Synthesis and characterization of mono- and bis-methano[60]fullerenyl amino acid derivatives and their reductive ring-opening retro-bingel reactions.

Article abstract of DOI:10.1021/jo025928j

The addition of N-(diphenylmethylene)glycinate esters (Ph2C=NCH2CO2R) 3-6 to [60]fullerene under Bingel conditions gives, respectively, the methano[60]fullerenyl iminoesters 7-10. Upon treatment of 7-9 with sodium cyanoborohydride, in the presence of a protic or a Lewis acid, a novel reductive ring-opening reaction occurred to give the corresponding 1,2-dihydro[60]fullerenyl glycine derivatives 11-13. Using tethered bis-N-(diphenylmethylene)glycinate esters 33 and 34derived from m- and p-benzenedimethanol scaffolds, the corresponding bis-methano[60]fullerenyl iminoesters 35-38 were synthesized under double Bingel reaction conditions. The m-benzenedimethanol derivative 33 gave the trans-4 (35) and cis-3 (36) regioisomeric bisadducts in a ratio of 80:20. The analogous para-tethered derivative 34 afforded the trans-3 (37) and trans-4 (38) regioisomers in a 80:20 ratio. The regiochemistry of the major bisadducts 35 and 37 (via the trans-esterified 39) were unequivocally determined using 2D INADEQUATE and C-C TOCSY NMR experiments. The regiochemistry of these bis-additions were unexpected on the basis of literature precedents. These results unequivocally show that the regiochemistry of tethered bis-additions is not solely dependent on the nature of the tether. A mixture of the trans-4 and cis-3 nonsymmetrical bisadducts 45 and 46 was obtained from the double-Bingel cyclopropanation of a bis-N-(diphenylmethylene)glycinate tether based on a 1,3-naphthyldimethanol scaffold. The regiochemistry of these compounds (45 and 46) was identified by correlation with the diethyl esters 40 and 47, prepared by trans-esterification of 35/45 and 36/46, respectively. The INADEQUATE and molecular modeling experiments allowed topological mapping of the fullerene surfaces of the bis-methano[60]fullerenes 38 and 42. Reductive ring-opening reactions on the tethered bis-methano[60]fullerenes 35-37, 45, and 46 gave none of the expected bis-fullerenylglycinates rather the reductive ring-opening-retro-Bingel products, the 1,2-dihydro[60]fullerenylglycinates 48, 49, 52, and 53. These compounds resulted from the reductive ring-opening of one methanoimino ester moiety and a retro-Bingel reaction of the other. Under analogous reductive ring-opening-retro-Bingel conditions, the nontethered bis-methano[60]fullerene 40 afforded the 1,2-dihydro[60]fullerenylglycinate 12. Thus, it was concluded that the tether was not the driving force for the reductive elimination of one of the methano groups.

Full text of DOI:10.1021/jo025928j

Syn th esis a n d Ch a r a cter iza tion of Mon o- a n d
Bis-m eth a n o[60]fu ller en yl Am in o Acid Der iva tives a n d Th eir
Red u ctive Rin g-Op en in g Retr o-Bin gel Rea ction s
Glenn A. Burley,† Paul A. Keller,*,† Stephen G. Pyne,*,† and Graham E. Ball‡
Department of Chemistry, University of Wollongong, Wollongong, New South Wales 2522, Australia,
and NMR Spectroscopy Unit, University of New South Wales, Sydney, New South Wales 2052, Australia
paul_keller@uow.edu.au; stephen_pyne@uow.edu.au
Received May 10, 2002
The addition of N-(diphenylmethylene)glycinate esters (Ph2CdNCH2CO2R) 3-6 to [60]fullerene
under Bingel conditions gives, respectively, the methano[60]fullerenyl iminoesters 7-10. Upon
treatment of 7-9 with sodium cyanoborohydride, in the presence of a protic or a Lewis acid, a
novel reductive ring-opening reaction occurred to give the corresponding 1,2-dihydro[60]fullerenyl
glycine derivatives 11-13. Using tethered bis-N-(diphenylmethylene)glycinate esters 33 and 34
derived from m- and p-benzenedimethanol scaffolds, the corresponding bis-methano[60]fullerenyl
iminoesters 35-38 were synthesized under double Bingel reaction conditions. The m-benzene-
dimethanol derivative 33 gave the trans-4 (35) and cis-3 (36) regioisomeric bisadducts in a ratio of
80:20. The analogous para-tethered derivative 34 afforded the trans-3 (37) and trans-4 (38)
regioisomers in a 80:20 ratio. The regiochemistry of the major bisadducts 35 and 37 (via the trans-
esterified 39) were unequivocally determined using 2D INADEQUATE and C-C TOCSY NMR
experiments. The regiochemistry of these bis-additions were unexpected on the basis of literature
precedents. These results unequivocally show that the regiochemistry of tethered bis-additions is
not solely dependent on the nature of the tether. A mixture of the trans-4 and cis-3 nonsymmetrical
bisadducts 45 and 46 was obtained from the double-Bingel cyclopropanation of a bis-N-(diphenyl-
methylene)glycinate tether based on a 1,3-naphthyldimethanol scaffold. The regiochemistry of these
compounds (45 and 46) was identified by correlation with the diethyl esters 40 and 47, prepared
by trans-esterification of 35/45 and 36/46, respectively. The INADEQUATE and molecular modeling
experiments allowed topological mapping of the fullerene surfaces of the bis-methano[60]fullerenes
38 and 42. Reductive ring-opening reactions on the tethered bis-methano[60]fullerenes 35-37, 45,
and 46 gave none of the expected bis-fullerenylglycinates rather the reductive ring-opening-retro-
Bingel products, the 1,2-dihydro[60]fullerenylglycinates 48, 49, 52, and 53. These compounds
resulted from the reductive ring-opening of one methanoimino ester moiety and a retro-Bingel
reaction of the other. Under analogous reductive ring-opening-retro-Bingel conditions, the non-
tethered bis-methano[60]fullerene 40 afforded the 1,2-dihydro[60]fullerenylglycinate 12. Thus, it
was concluded that the tether was not the driving force for the reductive elimination of one of the
methano groups.
In tr od u ction
incorporation of biomolecular principles (such as water
solubility and precise secondary/tertiary structure) with
the unique physicochemical properties of fullerenes
(sensitization of singlet oxygen; electron acceptor char-
acteristics) have produced molecular structures with a
variety of biological activities.12 For example, in 1993,
Friedman and co-workers recognized the fullerene sphere
can be accommodated inside the cylindrical hydrophobic
cavity of HIV protease.13 In an additional illustration, in
vitro studies of water-soluble [60]fullerene derivatives
containing hydrophilic functionalities demonstrated the
The pioneering investigations into the chemical reac-
tivity of [60]fullerene1-8 have provided a precedent
toward the design and synthesis of novel and sophisti-
cated architectures that may have applications in me-
dicinal chemistry and the material sciences.9-11 The
† University of Wollongong.
‡ University of New South Wales.
(1) Diederich, F.; Kessinger, R. Templated Org. Synth. 2000, 189-
218.
(2) Taylor, R. Synlett 2000, 776-793.
(3) Wilson, S. R.; Schuster, D. I.; Nuber, B.; Meier, M. S.; Maggini,
M.; Prato, M.; Taylor, R. Fullerenes: Chem. Phys. Technol. 2000, 91-
176.
(9) Da Ros, T.; Prato, M. Chem. Commun. 1999, 663-669.
(10) Prato, M. Top. Curr. Chem. 1999, 199, 173-187.
(11) Prato, M. J . Mater. Chem. 1997, 7, 1097-1109.
(12) Burley, G. A.; Keller, P. A.; Pyne, S. G. Fullerene Sci. Technol.
1999, 7, 973-1001.
(13) Friedman, S. H.; DeCamp, D. L.; Sijbesma, R. P.; Srdanov, G.;
Wudl, F.; Kenyon, G. L. J . Am. Chem. Soc. 1993, 115, 6506-6509.
(4) Diederich, F.; Kessinger, R. Acc. Chem. Res. 1999, 32, 537-545.
(5) Hirsch, A. Top. Curr. Chem. 1999, 199, 1-65.
(6) Diederich, F. Pure Appl. Chem. 1997, 69, 395-400.
(7) Hirsch, A. J . Phys. Chem. Solids 1997, 58, 1729-1740.
(8) Hirsch, A. Synthesis 1995, 895-913.
10.1021/jo025928j CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/31/2002
8316
J . Org. Chem. 2002, 67, 8316-8330

