Tether-directed selective synthesis of fulleropyrrolidine bisadducts

Article abstract of DOI:10.1021/jo052213i

Selective synthesis of C₆₀ bisadducts has been achieved by using the Prato 1,3-dipolar cycloaddition of tethered bis-azomethine ylides. New bis(benzaldehydes) 1-4 tethered by a rigid linker were prepared and used to direct the second cycloaddit

Full text of DOI:10.1021/jo052213i

Tether-Directed Selective Synthesis of Fulleropyrrolidine Bisadducts
Zhiguo Zhou,*,† David I. Schuster, and Stephen R. Wilson†
Department of Chemistry, New York UniVersity, 100 Washington Square East, New York, New York 10003
zhouz@lunainnoVations.com
ReceiVed October 24, 2005
Selective synthesis of C60 bisadducts has been achieved by using the Prato 1,3-dipolar cycloaddition of
tethered bis-azomethine ylides. New bis(benzaldehydes) 1-4 tethered by a rigid linker were prepared
and used to direct the second cycloaddition of azomethine ylide to C60. Equatorial, trans-4, trans-3, trans-
2, and trans-1 bisadducts have been selectively prepared with this approach. However, the introduction
of chiral centers in the pyrrolidine rings in the course of the reaction complicated the chemistry, as a
number of stereoisomers theoretically could be formed. The structure determination of the isomeric
bisadducts was made based on spectroscopic data and theoretical calculations. To our best knowledge,
this represents the first example of a systematic study on tether-directed selective synthesis of C60
fulleropyrrolidine bisadducts.
Introduction
each fullerene reaction, such as the Bingel-Hirsch reaction, the
Diels-Alder reaction, or the Prato reaction, requires a specific
design of tethers.1a,4 In particular, tether-controlled bisadditions
of malonates to C60 have been extensively studied.
Bis-functionalized fullerenes have been widely used in
biological studies, molecular devices, and advanced materials,
due to their defined three-dimensional structures containing a
variety of functional groups.1-3 Tether-controlled bis-function-
alization is critical to improve the yield of specific bisadduct
isomers and to avoid tedious chromatographic separations.1,2,4
Reviews on the diversity of methods for tether-directed multiple
functionalization of C60 have appeared, which pointed out that
Azomethine ylide [3+2] cycloaddition to C60 (the Prato
reaction) has been proven to be a very efficient and facile
functionalization method to prepare C60 derivatives for various
applications.5 The stepwise bisadditions of 1,3-dipolar azo-
methine ylides to C60 have been systematically studied, which
lead to eight isomeric bisadducts when symmetric azomethine
ylides are employed.6,7 The structural assignment of C60 fullero-
pyrrolidine bisadducts has been accomplished by means of UV-
vis, NMR, and transient EPR spectroscopy.6-9 Each bisadduct
shows unique absorption in the region of 400 to 750 nm and it
† Current address: Luna nanoWorks, 521 Bridge Street, Danville, VA 24541.
Phone: 434-4834234. Fax: 434-4834195.
(1) (a) Wilson, S. R.; Schuster, D. I.; Nuber, B.; Meier, M. S.; Maggini,
M.; Prato, M.; Talor, R. Organic Chemistry of Fullerenes. In Fullerenes:
Chemistry, Physics, and Technology; Kadish, K. M., Ruoff, R., Eds.; John
Wiley & Sons: New York, 2000. (b) Hirsch, A.; Bretreich, M. Fullerenes:
Chemistry and Reactions; Wiley-VCH: Weinheim, Germany, 2004. (c)
Hirsch, A. The Chemistry of the Fullerenes; Thieme Verlag: Stuttgart,
Germany, 1994.
(5) (a) Maggini, M.; Scorrano, G.; Prato, M. J. Am. Chem. Soc. 1993,
115, 9798. (b) Prato, M.; Maggini, M. Acc. Chem. Res. 1998, 31, 519.
(6) Kordatos, K.; Bosi, S.; Da Ros, T.; Zambon, A.; Lucchini, V. V.;
Prato, M. J. Org. Chem. 2001, 66, 2802.
(2) (a) Diederich, F.; Thilgen, C. Science 1996, 271, 317. (b) Wudl, F.
J. Mater. Chem. 2002, 12, 1959.
(3) A special issue on “Functionalized Fullerene Materials” in: Prato,
M.; Martin, N. Eds. J. Mater. Chem. 2002, 7, 1931-2159.
(4) Reviews on tether-directed selective synthesis of C60 multiple
adducts: (a) Diederich, F.; Kessinger, R. Acc. Chem. Res. 1999, 32, 537.
(b) Zhou, Z.; Wilson, S. R. Curr. Org. Chem. 2005, 9, 789. (c) 1a.
