Additions of azomethine ylides to fullerene C60 assisted by a removable anchor

Article abstract of DOI:10.1021/jo000076d

The addition of nitrile oxides to [60]fullerene, leading to isoxazolinofullerenes, can be reversed using reducing agents such as Mo(CO)₆ or DIBALH. Thus, this reaction can be used; in principle, for protection/deprotection of [60]fullerene or f

Full text of DOI:10.1021/jo000076d

J . Org. Chem. 2000, 65, 4289-4297
4289
Ad d ition s of Azom eth in e Ylid es to F u ller en e C60 Assisted by a
Rem ova ble An ch or
Tatiana Da Ros and Maurizio Prato*
Dipartimento di Scienze Farmaceutiche, Universita` di Trieste, Piazzale Europa 1, 34127 Trieste, Italy
Vittorio Lucchini*
Dipartimento di Scienze Ambientali, Universita` di Venezia, Dorsoduro 2137, 30133 Venezia, Italy
prato@univ.trieste.it
Received J anuary 19, 2000
The addition of nitrile oxides to [60]fullerene, leading to isoxazolinofullerenes, can be reversed
using reducing agents such as Mo(CO)6 or DIBALH. Thus, this reaction can be used, in principle,
for protection/deprotection of [60]fullerene or for solubilization purposes. The tether-controlled
tandem addition of nitrile oxides and azomethine ylides provides mainly cis-1 patterns. The
determination of the structure of bisadducts was obtained by NMR spectroscopy with the help of
HMQC, HMBC, and NOEDS techniques. The isoxazoline moiety could be removed using Mo(CO)6
leaving a fulleropyrrolidine derivative.
The control of multiple additions to fullerene C60 is an
issue of current high interest.1,2 With its several reactive
double bonds, C60 can be considered an ideal framework
for the construction of complex architectures. In fact, this
concept has been successfully developed by the Hirsch
and Diederich groups and applied to the synthesis of very
complex molecules with perfect control of fullerene ster-
eochemistry. The approach of the German and Swiss
groups is different. Hirsch has investigated in deep detail
the stepwise multiple additions of bromomalonates to C60
providing an excellent statistical means and taking
advantage of the high propensity of malonate anions to
attack equatorial and trans-3 sites.3-9
Instead, the cycloaddition of azomethine ylides to C60,17
another widely used fullerene functionalization method-
ology, is much less selective. For instance, five bisadducts
in the reaction of sarcosine and formaldehyde are formed
in approximately the same amounts. Furthermore, when
bisadducts start to be formed, trisadducts also appear,
thus making the whole reaction mixture very complex
and the separation of pure isomers very difficult.18,19
To study the possibility of controlling the reactivity of
these dipoles, we have carried out a systematic study
based on the use of a reversible anchorage. First, an
anchor (A) is attached to C60, then the azomethine ylide
is generated, which attacks intramolecularly a second
double bond of the same fullerene spheroid. The length
of the arm between the anchor and the pyrrolidine ring
can be varied to check its influence on regioselectivity.
Eventually, the anchor is removed and a fulleropyrroli-
dine is obtained (Scheme 1).20
The Diederich strategy is based on the template-
directed multifunctionalization: by careful choice of the
length of the arm, exclusively equatorial or cis-2 addends
have been obtained. The base reaction used for these
studies is again a cyclopropanation reaction, which offers
the advantage of being remarkably selective.10-16
Resu lts a n d Discu ssion
The reaction used to provide a reversible anchorage
to C60 is the cycloaddition of nitriloxides. This reaction
has been extensively studied by the groups of Meier and
Irngartinger.21-25 Among other methods, these reactive
species are easily generated in situ by dehydrohaloge-
(1) Diederich, F.; Kessinger, R. Acc. Chem. Res. 1999, 32, 537.
(2) Hirsch, A. Top. Curr. Chem. 1999, 199, 1.
(3) Hirsch, A.; Lamparth, I.; Karfunkel, H. R. Angew. Chem., Int.
Ed. Engl. 1994, 33, 437.
(4) Hirsch, A.; Lamparth, I.; Gro¨sser, T.; Karfunkel, H. R. J . Am.
Chem. Soc. 1994, 116, 9385.
(5) Lamparth, I.; Maichle-Mo¨ssmer, C.; Hirsch, A. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 1607.
(6) Hirsch, A.; Lamparth, I.; Gro¨sser, T.; Prato, M.; Lucchini, V.;
Wudl, F. In The Chemical Physics of Fullerenes 10 (and 5) Years Later;
Andreoni, W., Ed.; Kluwer Academic Publishers: Dordrecht,1996; 267.
(7) Hirsch, A.; Lamparth, I.; Schick, G. Liebigs Ann. 1996, 1725.
(8) Lamparth, I.; Herzog, A.; Hirsch, A. Tetrahedron 1996, 52, 5065.
(9) Djojo, F.; Hirsch, A. Chem. Eur. J . 1998, 4, 344.
(10) Isaacs, L.; Haldimann, R. F.; Diederich, F. Angew. Chem., Int.
Ed. Engl. 1994, 33, 2339.
(11) Cardullo, F.; Isaacs, L.; Diederich, F.; Gisselbrecht, J .-P.;
Boudon, C.; Gross, M. J . Chem. Soc.; Chem. Commun. 1996, 797.
(12) Nierengarten, J .-F.; Gramlich, V.; Cardullo, F.; Diederich, F.
Angew. Chem., Int. Ed. Engl. 1996, 35, 2101.
(13) Haldimann, R. F.; Kla¨rner, F.-G.; Diederich, F. Chem. Commun.
1997, 237.
(14) Cardullo, F.; Seiler, P.; Isaacs, L.; Nierengarten, J.-F.; Haldimann,
R. F.; Diederich, F.; Mordasini-Denti, T.; Thiel, W.; Boudon, C.;
Gisselbrecht, J .-P.; Gross, M. Helv. Chim. Acta 1997, 80, 343.
(15) Isaacs, L.; Diederich, F.; Haldimann, R. F. Helv. Chim. Acta
1997, 80, 317.
(16) Bourgeois, J .-P.; Echegoyen, L.; Fibbioli, M.; Pretsch, E.;
Diederich, F. Angew. Chem., Int. Ed. Engl. 1998, 37, 2118.
(17) Maggini, M.; Scorrano, G.; Prato, M. J . Am. Chem. Soc. 1993,
115, 9798.
(18) Lu, Q.; Schuster, D. I.; Wilson, S. R. J . Org. Chem. 1996, 61,
4764.
(19) Pasimeni, L.; Hirsch, A.; Lamparth, I.; Herzog, A.; Maggini, M.;
Prato, M.; Corvaja, C.; Scorrano, G. J . Am. Chem. Soc. 1997, 119,
12896.
(20) For reversible additions to C60, see: (a) An, Y.-Z.; Ellis, G. A.;
Viado, A. L.; Rubin, Y. J . Org. Chem. 1995, 60, 6353. (b) Kessinger,
R.; Crassous, J .; Herrmann, A.; Ru¨ttiman, M.; Echegoyen, L.; Dieder-
ich, F. Angew. Chem., Int. Ed. Engl. 1998, 37, 1919. (c) Da Ros, T.;
Prato, M.; Novello, F.; Maggini, M.; De Amici, M.; De Micheli, C. Chem.
Commun. 1997, 59.
10.1021/jo000076d CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/10/2000

4290 J . Org. Chem., Vol. 65, No. 14, 2000
Da Ros et al.
Sch em e 1
Sch em e 3
Sch em e 2
nation of chloroximes, obtained by chlorination of oximes.
The cycloaddition step can be performed at room tem-
perature in toluene, using NaHCO3 as the base (Scheme
2). Isolated yields were typically in the 20-40% range,
with a wide variety of substitutions allowed. Fullerene-
fused isoxazolines (colloquially termed isoxazolinof-
ullerenes) are relatively thermally stable and revert back
to [60]fullerene only at very high temperatures (280-
400 °C).25
Compounds 1 are also stable to acids. Addition of 10
equiv of trifluoroacetic acid to a solution of 1b in
chlorobenzene at reflux gave only traces of [60]fullerene
after 10 days. Addition of N-phenylmaleimide as retro-
cycloaddition trapping agent did not produce any forma-
tion of the corresponding adduct, even in chlorobenzene
at reflux.
ate C60 and the corresponding nitrile oxide, which would
in turn be reduced to nitrile by excess Mo(CO)6.
C60 was also obtained in the treatment of 1 with
DIBALH (10 equiv) at room temperature in toluene. In
this case, the reaction of 1a , besides the quantitative
production of [60]fullerene, yielded aldehyde 3 and amine
4 in 31 and 64% isolated yield, respectively (eq 2). Both
compounds were identified by comparison with authentic
samples. Also in the case of DIBALH, retrocycloaddition
to the nitrile oxide, followed by reduction, would give
nitrile 2. This latter compound can be further reduced
by DIBALH to aldehyde 3. Amine 4 may form from
rearrangement of the nitrile oxide to the corresponding
isocyanate,27 which is then reduced to 4. All attempts to
trap the transient nitrile oxide under reductive conditions
using strong dipolarophiles (N-phenylmaleimide) failed.