Mono- and Bis-methano[60]fullerenyl Amino Acid Derivatives
SCHEME 1
ability of [60]fullerenes to inhibit acutely and chronically
affected peripheral blood mononuclear cells with an EC50
of 7 µM.13,14
As part of a program aimed at the investigation of the
potential applications of [60]fullerene derivatives, we
have proposed a method for the synthesis of protected
versions of the mono- and disubstituted fullerenyl R-ami-
no acids 1 and 2. Derivatives of these compounds have
been obtained via the Bingel cyclopropanation methodol-
ogy using readily available N-(diphenylmethylene)glyci-
nate esters.15-17 Systematic protection/deprotection of the
carboxylate and amino functionalities of these protected
amino acids should allow the incorporation of R-fullerenyl
amino acids into biological macromolecules using con-
ventional peptide coupling methods. The resultant fullere-
nyl-containing structures would have unique electron
acceptor properties as well as interesting structural
features and biological activities. Indeed, there are
reports of polypeptide chains being terminally tagged
with fullerenes,18 while the insertion of the fullerene
spheroid into peptide chains has been demonstrated
using fulleroproline.9,19-23 The proposed R-fullerenyl amino
acids 1 and 2, however, would be expected to produce new
and interesting biomolecular structures and were there-
fore deemed worthy targets for synthesis.
TABLE 1. Yield s of th e Bin gel Cyclop r op a n a tion
P r od u cts 7-10 fr om N-(Dip h en ylm eth ylen e) Glycin a te
Ester s 3-6
compd
R group
tBu
yield (%)
7
8
46
72
31
46
Et
9
10
(+)-menthyl
O-glycolic
novel fullerenyl derivatives was made using the powerful
2D-INADEQUATE suite of experiments to map out
important 13C-13C connectivity patterns. Additionally,
the reductive ring-opening reactions of these bisadducts
are also described.
Syn th esis
of
Mon o- a n d
Bis-m eth a n o[60]-
fu ller en yl Im in o Ester s
From the outset of our studies, we aimed to produce
the methano[60]fullerenyl R-amino acid 1 or suitably
protected versions of this molecule. Although our efforts
toward the realization of 1 were thwarted, this paper
reports on the serendipitous discovery of a novel reduc-
tive ring-opening reaction of methano[60]fullerenes and
the synthesis of a fully protected version of the [60]-
fullerenylglycine 2, a true R-fullerenyl amino acid. We
also report the synthesis of a series of bismethano[60]-
fullerene amino acid derivatives via tether-directed re-
mote functionalization, yielding products of unexpected
regiochemistry. The unequivocal characterization of these
The reaction of [60]fullerene with active methylene
components (CH2WW′) in the presence of base and a
halogenating agent (the Bingel reaction)24 is a general
and versatile method for preparing methano[60]fullerenes
of the general formula C61WW′ (where W is an electron-
withdrawing group). While malonic esters have generally
been employed,25 we have found that under Bingel
conditions the reaction of [60]fullerene with N-(diphe-
nylmethylene)glycinate esters 3-6 efficiently provides
the corresponding methano[60]fullerenyl imino esters
7-10 (Scheme 1).
Thus treatment of a mixture of [60]fullerene and the
individual N-(diphenylmethylene)glycinate esters 3-6
with 1.0 molar equiv of carbon tetrabromide and 3.0
molar equiv of base (DBU) for 30 min afforded the
methano[60]fullerene derivatives 7-10, respectively,
after purification by silica gel column chromatography
(Table 1). A significant difference in the reaction times
was observed for Bingel adducts arising from N-(diphe-
nylmethylene)glycinate esters (30 min) versus the cor-
responding malonate esters (8 h),26 suggestive of the
greater acidity of the N-(diphenylmethylene)glycinate
ester methylene protons and their cognate R-bromo
derivatives.
(14) Sijbesma, R.; Srdanov, G.; Wudl, F.; Castoro, J . A.; Wilkins,
C.; Friedman, S. H.; DeCamp, D. L.; Kenyon, G. L. J . Am. Chem. Soc.
1993, 115, 6510-6512.
(15) Burley, G. A.; Keller, P. A.; Pyne, S. G.; Ball, G. E. Chem.
Commun. 1998, 2539-2540.
(16) Burley, G. A.; Keller, P. A.; Pyne, S. G.; Ball, G. E. Chem.
Commun. 2000, 1717-1718.
(17) Burley, G. A.; Keller, P. A.; Pyne, S. G.; Ball, G. E. Chem.
Commun. 2001, 563-564.
(18) Kurz, A.; Halliwell, C. M.; Davis, J . J .; Hill, H. A. O.; Canters,
G. W. Chem. Commun. 1998, 433-434.
(19) Bianco, A.; Da Ros, T.; Prato, M.; Toniolo, C. J . Pept. Sci. 2001,
7, 208-219.
(20) Pellarini, F.; Pantarotto, D.; Da Ros, T.; Giangaspero, A.; Tossi,
A.; Prato, M. Org. Lett. 2001, 3, 1845-1848.
(21) Bianco, A.; Bertolini, T.; Crisma, M.; Valle, G.; Toniolo, C.;
Maggini, M.; Scorrano, G.; Prato, M. J . Pept. Res. 1997, 50, 159-170.
(22) Bianco, A.; Maggini, M.; Scorrano, G.; Toniolo, C.; Marconi, G.;
Villani, C.; Prato, M. J . Am. Chem. Soc. 1996, 118, 4072-4080.
(23) Prato, M.; Bianco, A.; Maggini, M.; Scorrano, G.; Toniolo, C.;
Wudl, F. J . Org. Chem. 1993, 58, 5578-5580.
(24) Bingel, C. Chem. Ber. 1993, 126, 1957-1959.
(25) Diederich, F.; Isaacs, L.; Philp, D. Chem. Soc. Rev. 1994, 23,
243-255.
J . Org. Chem, Vol. 67, No. 24, 2002 8317

Burley et al.
The 13C NMR spectrum of 7 comprised 28 resonances
arising from the sp2 carbons of the fullerene core. Three
of these carbons were half the intensity of the remaining
fullerenyl sp2 carbons, indicative of Cs symmetry.27
Compounds 7-10 were identified as possessing “closed”
methano[60]fullerene structures rather than the “open”
methanoannulene structures by the presence of bridge-
head carbon resonances between δ 93 and 96.28,29 13C
NMR resonances located between δ 82 and 83 were
assigned to the fullerenyl sp3 carbons at the site of
substitution on the fullerene core. The ESMS spectrum
of 7 displayed a molecular ion (M+) at m/z 1013 while
the MALDI-TOF spectrum of 8 displayed a molecular ion
at m/z 985. An unusual peak was also observed at m/z
1452 in a number of MALDI-TOF spectra. This ion was
attributed to the formation of a methano[60]fullerene
dimer under MALDI-TOF conditions.30,31
SCHEME 2
The diphenylimine moiety is known for its lability in
acidic media;32 however, following the literature methods,
treatment of 7 with 1 M HCl at room temperature
resulted in a quantitative recovery of the starting mate-
rial. This was attributed to the electron-withdrawing
nature of the [60]fullerene sphere making the imino
nitrogen less basic and thus less susceptible to protona-
tion under these reaction conditions. This effect was also
observed in fulleropyrrolidines for which it has been
found that the nitrogen has a far reduced nucleophilicity
and basicity compared to its pyrrolidine analogue.33
Harsher acidic conditions gave rise to products that were
difficult to characterize due to the extreme insolubility
of these organic compounds in both water and organic
solvents. An attempted base hydrolysis of 8 using lithium
hydroxide in a mixture of THF/MeOH/H2O (10:5:1) at
room temperature for 24 h also returned unreacted
starting material. Treatment of the O-ethyl glycolic ester
TABLE 2. Yield s of Red u ctive Rin g-Op en in g P r od u cts
Sh ow n in Sch em e 2
product yields (%)
starting compds
reductive ring-opening [60]fullerene
14
7
8
9
11 (39)
12 (58)
13 (40)b
9
12
10
a
8
a
a
Due to the small scale of this reaction, isolation of 14 proved
b
difficult. The product was a 1:1 mixture of diastereomers.
Hydrogenation of 7 and 8 over Pd/C under a hydrogen
atmosphere provided only unreacted starting material.
Reduction of 7 using sodium borohydride resulted in an
uncharacterizable polar compound whereas the milder
reductant, sodium cyanoborohydride, adjusted to pH 4
with glacial acetic acid,36 yielded not the reduced second-
ary amine but rather the unexpected ring-opened 1,2-
dihydro[60]fullerenylglycine derivative 11 (Scheme 2).
Unfortunately, this reductive ring opening using glacial
acetic acid proved unreliable. However, treatment of 7-9
with boron trifluoride‚diethyl etherate (5.0 molar equiv)
followed by the addition of sodium cyanoborohydride
consistently yielded the ring-opened products 11-13,
respectively (Table 2), accompanied by the formation of
free [60]fullerene (9-12%). From the reductive ring
34
10 with BBr3 in dichloromethane solution afforded a
moderately soluble material that was also difficult to
characterize.
Red u ctive
Rin g-Op en in g
of
N-(Dip h en yl-
m eth ylen e)glycin a te Meth a n o[60]fu ller en e Ester s
Due to a lack of reactivity in hydrolyzing the diphe-
nylimine moiety of 7 and 8, an alternate deprotection
method was considered. The initial strategy was to
reduce the diphenyl imine group of 7/8 to its correspond-
ing secondary amine and subsequently cleave the result-
ing benzhydryl amino group using catalytic transfer
hydrogenation35 to afford the free primary amine.
t
opening of 8, the reduced addend 14 (R ) Bu) was also
isolated (Table 2). Reductive ring opening of the chiral
methano[60]fullerene 9 was attempted to investigate
whether a diasteroselective reaction could take place. 1H
NMR analysis of 13, however, revealed the formation of
a 1:1 diastereomeric mixture of ring-opened products
from integration of the corresponding fullerenyl protons
at δ 6.91 and 6.88 for each diastereomer.
(26) Camps, X.; Hirsch, A. J . Chem. Soc., Perkin Trans. 1 1997,
1595-1596.
(27) [60]Fullerene derivatives possessing CS-symmetry should com-
prise four-half-intensity 13C resonances. Only three-half-intensity 13C
resonances were observed due to the overlapping of peaks.
(28) Prato, M.; Lucchini, V.; Maggini, M.; Stimpfl, E.; Scorrano, G.;
Eiermann, M.; Suzuki, T.; Wudl, F. J . Am. Chem. Soc. 1993, 115,
8479-8480.
The proposed mechanism of this novel ring opening
under protic acid conditions is shown in Scheme 3. This
process may not necessarily be concerted, and the pro-
tonation steps may occur at different stages of the
pathway. The first step is activation of the diphenyl imine
functionality under protic acid conditions to form an
iminium cation 15. The first equivalent of hydride then
attacks the activated iminium carbon, with subsequent
cyclopropyl ring opening (see 16) giving rise to the
(29) Prato, M.; Suzuki, T.; Wudl, F.; Lucchini, V.; Maggini, M. J .
Am. Chem. Soc. 1993, 115, 7876-7877.
(30) Dragoe, N.; Tanibayashi, S.; Nakahara, K.; Nakao, S.; Shimo-
tani, H.; Xiao, L.; Kitazawa, K.; Achiba, Y.; Kikuchi, K.; Nojima, K.
Chem. Commun. 1999, 85-86.
(31) Dragoe, N.; Shimotani, H.; Hayashi, M.; Saigo, K.; De Betten-
court-Dias, A.; Balch, A. L.; Miyake, Y.; Achiba, Y.; Kitazawa, K. J .
Org. Chem. 2000, 65, 3269-3273.
(32) O’Donnell, M. J .; Polt, R. L. J . Org. Chem. 1982, 47, 2663-
2666.
(35) Anwer, M. K.; Spatola, A. F. Synthesis 1980, 929-932.
(36) Cox, E. D.; Hamaker, L. K.; Li, J .; Yu, P.; Czerwinski, K. M.;
Deng, L.; Bennett, D. W.; Cook, J . M. J . Org. Chem. 1997, 62, 44-61.
(33) Prato, M.; Maggini, M. Acc. Chem. Res. 1998, 31, 519-526.
(34) Isaacs, L.; Diederich, F. Helv. Chim. Acta 1993, 76, 2454-2464.
8318 J . Org. Chem., Vol. 67, No. 24, 2002