(7) Lu, Q.; Schuster, D. I.; Wilson, S. R. J. Org. Chem. 1996, 61, 4764.
(8) Cross, R. J.; Lu, Q.; Saunders, M.; Schuster, D. I.; Wilson, S. R.;
Zhao, H. J. Am. Chem. Soc. 1996, 118, 11454.
(9) Pasimeni, L.; Hirsch, A.; Lamparth, I.; Herzog, A.; Maggini, M.;
Prato, M.; Corvaja, C.; Scorrano, G. J. Am. Chem. Soc. 1997, 119, 12896.
10.1021/jo052213i CCC: $33.50 © 2006 American Chemical Society
Published on Web 01/27/2006
J. Org. Chem. 2006, 71, 1545-1551
1545

Zhou et al.
SCHEME 1. Schematic Representation of a New
Tether-Directed Approach
SCHEME 2. Tethered Bis(benzaldehydes) 1-4
was widely used to determine the bisaddition patterns.6 How-
ever, tether-controlled selective synthesis of fulleropyrrolidine
bisadducts via the Prato reaction has not been studied until the
recent report of D’Souza and co-workers on synthesis of Prato
bisadducts with a dibenzo-18-crown-6 bisaldehyde as the tether.
The D’Souza approach led to a bisadduct mixture containing
several isomers that was directly used for further studies without
separation.10 Previously, Prato reported tether-assisted double
[3+2] cycloadditions resulting in the formation of one pyrro-
lidine ring and one isoxazoline ring on C60 mainly with a cis-1
positional relationship.11 Nakamura and co-workers also reported
one example of tether-controlled double [3+2] cycloadditions
to C60 leading to two cyclopentene rings attached on the C60
cage.12 Very recently, Martin and co-workers reported a
regioselective synthesis of cis-1 bisadducts resulting in one
pyrrolidine ring and one cyclopentenone ring attached on the
fullerene surface, through an intramolecular Pauson-Khand
reaction starting with a fulleropyrrolidine monoadduct containing
a terminal alkyne moiety.13
Bisaldehydes 1, 2, 3, and 4 were prepared through the
alkylation of p-hydroxybenzaldehyde by R,R′-dibromo p-xylene,
R,R′-dibromo o-xylene, R,R′-dibromo m-xylene, and 4,4′-bis-
(bromomethyl) biphenyl, respectively (Scheme 2). The alkyla-
tion reaction was done at 80-90 °C in dry DMF in the presence
of K2CO3. In most cases, pure products were obtained by
filtration after a small amount of water was added to the reaction
mixture. If needed, column chromatography (silica, CH2Cl2/
EA, 95/5) was used to further purify the products. The typical
yield of this reaction was about 75-82%. All compounds were
1
characterized by H and 13C NMR and MS.
Selective Bisaddition of Azomethine Ylides Derived from
Xylene-Tethered Bisbenzaldehydes to C60. In a typical reac-
tion, C60 was reacted with sarcosine and bisaldehyde 1 in a ratio
of 1:4:1 for 4 h in refluxing ODCB. The reaction mixture was
then subjected to a flash column (silica, 3 × 30 cm2, toluene/
hexanes 80:20 as eluant) and three bisadduct isomers 5, 6, and
7 were isolated in the ratio of 80:12:8. The overall yield of
bisadducts was 70%. It should be noted that no preparative
HPLC was required for further purification. All three isomers
were characterized by UV-vis absorption spectroscopy, MALDI-
MS, 1H NMR, 13C NMR, and 2D NMR. As stated earlier, UV-
vis absorption spectroscopy is a routine and reliable tool to
determine the bisaddition patterns of C60 bisadducts.6 Herein,
we assigned the bisaddition patterns of compound 5-7 by
comparison of their UV-vis spectra with those of known C60
fulleropyrrolidine bisadducts.6,7 Both isomers 5 and 6 showed
the characteristic absorption of trans-3 fulleropyrrolidine bisad-
ducts in the fingerprint region of 400 to 750 nm, and the UV-
vis spectrum of isomer 7 is identical with that of a known
equatorial fulleropyrrolidine bisadduct (see Figure 1).6 For a
Results and Discussion
Design and Synthesis of Tethered Bisbenzaldehydes. In
the present study, we demonstrate a novel approach for tether-
controlled selective bisaddition of azomethine ylides to C60 and
report the design of new tethers, together with the synthesis
and structural characterization of several isomeric fulleropyr-
rolidine bisadducts. The basic problem was to find a readily
preparable linker to connect the two pyrrolidine rings at the
R-carbon atoms. Considering the formation mechanism of
azomethine ylides and the dimensions of C60, we began with a
benzene ring attached on the R-carbon of the pyrrolidine rings
to build the entire tether. Then a rigid linker (phenyl or biphenyl)
was needed to link the two benzene rings (Scheme 1). However,
the unavoidable introduction of chiral centers in the heterocycles
in the course of the reaction complicated the chemistry, as a
number of stereoisomers theoretically could be formed. The use
of phenyl benzylic ether moiety also gives the possibility to
cleave the linker, resulting in two phenols attached on the
pyrrolidine rings.