However, when Mo(CO)6 was added to a refluxing
chlorobenzene solution of 1, C60 was recovered in virtually
quantitative yield. The same happened when adducts 1
were treated with excess DIBALH (diisobutylaluminum
hydride) in toluene at room temperature.
The reactions were followed by TLC, and at the end
C60 was isolated and characterized by 13C NMR. The
reaction of 1a with Mo(CO)6 or DIBALH was studied in
detail. In the reaction with Mo(CO)6, compound 2 was
isolated in 91% yield and identified with an authentic
sample along with C60 (eq 1).
Once the reversibility of the anchorage was estab-
lished, the stage was set for the controlled cycloaddition
of azomethine ylides. The first step was the alkylation
of amino alcohols by tert-butyl bromoacetate to give esters
5 (Scheme 3). Then, the amine function was protected:
at this stage, it was possible to oxidize the alcohol by
PCC. The resulting aldehydes 7 were converted to oximes
by hydroxylamine hydrochloride in water and then to
chloroximes using N-chlorosuccinimide (NCS) in aceto-
nitrile. The cycloaddition to C60 produced isoxazolines 10,
in which the carboxylic acid and amine groups of the
glycine moiety were protected as tert-butyl ester and tert-
butyl carbamate, respectively. Treatment of 10 with
A plausible mechanism would envision Mo(CO)6-
induced retrocycloaddition.26 This reaction would gener-
(21) Irngartinger, H.; Ko¨hler, C. M.; Huber-Patz, U.; Kra¨tschmer,
W. Chem. Ber. 1994, 127, 581.
(22) Irngartinger, H.; Weber, A. Tetrahedron Lett. 1997, 38, 2075.
(23) Ingartinger, H.; Weber, A.; Escher, T.; Fettel, P. W.; Gassner,
F. Eur. J . Org. Chem. 1999, 2087, 7.
(24) Meier, M. S.; Poplawska, M. J . Org. Chem. 1993, 58, 4524.
(25) Meier, M. S.; Poplawska, M. Tetrahedron 1996, 52, 5043.
(26) Nitta, M.; Yi, A.; Kobayashi, T. Bull. Chem. Soc. J pn. 1985,
58, 991.
(27) Bianchi, G.; Gandolfi, R.; Gru¨nanger P. In The Chemistry of
Functional Groups, Supplement C, Wiley: New York, 1983; p 748.

Additions of Azomethine Ylides to Fullerene C60
J . Org. Chem., Vol. 65, No. 14, 2000 4291
F igu r e 1. Labeling of different isomers in the bisaddition to
isoxazolinofullerenes.
trifluoroacetic acid liberated both functionalities generat-
ing salts 11. These protonated glycines, suspended in
toluene, were heated to reflux in the presence of form-
aldehyde, inducing the intramolecular cycloaddition of
azomethine ylides. In the reactions of derivatives 11a and
11b one main product was isolated (respectively 12 and
13), whereas three different compounds were produced
in the case of 11c.
The complete characterization of the different isomers
and the determination of the exact structure were made
difficult by the absence of symmetry elements. Structural
assignments relied on UV-vis spectra, electrospray mass
spectrometry (ES-MS), elemental analysis, but especially
NMR techniques, such as 1H NMR, 13C NMR, HMQC,
HMBC, HH-COSY, and NOE, assisted by geometrical
optimizations with semiempirical PM3 procedure.28
Figure 1 provides a pictorial description of bis-addition
patterns. Since the isoxazoline ring is asymmetric we
distinguish between additions of the azomethine ylide on
the side of the imine carbon of isoxazoline (designated
by the suffix -C) and additions on the side of oxygen
(designated by the suffix -O).
F igu r e 2. HMBC spectrum of bisadduct 12. The resonance
labels refer to the structures reported in Scheme 3. Crosses
indicate cross peaks deriving from an incomplete suppression
In the course of these investigations, the most profit-
able diagnostic technique was the detection of long-range
correlations between proton and carbon atoms by means
of HMBC technique. Whenever this correlation was
found, a firm structural assignment was possible, whereas
when this interaction was missing the task was much
more difficult. The following is a succinct description of
the structural assignment of compounds 12-16. The
description refers to the HMBC of compounds 12-14
reported in Figures 2, 3, and 4, respectively. The struc-
tural determinations also allow the assignment (reported
1
of the J CH correlations.
Com p ou n d 13. The four pyrrolidine protons give
again distinct resonances, assigned as indicated in Figure
3. The H4 and H4′ resonances are attributed from the
2J correlation with the imine carbon C3. However, no
further correlation could be detected with carbon C2. The
structural assignment therefore rests upon the following
considerations. The pyrrolidine protons H8, H8′, H11,
and H11′ correlate with the three methylenic carbons C7,
C8, and C11 and also with three quaternary aliphatic
carbons not bound to oxygen. The 13C resonances cor-
relating with H8 and H8′ necessarily belong to C9 and
C10, so that the last correlation of H11′ is with carbon
C2 of the isoxazoline ring. This set of correlations again
points to the cis-1-C structure. The UV-vis is reported
in Figure 5b.
1
in the Experimental Section) of most H resonances and
of many 13C resonances.
Com p ou n d 12. The pyrrolidine protons show different
1H resonances, which have been assigned (with HMQC
and HMBC) as indicated in the upper trace of Figure 2.
The H4 and H4′ protons R to the imine carbon C3 are
2
assigned from the J correlation with this same carbon.
The H4 proton also shows 3J correlations with methylenic
Com p ou n d s 14-16. The longer aliphatic chain can
in principle allow for a different type of bisaddition. In
fact, the increased freedom of the arm brings about the
formation of three products.
carbons C5 and C6 and with the quaternary aliphatic
3
carbon C2. This same carbon C2 also gives J coupling
with the pyrrolidine proton H10′. This constitutes the
most convincing proof for structure 12. The attack of the
azomethine ylide is then of type cis-1-C with respect to
the original isoxazoline anchor, on the side of the imine
carbon. The aliphatic chain separating the isoxazoline
ring and the reactive azomethine ylide is too short to
allow a reaction to far sites. The UV-vis spectrum of 12
is reported in Figure 5a.
Com p ou n d 14. The 1H NMR shows again four signals
for the pyrrolidine protons, which could be assigned as
indicated in Figure 4. The structural assignment is
straightforward from the inspection of the HMBC spec-
3
trum. The pyrrolidine H9′ proton shows a J correlation
with the high-field aliphatic resonance at 98.39 ppm,
unambiguously attributed to the quaternary carbon C1
bound to oxygen. Thus, the structure of the bisadduct
corresponds to the cis-1-O type, with the pyrrolidine ring
oriented toward the oxygen of the isoxazoline moiety. The
(28) Spartan 4.0 program package, 1995, distributed by Wavefunc-
tion, Inc., Irvine, CA 92715.

4292 J . Org. Chem., Vol. 65, No. 14, 2000
Da Ros et al.
F igu r e 3. HMBC spectrum of bisadduct 13. See caption of
Figure 2.
F igu r e 4. HMBC spectrum of bisadduct 14. See caption of
Figure 2
UV-Vis spectrum reported in Figure 5c, very similar to
that of compound 13, shows that two different cis-1
adducts give similar absorption patterns.
5 Å. Thus, the analysis of the dipolar interaction net will
point toward the cis-3-C structure. The UV-vis spectrum
of 15 is reported in Figure 5d and is reminiscent of that
recorded for a cis-3 pattern by Taki et al.,29 thus cor-
roborating our tentative assignment.
Com p ou n d 16. This isomer was formed in very low
yields (2%) and was only characterized by ES-MS and
UV-vis spectrophotometry. The mass spectrum con-
firmed that 16 is an isomer of 14 and 15, whereas the
UV-vis spectrum, reported in Figure 5e, is similar to
that obtained by Taki et al. for a cis-2 isomer.29 Accord-
ingly, we tentatively assign a cis-2-C structure to isomer
16.
Compounds 12-15 were subjected to treatment by Mo-
(CO)6 in chlorobenzene at reflux. Except for derivatives
12, which gave mainly decomposition products, in all
cases the reaction gave the corresponding nitriles 17a ,b
as the only isolated products.
The reactions of 14 and 15 produced the same nitrile
derivative, thus confirming the isomeric nature of the two
reactants. The structure of nitrile 17a was also confirmed
by an independent synthesis. Nitrile-amine 18, prepared
according to the literature,30 was alkylated by t-butyl
bromoacetate to give aminoester 19, which was hydro-
Com p ou n d 15. The determination of the structure in
the present case is based more on the absence than on
the detection of diagnostic scalar or dipolar interactions,
and is therefore more speculative than the previous
examples. The discussion also rests upon the semiem-
pirical PM3 optimizations of the potential configurations
and conformations related to this compound. The cis-1-C
structures of compounds 12 and 13 and the cis-1-O
structure of compound 14 have been revealed by the
detection of 3J correlations between one pyrrolidine
proton and carbons C1 or C2 of the isoxazoline ring. No
such correlation was detected in the HMBC spectrum of
15 (not shown), suggesting junctions of the cis-2 or cis-3
type. The geometry optimizations reveal that the cis-2-C
and cis-3-C structures are by far more stable than the
corresponding cis-2-O and cis-3-O structures. One re-
markable feature of compound 15 is the absence in the
NOEDS spectra of dipolar interactions between any of
the methylenic protons R to the pyrrolidine nitrogen (H8,
H8′, H9, H9′, H12, and H12′) and any of the methylenic
proton R to the isoxazoline ring (H4 and H4′), indicating
that the minimal distance between protons of one set and
protons of the other is above 3.2 Å. In every conformer
of the cis-2-C structure such distances are below the
threshold, while in the conformer of the cis-3-C structure
(also the most stable conformer) all distances are above
(29) Taki, M.; Sugita, S.; Nakamura, Y.; Kasashima, E.; Yashima,
E.; Okamoto, Y.; Nishimura, J . J . Am. Chem. Soc. 1997, 119, 926.