Mono- and Bis-methano[60]fullerenyl Amino Acid Derivatives
SCHEME 3
SCHEME 5
anoborohydride (NaCNBD3) followed by an aqueous
(H2O) workup. Such an experiment could give insight
toward the origin of the proton source for the fullerenyl
proton (Hø). Reduction of 7 with sodium cyanoborodeu-
teride in the presence of boron trifluoride.diethyl etherate
followed by an aqueous workup afforded the ring-opened
compound 19 in 38% yield (Scheme 5). 1H NMR analysis
revealed 42% deuterium incorporation at both the HR and
Hâ positions, consistent with our proposed mechanism.
However, no insight into the origin of the fullerenyl
proton (Hø) was obtained. To examine if the proton source
arose from the workup conditions, a Lewis-acid-mediated
ring opening was performed using sodium cyanoborohy-
SCHEME 4
1
dride with D2O as the quenching agent (Scheme 5). H
NMR analysis showed no incorporation of deuterium in
11 after purification by column chromatography using
silica gel. Recently, we have found that related 1,2-
dihydrofullerene compounds undergo rapid exchange of
the fullerenyl proton (or deuteron, Hø) upon silica gel
chromatography thus possibly explaining the lack of
deuterium incorporation in the latter experiment.38 This
result was understandable and consistent with the
known relatively high acidity of 1,2-dihydro[60]fullerene
derivatives; for example, 1,2-C60(tBu)H has a pKa of 5.7.39
The ring opening of methano[60]fullerene derivatives
has been previously observed in spiroannelated methano-
[60]fullerenes whereupon a one-electron reduction causes
a homolytic cleavage of one of the bonds in the cyclopro-
pane ring. This ring opening, however, could only be
observed transiently using EPR spectroscopy before
proceeding irreversibly to an unknown product.40
Ch a r a cter iza tion of th e Rin g-Op en ed P r od u cts
1
The H NMR spectrum of the ring-opened product 11
revealed a three-proton coupled spin system at δ 5.27 (Hâ,
d, J ) 4.4 Hz), 4.83 (HR, d, J ) 15.6 Hz), and 3.61 (NH,
dd, J ) 15.6, 4.4 Hz). A singlet resonance at δ 6.84 was
assigned to the fullerenyl proton (Hø). This was consistent
with the chemical shifts of fullerenyl protons identified
in the literature.41 The fullerenyl sp2 region of the 13C
NMR spectrum of 11 revealed 47 of the possible 58 sp2
resonances, indicative of a fullerenyl adduct possessing
no symmetry elements. Closer inspection of the fullerenyl
sp2 section revealed a number of defined clusters of
resonances in particular regions of the 13C NMR spec-
trum. For example, both an upfield (δ 136-138) and a
downfield (δ 152-155) cluster of four resonances were
fullerenyl anion intermediate 17. The driving force for
such a ring opening is assumed to be the release of ring
strain and the stabilization of the incipient fullerenyl
carbanion 17 by the electron-deficient fullerene sphere.
Such ring opening of cyclopropane amino esters and acids
is known when a â-electron-withdrawing group is present
on the ring that can stabilize a developing carbanionic
center.37
The mechanism for the corresponding Lewis acid
promoted reductive ring-opening is assumed to proceed
via a different but related pathway (Scheme 4). The
corresponding expected intermediate fullerenyl carbanion
18 can be protonated to give 11-13 or undergo elimina-
tion of the addend to form free [60]fullerene and eventu-
ally 14.
(38) Mitchell, C. L. BMedChem(Hons) Thesis, University of Wol-
longong, 2001.
To explore the mechanism of this Lewis-acid activated
ring opening, corresponding ring-opening experiments
were performed using deuterium-labeled sodium cy-
(39) Fagan, P. J .; Krusic, P. J .; Evans, D. H.; Lerke, S. A.; J ohnston,
E. J . Am. Chem. Soc. 1992, 114, 9697-9699.
(40) Knight, B.; Martin, N.; Ohno, T.; Orti, E.; Rovira, C.; Veciana,
J .; Vidal-Gancedo, J .; Viruela, P.; Viruela, R.; Wudl, F. J . Am. Chem.
Soc. 1997, 119, 9871-9882.
(37) Pyne, S. G.; Schafer, K.; Skelton, B. W.; White, A. H. Aust. J .
Chem. 1998, 51, 127-135.
(41) Gan, L.; J iang, J .; Zhang, W.; Su, Y.; Shi, Y.; Huang, C.; Pan,
J .; Lue, M.; Wu, Y. J . Org. Chem. 1998, 63, 4240-4247.
J . Org. Chem, Vol. 67, No. 24, 2002 8319

Burley et al.
3
3
F IGURE 1. 8 Hz optimized HMBC (600 MHz, C6H6/CS2 1:1) expansion plots of 13 revealing J HC for Hø f CR and J HC for HR f
Cø. These assignments were identified by a J HC of 6.0 Hz.
3
F IGURE 2. (a) 2 Hz optimized HMBC (600 MHz, C6H6/CS2 1:1) spectrum of 11 showing 20 correlations from Hø into the fullerene
2
sp2 core. (b) Schlegel diagram of the ring-opened adduct 11. C3 and C12 were identified by a J HC coupling to Hø (red circles). C6
3
and C9 were identified by a J HC coupling to Hø (green circles). Blue-circled carbon atoms are those â to the site of functionalization
but could not be unambiguously determined from HMBC experiments to be C4, C5, C10, C11 or C7, C8, C13, C14.
observed relative to that for the main cluster of peaks
between δ 142-147.
tionalization site, and adjacent to Hø (red circles in Figure
2b).
The HMBC experiment identified a three-bond 1H-
13C correlation between Hø and CR (Figure 1). A corre-
sponding three-bond correlation between HR and Cø also
confirmed the 1,2-addition pattern. A 1,4 substitution
pattern (20) would not show such correlations since this
would represent coupling over five bonds between Hø/CR
and HR/Cø. A 2 Hz optimized HMBC experiment was also
The more upfield diastereotopic pair of this cluster of
four carbons was assigned C6 or C9 at δ 153.1 or 152.4,
respectively. These carbons were assigned as being R to
the functionalization site, but in the same hemisphere
as the addend (green circles in Figure 2b). Unequivocal
assignment of the individual carbons of the diastereotopic
pairs could not be determined using the HMBC experi-
ment. The most upfield group of carbons C4/C11 and C13/
C14, were also found to exist as diastereotopic pairs due
to the stereotopic center at the CR position. Although
these carbons could not be assigned unequivocally by the
HMBC experiment alone, there appeared to be a trend
in the nature of fullerene sp2 13C NMR chemical shifts
directly in the vicinity of functionalization. Fullerene sp2
carbons R to the functionalization site (C3, C6, C9 and
C12) appear to exist downfield when compared with the
remaining fullerene sp2 population (red and green circles,
Figure 2b).
1
performed on 11, allowing long-range H/13C correlations
to be observed. Interestingly, it was found that the single
proton resonance of Hø correlated to 20 fullerene sp2
carbons; i.e., one-third of the fullerene sphere was identi-
fied from a single proton resonance (Figure 2a).
Particular resonance clustering was apparent after
closer inspection of the nature of the coupling between
Hø and the fullerenyl sp2 carbons. Of the correlations
between Hø and the fullerenyl sp2 carbons, the most
downfield resonances δ 154.4 and 153.7, with the largest
J HC values, were assigned to C3 or C12, respectively.
2
These carbons both had a J HC of 10.8 Hz and exist as a
The group of four upfield fullerenyl sp2 carbons (δ
137.3-136.6) were assigned to either C4/C11 or C13/C14
diastereotopic pair as a consequence of the stereogenicity
of CR. These were assigned the carbons R to the func-
3
from their J HC of 6.0 Hz. This “upfield/downfield” effect
8320 J . Org. Chem., Vol. 67, No. 24, 2002

Mono- and Bis-methano[60]fullerenyl Amino Acid Derivatives
SCHEME 6a
a
Reagents: (i) DMAP (cat.), DCC (2.1 equiv), N-tert-butoxycarbonlyglycine, CH2Cl2; (ii) TFA; (iii) Ph2CdNH (2 equiv), CH2Cl2.
of fullerenyl sp2 carbons R and â to the site of function-
alization has also been observed in the methano[60]-
fullerene adduct 21 and has been reported for some
fullerene-organometallic complexes, for example the
osmium derivative 22, using the 2D INADEQUATE
experiment.42-44
verted to their respective ammonium trifluoroacetate
salts 29-31 by treatment with TFA.
Treating a suspension of these salts in dichloromethane
(DCM) with benzophenone imine for 24 h afforded the
transiminated diesters 32, 33, and 34 in 84, 76, and 73%
yields, respectively.
The individual double Bingel cyclopropanation reac-
tions of 32, 33, and 34 with [60]fullerene were attempted
using carbon tetrabromide (2.0 molar equiv) and DBU
(3.5 molar equiv) (Scheme 7). These reactions typically
took 1 h to reach completion on the basis of TLC analysis.
Purification required elution of the crude reaction mix-
ture through two silica gel columns with DCM/petroleum
spirit (90:10) as the eluent. Under these conditions, the
reactions using ortho-tethered bis-N-(diphenylmethyl-
ene)glycinate diester 32 did not afford a characterizable
product.
Earlier work has shown that tethered bis-malonate
esters undergo regioselective bis-cyclopropanation reac-
tions with [60]fullerene under Bingel conditions.46 For
example, both the ortho- and meta-substituted tethered
bismalonate analogues of 32 and 33 gave exclusively the
cis-2 regioisomer as determined by comparative UV-vis
spectroscopy and from its symmetry by 1D 13C NMR
spectroscopy. The corresponding para isomer afforded
predominantly the trans-4 adduct. In contrast, we have
found that treatment of [60]fullerene with our bisimino
ester 33 gives, under similar reaction conditions, two
regioisomeric adducts 35 and 36 in a ratio of 80:20 from
1H NMR analysis of the crude reaction mixture. These
compounds were readily separated by column chroma-
tography to afford 35 and 36 in 32 and 10% yields,
[60]F u ller en e
Teth er ed
Ester s
Bisfu n ction a liza tion
Bis-N-(d ip h en ylm eth ylen eglycin a te)
u sin g
In principle, the bis-cyclopropanation of [60]fullerene
using tethered bis-N-(diphenylmethylene)glycinate esters
followed by our reductive ring-opening methodology
would allow protected bis-amino acid functionalities to
be incorporated into precise locations on the surface of
the fullerene sphere. To produce regioselective multi-
functionalized fullerenyl amino acids, a tether-directed
methodology was adopted.1,45 The tethers chosen for
bisfunctionalization of [60]fullerene were the benzene-
dimethanols 23-25 that have been used extensively by
the Diederich group for the malonate-derived biscyclo-
propanation of [60]fullerene.46 The tethered bis-N-(diphe-
nylmethylene)glycinate diesters 32-34 were synthesized
as shown in Scheme 6. DCC-mediated bis-esterification
of o-, m-, and p-benzenedimethanol (23-25) afforded the
bisglycine esters 26-28, respectively. These were con-
1
respectively (Scheme 7). The H NMR of pure samples
of 35 and 36 showed resonances for the two pairs of
diastereotopic methylene protons [δ 5.06 and 5.71, J )
11.2 Hz for 35; δ 5.41 and 5.31, J ) 11.0 Hz for 36]
consistent with a tethered bis-methano[60]fullerene struc-
ture. 13C NMR spectroscopy revealed 31 peaks associated
with the fullerenyl sp2 carbons in 35, consistent with its
Cs-symmetry; three of these carbons were identified as
being of half-intensity compared to the remaining car-
bons.27 The 13C NMR spectrum of 36 revealed 30 full-
intensity peaks associated with the fullerenyl sp2 carbons,
typical of a molecule exhibiting C2-symmetry. Further-
more, the MALDI-TOF spectrum of 35 and 36 showed a
characteristic parent molecular ion at m/z 1296. The UV-
(42) Hawkins, J . M.; Loren, S.; Meyer, A.; Nunlist, R. J . Am. Chem.
Soc. 1991, 113, 7770-7771.
(43) Hawkins, J . M.; Meyer, A.; Lewis, T. A.; Bunz, U.; Nunlist, R.;
Ball, G. E.; Ebbesen, T. W.; Tanigaki, K. J . Am. Chem. Soc. 1992, 114,
7954-7955.
(44) Burley, G. A.; Keller, P. A.; Pyne, S. G.; Ball, G. E. Magn. Reson.
Chem. 2001, 39, 466-470.
(45) Breslow, R. Acc. Chem. Res. 1980, 13, 170-177.
(46) 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.
J . Org. Chem, Vol. 67, No. 24, 2002 8321