C
60 bisadduct prepared using our approach, the connectivity of
the tether linkage14 between the two pyrrolidine rings is another
problem to be solved in addition to the bisaddition pattern. The
structure determination of the tether linkage is complicated by
(10) Smith, P. M.; McCarty, A. L.; Nguyen, N. Y.; Zandler, M. E.;
D’Souza, F. Chem. Commun. 2003, 1754.
(11) Da Dos, T.; Prato, M.; Lucchini, V. V. J. Org. Chem. 2000, 65,
4289.
(12) (a) Nakamura, E.; Isobe, H.; Tokuyama, H.; Sawamura, M. J. Chem.
Soc., Chem. Commun. 1996, 1747. (b) Isobe, H.; Tokuyama, H.; Sawamura,
M.; Nakamura, E. J. Org. Chem. 1997, 62, 5034.
(13) (a) Martin, N.; Altable, M.; Filippone, S.; Martin-Domenech, A.
Chem. Commun. 2004, 1338. (b) Martin, N.; Altable, M.; Filippone, S.;
Martin-Domenech, A.; Poater, A.; Sola`, M. Chem. Eur. J. 2005, 11, 2716.
(14) The nature of the tether linkage between the two pyrrolidine rings
is complicated by two factors: (1) the tether (-phenyl-OCH2-xylene/
biphenyl-CH2O-phenyl-) could be bound to either of the two R-carbon
atoms of each pyrrolidine ring, which gives four combinations, and (2) the
tertiary carbons to which the tether is attached are chiral. Thus, there could
be as many as 16 theoretically possible tether linkages between the two
pyrrolidine rings, depending on the symmetry of the bisaddition pattern.
Numerous attempts to obtain crystals of bisadducts isomers suitable for
X-ray crystallographic analysis failed.
1546 J. Org. Chem., Vol. 71, No. 4, 2006

Synthesis of Fulleropyrrolidine Bisadducts
FIGURE 1. UV-vis absorption spectra of equatorial bisadducts 7, 8 and 12, trans-3 bisadducts 5, 6, and 11, and trans-4 bisadducts 9 and 13.
both the introduction of two stereogenic centers and the
existence of a total of four R-carbon atoms in the two pyrrolidine
rings, which gives a number of possible ways to link the two
pyrrolidine rings.14 However, with the aid of theoretical calcula-
tions, assignment of the structures of the bisadducts could be
made from the spectral data.
1
The H and 13C NMR data clearly show that isomer 6 is C2
symmetric, and isomers 5 and 7 are C1 symmetric. The C2
symmetry of compound 6 also matches the symmetry of the
trans-3 bisaddition pattern. The 1H NMR spectrum of bisadduct
6 has one singlet methyl peak, two doublet peaks for the
pyrrolidine methylene protons, two doublet benzylic proton
peaks, and one singlet peak for the pyrrolidine methine proton.
Due to the chiral environment, the two protons of the pyrrolidine
methylene are diastereotopic and similarly the two benzylic
protons are also diastereotopic.15 In its 13C NMR spectrum, there
are 37 sp2 carbon signals, including 28 fullerene-based sp2
carbon signals and 6 sp3 carbon peaks. The proton and carbon
NMR spectra of bisadducts 5 and 7 show twice the correspond-
ing peaks of compound 6. COSY spectra of bisadduct isomers
helped assign the diastereotopic pairs, as shown in Figure 2
(COSY spectrum of bisadduct 5 with C1 symmetry, showing
the aliphatic region except for the two methyl peaks). Thus,
the two singlet peaks at 4.14 and 4.41 ppm are from the two
methine protons of the pyrrolidine rings. There are eight doublet
methylene proton peaks, which can be seen as four diaste-
reotopic pairs. Peaks at 3.82 and 4.86, 4.08 and 4.78 ppm are
assigned to the benzylic methylene protons, and peaks at 4.83
and 5.22, 4.94 and 5.04 ppm are assigned to the methylene
protons of the pyrrolidine rings by comparison of their chemical
shifts and J-coupling constants with those of several fullero-
pyrrolidine monoadducts having similar structures.15
FIGURE 2. COSY spectrum of bisadduct 5 showing aliphatic protons
except for the two methyl groups.