(30) Knouzi, N.; Vaultier, M.; Carrie´, R. Bull. Soc. Chim. Fr. 1985,
5, 815.

Additions of Azomethine Ylides to Fullerene C60
J . Org. Chem., Vol. 65, No. 14, 2000 4293
Sch em e 4
1-C bisadducts are obtained, characterized by relatively
small distances between the imine carbon and the
pyrrolidine nitrogen. This parallels the tendency on
unhindered additions to proceed in a cis-1 fashion as
observed by Hirsch and Djojo.7,9 With the longer 5-me-
thylene tether, the cis-1-O and cis-3-C bis bisadducts are
obtained. It is remarkable that in this case no cis-1-C
compound was observed, probably because this addition
modality requires an energetically unfavored twisting of
the long methylenic chain.
In all cases, nitrile oxide cycloaddition could be re-
versed, allowing the isolation of monopyrrolidine deriva-
tives.
The methodology reported in this paper has the
potential of allowing a reversible tether-controlled cy-
cloaddition of azomethine ylides in complex fullerene
architectures. Since cis-1 bisadducts were never observed
in the addition of azomethine ylides to C60, as a matter
of fact, the possibility of generating cis-1 structures might
be helpful for the exploitation of unusual multiple addi-
tion patterns.
Exp er im en ta l Section
1
Gen er a l Meth od s. H NMR spectra were recorded at 200
or 400 MHz and 13C spectra at 50 or 100 MHz. Chemical shifts
(δ) are given in parts per million relative to tetramethylsilane.
The NOE spectra have been obtained in the differential mode
(NOEDS).31 The heterocorrelated reverse-mode HMQC32-34
and HMBC34,35 (multiple bond HMQC) spectra have been
acquired from a total of 256 t1 measurements in the phase
sensitive acquisition mode, with 16 (HMQC) or 32 (HMBC)
scans for each t1 value. The delay for the BIRD filter is
1
matched to the average J CH ) 140 Hz. The fixed delay for
the detection of multiple bond correlations is tuned to nJ CH
)
5 Hz. FT-IR spectra were recorded using NaCl cells or mixtures
compound/KBr (DRIFT system). C60 was purchased from
Bucky-USA (99.5%), all other reagents and solvents were used
as purchased from Fluka, Aldrich, J . T. Baker, and Cambridge
Isotope Laboratories; silica gel NM Kieselgel 60 (70-230 mesh
ASTM) was obtained from Macherey-Nagel and Merck.
Gen er a l Syn th esis of 3′-Su bstitu ted [5,6]F u ller en e-C60
-
Ih -[1,9-d ]isoxa zole (1). The syntheses of oximes and chloro-
ximes were performed according to the literature.36-39
Hydroxylamine hydrochloride (321 mg, 4.6 mmol) and Na2-
CO3‚10 H2O (1.32 g, 4.6 mmol) were added to a cold solution
(31) Neuhaus, D.; Williamson, M. The Nuclear Overhauser Effect
in Structural and Conformational Analysis; VCH: New York, 1989.
(32) Bax, A.; Griggey, R. H.; Hawhins, B. L. J . Magn. Reson. 1983,
55, 301.
F igu r e 5. UV-vis spectra of compounds 12-16, registered
in cyclohexane.
(33) Bax, A.; Subramanian, S. J . Magn. Reson. 1986, 67, 565.
(34) Summers, M. F.; Marzilli, L. G.; Bax, A. J . Am. Chem. Soc.
1986, 108, 4285.
(35) Bax, A.; Summers, M. F. J . Am. Chem. Soc. 1986, 108, 2093.
(36) Summers, J . B.; Gunn, B. P.; Martin, J . G.; Martin, M. B.;
Mazdiyasni, H. J . Med. Chem. 1988, 31, 1960.
lyzed to amino acid 20. The latter was condensed with
formaldehyde in the presence of C60 to produce 17a in
34% isolated yield (Scheme 4).
In conclusion, the intramolecular cycloaddition of
azomethine ylides to an isoxazolinofullerene appears to
be determined by the length of the tether. With relatively
short tethers (three or four methylene units), only cis-
(37) Armand, J . Bull. Soc. Chim. Fr. 1968, 4585.
(38) Williams, T. M.; Mosher, H. S. Tetrahedron Lett. 1985, 26, 6269.
(39) Balsamo, A.; Breschi, M. C.; Chiellini, G.; Cozzini, P.; Domiano,
P. Eur. J . Med. Chem. Chim. Ther. 1996, 31, 291.

4294 J . Org. Chem., Vol. 65, No. 14, 2000
Da Ros et al.
of aldehyde (3.1 mmol) in water. The mixture was stirred for
45 min at 0 °C, the water was removed, and the crude was
washed with ethyl acetate. The crude oximes, obtained by
evaporation of the solvent under reduced pressure, were
sufficiently pure (1H NMR) and were used without further
purification. N-Chlorosuccinimide (283 mg, 2.1 mmol) was
added to a solution of oxime (2.1 mmol) in acetonitrile (5 mL)
in 30 min. The mixture was stirred for 2 h, the solvent was
removed, and the crude was washed with CCl4. The chloroximes
were used without further purification. Addition of nitrile
oxides to C60 were carried out according to reported methodol-
ogy.21,22,24,25 Compounds 1b and 1d were synthesized according
to the literature.21
To a solution of C60 (200 mg, 0.278 mmol) in toluene (150
mL) were added 0.556 mmol of hydroximoyl chloride and 150
mg (1.8 mmol) of NaHCO3. The suspension was stirred at room
temperature, washed with water, dried over anhydrous Na2-
SO4, and purified by chromatography.
N -H yd r oxy-4-(p h e n ylm e t h oxy)b e n ze n e ca r b oxim i-
d oyl Ch lor id e. C14ClH12NO2 (MW 261.710) 544 mg, 2.07
mmol. 1H NMR (200 MHz, CDCl3): δ 7.80 (m, 2H), 7.41 (m,
5H), 6.99 (m, 2H), 5.11 (s, 2H). 13C NMR (50 MHz, CDCl3): δ
174.3, 136.3, 128.7, 128.6, 128.2, 127.4, 114.7, 70.1.
3′-(2,2-Dim et h yl-1,3-d ioxola n -4-yl)-(S)-[5,6]fu ller en o-
C60-Ih -[1,9-d ]isoxa zole (1f). C66H9NO3 (MW 863.813). Yield:
34% (82.0 mg, 0.094 mmol). Reaction time: 4 h; eluant toluene/
petroleum ether 4/1; precipitated by CS2/diethyl ether. 1H NMR
(200 MHz, CDCl3/CS2): δ 5.54 (dd, J ) 5.8, 6.6 Hz, 1H), 4.82
(dd, J ) 5.9, 8.5 Hz, 1H), 4.52 (dd, J ) 6.6, 8.4 Hz, 1H), 1.51
(s, 3H), 1.46 (s, 3H). 13C NMR (50 MHz, CDCl3/CS2): δ 153.2,
147.7, 147.1, 146.3, 146.2, 146.2, 146.0, 145.9, 145.9, 145.8,
145.5, 145.4, 145.3, 145.2, 145.2, 145.1, 144.8, 144.6, 144.2,
144.1, 144.1, 144.0, 143.9, 143.6, 142.9, 142.8, 142.7, 142.7,
142.3, 142.3, 142.2, 142.1, 142.0, 141.8, 141.7, 141.6, 140.3,
140.1, 136.8, 136.5, 135.9, 111.2, 103.7, 78.2, 72.1, 67.3, 26.1,
25.4. UV-vis (cyclohexane): λmax nm 678, 459, 425, 315, 254.
Anal. Calcd for C66H9NO3: C, 91.77; H, 1.05; N, 1.62. Found:
C, 91.3; H, 1.00; N, 1.58.
Rea ction s w ith Mo(CO)6: Gen er a l P r oced u r e. To a
solution of 1a (20 mg, 2.1 × 10-2 mmol) in chlorobenzene (10
mL) were added 16.6 mg (6.3 × 10-2 mmol) of Mo(CO)6 and
80 µL of methanol. The mixture was heated to reflux for 1.5
h, and the products were purified by chromatography (toluene).
There were recovered C60 (10.91 mg, 1.5 × 10-2 mmol, yield
71%) and 4-benzyloxy-benzonitrile 2 (4 mg, 1.9‚10-2 mmol,
1
yield 91%). H NMR (200 MHz, CDCl3): δ 7.59 (m, 2H), 7.41
(m, 5H), 7.02 (m, 2H), 5.12 (s, 2H).
