2.0-
3.5 (m, 12H), 3.86 (s, 3H), 6.7-6.9 (m, 2H), 6.98 (d, J ) 9.0 Hz,
2H), 7.1-7.2 (m, 1H), 7.2-7.3 (m, 1H), 7.26 (d, J ) 9.0 Hz, 2H),
4764 J. Org. Chem., Vol. 71, No. 13, 2006

Construction of Dissymmetric [60]Fullerene-Centered Triads
8.71 (s, 1H), 10.51 (s, 1H); MALDI-TOF-MS (dithranol) for [M
+ H]+ C83H26NO calcd 1068.20, found 1068.14.
(m, 3H), 8.2-8.3 (m, 4H), 8.70 (s, 1H), 8.78 (d, J ) 9.3 Hz, 1H),
9.04 (s, 1H); 13C NMR (CDCl3) δ 24.09, 25.34, 28.91, 29.79, 34.86,
36.70, 47.84, 49.98, 55.55, 78.73, 114.46, 115.98, 122.24, 123.13,
124.81, 125.19, 125.24, 125.69, 126.28, 127.04, 127.28, 127.68,
130.04, 130.15, 130.78, 131.38, 131.50, 137.25, 137.52, 138.41,
138.66, 139.10, 139.95, 139.83, 140.14, 140.96, 141.02, 141.55,
141.81, 141.90, 142.6, 142.84, 143.05, 143.21, 143.54, 143.63,
143.78, 143.96, 144.00, 144.04, 144.22, 144.32, 144.44, 144.47,
144.69, 144.75, 144.85, 145.19, 145.14, 145.35, 145.45, 145.61,
145.64, 145.76, 145.95, 146.09, 146.30, 146.35, 146.48, 146.77,
147.08, 147.16, 149.47, 149.90, 157.45, 158.53, 160.45; MALDI-
TOF-MS (dithranol) for [M + H]+ C99H35N2O calcd 1267.27, found
1267.27.
3b(R1 ) p-NPhe): a mixture with 3b′(R2 ) p-NPhe) (3b(R1 )
p-NPhe):3b′(R2 ) p-NPhe) ) 96:4). 1H NMR (CDCl3) δ 2.0-3.2
(m, 11H), 3.2-3.5 (m, 1H), 6.7-6.9 (m, 2H), 7.1-7.2 (m, 1H),
7.2-7.3 (m, 1H), 7.31 (d, J ) 8.7 Hz, 2H), 8.34 (d, J ) 8.7 Hz,
2H), 8.68 (s, 1H), 10.51 (s, 1H); MALDI-TOF-MS (dithranol) for
[M + H]+ C82H23N2O3 calcd 1083.17, found 1083.16.
3b(R1 ) 1-Pyn): a mixture with 3b′(R2 ) 1-Pyn) (3b(R1 )
1-Pyn):3b′(R2 ) 1-Pyn) ) 95:5). 1H NMR (CDCl3) δ 2.0-3.5 (m,
12H), 6.7-7.0 (m, 2H), 7.1-7.2 (m, 1H), 7.4 (m, 1H), 7.73 (d, J
) 8.1 Hz, 1H), 8.0-8.1 (m, 3H), 8.2-8.3 (m, 4H), 8.71 (d, J )
9.3 Hz, 1H), 8.96 (s, 1H), 10.51 (s, 1H); MALDI-TOF-MS
(dithranol) for [M + H]+ C92H28NO calcd 1062.22, found 1062.20
3b(R1 ) TPP): a mixture with 3b′(R2 ) TPP) (3b(R1 ) TPP):
Synthesis of Dissymmetric Bis-imine 4b(R1 ) 1-Pyn, R2 )
p-MPhe). The condensation was conducted by a procedure similar
to that for the synthesis of 4b(R1 ) p-MPhe, R2 ) 1-Pyn) by using
3b(R1 ) 1-Pyn) containing 5% of 3b′(R2 ) 1-Pyn) to give the
dissymmetric bis-imine 4b(R1 ) 1-Pyn, R2 ) p-MPhe) containing
5% of 4b(R1 ) p-MPhe, R2 ) 1-Pyn) (75%). The analytical sample
of 4b(R1 ) 1-Pyn, R2 ) p-MPhe) (containing 4b(R1 ) p-MPhe,
R2 ) 1-Pyn) <1%) was obtained by recycling preparative HPLC.
4b(R1 ) 1-Pyn, R2 ) p-MPhe): IR (KBr) 2923, 2851, 1636,
1
3b′(R2 ) TPP) ) 97:3). H NMR (CDCl3) δ 2.0-3.5 (m, 12H),
6.8-7.2 (m, 4H), 7.63 (d, J ) 8.1 Hz, 2H), 7.7-7.9 (m, 9H), 8.1-
8.3 (m, 6H), 8.33 (d, J ) 8.1 Hz, 2H), 8.8-8.9 (m, 7H), 8.94 (d,
J ) 4.8 Hz, 2H), 10.4 (s, 1H), 12.21 (s, 2H); MALDI-TOF-MS
(dithranol) for [M + H]+ C120H47N5O calcd 1574.39, found 1574.33.