of formation as shown in Scheme 3. The AM1 heats of
formation of compounds 5 and 6 are 1233.4 and 1235.1 kcal/
mol, respectively. The C1-symmetric trans-3 bisadduct 5 has
lower energy than the C2-symmetric trans-3 bisadduct 6 by 1.7
kcal/mol.17 This is consistent with the experimental data that
the major trans-3 isomer has no symmetry and the minor trans-3
1
isomer has C2 symmetry, as demonstrated by their H and 13C
(16) Theoretical calculations have been used in the structure determination
of fullerene bisadducts: (a) Hirsch, A.; Lamparth, I.; Grosser, T.; Karfunkel,
H. R. J. Am. Chem. Soc. 1994, 116, 9385. (b) Friedman, S. H.; Kenyon, G.
L. J. Am. Chem. Soc. 1997, 119, 447. (c) Dietel, E.; Hirsch, A.; Eichhorn,
E.; Reiker, A.; Hackbarth, S.; Rober, B. Chem. Commun. 1998, 1981. (d)
Taki, M.; Sugita, S.; Nakamura, Y.; Kasashima, E.; Yashima, E.; Okamoto,
Y.; Nishimura, J. J. Am. Chem. Soc. 1997, 119, 926. (e) Djojo, J.; Herzog,
A.; Lamparth, I.; Hampel, F.; Hirsch, A. Chem. Eur. J. 1996, 2, 1537. (f)
Reference 12b.
(17) See Supporting Information for the AM1 energy calculation of all
bisadduct isomers with use of the Spartan 04 by Wavefunction. Given the
endothermicity of the present reaction, this thermodynamic argument can
be readily transformed into a kinetic one by virtue of the Hammond
postulate.
AM1 molecular modeling was used to assist in establishing
the isomeric structures of three bisadducts, as a number of
reports have used theoretical calculations for structure deter-
mination of C60 bisadducts.16 Out of all the possible isomers of
trans-3 bisadducts, only two of them have relatively low heats
(15) (a) Wilson, S. R.; Wang, Y.; Cao, J.; Tan, X. Tetrahedron Lett.
1996, 37, 775. (b) Tan, X.; Schuster, D. I.; Wilson, S. R. Tetrahedron Lett.
1998, 39, 4187.
J. Org. Chem, Vol. 71, No. 4, 2006 1547

Zhou et al.
FIGURE 3. 1H NMR spectrum of bisadduct 10.
SCHEME 3. Fulleropyrrolidine Bisadducts Obtained from Bisaldehyde 1
SCHEME 4. Fulleropyrrolidine Bisadducts Obtained from Bisaldehyde 2
NMR spectra. On the basis of theoretical calculations and
spectroscopic data, the structures of bisadducts 5 and 6 were
assigned as shown in Scheme 3.
column chromatography (silica, toluene/hexanes 80:20). Their
bisaddition patterns were assigned by comparison of their UV-
vis absorption spectra with those of known equatorial, trans-4,
and trans-3 bisadducts, respectively (Figure 1).6,7 All three
Similar theoretical calculations showed that there is only one
compound having significantly lower AM1 heats of formation
of 1236.5 kcal/mol among all of the possible equatorial
bisadduct isomers.17 The equatorial bisadduct is apparently
nonsymmetric as depicted by its NMR data because two chiral
centers were introduced in the pyrrolidine rings. Thus, the
structure of the bisadduct 7 was assigned as shown in Scheme
3. Each structure in Scheme 3 represents a racemate. In
summary, bisaddition of azomethine ylides derived from bis-
aldehyde 1 and sarcosine to C60 selectively led to the formation
of three bisadduct isomers with two bisaddition patterns, with
92% selectivity for trans-3 bisadducts.
1
compounds were characterized by means of MALDI-MS, H
NMR, 13C NMR, and 2D NMR as well. The equatorial bisadduct
8 and trans-3 bisadduct 10 have no symmetry elements
according to their NMR spectra, while bisadduct 9 is Cs
symmetric, matching the symmetry of the trans-4 bisaddition
pattern. There are 39 sp2 carbon signals (30 of which are
fullerene-based carbon peaks) and 6 sp3 carbon signals in the
13C NMR spectrum of compound 9. Due to the presence of
chiral centers, the protons of the methylene groups (-N-CH2-
and -O-CH2-) are diastereotopic as is clearly shown in the
proton NMR spectrum of compound 10 (Figure 3). In a manner
similar to bisadducts 5-7, the tether linkages of bisadducts
8-10 were assigned on the basis of spectroscopic data with
the aid of theoretical calculations (see the Supporting Informa-
tion). The heats of formation of equatorial bisadduct 8 are 1234.8
Reaction of bisaldehyde 2 with C60 and sarcosine in a ratio
of 1:1:4 in refluxing ODCB yielded three isomeric bisadducts
8, 9, and 10, with relative yields of 80%:15%:5% (Scheme 4).