3′-[4-(P h en ylm eth oxy)p h en yl][5,6]fu ller en o-C60-Ih -[1,9-
d ]isoxa zole (1a ). C74H11NO2 (MW 945.918). Yield: 37% (97.5
mg, 0.10 mmol, yield on C60 reacted: 60%). Reaction time: 4
h; eluant toluene/petroleum ether 4/1; precipitated by CS2/
diethyl ether. 1H NMR (200 MHz, CDCl3/CS2): δ 8.15 (m, 2H),
7.43 (m, 4H), 7.38 (m, 1H), 7.13 (m, 2H), 5.14 (s, 2H). 13C NMR
(50 MHz, CDCl3/CS2): δ 160.4, 152.3, 147.5, 147.1, 146.3,
146.1, 145.8, 145.4, 145.3, 145.1, 145.0, 144.9, 144.7, 144.3,
144.0, 142.9, 142.7, 142.4, 142.2, 142.0, 141.6, 140.2, 136.9,
136.5, 136.2, 130.3, 128.6, 128.1, 127.2, 121.6, 115.3, 69.9. UV-
vis (cyclohexane): λmax nm 685, 550 (sh), 458 (sh), 425, 402
(sh), 315, 256, 219. Anal. Calcd for C74H11NO2: C, 93.96; H,
1.17; N, 1.48. Found: C, 91.7; H, 0.95; N, 1.49.
Rea ction s w ith DIBALH: Gen er a l P r oced u r e. To a cold
solution of 1a (20 mg, 2.1 × 10-2 mmol) in anhydrous toluene
(10 mL), under nitrogen, were added 210 µL of DIBALH (1M
solution in hexane). The solution was stirred for 2 h at room
temperature, and then the mixture was washed with water
and the organic layer dried over anhydrous Na2SO4. The
products were purified by chromatography (petroleum ether/
ethyl acetate 9/1). Aldehyde 3. Yield: 31% (1.36 mg, 6.4 × 10-3
mmol). 1H NMR (200 MHz, CDCl3): δ 9.89 (s, 1H), 7.84 (m,
2H), 7.40 (m, 5H), 7.08 (m, 2H), 5.16 (s, 2H). Amine 4. Yield:
64% (2.86 mg, 1.34 × 10-2 mmol). 1H NMR (200 MHz,
CDCl3): δ 7.37 (m, 5H), 6.89 (m, 2H), 6.58 (m, 2H), 5.00 (s,
2H), 2.81 (s, 3H).
[5,6]F u ller en o-C60-Ih -[1,9-d ]isoxa zol-3′-ylp h en ylm eth a -
n on e (1c). C68H5NO2 (MW 867.804). Yield: 36% (86.32 mg,
0.1 mmol). Reaction time: 30 min; eluant toluene/petroleum
Experiments performed with both procedures on all com-
pounds 1 gave yields of C60 ranging between 70 and 90%.
Syn th esis of 4-(P h en ylm eth oxy)ben zon itr ile (2).40 To
a solution of 4-cyanophenol (100 mg, 0.84 mmol) in anhydrous
acetonitrile (2 mL) were added 116 mg (0.42 mmol) of silver
carbonate and benzyl bromide (100 µL, 144 mg, 0.84 mmol).
The mixture was stirred under N2 in the dark for 18 h at room
temperature and was filtered on Celite, and the product was
purified by chromatographic column (petroleum ether/ethyl
acetate 9/1). C14H11NO (MW 209.250). Yield: 85% (150 mg,
ether 4/1; precipitated by CS2/diethyl ether. IR (KBr): (cm-1
)
1653, 575. 1H NMR (200 MHz, CDCl3/CS2): δ 8.54 (m, 2H),
7.68 (m, 3H). 13C NMR (50 MHz, CDCl3/CS2): δ 184.7, 151.1,
147.6, 147.0, 146.9, 146.2, 146.1, 145.8, 145.8, 145.5, 145.1,
145.0, 144.5, 144.1, 144.0, 142.9, 142.7, 142.6, 142.4, 142.3,
142.2, 142.0, 141.6, 140.1, 140.0, 136.9, 136.0, 135.9, 134.0,
130.6, 128.5, 128.1. UV-vis (cyclohexane): λmax nm 673, 460,
426, 314, 254. Anal. Calcd for C68H5NO2: C, 94.12; H, 0.58;
N, 1.61. Found: C, 92.92; H, 0.61; N, 1.38.
1
0.72 mmol). H NMR (200 MHz, CDCl3): δ 7.58 (m, 2H), 7.39
(m, 5H), 6.98 (m, 2H), 5.18 (s, 2H).
N-H yd r oxy-2-[2-(2-m et h oxyet h oxy)et h oxy]et h a n im i-
d oyl Ch lor id e. Oxim e. C7H15NO4 (MW 177.202). Yield: 87%
(476 mg, 2.7 mmol). 1H NMR (200 MHz, CDCl3), two isomers:
9.22 and 9.07 (bs, 1H), 7.45 and 6.87 (t, J ) 5.7, 3.6 Hz
respectively, 1H), 4.34 and 4.09 (d, J ) 3.6, 5.6 Hz, respec-
tively, 2H), 3.61 (m, 6H), 3.54 (m, 2H), 3.34 (s, 3H). 13C NMR
(50 MHz, CDCl3): δ 150.7, 147.9, 71.6, 70.3, 70.2, 70.2, 70.1,
69.6, 67.6, 64.9, 58.8. EI-MS: 177 (M+, 2), 103 (15), 89 (60),
59 (100). Ch lor oxim e. C7ClH14NO4 (MW 211.647) 270 mg, 1.3
mmol (quantitative yield). 1H NMR (200 MHz, CDCl3): δ 9.11
(bs, 1H), 4.28 (s, 2H), 3.66 (m, 6H), 3.55 (m, 2H), 3.38 (s, 3H).
13C NMR (50 MHz, CDCl3): δ 173.0, 71.8, 71.2, 70.5, 70.3, 70.1,
70.0, 69.5, 68.7, 5 9.0.
Syn th esis of N-Meth yl-4-(ph en ylm eth oxy)ben zen am in e
(4).41 To a cold solution of 4-benzyloxyaniline hydrochloride
(500 mg, 2.12 mmol) in methanol (5 mL) were added paraform-
aldehyde (57.2 mg, 1.9 mmol) and sodium cyanoborohydride
(133 mg, 2.11 mmol). After 2.5 h, the solvent was evaporated,
water (10 mL) was added to the crude, and the crude was then
washed with ethyl acetate. The organic layer was dried over
anhydrous Na2SO4, concentrated, and purified by chromatog-
raphy (petroleum ether/ethyl acetate 9/1). C14H15NO (MW
213.282). Yield: 11% (50 mg, 0.23 mmol). 1H NMR (200 MHz,
CDCl3): δ 7.28 (m, 5H), 6.78 (m, 2H), 6.48 (m, 2H), 4.90 (s,
2H), 2.70 (s, 3H).
Syn th esis of Glycin e N-(ω-Hyd r oxya lk yl)-1,1-d im eth -
yleth yl Ester s (5). To a solution of amino alcohol (100 mmol)
in 100 mL of diethyl ether at 0 °C, tert-butyl bromoacetate
(3.8 mL, 25.6 mmol) in diethyl ether (25 mL) was dropped over
a period of 2 h. The solution was brought to room temperature
and stirred for 3 h. The mixture was washed with water, and
the organic phase was dried over anhydrous Na2SO4. The
solvent was concentrated at reduced pressure, and the product
was purified by chromatography (ethyl acetate /methanol 9/1).
3′-[(2-(2-Meth oxyeth oxy)eth oxy]m eth yl[5,6]fu ller en o-
60-Ih -[1,9-d ]isoxa zole (1e). C67H13NO4 (MW 895.855).
C
Yield: 30% (74.0 mg, 0.084 mmol). Reaction time: 6 h; eluant
toluene/ethyl acetate 9/1; precipitated by dichloromethane/
methanol. 1H NMR (200 MHz, CDCl3): δ 4.96 (s, 2H), 3.82
(m, 2H), 3.57 (m, 2H), 3.51 (m, 2H), 3.42 (m, 2H), 3.29 (s, 3H).
13C NMR (50 MHz, CDCl3): δ 151.7, 147.6, 146.1, 146.1, 146.0,
145.8, 145.7, 145.7, 145.3, 145.1, 145.0, 144.7, 144.7, 144.0,
143.9, 143.8, 142.7, 142.6, 142.6, 142.2, 142.2, 142.1, 141.9,
141.6, 140.3, 134.0, 136.6, 136.1, 103.2, 78.0, 71.8, 70.5, 70.4,
70.4, 70.1, 65.6, 58.8. UV-vis (cyclohexane): λmax nm 460, 425,
401 (sh), 314, 254. Anal. Calcd for C67H13NO4: C, 89.83; H,
1.46; N, 1.56. Found: C, 86.53; H, 1.30; N, 1.31.
(40) Mauleon, D.; Granados, R.; Minguillon, C. J . Org. Chem. 1983,
48, 3105.
(41) Robinson, B. J . Chem. Soc. 1965, 3336.

Additions of Azomethine Ylides to Fullerene C60
J . Org. Chem., Vol. 65, No. 14, 2000 4295
5a . C10H21NO3 (MW 203.284). Yield: 25% (1.3 g, 6.4 mmol).