Burley et al.
SCHEME 7a
a
Reagents: (i) DBU (3.5 equiv), CBr4 (2 rquiv), C6H5Cl.
SCHEME 8
vis spectrum of 35 showed bands between 400 and 800
nm that suggested a trans-4 structure,47 but this conclu-
sion was not definitive due to the lack of adequate
reference compounds. The corresponding UV-visible
spectrum for 36 exhibited characteristics of both a cis-2
and a cis-3 bis-methano[60]fullerene,47 therefore render-
ing regiochemical assignment by UV-visible spectros-
copy as not definitive.
Treatment of [60]fullerene with 34 under Bingel condi-
tions afforded two regioisomers in an 80:20 ratio from
1H NMR analysis with the isolated yields of 37 and 48
being 37 and 10%, respectively. The MALDI-TOF spectra
for both 37 and 38 showed a characteristic parent ion at
m/z 1296, consistent with the MALDI-TOF spectra of
compounds 35 and 36. Both compounds 37 and 38
exhibited characteristics in their 1H NMR spectra of a
tethered bismethano[60]fullerene [doublets at δ 5.21 and
5.58, J ) 11.6 Hz for 37; doublets at δ 5.17 and 5.72, J
) 14.4 Hz for 38]. Due to the extreme insolubility of 38,
SCHEME 9
a
13C NMR spectrum could not be acquired48 however
The UV-vis spectrum of 39 had characteristic bands
in the 400-800 nm region that beared resemblance to a
trans-3 bis-methano[60]fullerene, which was consistent
with its C2-symmetry. The corresponding UV-vis spec-
trum for 38 revealed an almost identical spectrum to that
of 35. Both 35 and 38 possess Cs-symmetry, suggesting
identical regiochemistry. This was confirmed by their
transesterification reactions to form the same bis-methano-
[60]fullerene 40 (Scheme 9).
The similarity in the UV-vis spectra for the two
distinct regioisomers 36 and 38 gave rise to ambiguities
in the assignment of the absolute regiochemistry. Such
ambiguities have been noted elsewhere49 and the assign-
ment of regiochemistries based upon comparative tech-
niques has its limitations when no suitable comparison
can be made, e.g., higher order substitution patterns. In
transesterification of 38 using K2CO3 in a 1:1 mixture of
THF/EtOH afforded 39 that was readily soluble in a
range of organic solvents (Scheme 8).
The 13C NMR of 39 indicated that it had C2-symmetry,
characterized by 30 full-intensity sp2 resonances, whereas
38 had Cs-symmetry, characterized by 29 sp2 resonances,
three being half-intensity.27 The bis-methano[60]fullerene
adducts 35-38 all exhibited a single cyclopropyl bridge-
head carbon (ca. δ 96) and two fullerenyl sp3 carbons (ca.
δ 82) in their 13C NMR spectra.
(47) Djojo, F.; Herzog, A.; Lamparth, I.; Hampel, F.; Hirsch, A.
Chem.sEur. J . 1996, 2, 1537-1547.
(48) A range of solvents (C6D6, (CD3)2SO, CS2, dichlorobenzene-d4)
were tried in an effort to increase the solubility of 40; however, these
were ineffective.
8322 J . Org. Chem., Vol. 67, No. 24, 2002

Mono- and Bis-methano[60]fullerenyl Amino Acid Derivatives
F IGURE 3. Schlegel diagram of 35, showing the carbon numbering system and key connectivities (gray lines) from NMR. The
carbon atoms that lie on the plane of symmetry (C19, C20, C46, C47) are identified by gray circles. The tether moiety on the
Schelgel diagram has been removed for clarity. Numbering system according to Thilgen et al.50
TABLE 3. Ch em ica l Sh ifts (δ), P ea k Assign m en ts, a n d
our case, UV-vis spectroscopy could not be used as a
definitive characterization tool in this study for the
assignment of the regiochemistry of the bisadducts 35-
38 and unequivocal evidence for their structures came
from 2D INADEQUATE experiments.
Ca r bon -Ca r bon Cou p lin g Con sta n ts (1J CC) for th e
[60]fu ller en e Ca ge of 35a
carbon no. chemical shift (δ, ppm)
1J CC (Hz) (carbon no.)
1, 35
2, 34
3, 16
4, 17
5, 18
6*, 36
7, 37
8, 53
9, 52
10, 51
11, 50
12, 33
13, 32
14, 15
19#
81.4
81.3
(2)**, (6) 44, (9) 44
(1)**, (3) 40, (12) 41
(2) 41, (4) 70, (14) 59
(3) 70, (5) 53
145.7
129.0
136.2
150.6
146.5
146.4
149.6
147.1
136.2
146.6
145.3
143.5
142.2
148.7
139.4
141.1
141.3
140.9
141.9
143.4
148.3
140.3
145.3
138.7
141.8
145.5
145.5
145.5
150.6
145.7
2D INADEQUATE Exp er im en ts
As discussed earlier, 13C NMR spectroscopy revealed
31 peaks associated with the fullerenyl carbons in 35.
The resonance at δ 150.9 was shown to arise from the
fortuitous overlap of one full-intensity peak and one-half-
intensity peak. Hence, 35 has 32 unique fullerene
carbons, four of which are half-intensity peaks (labeled
as gray circles in Figure 3), indicative of a bis-methano-
[60]fullerene with Cs-symmetry. To distinguish between
the three possible structural isomers, cis-1, cis-2, and
trans-4, INADEQUATE experiments were performed on
a 10% 13C enriched sample of 35.
(4) 53, (6) 73, (19) 57
(1) 45, (5) 73, (7) 57
(6) 57, (8)**, (21) 67
(7)**, (9) 56, (24) 67
(1) 45, (8) 56, (10) 72
(9) 72, (11) 53, (26) 57
(10) 53, (12) 71, (28) 57
(11) 71, (13) 56, (2) 41
(12) 56, (14) 54, (30) 68
(13) 54, (15) 59
(5) 57, (20) 67
(19) 67, (21) 56
(7) 67, (20) 56, (22) 57
(21) 57, (23)**
(22)**, (24)**, (42) 56
(8) 67, (23)**, (25) 56,
(24) 56, (26) 68, (43) 56
(10) 57, (25) 68, (27) 55
(26) 55, (28) 55, (44/45) 68
(11) 57, (27) 55, (29) 68
(28) 68, (30) 56, (47) 54
(29) 56, (13) 68
20#
21, 38
22, 39**
23, 40**
24, 54
25, 55
26, 60
27, 59
28, 59
29, 48
30, 31
42, 41
43, 56
44, 57
45, 58
46*#
The assignment of the regiochemistry of the bis-
methano[60]fullerene 35 was achieved by identifying
correlations from the half-intensity peaks (located on the
symmetry plane) to the fullerenyl sp3 carbons (locating
the site of substitution). The above-mentioned three
possible regioisomers would be expected to show two, one
and three-bond separations, respectively, between a
fullerenyl sp3 hybridized carbon and its nearest carbon
on the plane of symmetry (i.e., half-intensity peak). These
experiments revealed a three-bond connectivity (shown
as gray lines in Figure 3) between C1 (sp3 carbon) and
C19 (half-intensity peak) providing unequivocal evidence
for its trans-4 structure. Starting from C19, correlations
were observed to the other half-intensity peak (C20) with
a relatively large coupling constant (1J CC ) 67 Hz) typical
for 6,6 ring fusion carbons and one to C5 with a smaller
1J CC (57 Hz) typical for 6,5 ring fusion carbons.42 Carbon-5
(23)**, (43) 55
(25) 56, (42) 55, (44/45)**
(11)**, (45)**
(27) 68, (44)**, (46) 56
(45) 56, (47) 68
(46) 68, (29) 57
47#
a
Key: *Denotes peak has two resonances; one full intensity and
one-half intensity. **Denotes coupling not first order. Peaks
positioning consistent with structure model. #Denotes half-
intensity peaks.
showed correlations to C6 (1J CC ) 73 Hz) and C4 (1J CC
)
symmetry. Further corroborative evidence for this struc-
ture was the observation that C4 showed only two
correlations (to C3 and C5) consistent with the magnetic
equivalence of C4 and C17 due to their positions relative
to the plane of symmetry. The complete assignment for
the fullerenyl carbons of 35 is summarized in Table 3.
Due to the insolubility of 37 the 13C-13C connectivity
experiments were conducted on its transesterified prod-
53 Hz), consistent with their 6,6 and 5,6 ring fusion
positions, as well as to C19. Carbon-6 showed a correla-
tion to the sp3 carbon C1, unequivocally confirming the
position of the cyclopropane ring relative to the plane of
(49) Pasimeni, L.; Hirsch, A.; Lamparth, I.; Herzog, A.; Maggini, M.;
Prato, M.; Corvaja, C.; Scorrano, G. J . Am. Chem. Soc. 1997, 119,
12896-12901.
J . Org. Chem, Vol. 67, No. 24, 2002 8323