Three compounds were isolated in pure form by using flash
1548 J. Org. Chem., Vol. 71, No. 4, 2006

Synthesis of Fulleropyrrolidine Bisadducts
TABLE 1. Bisaddition of Tethered Azomethine Ylides to C60
(benzaldehyde)s, in order to prepare trans-2 and trans-1 bisad-
ducts. In a manner similar to the above-described procedures,
bisaldehyde 4 was reacted with C60 and sarcosine (1:1:4) to
prepare bisadducts in refluxing ODCB (Scheme 6).
bisadducts
(rel ratio)
bisaddition
patterns
bis(benzaldehydes)
symmetry
1
2
3
5 (80%)
6 (12%)
7 (8%)
8 (80%)
9 (15%)
10 (5%)
11 (5%)
12 (35%)
13 (60%)
trans-3
trans-3
equatorial
equatorial
trans-4
trans-3
trans-3
equatorial
trans-4
C1
C2
C1
C1
Cs
C1
C2
C1
C1
(p-xylene-tethered)
Two bisadduct isomers and a small amount of monoadduct
were isolated by using flash chromatography (silica, 3 × 30
cm2, toluene/hexanes 90:10 as eluant) and characterized by
MALDI-MS, NMR, and UV-vis. The overall yield of the two
bisadducts was 68%, and the ratio between compounds 14 and
15 was 2:3. Bisadduct 14 showed the unique absorption
spectrum of a trans-1 bisadduct, with two major absorption peaks
at 460 and 491 nm.6,7 The UV-vis spectrum of bisadduct 15 is
identical with that of a known trans-2 fulleropyrrolidine
bisadduct in the fingerprint region of 400 to 750 nm, with four
main peaks at 433, 479, 656, and 725 nm.6,7 Therefore, the two
bisadducts were assigned as trans-1 and trans-2 isomers. Because
of the introduction of two chiral centers in the pyrrolidine rings
and the presence of a biphenyl moiety, neither bisadduct is
symmetric. This was evident from their NMR data, which show
two methyl peaks, two singlet methine peaks, four doublet
benzylic proton peaks, and four doublet pyrrolidine methylene
peaks (AB quartet) for each compound. Theoretical calculations
were conducted to help assign the topology of the tether linkage
for both of the trans-2 and trans-1 bisadducts. The calculations
revealed that one out of the four possible trans-1 isomers shown
in Scheme 6 has a significantly lower heat of formation, 1255.4
kcal/mol, which is 12.3 kcal/mol lower than that of the second
lowest energy structure. As far as the trans-2 bisadducts are
concerned, 16 possible isomers were optimized, revealing that
the structure shown in Scheme 6 has the lowest heat of
formation, 1253.2 kcal/mol. On the basis of both the spectro-
scopic data and theoretical calculations, the two bisadducts
isolated from the double [3+2] cycloaddition of azomethine
ylides derived from bis(benzaldehyde) 4 are assigned as shown
in Scheme 6.
(o-xylene-tethered)
(m-xylene-tethered)
kcal/mol, which is 8.1 kcal/mol lower than that of the second
lowest energy structure.17 The calculated structure with the
lowest heats of formation among all possible trans-4 bisadduct
isomers is Cs symmetric, which matches the NMR data of the
isolated trans-4 bisadduct (Scheme 4).17
When bisaldehyde 3 was reacted with C60 and sarcosine in
refluxing ODCB, three bisadduct isomers were also isolated in
an overall yield of 68%. Bisadducts 11, 12, and 13 showed the
characteristic absorption of trans-3, equatorial, and trans-4
bisadducts, respectively (Figure 1).6,7 The relative yield of the
three bisadducts 11, 12, and 13 was 5:35:60, which was different
from the ratio of the three bisadducts (trans-3, equatorial, and
trans-4) formed from the double Prato reaction using o-xylene
tethered bisaldehyde 2 where the equatorial isomer is the only
major product. All three isomers were characterized by absorp-
1
tion spectroscopy, MALDI-MS, H NMR, 13C NMR, and 2D
NMR. In a similar manner, the tether linkages of bisadducts
11-13 were assigned on the basis of spectroscopic data with
the aid of theoretical calculations (see Scheme 5 and the
Supporting Information for AM1 energy calculation).