1H NMR (200 MHz, CDCl3): δ 3.59 (t, J ) 5.3 Hz, 2H), 3.28
(s, 2H), 3.16 (broad s, 2H), 2.64 (t, J ) 5.7 Hz, 2H), 1.63 (m,
4H), 1.45 (s, 9H). 13C NMR (50 MHz, CDCl3): δ 171.0, 81.5,
62.4, 50.9, 49.2, 31.7, 28.0, 27.9. EI-MS: 203 (M+, 2), 102 (100),
88 (25).
7c. C17H31NO5 (MW 329.440). Yield: 55% (570 mg, 1.73
mmol). IR (NaCl): (cm-1) 1745, 1700. 1H NMR (200 MHz,
CDCl3): δ 9.66 (s, 1H), 3.72 and 3.64 (s, 2H), 3.15 (m, 2H),
2.35 (t, J ) 7.2 Hz, 2H), 1.54 (m, 4H), 1.37 (s, 9H), 1.33 (s,
9H), 1.25 (m, 2H). 13C NMR (50 MHz, CDCl3): δ 202.6, 169.1,
155.8, 155.2, 81.2, 79.8, 79.8, 50.1, 49.5, 48.1, 48.1, 43.7, 33.8,
28.3, 28.2, 28.0, 27.8, 26.2, 24.4, 21.7.
Syn th esis of Glycin e N-[(1,1-Dim eth yleth oxy)ca r bon -
yl]-N-[ω-(N′-h yd r oxya lk a n im id oyl)-1,1-d im eth yleth yl Es-
ter s (8). A water solution of hydroxylamine hydrochloride (106
mg, 1.5 mmol) and Na2CO3‚10 H2O (440 mg, 1.5 mmol) was
added to a solution of 7 (1.0 mmol) in dioxane (10 mL). The
mixture was stirred for 18 h, the solvent was evaporated at
reduced pressure, and the crude was extracted by ethyl
acetate. The oximes were sufficiently pure to be used without
further purification.
8a . C15H28N2O5 (MW 316.401). Yield: 88% (280 mg, 0.88
mmol). 1H NMR (200 MHz, CDCl3), two isomers: δ 7.80 (broad
s, 1H), 7.40 and 6.70 (broad t, J ) 5.7 Hz, 1H), 3.83 and 3.74
(d, J ) 1.8 Hz, 2H), 3.28 (m, 2H), 2.38 and 2.22 (m, 2H), 1.72
(m, 2H), 1.46 (s, 9H), 1.43 (s, 9H). 13C NMR (50 MHz, CDCl3):
δ 169.2, 151.3, 81.5, 80.1, 67.1, 50.4, 49.8, 48.2, 47.9, 47.6, 28.3,
28.1, 26.9, 25.2, 24.8.
5b. C11H23NO3 (MW 217.311). Yield: 89% (4.9 g, 22.8 mmol).
1
IR (NaCl): (cm-1) 3369, 1735. H NMR (200 MHz, CDCl3): δ
3.62 (t, J ) 6.1 Hz, 2H), 3.29 (s, 2H), 2.60 (t, J ) 6.9 Hz, 2H),
1.92 (bs, 2H) 1.56 (m, 6H), 1.46 (s, 9H). 13C NMR (50 MHz,
CDCl3): δ 170.2, 81.7, 62.0, 50.7, 48.9, 32.1, 28.6, 28.0, 23.1.
EI-MS: 217 (M+, 5), 116 (100), 88 (60).
5c. C12H25NO3 (MW 231.338). Yield: 84% (5.0 g, 21.6 mmol).
1
IR (NaCl): (cm-1) 3320, 1733. H NMR (200 MHz, CDCl3): δ
3.49 (t, J ) 6.5 Hz, 2H), 3.18 (s, 2H), 2.49 (t, J ) 6.9 Hz, 2H),
2.38 (broad s, 2H), 1.49-1.38 (m, 4H), 1.38 (s, 9H), 1.30-1.25
(m, 4H). 13C NMR (50 MHz, CDCl3): δ 171.6, 81.1, 62.3, 51.5,
49.3, 32.6, 29.8, 28.0, 26.9, 25.5. EI-MS: 231 (M+, 2), 130 (100),
88 (90).
Syn th esis of Glycin e N-[(1,1-Dim eth yleth oxy)ca r bon -
yl]-N-(ω-h yd r oxya lk yl)-1,1-d im eth yleth yl Ester s (6). To
a solution of 5 (9.3 mmol) in dioxane were added 2.03 g (9.3
mmol) of di-tert-butyl dicarbonate and a water solution of
sodium acetate (790 mg, 9.3 mmol). The mixture was stirred
at room temperature for 3 h. After the solvent was removed
at reduced pressure, water was added and the mixture
extracted with ethyl acetate. The organic phase, dried over
anhydrous Na2SO4, was concentrated and the product was
purified by chromatography (petroleum ether/ethyl acetate
4/1).
8b. C16H30N2O5 (MW 330.428). Yield 99% (330 mg, 1.0
1
mmol). H NMR (200 MHz, CDCl3): δ 7.60 (bs, 1H), 7.40 and
6.70 (t, J ) 6.0, 5.5 Hz, 1H), 3.82 and 3.77 (s, 2H), 3.46 (m,
2H), 2.39 and 2.22 (m, 2H), 1.52 (m, 4H), 1.46 (s, 9H), 1.42 (s,
9H). 13C NMR (50 MHz, CDCl3): δ 169.2, 155.7, 155.4, 152.3,
152.1, 151.7, 151.5, 81.4, 79.9, 50.2, 49.6, 48.0, 29.2, 28.3, 28.1,
27.7, 24.6, 23.7, 23.3.
6a . C15H29NO5 (MW 303.402). Yield: 92% (2.6 g, 8.6 mmol).
1H NMR (200 MHz, CDCl3): δ 3.83 and 3.74 (s, 2H), 3.66
(broad t, 2H), 3.29 (m, 2H), 1.56 (m, 4H), 1.46 (s, 9H), 1.42 (s,
9H). 13C NMR (50 MHz, CDCl3): δ 169.2, 155.5, 81.4, 79.9,
62.4, 50.2, 49.6, 48.1, 29.8, 29.6, 28.3, 28.0, 24.8, 24.7. EI-MS:
303 (M+, 1), 146 (40), 102 (100).
8c. C17H32N2O5 (MW 344.455). Yield: 99% (340 g, 0.99
mmol). IR (NaCl): (cm-1) 3380, 1746, 1697. 1H NMR (200 MHz,
CDCl3): δ 7.82 (broad s, 1H), 7.39 and 6.69 (t, J ) 6.0, 5.5 Hz,
respectively, 1H), 3.82 and 3.72 (s, 2H), 3.23 (m, 2H), 2.36 and
2.20 (m, 2H), 1.55-1.24 (m, 6H), 1.46 (s, 9H), 1.42 (s, 9H). EI-
MS: 344 (M+).
6b. C16H31NO5 (MW 317.429). Yield: 98% (2.9 g, 9.1 mmol).
IR (NaCl): (cm-1) 3451, 1747, 1697. 1H NMR (200 MHz,
CDCl3): δ 3.82 and 3.73 (s, 2H), 3.62 (t, J ) 6.2 Hz, 2H), 3.25
(m, 2H), 1.65 (m, 6H), 1.45 (s, 9H), 1.42 (s, 9H). 13C NMR (50
MHz, CDCl3): δ 169.2, 155.7, 155.4, 81.3, 79.8, 62.2, 50.2, 49.6,
48.4, 48.3, 32.2, 28.3, 28.2, 28.0, 27.9, 22.9, 22.8. EI-MS: 317
(M+, 5), 261 (10), 204 (30), 117 (100).
Syn th esis of Glycin e N-[(1,1-Dim eth yleth oxy)ca r bon -
yl]-N-[ω-N′-h yd r oxy-ω-ch lor oa lk a n im id oyl)-1,1-d im eth yl-
eth yl Ester s (9). An acetonitrile solution of 8 (0.36 mmol in
3 mL) and NCS (48.6 mg, 0.36 mmol) was stirred for 2 h, and
then the solvent was evaporated and the crude residue was
washed with CCl4. The mixture was filtered, and the solvent
was removed affording the product.
6c. C17H33NO5 (MW 331.456). Yield: 97% (3.0 g, 9.0 mmol).
9a . C15ClH27N2O5 (MW 350.846), 126 mg, 0.36 mmol. IR
(NaCl): (cm-1) 3310, 1745, 1710. H NMR (200 MHz, CDCl3):
1
1
IR (NaCl): (cm-1) 1747, 1698. H NMR (200 MHz, CDCl3): δ
3.76 and 3.67 (s, 2H), 3.56 (dt, J ) 2.7, 6.2 Hz, 2H), 3.18 (dt,
J ) 2.5, 7.1 Hz, 2H), 2.23 (broad s, 1H), 1.55-1.43 (m, 4H),
1.41 (s, 9H), 1.37 (s, 9H), 1.34-1.24 (m, 4H). 13C NMR (50
MHz, CDCl3): δ 169.2, 155.5, 155.4, 81.3, 79.8, 62.5, 62.3, 50.1,
49.5, 48.2, 48.0, 32.5, 28.2, 28.0, 26.5, 26.1, 25.4, 25.1. EI-MS:
331 (M+, 3), 230 (10), 202 (20), 174 (20), 130 (100).