Burley et al.
TABLE 4. Ch em ica l Sh ifts (δ), P ea k Assign m en ts, a n d
Ca r bon -Ca r bon Cou p lin g Con sta n ts (1J CC) for th e
[60]F u ller en e Ca ge of 39
chemical shift
carbon no.
(δ, ppm)
1J CC (Hz) (carbon no.)
9, 51
6, 49
153.9
153.3
151.2
148.5
148.5
145.4
148.3
147.6
(1, 50) 44; (7/8, 59/60); 57; (10, 52) 72
(1, 50) 44; (7/8, 59/60) 57; (5, 48) 72
(13, 16) 58; (11, 35) 71; (2, 33) 40
(21, 58) 57; (38, 45) 56; (19, 47)
(12, 34) 58; (14, 15) 55; (17, 30) 67
(19, 47); (28, 36) 67; (17, 30) 55
(14, 15) 58; (4, 31) 71; (2, 33) 42
(7/8, 59/60) N/A; (21, 58) 68; (6, 49) 57;
(25, 55); (9, 51) 57
12, 34
20, 46
13,16
18, 29
3, 32
7/8, 59/60
7/8, 59/60
147.6
(7/8, 59/60) N/A; (21, 58) 68; (6, 49) 57;
(25, 55); (9, 51) 57
F IGURE 4. Schlegel diagram of one enantiomer of 39 showing
connectivities (green) from the site of substitution (C2) to the
magnetically equivalent carbons (C14 and C15). Axis of
symmetry is shown in red while red dots signify entry and
exit of the axis of symmetry. The methano substitutents on
the Schelgel diagram have been removed for clarity. Number-
ing system according to Thilgen et al.50
37, 27
25, 54
14*, 15
39, 44
23, 56
26, 53
38, 45
22, 57
24, 55
19, 47
40, 43
11, 35
41*, 42
21, 58
28, 36
10, 52
17, 30
4, 31
147.6
147.2
145.4
144.9
144.7
144.6
144.3
143.8
143.7
143.6
143.2
142.0
141.6
141.3
140.2
138.9
138.2
136.0
134.9
81.9
(26, 53); (38, 45) 67; (28, 36) 55
(40, 43) 56; (24, 55) 56; (26, 53) 67
(3, 32) 58; (13, 16) 55
(38, 45) 56; (22, 57) 56; (40, 43) 68
(22, 57) 68; (24, 55); (41, 42) 56
(10, 52) 57; (27, 37); (25, 54) 67
(20, 46) 56; (39, 44) 56; (27, 37) 67
(21, 58) 56; (39, 44) 56; (23, 56)
(7/8, 59/60); (25, 54) 56; (23, 56)
(5, 48) 57; (18, 29); (20, 46)
uct 39 using a 13C enriched sample. The 13C NMR of the
C2-symmetrical bisadduct 39 comprised 30 observed
fullerenyl peaks; two fullerenyl sp3 carbons and 28
fullerenyl sp2 carbons (Figure 4). No half-intensity peaks
were observed, since the axis of symmetry in 39 bisects
two sets of bonds (at the point of entry and exit on each
side of the fullerene sphere) in C2-symmetrical adducts,
rather than a symmetry plane passing through two sets
of bonds as in 35. To aid the assignment of resonances
(41, 42) 56; (39, 44) 68; (25, 54) 56
(12, 34) 71; (28, 36) 57; (10, 52) 54
(40, 43) 56; (23, 56) 56
(22, 57) 56; (7/8, 59/60) 68; (20, 46) 57
(11, 35) 57; (27, 37) 55; (18, 29) 67
(11, 35) 54; (26, 53) 57; (9, 51) 72
(4, 31) 57; (18, 29) 55; (13, 16) 67
(17, 30) 57; (5, 48) 54; (3, 32) 71
(4, 31) 54; (19, 47) 57; (6, 49) 72
(9, 51) 44; (6, 49) 44; (30) N/A
(12, 34) 40; (3, 32) 42; (1, 50) N/A
5, 48
1, 50
2, 33
close together, a series of 13C-13C TOCSY experiments
2-5
were conducted, enabling the identification of
J
CC
81.6
couplings.43
*Denotes resonance having two correlations.
The three possible regioisomers that have a C2-axis of
symmetry are the cis-3, trans-3, and trans-2 isomers.
These regioisomers would be expected to show one, two,
and three bond separations, respectively, between a
fullerenyl sp3-hybridized carbon and its nearest carbon
exhibiting two correlations (i.e., the carbon bond at which
the axis of symmetry is bisected). The 2D INADEQUATE
experiments revealed a two-bond connectivity between
C2 (sp3 carbon) and C14 (a peak exhibiting two correla-
tions). Starting from C2 (sp3 carbon), correlations were
observed to resonances corresponding to C3 and C12 with
1J CC of 42 and 40 Hz, respectively, typical for couplings
between sp3 and sp2 ring fusion carbons. Carbon-3
types of bond lengths, consistent with the observed bond
length types of analogous fullerene derivatives derived
1
from both X-ray crystallographic analysis and J CC
1
values.42,44,51 The smallest observed J CC value (44 Hz)
corresponded to the sp3-sp2 bond located at the site of
substitution.
Information concerning the bond lengths in compounds
35 and 39 was obtained by correlating geometry-
1
optimized (PM3)52 bond lengths to measured J CC values
(Figure 5). These measured values and calculated bond
lengths were consistent with the [5]radialene substruc-
ture of the [60]fullerene cage in both 35 and 39 (Figure
6). In fact, a good correlation was obtained between the
1
exhibited correlations to C4, with a large J CC (71 Hz)
consistent with a 6,6-fusion, and to C14, a carbon with
1
1
only two correlations, with a smaller J CC (58 Hz),
measured J CC values and the calculated bond lengths
1
providing unequivocal evidence for the trans-3 regio-
chemistry of 39 (Figure 4). The other two-correlation
resonance (at the point of exit of symmetry axis) was
identified as C39 (C40). These resonances showed a five-
bond connectivity to the sp3 carbon C50. Complete
chemical shifts, peak assignments, and carbon-carbon
coupling constants for 39 are shown in Table 4.
(Figure 5). The C-C bonds with larger J CC values (67-
73 Hz) and calculated shorter bond lengths (1.37-1.39
Å) corresponded to 6,6 ring-fused bonds. Of these bond
types, those in close proximity to the site of functional-
ization were noticeably shorter still (see A-D in Figure
5a,b) for both structures. The second type of fullerenyl
1
sp2 C-C bonds displayed smaller J CC (53-58 Hz) and
calculated larger bond lengths (1.42-1.48 Å) corre-
sponded to 5,6 ring-fused bonds. Of these 5,6 ring-fused
Top ology of Bis-m eth a n o[60]fu ller en e Der iva -
tives 35 a n d 49
(50) Thilgen, C.; Herrmann, A.; Diederich, F. Helv. Chim. Acta 1997,
80, 183-199.
Using 2D INADEQUATE experiments, all fullerenyl
carbons in 35 and 39 were unambiguously assigned
(Tables 3 and 4). Both compounds displayed three
(51) Paulus, E. F.; Bingel, C. Acta Crystallogr., Sect. C: Cryst. Struct.
Commun. 1995, C51, 143-146.
(52) Spartan Semiempirical (PM3) program: SGI/V5.1.1
8324 J . Org. Chem., Vol. 67, No. 24, 2002

Mono- and Bis-methano[60]fullerenyl Amino Acid Derivatives
The second type of C-C bonds were those associated
with 5,6 ring fused carbons. A number of these carbons
in 35 exhibited a bond shortening, depicted by a corre-
1
sponding increase in J CC (59 Hz versus the average of
55 Hz; for C3-C14 shown in green in Figure 6a), however
no shortening was observed in these corresponding bonds
for 39. Other 5,6 ring fused bonds showed a lengthening,
1
characterized by smaller J CC values (53 Hz versus the
average 55 Hz) and calculated longer C-C bond lengths
(1.47 Å). The fullerenyl cage of 35 exhibits comparatively
more distortion when compared to 39, most likely as a
consequence of the closer proximity of the functionalized
sites in 35 and the removal of the effects of the tether in
39. This is indicative of the changed topology of the [60]-
fullerene surface with an alternating lengthening and
shortening of the bonds proximal to each cyclopropyl unit
to compensate for the induced distortion arising from the
longer sp3 bonds. This effect is clearly most prominent
in the region between the two sets of fullerenyl sp3
carbons. The shortening of bonds local to sites of substi-
tution has been noted before from X-ray analysis of 1,2-
difunctionalized [60]fullerenes as well as in earlier
studies of mono-methano[60]fullerenyl adducts due to
geometrical distortion of the [60]fullerene cage to a
teardrop-like structure with elongation along an axis
through the poles.5 This effect is manifested in the
calculated structure of 35 with elongation occurring along
two axes, each bisecting a cyclopropyl ring. This results
in an increased concavity of the [60]fullerene cage topol-
ogy in the region between the two substituents.
F IGURE 5. Plot of calculated (PM3) carbon-carbon bond
1
lengths (Å) versus J CC (Hz) showing three groupings of carbon
In summary, the regiochemistry of bisadducts 35 and
39 were unequivocally assigned as trans-4 and trans-3,
respectively, using 2D INADEQUATE experiments. Com-
pound 39 was synthesized via transesterification of 37
thus the regiochemistry of 37 is also trans-3. The tethered
bisadduct 38 was also assigned as trans-4 as a result of
the transesterification of 35 and 39 affording the same
product 40 (Scheme 9). Although 36 was not assigned
unequivocally by 13C-13C connectivity experiments, it is
most likely to have the cis-3 structure based on its C2
symmetry and the relative energy of its calculated
structure.
bonds: 6,6 ring fusion, 5,6 ring fusions, and sp2-sp3 carbon
bonds for (a) 35 and (b) 39.
bonds, longer than normal bond lengths were identified
for 35 (see F and G in Figure 5a and Figure 6a) and 39
(see E for Figures 5b and 6b) close to the site of
functionalization. Uniquely, compound 35 displays a
significantly shorter 5,6 ring fusion bond (bond E, Figure
5a) close to the site of functionalization. This shortened
5,6 bond-length was not observed in compound 39, most
likely due to the more remote functionalization pattern
(trans-3) of 39 compared to compound 35 (trans-4).
F IGURE 6. Semiempirical (PM3) structures of (a) 35 and (b) 39 showing shorter 6,6 bonds (in red), longer 5,6 bond (in green),
and shorter 5,6 bonds (in blue). The tethering group has been removed for clarity.
J . Org. Chem, Vol. 67, No. 24, 2002 8325