Table 1 summarizes the results of bisadditions of tethered
azomethine ylides derived from bis(aldehydes) 1-3 to C60,
together with their relative yields and isomeric structures
assigned from spectral data and calculations. Bisaddition of
p-xylene tethered azomethine ylides to C60 mainly formed
trans-3 bisadducts with a selectivity of 92%, and bisaddition of
o-xylene tethered azomethine ylides to C60 mainly gave equato-
rial bisadducts with 80% selectivity, while both trans-4 and
equatorial bisadducts could be formed in the ratio of 60:35 when
m-xylene tethered bis(benzaldehydes) was used. The difference
in bisaddition selectivity in these three cases can be explained
by the varying distance and geometry of the two azomethine
ylides due to the isomeric xylene tethers.
Selective Bisaddition of Azomethine Ylides Derived from
Biphenyl-Tethered Bisbenzaldehydes to C60. Among the eight
geometrical bisadduct isomers isolated from the sequential
additions of 2 equiv of azomethine ylides, the trans-1 compound
is almost always the least abundant one.6,7 Therefore, it is
necessary to develop a tether-directed approach to give access
to various trans-1 fulleropyrrolidine bisadducts. It has been
shown to be very difficult to develop extended tethers with
suitable length and conformation that could span the entire C60
cage and direct the second addition onto the trans-1 and even
trans-2 positions, when tether-directed synthesis of C60 bisad-
ducts through cyclopropanation reactions was studied.18 Here
we extended our study to a longer spacer, biphenyl-tethered bis-
Monoaddition of Tethered Azomethine Ylides to C60.
Monoaddition of azomethine ylides derived from bis(benzal-
dehydes) 1-4 and sarcosine to C60 was also studied. A 1:1:1
mixture of bis(benzaldehyde), sarcosine, and C60 was refluxed
in toluene for 4 h and the corresponding monoadduct was
virtually the only separable product, purified by silica flash
chromatography (Scheme 7). The typical yield was around 70%.
Monoadducts 16-19 prepared from compounds 1-4, respec-
tively, were characterized by MALDI-MS, 1H NMR, 13C NMR,
and UV-vis. For instance, a proton peak at 9.79 ppm and a
sp2 carbon signal at 189.2 ppm corresponding to aldehyde
functionality are present in the NMR spectra of monoadduct
18. Interestingly, the monoadduct was still the only major
product even when a large excess of sarcosine was used in this
reaction in refluxing toluene. However, at elevated temperature,
such as in refluxing chlorobenzene or ODCB, bisadducts were
formed and only trace amounts of monoadduct could be
detected. In fact, the same reactivity was observed for all four
bisaldehydes. This temperature effect could be used to control
the bisadditions of two different azomethine ylides (from two
different amino acids) to C60. This is important when two
different groups are attached to the two pyrrolidine nitrogen
atoms.
Potential Applications of Fullerene Bisadducts Prepared
by the Current Approach. C60 is a 3D molecular platform,
which can anchor two, three, or even more building blocks,
such as pyridine and polypyridine coordination ligands, on the
(18) (a) Rubin, Y. Chem. Eur. J. 1997, 3, 1009. (b) Bourgeoise, J.-P.;
Echegoyen, L.; Fibbioli, M.; Pretsch, E.; Diederich, F. Angew. Chem., Int.
Ed. Engl. 1998, 37. 2118. (c) Reuther, U.; Brandmuller, T.; Donaubauer,
W.; Hampel, F.; Hirsch, A. Chem. Eur. J. 2002, 8, 2261.
J. Org. Chem, Vol. 71, No. 4, 2006 1549

Zhou et al.
SCHEME 5. Fulleropyrrolidine Bisadducts Obtained from Bisaldehyde 3
SCHEME 6. Tether-Directed Synthesis of Trans-1 and
Trans-2 Bisadducts
our lab have shown the existence of direct electronic coupling
between the pyridine nitrogen atom and the C60 core in fullero-
pyrrolidines.21 Metal-ligand coordination has been studied as
the key motif in the rational design of supramolecular linear
arrays and large metallocyclic polygons.22 Coordination driven
self-assembly of these fullerene polypyridyl building blocks may
lead to novel supramolecular architectures. For example,
coordination of trans-1 C60 bisadducts to transition metal could
generate a linear oligomeric structure and coordination of C60
equatorial bisadducts to transition metals may lead to the
formation of square-shaped metallocycles (Figure 4). Our
approach provides a general method for the selective synthesis
of fulleropyrrolidine bisadducts such as trans-1, equatorial, and
trans-3 adducts.
SCHEME 7. Monoaddition of Bis(aldehydes) 1-4 to C60
FIGURE 4. Conceptual description of coordination-driven self-
assembly of fullerene-containing supramolecular structures. Top: Linear
structure from trans-1 bisadducts. Bottom: Square-shaped structure from
equatorial bisadducts.