Syn th esis of Glycin e N-[(1,1-Dim eth yleth oxy)ca r bon -
yl]-N-(ω-oxyalkyl)-1,1-dim eth yleth yl Ester s (7). To a dichlo-
romethane solution of 6 (3.15 mmol in 50 mL) was added PCC
(3.4 g, 15.8 mmol) in one portion. The mixture was stirred at
room temperature for 1 day. Celite and ethyl ether (25 mL)
were added, and the mixture was stirred for 15 min and then
filtered on silica gel. The eluted was reduced to a small volume,
and the product was loaded on top of a SiO2 column and
purified by chromatography (petroleum ether/ethyl acetate
7/3).
7a . C15H27NO5 (MW 301.386). Yield: 40% (380 mg, 1.26
mmol). IR (NaCl): (cm-1) 1750, 1700, 1655. 1H NMR (200 MHz,
CDCl3): δ 9.75 (s, 1H), 3.79 and 3.71 (s, 2H), 3.26 (m, 2H),
2.52 (m, 2H), 1.81 (m, 2H), 1.44 (s, 9H), 1.40 (s, 9H). 13C NMR
(50 MHz, CDCl3): δ 201.9, 201.5, 169.1, 155.4, 81.4, 80.2, 80.0,
50.3, 49.7, 47.6, 41.1, 40.9, 28.2, 28.0, 20.9, 20.8. EI-MS: 301
(M+, 1), 257 (10), 172 (35), 100 (100).
7b. C16H29NO5 (MW 315.413). Yield: 43% (430 mg, 1.36
mmol). IR (NaCl): (cm-1) 1746, 1696. 1H NMR (200 MHz,
CDCl3): δ 9.70 (t, J ) 1.5 Hz, 1H), 3.82 and 3.72 (s, 1H), 3.23
(m, 2H), 2.47 (t, J ) 6.6 Hz, 2H), 1.56 (m, 4H), 1.46 (s, 9H),
1.42 (s, 9H). 13C NMR (50 MHz, CDCl3): δ 202.2, 201.9, 169.1,
155.3, 81.3, 79.8, 50.1, 49.6, 48.0, 47.9, 43.4, 28.2, 28.0, 27.6,
19.1. EI-MS: 214 (10), 186 (40), 114 (100).
δ 9.56 and 9.26 (broad s, 1H), 3.77 and 3.69 (s, 2H), 3.22 (m,
2H), 2.47 (t, J ) 7.3 Hz, 2H), 1.80 (m, 2H), 1.39 (s, 9H), 1.36
(s, 9H). 13C NMR (50 MHz, CDCl3): δ 171.4, 169.1, 155.6,
155.4, 81.5, 81.4, 80.3, 80.0, 50.3, 50.1, 47.5, 47.3, 33.9, 29.4,
28.1, 27.9, 25.0, 24.8.
9b. C16ClH29N2O5 (MW 364.873), 84 mg, 0.23 mmol. IR
1
(NaCl): (cm-1) 3257, 1740, 1630. H NMR (200 MHz, CDCl3):
δ 9.57 and 9.51 (broad s, 1H), 3.78 and 3.69 (s, 2H), 3.21 (m,
2H), 2.46 (t, J ) 6.8 Hz, 2H), 1.56 (m, 4H), 1.41 (s, 9H), 1.37
(s, 9H). 13C NMR (50 MHz, CDCl3): δ 171.3, 169.2, 155.4, 81.5,
80.2, 50.1, 49.5, 47.8, 36.1, 29.5, 28.1, 27.9, 27.1, 26.9, 23.3.
9c. C17ClH31N2O5 (MW 378.900), 130 mg, 0.34 mmol. 1H
NMR (200 MHz, CDCl3): δ 9.37 and 9.12 (broad s, 1H), 3.78
and 3.70 (s, 2H), 3.19 (m, 2H), 2.44 (t, J ) 6.9 Hz, 2H), 1.59
(m, 4H), 1.42 (s, 9H), 1.38 (s, 9H), 1.28 (m, 2H). 13C NMR (50
MHz, CDCl3): δ 171.3, 169.2, 155.4, 81.7, 79.9, 60.2, 50.2, 50.0,
49.5, 47.9, 36.4, 29.6, 28.1, 27.9, 27.1, 26.9, 21.3, 14.2.
Syn th esis of Glycin e N-[(1,1-Dim eth yleth oxy)ca r bon -
yl]-N-(ω-[5,6]fullereno-C60-Ih-[1,9-d]isoxazol-3′-ylalkyl)-1,1-di-
m eth yleth yl Ester s (10). A toluene solution of C60 (200 mg,
0.28 mmol in 100 mL), hydroximoyl chlorides 9 (0.74 mmol),
and NaHCO3 (150 mg, 1.8 mmol) was stirred for 4 h. The
reaction mixture was loaded on top of a column, and the
product was purified by chromatography (toluene/ethyl acetate
9/1).
Glycin e N-[(1,1-Dim eth yleth oxy)ca r bon yl]-N-(3-[5,6]-
fu ller en o-C60-Ih -[1,9-d ]isoxa zol-3′-ylp r op yl)-1,1-d im eth yl-
eth yl Ester (10a ). C75H26N2O5 (MW 1035.054). Yield: 34%
(98.54 mg, 0.095 mmol, yield on reacted fullerene: 54%). IR
(KBr): (cm-1) 1741, 1700, 526. 1H NMR (200 MHz, CDCl3): δ

4296 J . Org. Chem., Vol. 65, No. 14, 2000
Da Ros et al.
3.94 and 3.86 (s, 2H), 3.59 (m, 2H), 3.11 (m, 2H), 2.36 (m, 2H),
1.50 (s, 9H), 1.46 (s, 9H). 13C NMR (50 MHz, CDCl3): δ 169.2,
169.1, 155.7, 155.6, 154.9, 154.8, 147.8, 147.2, 146.3, 146.2,
146.0, 145.9, 145.6, 145.6, 145.3, 145.2, 145.1, 145.0, 144.9,
144.7, 144.3, 144.1, 143.0, 142.8, 142.4, 142.2, 142.1, 141.8,
140.7, 140.1, 136.9, 136.9, 136.8, 136.7, 81.6, 81.5, 80.5, 80.6,
80.5, 80.3, 80.1, 50.6, 50.0, 48.2, 48.0, 28.5, 28.3, 28.2, 26.2,
26.1, 25.6, 25.3. UV-vis (cyclohexane): λmax nm 685, 456, 426,
412 (sh), 402 (sh), 313, 255. Anal. Calcd for C75H26N2O5: C,
87.03; H, 2.53; N, 2.71. Found: C, 86.9; H, 2.75; N, 2.62.
Glycin e N-[(1,1-Dim eth yleth oxy)ca r bon yl]-N-(4-[5,6]-
fu ller en o-C60-Ih -[1,9-d ]isoxa zol-3′-ylbu tyl)-1,1-d im eth yl-
eth yl Ester (10b). C76H28N2O5 (MW 1049.081). Yield: 34%
(101.0 mg, 0.096 mmol, yield on reacted fullerene: 79%). IR
(NaCl): (cm-1) 1741, 1693. 1H NMR (200 MHz, CDCl3): δ 3.90
and 3.82 (s, 2H), 3.40 (m, 2H), 3.11 (t, J ) 7.4 Hz, 2H), 2.15
(m, 2H), 1.86 (m, 2H), 1.50 (s, 9H), 1.44 (s, 9H). 13C NMR (50
MHz, CDCl3): δ 169.2, 155.6, 155.4, 154.9, 154.7, 147.8, 147.2,
146.3, 146.2, 145.9, 145.6, 145.4, 145.3, 145.2, 145.2, 145.1,
144.8, 144.7, 144.3, 144.1, 144.1, 142.9, 142.7, 142.3, 142.2,
142.1, 141.8, 140.7, 140.1, 136.8, 136.7, 81.4, 80.5, 80.5, 80.0,
79.9, 50.3, 49.6, 48.0, 29.7, 28.4, 28.3, 28.1, 27.7, 23.9, 23.8.
UV-vis (cyclohexane): λmax nm 686, 459, 424, 316, 255. Anal.
Calcd for C76H28N2O5: C, 87.01; H, 2.69; N, 2.67. Found: C,
86.40; H, 2.42; N, 2.57.