Burley et al.
SCHEME 10a
SCHEME 11
SCHEME 12a
a
Reagents: (i) N-tert-butoxycarbonylglycine (2 equiv), DMAP
(0.1 equiv), DCC (2.2 equiv); (ii) TFA; (iii) Ph2CdNH (2 equiv),
CH2Cl2/MeCN; (iv) C60 (1 equiv), DBU (4.5 equiv), CBr4 (2 equiv),
C6H5Cl.
Non sym m etr ica l Teth er ed [60]F u ller en e Bis-
a d d ition
As an extension of these studies, we examined the use
of a novel naphthyl tether in an effort to break the
symmetry of the resultant [60]fullerene bisadducts. This
was expected to make the resulting ring-opened products
more readily characterized. The nonsymmetrical bis-N-
(diphenylmethylene)glycinate tether 44 was synthesized
according to the procedure illustrated in Scheme 10.
The double-Bingel cyclopropanation reaction of 44 with
[60]fullerene was attempted using conditions described
above for the synthesis of 35-39. Purification of the crude
reaction products required elution through two silica gel
columns with DCM/petroleum spirit (90:10) to afford the
two regioisomers 45 and 46 in yields of 9 and 5%,
respectively.
a
Reagents: (i) (1) BF3‚(OEt2), 0 °C, (2) NaCNBH3, CH2Cl2/
MeCN.
and 46 (Scheme 11), respectively, displayed identical
spectra to the transesters of 35 and 36, indicative of 45
and 46 possessing identical regiochemistry to 35 (trans-
4) and 39 (cis-3), respectively.
Rin g-Op en in g
Teth er ed Bis-m eth a n o[60]fu ller en es
Retr o-Bin gel
Rea ction s
of
The double-reductive ring opening of the tethered
bisadducts 35-37, in direct analogy to the monoadduct
7 (Scheme 5), was anticipated to produce the correspond-
ing double ring-opened product A (Scheme 12). Treat-
ment of 35-37 under the typical reductive conditions
yielded the unexpected monoadducts 48 and 49 and [60]-
fullerene. These compounds arise formally from a tandem
reductive ring-opening retro-Bingel reaction and a double-
retro-Bingel reaction, respectively. Similar reductive
retro-Bingel reactions of both malonate-derived mono-
and bis-methano[60]fullerenes have been observed both
chemically53 and electrochemically.54-60 However, the
conditions reported here are milder compared to these
reports and should therefore be more applicable to
complex systems containing multiple functionalities. The
product yields are summarized in Table 5.
The MALDI-TOF spectrum of both 45 and 46 displayed
a molecular ion at m/z 1346 and fullerenyl anion at m/z
720. The 1H NMR spectrum of 45 and 46 showed
resonances for the four pairs of diastereotopic benzyl
protons (δ 6.43, 6.04, 5.24, 5.05, J ca. 11 Hz for 45; δ
6.16, 5.87, 5.40, 5.23, J ca. 15 Hz for 46). The aromatic
region revealed a complex region of naphthyl tethered
and diphenylimine proton resonances between δ 7.0-8.4.
The 13C NMR spectra of both 45 and 46 comprised 56
sp2 fullerene resonances corresponding to the nonsym-
metrical nature of the [60]fullerene core as a consequence
of a lack of symmetry. In addition to the fullerenyl 56
sp2 resonances observed for both nonsymmetrical bisad-
ducts, four fullerenyl sp3 resonances (δ 81.9, 81.7, 81.5,
81.3 for 45; δ 82.4, 81.9, 81.89, 81.88 for 46) and two
cyclopropane bridgehead carbons (δ 97.1, 96.7 for 45; δ
96.6, 95.9 for 46) were observed.
Compounds 50 and 51 were not isolated due to the
small scale of these reactions however, based on the
recovery of [60]fullerene and the isolation of 16 in the
reductive ring-opening of 14, the formation of 50 and 51
1
The UV-vis, H NMR, and 13C NMR spectra of the
corresponding trans esters, 40 and 47, of 45 (Scheme 9)
8326 J . Org. Chem., Vol. 67, No. 24, 2002

Mono- and Bis-methano[60]fullerenyl Amino Acid Derivatives
TABLE 5. Yield s of th e Dou ble-Rin g-Op en in g P r od u cts
δ 5.89, 5.72, 5.63*, and 5.35*, each with a coupling of
about 12 Hz. The three proton spin coupled spectrum
corresponded to the reduced addend protons HR (δ 4.95
m), Hâ/â′ (δ 5.23, m, 2Η), and NH/NH′ (δ 3.64, bs, 2H).
The reduced, cleaved addend portion consisted of singlet
resonances at δ 5.44 (Hꢀ), δ 4.82*, 4.78 (Hγ), and δ 3.38,
3.34* (Hφ).
48/49 fr om th e Rin g-Closed Teth er ed Bisa d d u cts 35-37
product yields (%)
starting material reductive ring-opened product [60]fullerene
35
36
37
48 (42)
49 (44)
50 (31)
(12)
(14)
(12)
P r op osed Mech a n ism of Red u ctive Rin g-Op en in g
Rea ction s
was assumed. The monofunctionalized structure of 48
and 49 was evident from the UV-vis spectra of these
compounds. Both compounds 48 and 49 displayed absor-
bances at 430, 640, and 705 nm. The absorbance at 430
nm was also found in the UV-vis spectra of the 1,2-
dihydrofullerenes 11-13 as well as other related deriva-
In principle, the product 48 could arise from the anionic
intermediates B or C. The driving force for mono-
elimination of the tether from either structure might be
the relief of ring strain upon expulsion of one arm of the
tether. In the case of B, a further driving force may be
the conversion of a fullerenyl dianion intermediate to a
thermodynamic more stable fullerenyl monoanionic sys-
tem. Clearly, the rate of monoelimination of the addend
is much faster than the rate of elimination of the entire
addend as indicated by the relative isolated yields of 48
versus [60]fullerene (Table 5).
1
tives reported elsewhere.61 The H NMR spectrum of 48
revealed a one proton singlet at δ 6.84 that corresponded
to a single fullerene proton (Hø). The addend region of
48 revealed two doublets at δ 5.41 and 5.24 (J ) 11.9
Hz) corresponding to the diastereotopic benzyl protons
(Hδ/Hδ′). The other benzylic protons (Hꢀ) resonated as a
two proton singlet at δ 5.07, whereas the two proton
singlet at δ 3.37 was identified as corresponding to the
methylene protons (Hφ). A singlet one proton resonance
at δ 4.84 corresponded to the benzhydryl resonance (Hγ).
A three proton coupled spin system was identified as HR
(δ 4.98, d, J ) 12.3 Hz), Hâ (δ 5.28, d, J ) 2.7 Hz) and
NH (δ 3.66, dd, J ) 12.3, 2.6 Hz). The 13C NMR spectrum
of the fullerenyl sp2 region of 48, like that of 11, revealed
a structure lacking a plane of symmetry due to the newly
formed stereogenic carbon at C61 (60R). A single set of
fullerenyl sp3 resonances at Cø (δ 58.9), and C1 (δ 67.3)
were observed in addition to resonances corresponding
to the addend CR (δ 70.4), Câ (δ 66.4) Cδ (δ 67.7), Cꢀ (δ
66.1), Cφ (δ 49.1), and Cγ (δ 66.6). These carbons were
readily assigned from HSQC and HMBC experiments.
Similarly, double reductive ring-opening reaction of
compounds 45 and 46 afforded 52 and 53 in a combined
yield of 42% and free [60]fullerene (12%) (Scheme 13).
Although 52 and 53 could not be separated by HPLC,
1H NMR analysis revealed a 60:40 ratio of compounds,
although the major and minor compounds could not be
unequivocally ascertained, even after 2D NMR analysis
using NOESY and HMBC experiments. The 60:40 ratio
was observed in both 1H NMR and 13C NMR spectra
between cognate resonances (resonances for the major
isomer are indicated below with a *). Two fullerenyl
proton resonances were situated at δ 6.83* and 6.78. The
diastereotopic benzyl doublets (Hδ/δ′) were identified at
To examine the influence of the tether on this ring
opening-retro-Bingel reaction, the diethyl ester 40 was
subjected to similar reduction conditions to those de-
scribed for 35-37. This reaction yielded the ring-opened-
retro-Bingel product 12 in 51% yield and a small amount
of [60]fullerene (10%) (Scheme 14). In comparison, the
mono-ester 12 was also prepared in 58% yield from
reductive ring opening of the methano[60]fullerene 8
(Scheme 14).
Con clu sion s
In conclusion, we have demonstrated the synthetic
versatility of the Bingel cyclopropanation reaction beyond
malonate additions to [60]fullerene, providing a range of
novel protected methano[60]fullerenyl amino acids de-
rivatives. Using tethered bisimino esters, the regiochem-
istry of the [60]fullerenyl bisadducts provided unique and
unexpected regiochemistry when compared to their teth-
ered bismalonate counterparts. This study clearly dem-
onstrates that much has yet to be understood about
tethered fullerene reactions before generalizations on
regiochemical outcomes can be made. These differences
in regiochemistry may indicate that these reactions
proceed via different mechanisms and experiments are
in progress to understand these differences.
(53) Moonen, N. N. P.; Thilgen, C.; Diederich, F.; Echegoyen, L.
Chem. Commun. 2000, 335-336.
(54) Echegoyen, L.; Diederich, F.; Echegoyen, L. E. Fullerenes: Chem.
Phys. Technol. 2000, 1-51.
(55) Fender, N. S.; Nuber, B.; Schuster, D. I.; Wilson, S. R.;
Echegoyen, L. J . Chem. Soc., Perkin Trans. 2 2000, 1924-1928.
(56) Kessinger, R.; Fender, N. S.; Echegoyen, L. E.; Thilgen, C.;
Echegoyen, L.; Diedrich, F. Chem.sEur. J . 2000, 6, 2184-2192.
(57) Echegoyen, L. E.; Djojo, F. D.; Hirsch, A.; Echegoyen, L. J . Org.
Chem. 2000, 65, 4994-5000.
(58) Nuretdinov, I. A.; Yanilkin, V. V.; Gubskaya, V. P.; Maksimyuk,
N. I.; Berezhnaya, L. S. Russ. Chem. Bull. 2000, 49, 427-430.
(59) Beulen, M. W. J .; Echegoyen, L.; Rivera, J . A.; Herranz, M. A.;
Martin-Domenech, A.; Martin, N. Chem. Commun. 2000, 917-918.
(60) Kessinger, R.; Crassous, J .; Hermann, A.; Ruuttimann, M.;
Echegoyen, L.; Diederich, F. Angew. Chem., Int. Ed. 1998, 37, 1919-
1922.
Additionally, a novel ring-opening reaction and a
tandem reductive ring-opening retro-Bingel reaction were
discovered, yielding a new class of 1,2-dihydro[60]-
fullerenylglycine derivatives. Although deprotection of
(61) Okamura, H.; Murata, Y.; Minoda, M.; Komatsu, K.; Miyamoto,
T.; Wan, T. S. M. J . Org. Chem. 1996, 61, 8500-8502.
J . Org. Chem, Vol. 67, No. 24, 2002 8327