The cleavage of the tether (phenyl or biphenyl) at the phenyl
benzylic ether bond has been achieved by dealkylation with
BBr3, which led to the formation of two phenols attached on
the R-carbon of the pyrrolidine rings in the resulting nontethered
fulleropyrrolidine bisadducts.23 A variety of functional groups
can be incorporated into the bisadducts by reacting with the
phenols.
cage surface with defined geometry.19,20 Coordination of such
building blocks to transition metals could lead to the formation
of novel fullerene-containing supramolecular architectures with
interesting optical and electronic properties.20 Polypyridine units
could be attached onto the nitrogen atoms of fulleropyrrolidines
by the current bisaddition method and they are potential
candidates for molecular electronics, since previous studies in
Summary
In summary, we have established a general tether-directed
approach for selective preparation of fulleropyrrolidine bisad-
(21) (a) Tat, F. T.; Zhou, Z.; MacMahon, S.; Song, F.; Rheingold, A.;
Echegoyen, L.; Wilson, S. R. J. Org. Chem. 2004, 69, 4602. (b) Wilson, S.
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1550 J. Org. Chem., Vol. 71, No. 4, 2006

Synthesis of Fulleropyrrolidine Bisadducts
90:10) as eluant. A typical flash column was a 30 mm × 300 mm
ducts with trans-1, trans-2, trans-3, trans-4, and equatorial
bisaddition patterns, representing the first systematic study of
this reaction, to the best of our knowledge. The nature of the
tether linkages between the pyrrolidine rings is complicated by
the unavoidable introduction of two new stereogenic centers.
However, with the aid of computational studies, assignment of
the structures of the bisadducts could be made from the spectral
data. Most importantly, this approach provides a general access
to the selective synthesis of fulleropyrrolidine bisadducts, where
the same or different R-amino acids could be used. All of the
bisadduct isomers could be purified by using flash column
chromatography.
silica column). Overall yields for bisadducts were in the range of
1
65-70%. H NMR (400 MHz, acetone-d6/CS2 1:2) of bisadduct
5: δ 2.55 (s, 3H), 2.62 (s, 3H), 3.94 (d, 1H), 4.20 (d, 1H), 4.32 (s,
1H), 4.59 (s, 1H), 4.87 (d, 1H), 4.93 (d, 1H), 4.96 (d, 1H), 5.03 (d,
1H), 5.11 (d, 1H), 5.24 (d, 1H), 6.74 (m, 4H), 7.15 (m, 1H), 7.30
(m, 1H), 7.38-7.44 (m, 6H). 13C NMR (100 MHz acetone-d6/CS2
1:2) of bisadduct 5: δ 40.1, 40.3, 68.4, 68.7, 68.9, 69.7, 70.4, 70.6,
76.5, 77.2, 83.0, 84.3, 128.4 (2C), 128.9, 129.3 (4C), 129.4, 129.7,
129.9 (4C), 135.3, 136.4, 137.2, 137.3 (2C), 137.6, 137.8 (2C),
139.7, 140.0, 141.2, 141.5, 141.8, 141.9 (2C), 142.0, 142.3, 143.0,
143.1, 143.4, 144.1, 144.4, 144.5, 144.7, 145.1, 145.2, 145.3, 145.5,
145.6, 145.7 (2C), 145.8, 145.9 (4C), 146.0, 147.6, 148.3, 148.5,
148.6, 148.8, 148.9, 149.0, 149.1, 149.4, 149.5, 149.7, 149.9, 150.1,
150.5, 153.8, 154.5, 155.4, 155.6, 157.2, 157.7, 158.3 (3C), 158.4,
158.8 (2C). MALDI-MS: m/z 1121.4 (MH+). (See NMR and mass
data of bisadducts 6-15 in the Supporting Information.)
Experimental Section
General Procedure for the Synthesis of Bisaldehydes 1-4.