Glycin e N-[(1,1-Dim eth yleth oxy)ca r bon yl]-N-(5-[5,6]-
fu ller en o-C60-Ih -[1,9-d ]isoxa zol-3′-ylp en til)-1,1-d im eth yl-
eth yl Ester (10c). C77H30N2O5 (MW 1063.108). Yield: 38%
(112.1 mg, 0.105 mmol, yield on reacted fullerene: 74%). IR
(NaCl): (cm-1) 1740, 1695. 1H NMR (200 MHz, CDCl3): δ 3.87
and 3.78 (s, 2H), 3.32 (m, 2H), 3.07 (t, J ) 7.6 Hz, 2H), 2.15
(m, 2H), 1.66-1.58 (m, 4H), 1.48 (s, 9H), 1.43 (s, 9H). 13C NMR
(50 MHz, CDCl3): δ 169.3, 155.8, 155.4, 155.1, 155.0, 147.9,
147.3, 146.4, 146.4, 146.3, 146.1, 146.0, 145.7, 145.5, 145.4,
145.3, 145.2, 145.0, 145.0, 144.8, 144.4, 144.2, 143.0, 142.9,
142.5, 142.5, 142.3, 142.3, 142.2, 141.9, 140.8, 140.2, 137.0,
136.8, 81.5, 81.5, 80.7, 80.0, 79.9, 50.4, 49.8, 48.5, 48.3, 29.8,
28.7, 28.6, 28.4, 28.3, 28.3, 28.2, 26.9, 26.8, 26.6, 26.4. UV-
vis (cyclohexane): λmax nm 688, 460, 425, 314, 255. ES-MS
(THF/methanol 4/1): m/z 950 (M - 2 isobutene). Anal. Calcd
for C77H30N2O5: C, 87.0; H, 2.84; N, 2.64. Found: C, 85.6; H,
2.90; N, 2.53.
Syn th esis of N-(ω-[5,6]fu ller en o-C60-Ih -[1,9-d ]isoxa zol-
3′-yla lk yl)glycin e Tr iflu or oa cetic Sa lts (11). A dichloro-
methane solution of 10 (0.05 mmol in 5 mL) and trifluoroacetic
acid (5 mL) was stirred for 18 h, the solvent was evaporated,
and the residue was washed with toluene (three times).
N-(3-[5,6]F u ller en o-C60-Ih -[1,9-d ]isoxa zol-3′-ylp r op yl)-
glycin e Tr iflu or oa cetic Sa lt (11a ). C68F3H11N2O5 (MW
992.851). Yield: 99% (49.54 mg, 0.05 mmol). ES-MS (CH3CN/
trifluoroacetic acid 1/0.01): m/z 879 (MH+), 901 (M + Na)+.
N-(4-[5,6]F u ller en o-C60-Ih -[1,9-d ]isoxa zol-3′-ylb u t yl)-
glycin e Tr iflu or oa cetic Sa lt (11b). C69F3H13N2O5 (MW
1006.879). Yield: 99% (50.23 mg, 0.05 mmol). ES-MS (CH3-
CN/trifluoroacetic acid 1/0.01): m/z 893 (MH+), 915 (M + Na)+.
N-(5-[5,6]F u ller en o-C60-Ih -[1,9-d ]isoxa zol-3′-ylp en tyl)-
glycin e Tr iflu or oa cetic Sa lt (11c). C70F3H15N2O5 (MW
1020.906). Yield: 99% (50.93 mg, 0.05 mmol). ES-MS (CH3-
CN /trifluoroacetic acid 1/0.01): m/z 907 (MH+), 929 (M + Na)+.
Syn th esis of 12-16. In 150 mL of toluene, 11 (0.03 mmol)
and paraformaldehyde (18 mg, 0.6 mmol) were suspended and
the mixture was heated to reflux for 4 h. After concentration
at reduced pressure, the products were purified by chroma-
tography (toluene/ethyl acetate 9/1).
142.99, 142.91, 142.87, 142.66, 142.38, 142.17, 141.53, 141.44,
141.16, 141.08, 140.86, 139.51, 139.12, 138.92, 138.72, 135.49,
134.18, 130.73, 99.31 (C1), 77.02 (C2), 74.10 (C9), 72.00 (C8),
70.12 (C7), 69.71 (C10), 50.74 (C6), 27.68 (C5), 25.26 (C4). UV-
vis (cyclohexane): λmax nm 705 (sh), 668 (sh), 647 (sh), 485
(sh), 424, 448, 401 (sh), 325 (sh), 303, 256. ES-MS (toluene/
methanol/trifluoroacetic acid 4/1/0.01): m/z 847 (MH+). Anal.
Calcd for C66H10N2O: C, 93.61; H, 1.19; N, 3.31. Found: C,
90.1; H, 1.14; N, 3.18.
Bisa d d u ct 13 (3′,1′′-Bu ta n o-1”H-p yr r olo[3′′,4′′:10,11]-
[5,6]fu ller en o-C60-Ih -[1,9-d ]isoxa zole). C67H12N2O (MW
1
860.855). Yield: 67% (17.29 mg, 0.020 mmol). H NMR (400
MHz, CS2/benzene-d6): δ 4.88 (dd, H11, J 11,11′ ) 11.9 Hz, J 8,11
) 2.5 Hz), 4.31 (dd, H8, J 8,8′ ) 9.1 Hz), 4.00 (d, H8′), 3.39 (m,
one H7 proton), 3.24 (d, H11′), 3.12 (m, H4), 2.87 (m, one H7
proton), 2.71 (m, H4′), 2.65 (m, one H5 proton), 2.31 (m, one
H5 proton), 2.27 (m, one H8 proton), 2.02 (one H6 proton). 13
C
NMR (100 MHz, CS2/benzene-d6): δ 158.17 (C3), 152.78 (C14),
149.65 (C12), 149.46, 149.17, 148.85, 148.66, 148.16, 147.86,
147.27, 147.09 (C13), 146.96, 146.57, 146.52, 146.45, 146.30,
146.26, 145.99 (two carbons), 145.77, 145.45, 145.17, 145.06,
145.04, 145.02, 144.98, 144.93, 144.82, 144.80, 144.70, 144.62,
144.60, 144.47, 144.20, 143.61, 143.42, 143.35, 143.32, 142.95,
142.79, 142.77, 142.75, 142.48, 142.39, 142.30, 141.53, 141.36,
141.26, 141.10, 140.85, 140.68, 139.88, 139.10, 139.03, 136.70,
135.25, 132.53, 99.24 (C1), 77.31 (C2), 70.75, 69.15 (C10), 65.80
(C11), 65.13 (C8), 50.17 (C7), 32.64, 30.44 (C5), 28.63 (C6),
27.89 (C4). UV-Vis (cyclohexane): λmax nm 706, 671, 642, 519
(sh), 425, 400 (sh), 329 (sh), 257. MALDI-MS: m/z 860 (M+).
Anal. Calcd for C67H12N2O: C, 93.48; H, 1.41; N, 3.25. Found:
C, 91.78; H, 1.57; N, 3.06.
Bisa d d u cts 14-16. C68H14N2O (MW 874.882), three iso-
mers, total yield 87%. The derivative 16 was obtained in very
low quantity and was only partially characterized.
Bisa d d u ct 14. Yield: 54% (14.16 mg, 0.016 mmol). 1H NMR
(400 MHz, CS2/benzene-d6): δ 5.11 (dd, H9, J 9,9′ ) 8.8 Hz, J 9,12
) 2.7 Hz), 4.11 (dd, H12, J 12,12′ ) 8.5 Hz), 3.17 (d, H9′), 3.13
(d, H12′), 3.09 (m, H8), 2.76 (m, one H4 proton), 2.59 (m, H8′),
2.55 (m, one H4 proton), 2.45 (m, one H6 proton), 1.86 (m, one
H5 proton), 1.82 (m, one H6 proton), 1.75 (m, one H5 proton),
1.57 (m, one H7 proton), 1.46 (m, one H7 proton). 13C NMR
(100 MHz, CS2/benzene-d6): δ 154.39 (C3), 154.28 (C14),
151.47 (C13), 149.32, 149.05, 148.90, 148.77, 148.52, 147.83,
147.47, 147.41, 147.29, 146.92, 146.87, 146.85, 146.59, 146.53,
146.22, 146.01, 145.22, 145.19 (two carbons), 145.15 (two
carbons), 145.04, 154.01, 144.98, 144.82, 144.79, 144.75,
144.49, 144.22, 144.15, 144.08, 143.99, 143.93, 143.77, 143.68,
143.14, 143.12, 142.95, 142.70, 142.68, 142.38, 142.31, 142.26,
142.13, 142.76, 141.35, 141.18, 140.70, 139.20, 139.15, 138.12,
137.60, 137.37, 135.70, 98.39 (C1), 77.85 (C2), 71.17 (C10),
69.68 (C11), 66.43 (C9), 63.51 (C12), 53.98 (C8), 29.73 (C5),
27.52 (C7), 25.99 (C4), 25.00 (C6). UV-Vis (cyclohexane): λmax
nm 704, 666 (sh), 634 (sh), 488 (sh), 427, 402 (sh), 325 (sh),
255. MALDI-MS: m/z 874 (M+).
Bisa d d u ct 15. Yield: 31% (8.13 mg, 0.009 mmol). 1H NMR
(400 MHz, CS2/benzene-d6): δ 4.54 (d, H12′, J 12,12′ ) 11.9 Hz),
4.34 (dd, H9, J 9,12 ) 2.7 Hz), 4.31 (dd, H12), 4.15 (d, H9′, J 9,9′
) 12.5 Hz), 3.41 (m, H8′), 3.10 (m, H8), 3.02 (m, H4′), 2.60 (m,
H4′), 1.69-1.56 (multiplets, the six H5, H6 and H7 protons).