Burley et al.
All reactions were performed in standard glassware under an
inert atmosphere of nitrogen. Evaporation and concentration
in vacuo were done at water-aspirator pressure, and com-
pounds were dried at 10-2 Torr. Flash column chromatography
was performed using silica 60 (230-400 mesh, 0.040-0.063
mm). Petroleum spirit refers to a hydrocarbon fraction with a
boiling point of 40-60 °C.
SCHEME 13
UV-vis spectra were recorded on a Shimadzu UV-1601 (λmax
in nm (ꢀ)). Mass spectral data were recorded on a Shimadzu
QP-5000 for MS(CI) data. MS(ES) were recorded on a VG
Quattro-triple quadrapole via a direct insertion technique and
an electron beam energy of 70 eV and a source temperature
of 200 °C. High-resolution mass spectra (CI) were obtained
using a QTOF mass spectrometer. MALDI-TOF spectra were
recorded on a Bruker BIFLEX mass spectrometer in the
negative ion mode using 9-nitroanthracene as matrix. 1H NMR
spectra were acquired on a Varian Unity 300 or 400 spectrom-
eter at 300.1 and 399.9 MHz, respectively, or a Bruker DMX-
600 spectrometer at 600.2 MHz. 13C NMR spectra were
acquired on Varian Unity 300 or 400 spectrometer at 75.4 and
100.0 MHz, respectively, or a Bruker DMX-600 spectrometer
at 150.9 MHz. Deuterated solvents CDCl3, D2O, C6D6 were
obtained commercially and were greater than 99.5 atom % d.
All chemical shifts are reported relative to TMS (δ 0.00). The
2D INADEQUATE experiments for 10% 13C-enriched samples
of 35 and 39 were performed on a Bruker DMX 600 spectrom-
eter fitted with a Bruker TXI-XYZ 1H/13C/15N probe. The
samples (ca. 16 mg for each compound) were dissolved in CS2/
CDCl3 (6:4) (ca. 250 µL) in a Shigemi tube, and the spectra
were recorded at 288 K. A standard pure phase (States-TPPI)
double quantum spectrum with power-gated proton decoupling
was employed. A spectral width of 13020.8 Hz was used in
both dimensions resulting in deliberate folding in F1, which
will not cause any ambiguity of peak assignments. 2048 × 8192
Total points were collected in t1 and t2, respectively. A recycle
delay of 9 s and 16 scans per increment were employed.
Computer modeling was performed on a Silicon Graphics O2
Workstation using the Spartan Semiempirical (AM1 and PM3)
program: SGI/V5.1.1. Geometry optimization model: RHF/
AM1 and RHF/PM3 were used for semiempirical calculations.
the [60]fullerenylglycine derivatives has so far been
unsuccessful, methods for the selective deprotection of
these compounds is currently under investigation. Fur-
thermore, we have demonstrated the importance of 2D
INADEQUATE NMR experiments for the unequivocal
assignment of the regiochemistry of [60]fullerenyl bisad-
ducts which are more superior than the more widely used
comparative techniques (UV-visible). These experiments
also provided useful topological information of the [60]-
fullerenyl sphere upon functionalization. Such techniques
will be invaluable in future studies of multifunctionalized
[60]fullerenes.
Bin gel Rea ction s. ter t-Bu tyl 61-Dip h en ylm eth ylid e-
n eam in o-1,2-m eth an o[60]fu ller en e-61-car boxylate (7). 1,8-
Diazabicyclo[5.4.0]undec-7-ene (DBU) (0.18 mL, 1.2 mmol) was
added at rt to a solution containing [60]fullerene (0.22 g, 0.31
mmol), carbon tetrabromide (0.13 g, 0.397 mmol), and 3 (0.11
g, 0.40 mmol) in toluene (250 mL). The solution was stirred
for 2 h. The crude material was filtered through a short plug
of silica gel (5 cm), eluting first with toluene (to retrieve
unreacted [60]fullerene) and then with DCM. Column chro-
matography eluting with (90:10 DCM/petroleum spirit) and
recrystallization from DCM/diethyl ether provided 7 as a
brown amorphous solid (0.14 g, 46%). UV-vis (DCM): 430
(18 000), 610 (1800), 690 (800) nm. 1H NMR (CDCl3, 300
MHz): δ 1.60 (s, 9H), 7.31 (t, 2H J ) 7.5 Hz), 7.42 (t, 4H, J )
7.5 Hz), 8.05 (d, 4H, J ) 7.8 Hz). 13C NMR (CDCl3, 75 MHz):
δ 162.4, 153.7, 149.3, 147.8, 146.6, 146.2 (2 × C), 146.1, 145.7,
145.5, 145.4, 145.1, 144.5, 143.3, 143.06, 142.7, 142.6, 142.2
(2 × C), 142.1, 141.7 (2 × C), 140.0, 139.5, 136.8, 135.0, 130.0,
Exp er im en ta l Section
Toluene and THF were distilled from sodium benzophenone
ketyl. Dichloromethane (DCM) was distilled from phosphorus
pentoxide. Acetonitrile (MeCN) was distilled from potassium
carbonate. [60]Fullerene and 10% 13C-enriched [60]fullerene
were purchased from MER Corp., Tucson, AZ 85706. Com-
pounds 3 and 4 were purchased from a commercial supplier.
SCHEME 14
8328 J . Org. Chem., Vol. 67, No. 24, 2002