3b(R1 ) 4-Pyd): a mixture with 3b′(R2 ) 4-Pyd) (3b(R1 )
1
4-Pyd):3b′(R2 ) 4-Pyd) ) 89:11). H NMR (CDCl3) δ 2.0-3.5
1
(m, 12H), 3.86 (s, 3H), 6.7-6.9 (m, 2H), 6.98 (d, J ) 9.0 Hz, 2H),
7.1-7.2 (m, 1H), 7.2-7.3 (m, 1H), 7.26 (d, J ) 9.0 Hz, 2H), 8.71
(s, 1H), 10.51 (s, 1H); MALDI-TOF-MS (dithranol) for [M + H]+
C81H23N2O calcd 1039.18, found 1038.25.
1503, 1458, 1246, 1180, 1035, 843, 524; H NMR (CDCl3) δ
1.9-2.1 (m, 1H), 2.4-2.8 (m, 7H), 3.0-3.3 (m, 3H), 3.4-3.6 (m,
1H), 3.86 (s, 3H), 6.8-6.9 (m, 2H), 6.99 (d, J ) 9 Hz, 2H), 7.2
(m, 1H), 7.31 (d, J ) 9 Hz, 2H), 7.4 (m, 1H), 7.73 (d, J ) 8.1 Hz,
1H), 8.0-8.1 (m, 3H), 8.2-8.3 (m, 4H), 8.71 (d, J ) 9.3 Hz, 1H),
8.79 (s, 1H), 8.96 (s, 1H); 13C NMR (CDCl3) δ 23.74, 25.72, 28.73,
30.07, 35.04, 36.26, 47.43, 50.42, 55.58, 78.89, 114.55, 115.99,
122.23, 123.12, 124.86, 125.04, 125.14, 125.18, 125.28, 125.67,
126.24, 126.96, 127.31, 127.54, 130.02, 130.76, 131.44, 131.56,
137.47, 137.62, 138.42, 138.69, 138.98, 139.68, 140.14, 140.90,
141.58, 141.82, 141.85, 141.93, 142.71, 142.87, 143.06, 143.19,
143.49, 143.66, 143.77, 143.81, 143.99, 144.07, 144.24, 144.35,
144.38, 144.42, 144.46, 144.64, 144.68, 144.98, 145.22, 145.22,
145.35, 145.50, 145.62, 145.64, 145.76, 145.95, 146.36, 146.47,
146.51, 146.54, 146.80, 147.11, 147.16, 149.54, 150.15, 157.59,
158.71, 160.35; MALDI-TOF-MS (dithranol) for [M + H]+
C99H35N2O calcd 1267.27, found 1267.27.
Mono-imination of 1c-e with Aniline. The mono-imination
was conducted in a similar procedure to that for the mono-imination
of 1b with aromatic amines as described above.
Synthesis of Dissymmetric Bis-imine 4b(R1 ) p-MPhe, R2 )
1-Pyn). To a CH2Cl2 solution (12 mL) of 3b(R1 ) p-MPhe)
(containing 5% 3b′(R2 ) p-MPhe), 12 mg, 12 µmol) and DABCO
(300 mg, 2.7 mmol) were successively added a CH2Cl2 solution of
1-pyrenamine (2.5 mg, 12 µmol) and TiCl4 (55 mg, 288 µmol).
After being stirred overnight at room temperature, the mixture was
subjected to a short alumina column chromatography eluted by
CH2Cl2. The resultant solution was concentrated under reduced
pressure, and the resultant residue was subjected to preparative GPC
to give the dissymmetric bis-imine 4b(R1 ) p-MPhe, R2 ) 1-Pyn)
containing 6% of 4b(R1 ) 1-Pyn, R2 ) p-MPhe) (11 mg, 8.7 µmol,
75%). The analytical sample of 4b(R1 ) p-MPhe, R2 ) 1-Pyn)
(containing 4b(R1 ) 1-Pyn, R2 ) p-MPhe) <1%) was obtained by
recycling preparative HPLC.
Supporting Information Available: Synthetic procedures
and characterization data of 2a-d; structural assignment of bis-
(formylmethano)C60s; 1H and 13C NMR spectra of 3b, 4b(R1
) p-MPhe, R2 ) 1-Pyn), and 4b(R1 ) 1-Pyn, R2 ) p-MPhe).
This material is available free of charge via the Internet at
http://pubs.acs.org.
4b(R1 ) p-MPhe, R2 ) 1-Pyn): IR (KBr) 2925, 2852, 1636,
1504, 1458, 1246, 1181, 1036, 842, 525; 1H NMR (CDCl3) δ 2.0-
3.0 (m, 10H), 3.2-3.3 (m, 1H), 3.6-3.8 (m, 1H), 3.86 (s, 3H),
6.8-6.9 (m, 2H), 6.98 (d, J ) 9 Hz, 2H), 7.1-7.2 (m, 1H), 7.26
(d, J ) 9 Hz, 2H), 7.5 (m, 1H), 7.73 (d, J ) 8.1 Hz, 1H), 8.0-8.1
JO060110+
J. Org. Chem, Vol. 71, No. 13, 2006 4765