To a solution of dibromide (10 mmol) and p-hydroxybenzaldehyde
(2.95 g, 24 mmol) in 30 mL of DMF (dried with standard
procedure) was added K2CO3 (4.14 g, 30 mmol). The mixture was
stirred at 100 °C for 6-8 h until the complete consumption of
dibromide monitored by TLC. Then the reaction mixture was cooled
to room temperature and diluted with 30 mL of water, and the
precipitates were collected through gravity filtration. TLC (CH2-
Cl2/EA, 95/5) showed it was pure product in most cases. If needed,
column chromatography (silica, CH2Cl2/EA, 95/5) was used to
further purify the products. The typical yield of this alkylation
General Procedure for the Synthesis of Fulleropyrrolidine
Monoadducts. A mixture of C60 (36 mg, 0.05 mmol), sarcosine
(3.6 mg, 0.20 mmol), and bisaldehydes 1, 2, 3, or 4 (0.05 mmol)
in 40 mL of toluene was refluxed for 3 h. The mixture was washed
with H2O twice, dried over Na2SO4, and concentrated. The residue
was subjected to column chromatography (silica) with toluene as
eluant. The typical yield for monoadduct was 70%. 1H NMR (400
MHz CDCl3) of 16: δ 2.75 (s, 3H), 4.26 (d, 1H), 4.90 (s, 1H),
4.99 (d, 1H), 5.09 (s, 2H), 5.16 (s, 2H), 6.95 (d, 2H), 7.04 (d, 2H),
7.09 (m, 1H), 7.40 (m, 4H), 7.69 (m, 1H), 7.75 (d, 2H), 9.80 (s,
1H). 13C NMR (100 MHz CDCl3) of 16: δ 40.5, 69.2, 69.8, 70.5
(2C), 78.2, 83.6, 115.5 (2C), 125.6, 128.5 (2C), 129.0, 129.5, 129.6,
131.0, 131.8 (2C), 136.5, 136.6, 136.7, 137.3, 137.5, 137.8, 140.2,
140.6, 140.8, 140.9, 142.2, 142.3, 142.5, 142.6, 142.7 (2C), 142.8,
142.9 (2C), 143.0 (2C), 143.1 (2C), 143.2, 143.3, 143.4, 143.7,
143.9, 145.1 (2C), 145.4, 145.5, 145.8, 145.9 (2C), 146.0 (2C),
146.1, 146.2, 146.3 (2C), 146.4, 146.5, 146.6 (2C), 146.8, 146.9
(2C), 147.0 (2C), 147.2, 147.4, 147.6, 147.9, 154.5, 154.9, 157.3,
159.5, 164.2, 189.9. MALDI-MS: m/z 1066.2 (M+). (See NMR
and mass data of monoadducts 17-19 in the Supporting Informa-
tion.)
1
reaction was 75-82%. H NMR (400 MHz CDCl3) of 1: δ 5.15
(s, 4H), 7.04 (d, 4H), 7.45 (s, 4H), 7.86 (d, 4H), 9.91 (s, 2H). 13C
NMR (100 MHz CDCl3) of 1: δ 69.9, 115.2, 128.0, 130.5, 132.1,
136.4, 163.7, 190.8. MALDI-MS: m/z 347.2 (MH+). 1H NMR (400
MHz CDCl3) of 2: δ 5.25 (s, 4H), 7.08 (d, 4H), 7.42 (dd, 2H),
7.53 (dd, 2H), 7.82 (d, 4H), 9.88 (s, 2H). 13C NMR (100 MHz
CDCl3) of 2: δ 68.5, 117.0, 129.1, 129.4, 130.4, 132.2, 134.3,
163.0, 191.0. MALDI-MS: m/z 347.4 (MH+). 1H NMR (400 MHz
CDCl3) of 3: δ 5.18 (s, 4H), 7.08 (d, 4H), 7.42-7.47 (m, 3H),
7.52 (s, 1H), 7.86 (d, 4H), 9.90 (s, 2H). 13C NMR (100 MHz CDCl3)
of 3: δ 70.0, 115.2, 126.6, 127.5, 129.3, 130.2, 132.1, 136.9, 162.8,
191.5. MALDI-MS: m/z 347.2 (MH+). 1H NMR (400 MHz CDCl3)
of 4: δ 5.25 (s, 4H), 7.11 (d, 4H), 7.52 (d, 4H), 7.65 (d, 4H), 7.85,
(d, 4H), 9.93 (s, 2H). 13C NMR (100 MHz CDCl3) of 4: δ 70.5,
115.2, 127.3, 128.0, 130.5, 132.1, 135.0, 140.5, 163.6, 190.7.
MALDI-MS: m/z 422.8 (M+).
Acknowledgment. We are grateful for financial support from
the National Science Foundation of the United States (CHE
0097089).
General Procedure for the Synthesis of Fulleropyrrolidine
Bisadducts. A mixture of C60 (36 mg, 0.05 mmol), sarcosine (7.2
mg, 0.40 mmol), and bisaldehydes 1-4 (0.05 mmol) in 10 mL of
ODCB was refluxed for 4 h. The mixture was washed with H2O
twice, dried over Na2SO4, and concentrated. The residue was
subjected to column chromatography with toluene/hexanes (70:30-
Supporting Information Available: NMR and mass data of
bisadducts 6-15 and monoadducts 17-19 and selected spectra and
AM1 calculation findings. This material is available free of charge
via the Internet at http://pubs.acs.org.
JO052213I
J. Org. Chem, Vol. 71, No. 4, 2006 1551