Mono- and Bis-methano[60]fullerenyl Amino Acid Derivatives
128.6, 96.0, 84.3, 82.6, 30.3. MS (ES) (+ve ion mode): m/z 1013
washed with saturated ammonium chloride solution (10 mL),
followed by saturated sodium bicarbonate solution (10 mL).
The organic layer was dried (MgSO4) and concentrated in
vacuo. Column chromatography, eluting with toluene/hexane
(1:1), provided 11 as a brown amorphous solid (0.008 g, 39%).
UV-vis (DCM) 410 (sh, 5000), 440 (3000) nm. 1H NMR (C6D6/
CS2 60:40, 400 MHz): δ 1.52 (s, 9H), 3.61 (dd, 1H, J ) 15.6,
4.4 Hz), 4.83 (d, 1H, J ) 15.6 Hz), 5.27 (d, 1H, J ) 4.4 Hz),
6.84 (s, 1H), 7.20 (m, 2H), 7.28 (t, 2H, J ) 10.4 Hz), 7.33 (t,
2H, J ) 10.4 Hz), 7.56 (d, 2H, J ) 10.4 Hz), 7.66 (d, 2H, J )
10.4 Hz). 13C NMR (C6D6, CS2 (60:40), 75 MHz): δ 171.0, 154.4,
153.7, 153.1, 152.4, 147.7, 147.5, 147.4, 146.9, 146.7, 146.64,
146.6, 146.5, 146.4, 146.1, 146.0, 145.9, 146.82, 146.8, 145.7,
146.6, 145.0, 144.8, 144.7, 143.7, 143.5, 142.9, 142.7, 142.6,
142.4, 142.0, 141.9, 141.8, 141.76, 140.7, 139.8, 139.6, 137.3,
136.9, 136.64, 136.6, 129.2, 129.1, 128.6, 127.9, 127.7, 82.8,
76.9, 68.2, 66.7, 58.8, 28.4. MS (ES) (+ve ion mode): m/z 1017
(M+), 720 (C60).
(M+), 720 (C60).
en d o,en d o-(m -P h en ylen ed im eth yl)-61,62-bis-(N-d ip h e-
n y lm e t h y lid e n e a m in o )-1,2:34,35-b is (m e t h a n o )[60]-
fu ller en e-61,62-d ica r boxyla te (35) a n d en d o,en d o-(m -
P h e n y le n e d im e t h y l)-61,62-b is -(N -d ip h e n y lm e t h y l-
id en ea m in o)-1,2:16,17-bis(m eth a n o)[60]fu ller en e-61,62-
d ica r boxyla te (36). DBU (0.45 mL, 3.01 mmol) was added
at rt to a solution containing [60]fullerene (0.43 g, 0.60 mmol),
carbon tetrabromide (0.54 g, 1.42 mmol), and 33 (0.47 g, 0.81
mmol) in chlorobenzene (200 mL). The solution was stirred
for 2 h. The crude material was filtered through a short plug
of silica gel (5 cm), eluting first with toluene (to retrieve
unreacted [60]fullerene) and then with DCM. Column chro-
matography eluting with (90:10 DCM/petroleum spirit) and
recrystallization from DCM/diethyl ether provided 35 (0.25 g,
32%) and 36 (0.08 g, 10%) as brown amorphous solids. 35. UV-
vis (DCM): 320 (15 000), 630 (250), 690 (150) nm. 1H NMR
(CDCl3, 400 MHz): δ 5.06 (d, 2H, J ) 11.2 Hz), 5.71 (d, 2H, J
) 11.2 Hz), 7.07 (t, 1H, J ) 7.6 Hz), 7.14 (s, 1H), 7.30 (t, 2H,
J ) 7.6 Hz), 7.40 (t, 4H, J ) 7.2 Hz), 7.46 (t, 4H, J ) 7.2 Hz),
7.55 (t, 4H, J ) 7.2 Hz), 7.92 (d, 4H, J ) 8.4 Hz), 8.04 (d, 4H,
J ) 8.4 Hz). 13C NMR (CDCl3, 100 MHz): δ 68.0, 81.5, 81.8,
97.1, 127.9, 128.0, 128.3, 129.4, 129.6, 136.4, 137.7, 138.9,
139.6, 140.6, 140.9, 141.27, 141.3, 141.4, 141.5, 142.1, 142.5
(ipso), 143.6, 143.9, 145.6, 145.68, 145.8, 145.8, 145.9, 146.0,
146.7, 146.8, 146.82, 147.4, 148.6, 149.0, 149.9, 150.9, 160.7,
161.3. MALDI-TOF (-ve ion mode, 9-nitroanthracene): m/z
1296 (M-), 720 (C60-). 36. UV-vis (DCM): 320 (19 000), 430
E t h yl
1,2-Dih yd r o-r-d ip h e n ylm e t h yla m in o[60]-
fu ller en yl Aceta te (12). Boron trifluoride‚diethyl etherate
(0.072 g, 508 µmol) was added dropwise over 1 min to a
solution of 8 (0.050 g, 51 µmol) in DCM (50 mL) at 0 °C under
a nitrogen atmosphere. The reaction mixture was allowed to
warm to rt over a 30 min period when MeCN (25 mL) was
added. Sodium cyanoborohydride (0.005 g, 80 µmol) was added
to the reaction mixture, which was stirred for 90 min and then
concentrated in vacuo. The reaction mixture was redissolved
in chloroform (100 mL) and washed with saturated ammonium
chloride solution (10 mL), followed by saturated sodium
bicarbonate solution (10 mL). The organic layer was dried
(MgSO4) and concentrated in vacuo. Column chromatography
using flash silica gel and eluting with toluene/hexane (1:1)
provided 12 (0.029 g, 58%) as a brown amorphous solid. UV-
vis (DCM): 410 (sh, 5000), 440 (3000) nm. 1H NMR (C6D6/CS2
60:40, 400 MHz): δ 1.19 (t, 3H, J ) 7.2 Hz), 3.59 (bs, 1H),
4.23 (q, 2H, J ) 7.2 Hz), 4.94 (s, 1H), 5.26 (s, 1H), 6.84 (s,
1H), 7.20 (m, 2H), 7.28 (t, 2H, J ) 10.4 Hz), 7.33 (t, 2H, J )
10.4 Hz), 7.56 (d, 2H, J ) 10.4 Hz), 7.66 (d, 2H, J ) 10.4 Hz).
13C NMR (C6D6, CS2 (60:40), 75 MHz): δ 171.8, 154.4, 153.5,
152.9, 152.0, 147.8, 147.4, 147.39, 147.38, 146.73, 146.71,
146.7, 146.5, 146.0, 145.97, 145.95, 145.72, 145.7, 145.0, 144.7,
143.6, 143.5, 143.49, 143.3, 143.0, 142.7, 142.6, 142.4, 142.0,
141.99, 141.9, 140.9, 140.8, 140.0, 139.7, 137.5, 136.8, 136.7,
136.5, 129.3, 129.2, 128.6, 128.0, 70.8, 68.1, 66.8. 61.8, 58.1,
14.9. MALDI-MS: (-ve ion mode, 9-nitroanthracene): m/z 720
(C60).
1
(sh, 1700), 450 (sh, 1400), 640 (280), 695 (190) nm. H NMR
(CDCl3, 400 MHz): δ 5.31 (d, 2H, J ) 11.2 Hz), 5.41 (d, 2H, J
) 11.2 Hz), 6.95 (s, 1H), 7.18 (m, 3H), 7.23 (t, 4H, J ) 7.6 Hz),
7.37 (dd, 4H, J ) 7.2 Hz, 1.6 Hz), 7.50 (dd, 4H, J ) 7.6 Hz, 1.2
Hz), 7.62 (t, 4H, J ) 8.4 Hz), 8.17 (d, 4H, J ) 7.6 Hz), 8.21 (d,
4H, J ) 7.6 Hz). 13C NMR (CDCl3, 100 MHz): δ 68.5, 81.8,
82.4, 96.0, 128.3, 128.6, 129.6, 129.9, 131.4, 134.6, 134.8, 138.5,
139.2, 140.7, 141.0, 141.2, 141.8, 143.4, 143.5, 143.9, 144.1,
144.11, 144.3, 144.4, 144.7, 144.9, 145.0, 145.9, 147.3, 147.4,
147.5, 147.8, 148.6, 148.9, 149.0, 149.2, 150.9, 153.4,
154.4, 161.0, 161.1. MALDI-TOF (-ve ion mode, 9-nitroan-
thracene): m/z 1296 (M-), 720 (C60-).
Tr a n sester ifica tion s. Dieth yl en d o,en d o-61,62-Bis(N-
d ip h en ylm eth ylid en ea m in o)-1,2:33,50-bis(m eth a n o)[60]-
fu ller en e-61,62-d ica r boxyla te (39). Solid potassium car-
bonate (0.010 g, 0.71 mmol) was added to a solution of 37 (0.04
g, 0.003 mmol) in THF/EtOH (2:1) (100 mL), and the mixture
was stirred at rt for 1.5 h. The mixture was then filtered, and
the solvent was removed in vacuo. Column chromatography
(flash silica gel, DCM/petroleum spirit 90:10) followed by
recrystallization (chloroform/diethyl ether) yielded 39 (0.012
g, 32%) as a brown amorphous solid. UV-vis (DCM): 330
3′-[(Dip h en ylm eth yl(a m in o)a cetoxym eth yl]n a p h th yl-
1,2-d ih y d r o -r-d ip h e n y lm e t h y la m in o [60]fu lle r e n y l
Aceta te (52) a n d 1′-[(Dip h en ylm eth yl(a m in o)a cetoxy-
m et h yl]n a p h t h yl-1,2-d ih yd r o-r-d ip h en ylm et h yla m in o-
[60]-fu ller en yl Aceta te (53). The title compound was pre-
pared from boron trifluoride‚diethyl etherate (0.095 g, 668
µmol), (45/46) (0.090 g, 67 µmol), and sodium cyanoborohydride
(0.04 g, 0.67 mmol) using a procedure analogous to that
described above for the synthesis of 12 to yield [60]fullerene
(0.006 g, 12%) and (52/53) (0.042 g, 42%). UV-vis (DCM): 330
(sh, 15 000), 435 (3000) nm. 1H NMR (C6D6/CS2 60:40, 400
MHz) (where possible the resonances of the major isomer are
shown with a *, integration values are relative values for each
isomer): δ 3.34* (s, 2H), 3.38 (s, 2H), 3.64 (bs, 2H), 4.78 (s,
2H), 4.82* (s, 2H), 4.95 (bd, 2H, J ) 8.1 Hz), 5.23 (m, 2H),
5.35* (d, 1H, J ) 11.6 Hz), 5.44 (s, 2H), 5.63* (d, H, J ) 11.6
Hz), 5.72 (d, J ) 12.4 Hz), 5.89 (d, 1H, J ) 12 Hz), 6.78 (s,
1H), 6.83* (s, 1H), 7.16 (m, 14H), 7.38 (m, 55H), 7.70 (m, 30H).
13C NMR (C6D6, CS2 (60:40), 75 MHz): δ 172.3, 172.2, 172.1,
153.81, 153.8, 152.78, 152.7, 151.8, 151.7, 150.84, 150.8, 147.4,
147.1, 146.93, 146.91, 146.9, 146.73, 146.7, 146.3, 146.28,
146.11, 146.1, 146.0, 145.6, 145.59, 145.5, 145.48, 145.4,
145.37, 145.3, 145.21, 145.2, 145.18, 145.1, 145.0, 144.6, 144.5,
144.3, 144.26, 144.2, 143.4, 143.0, 142.98, 142.9, 142.5, 142.4,
142.39, 142.3, 142.2, 142.1, 142.02, 142.01, 142.0, 141.9, 141.8,
141.6, 141.5, 141.3, 141.2, 141.17, 141.13, 141.11, 141.1, 140.3,
1
(15 000), 430 (sh, 180), 620 (210), 690 (80) nm. H NMR (300
MHz, CDCl3): δ 1.42 (t, 6H, J ) 6.9 Hz), 4.49 (q, 4H, J ) 6.9
Hz), 7.37 (t, 4H, J ) 7.5 Hz), 7.49 (m, 4H, J ) 7.5 Hz), 7.64 (t,
4H, J ) 7.5 Hz), 8.09 (d, 4H, J ) 7.5 Hz), 8.25 (d, 4H, J ) 7.5
Hz). 13C NMR (75 MHz, CDCl3): δ 162.2, 160.5, 154.3, 153.6,
151.5, 148.8, 148.7, 148.67, 148.6, 147.98, 147.95, 147.9, 147.4,
145.7, 145.2, 145.1, 145.0, 144.5, 144.1, 144.0, 143.9, 143.5,
142.3, 141.9, 141.5, 141.1, 140.9, 140.5, 139.2, 138.5, 136.4,
135.1, 130.0, 129.8, 128.5, 128.34, 128.3, 95.9, 82.3, 81.9, 63.0,
14.2. MALDI-TOF (-ve ion mode, 9-nitroanthracene): m/z
1250 (M-), 720 (C60-).
Red u ctive Rin g-Op en in g Rea ction s. ter t-Bu tyl 1,2-
Dih yd r o-r-d ip h en ylm eth yla m in o[60]fu ller en yl Aceta te
(11). Sodium cyanoborohydride (0.005 g, 80 µmol) was added
at rt over a 5 min period to an acidified solution (adjusted to
pH 4 with glacial acetic acid) of 7 (0.02 g, 20 µmol) in THF (20
mL)/MeOH (5 mL). The pH of the brown solution was
maintained at pH 4 by the further addition of glacial acetic
acid. Upon no further change in pH, the reaction mixture was
stirred for a further 2 h and concentrated in vacuo. The
reaction mixture was redissolved in chloroform (20 mL) and
J . Org. Chem, Vol. 67, No. 24, 2002 8329

Burley et al.
140.2, 140.18, 140.1, 139.3, 139.2, 139.0, 138.7, 137.2, 137.1,
136.4, 136.2, 136.19, 136.1, 136.0, 135.9, 133.7, 133.4, 132.4,
132.3, 131.9, 131.87, 131.6, 131.4, 130.5, 130.0, 129.0, 128.8,
128.5, 128.48, 128.3, 128.2, 128.1, 128.0, 127.9, 127.6, 127.3,
127.25, 127.2, 126.6, 123.5, 123.4, 70.2, 67.7, 67.6, 67.4, 66.5,
66.51, 66.3, 66.2, 65.3, 64.4, 58.8, 58.6, 49.0, 48.9. MALDI-
MS: (-ve ion mode, 9-nitroanthracene): m/z 720 (C60).
g, 51%) as a brown amorphous solid. Spectral data were
identical to the synthesis of 12 from 8 as described above.
Ack n ow led gm en t. We thank the Australian Re-
search Council for financial support and for a Ph.D.
scholarship to G.A.B.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for the synthesis of compounds 6, 8-10, 13, 27-34,
40, and 42-49. 1H and/or 13C NMR data of [60]fullerene
derivatives 7, 8, 11, 13, 35-37, 45-46, 48, and 52/53. UV-
vis spectra of 35-39 and 48. INADEQUATE spectra of 35 and
39. This material is available free of charge via the Internet
at http://pubs.acs.org.
E t h yl
1,2-Dih yd r o-r-d ip h e n ylm e t h yla m in o[60]-
fu ller en yl Aceta te (12) fr om Dieth yl en d o,en d o-61,62-Bis-
(N-d ip h en ylm eth ylid en ea m in o)-1,2:34,35-bis(m eth a n o)-
[60]fu ller en e-61,62-d ica r boxyla te (40). The title compound
was prepared from boron trifluoride‚diethyl etherate (0.111
g, 779 µmol), 40 (0.082 g, 66 µmol), and sodium cyanoborohy-
dride (0.049 g, 779 µmol) using a procedure analogous to that
described above for the synthesis of 12 from 8 yielded 12 (0.033
J O025928J
8330 J . Org. Chem., Vol. 67, No. 24, 2002