13C NMR (100 MHz, CS2/benzene-d6): δ 154.10 (C3), 153.35
(C15), 150.77 (C16), 149.32, 148.94, 148.66, 148.33, 148.20,
148.02, 147.97, 147.80 (C13), 147.76, 147.49, 147.10, 146.71,
146.53, 146.46, 146.37, 146.31, 146.26, 146.15, 145.91, 145.88,
145.86, 145.63, 145.09, 144.95, 144.92, 144.68, 144.50, 144.17,
144.13, 143.17, 143.04 (two carbons), 142.74, 142.67, 142.60,
142.55, 142.50, 142.43, 142.38, 142.18, 142.10, 140.29, 140.00,
139.89, 139.35, 138.88, 138.37, 137.66, 136.04, 135.85, 135.49,
143.82, 131.38 (C14), 123.61, 99.30 (C1), 75.52 (C2), 73.82
(C11), 69.99 (C12), 69.05 (C10), 65.90 (C9), 50.69 (C8), 30.45,
30.35, 27.18, 25.68 (C4). UV-vis (cyclohexane): λmax nm 715,
634, 554 (sh), 470 (sh), 442 (sh), 310 (sh), 258. MALDI-MS:
m/z 874 (M+).
Bisa d d u ct 12. C66H10N2O (MW 846.828). Yield: 65% (16.63
mg, 0.019 mmol). 1H NMR (400 MHz, CS2/benzene-d6): δ 4.95
(dd, H10, J 10,10′ ) 14.9 Hz, J 7,10′ ) 2.8 Hz), 4.74 (d, H7′, J 7,7′
)
12.3 Hz), 4.32 (dd, H7), 3.80 (dd, H10), 3,51 (m, H6 and H6′),
3.33 (m, H4), 2.85 (m, H4′), 2.31 (m, H5 and H5′).13C NMR
(100 MHz, CS2/benzene-d6): δ 156.96 (C3), 154.12 (C13),
150.93 (C11), 149.15, 148.97, 148.81 (C12), 148.70, 148.66,
147.91, 147.88, 147.06, 147.02, 146.58, 146.44, 146.25, 146.12,
145.99, 145.85, 145.79, 145.62, 145.47, 145.24, 145.20, 145.03,
144.97, 144.93, 144.92, 144.90, 144.87, 144.62, 144.58, 144.38
(two carbons), 144.37, 143.63, 143.61, 143.52, 143.30, 143.10,
Bisa d d u ct 16. Yield: 2% (0.52 mg, 6 × 10-4 mmol). UV-
vis (cyclohexane): λmax nm 668 (sh), 631 (sh), 580 (sh), 493

Additions of Azomethine Ylides to Fullerene C60
J . Org. Chem., Vol. 65, No. 14, 2000 4297
(sh), 445 (sh), 375 (sh), 315, 258, 240. ES-MS (toluene/
methanol/trifluoroacetic acid 4/1/0.01): m/z 875 (MH+).
Gen er a l Rea ction w ith Mo(CO)6. To a solution of bis-
adduct (5.8 × 10-3 mmol) in chlorobenzene (5 mL) Mo(CO)6
(2.3 mg, 8.7 × 10-3 mmol) was added. The mixture was heated
to reflux for 4 h. After cooling, the product was purified by
chromatography (toluene/ethyl acetate 9/1) and precipitated
by CHCl3/methanol.
product was purified by chromatography (ethyl acetate).
C11H20N2O2 (MW 212.152). Yield: 43% (115 mg, 0.54 mmol).
IR (NaCl): (cm-1) 2260, 1740, 1680. 1H NMR (200 MHz,
CDCl3): δ 3.28 (s, 2H), 2.63 (t, J ) 6.5 Hz, 2H), 2.38 (t, J )
6.8 Hz, 2H), 1.68 (m, 4H), 1.46 (s, 9H). 13C NMR (50 MHz,
CDCl3): δ 171.6, 119.5, 81.2, 51.4, 48.2, 29.6, 28.8, 28.0, 23.0,
16.9.
Syn th esis of N-(5-Cya n op en tyl)glycin e (20). Trifluoro-
acetic acid (1 mL) was added to a solution of 19 (58 mg, 0.27
mmol) in dichloromethane (3 mL) and the mixture was stirred
at room temperature for 6 h. The solvent and the excess of
trifluoroacetic acid were removed by evaporation and the
product washed four times by toluene. The product was used
without further purification. C9F3H11N2O4 (MW 270.083), 72.9
mg, 0.27 mmol.
2′H-[5,6]Fu ller en o-C60-Ih -[1,9-d]pyr r ole-1′(5′H)-pen tan e-
n itr ile 17b. C67H12N2 (MW 844.856). Yield: 21% (1.04 mg,
1.23 × 10-3 mmol). 1H NMR (200 MHz, CDCl3): δ 4.42 (s, 4H),
3.16 (t, J ) 6.6 Hz, 2H), 2.63 (t, J ) 6.5 Hz, 2H), 2.10 (m, 4H).
13C NMR (50 MHz, CDCl3): δ 154.8, 149.9, 147.2, 146.2, 146.0,
145.3, 145.2, 144.5, 143.0, 142.6, 142.2, 142.0, 141.8, 140.2,
140.1, 136.1, 119.7, 70.5, 67.9, 53.7, 29.7, 23.6, 14.2. ES-MS
(toluene/methanol/trifluoroacetic acid 4/1/0.01): m/z 845 (MH+).
2′H-[5,6]F u ller en o-C60-Ih -[1,9-d ]p yr r ole-1′(5′H)-esa n e-
n itr ile (17c) fr om 14 or 15. C68H14N2 (MW 858.883). 1H NMR
(200 MHz, CDCl3): δ 4.42 (s, 4H), 3.14 (t, J ) 7.0 Hz, 2H),
2.50 (t, J ) 6.4 Hz, 2H), 2.02 (m, 2H), 1.89 (m, 4H). 13C NMR
(50 MHz, CDCl3): δ 154.8, 146.1, 145.9, 145.3, 144.4, 142.5,
142.1, 141.8, 140.1, 136.1, 119.5, 70.5, 67.9, 54.5, 28.1, 26.9,
25.5, 17.3. ES-MS (toluene/methanol/formic acid 4/1/0.01): m/z
859 (MH+).
Syn th esis of 2′H-[5,6]F u ller en o-C60-Ih -[1,9-d ]p yr r ole-1′-
(5′H)-p en ta n en itr ile (17b). To a solution of C60 (100 mg,
0.139 mmol) in toluene (50 mL) were added 20 (72 mg, 0.27
mmol) and paraformaldehyde (12.5 mg, 0.417 mmol). The
mixture was heated to reflux for 45 min. The cold solution was
washed with a basic solution, the organic layer was dried over
anhydrous Na2SO4, and the product was purified by chroma-
tography (toluene). The compound was precipitated by dichlo-
romethane/methanol. C67H12N2 (MW 844.856). Yield: 34%
Syn th esis of 5-Am in ova ler on itr ile (18).30 Sodium azide
(600 mg, 9.25 mmol) was added to a solution of 5-bromo-
valeronitrile (720 µL, 6.17 mmol) in DMSO (10 mL). After 18
h of stirring at room temperature, 20 mL of water was added,
and the solution was extracted by diethyl ether. C5H8N4 (MW
1
(39.43 mg, 0.047 mmol). IR (KBr): (cm-1) 2244, 524. H NMR
(200 MHz, CDCl3): δ 4.42 (s, 4H), 3.17 (t, J ) 6.1 Hz, 2H),
2.64 (t, J ) 6.8 Hz, 2H), 2.10 (m, 4H). 13C NMR (50 MHz,
CDCl3): δ 155.0, 154.4, 153.6, 150.9, 146.8, 146.2, 146.0, 145.9,
145.3, 144.5, 143.0, 142.5, 142.3, 141.8, 140.1, 136.1, 135.2,
119.9, 70.7, 68.0, 53.6, 30.0, 23.7, 16.9. UV-vis (cyclohex-
ane): λmax nm 700, 462, 430, 403 (sh), 327, 308, 255. ES-MS
(toluene/methanol/formic acid 4/1/0.01): m/z 845 (MH+).
124.075). Yield: 99% (764 mg, 6.16 mmol). IR (NaCl): (cm-1
)
2240, 1250. 1H NMR (200 MHz, CDCl3): δ 3.35 (bt, J ) 5.4
Hz, 2H), 2.39 (m, 2H), 1.74 (m, 4H). 13C NMR (50 MHz,
CDCl3): δ 119.1, 50.4, 27.8, 22.7, 16.8. Triphenylphosphine
(3.24 g, 12.3 mmol) and water (300 µL) were added to the azide
(1.5 g, 12.3 mmol) dissolved in THF (12.3 mL). After 18 h at
room temperature, the solvent was removed and the residue
washed with petroleum ether/diethyl ether 1/1 (50 mL). Ethyl
acetate was added to the crude product, and an acid-basic
double extraction was performed. C5H10N2 (MW 98.084).
Ack n ow led gm en t. We thank MURST for financial
support (cofin. ex 40%, prot. n. 9803194198).
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and/
or 13C NMR spectra for compounds N-hydroxy-4-(phenyl-
methoxy)-benzenecarboximidoyl chloride, 1a ,c, 3,6,9-trioxa-
decanaldehyde-oxime, N-hydroxy-2-[2-(2-methoxy-ethoxy)-
ethoxy]ethanimidoyl chloride, 1e,f, 2, 4, 5a -c, 6a -c, 7a -c,
8a -c, 9a -c, 17a , and 19. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
Yield: 99% (1.2 g, 12.2 mmol). H NMR (200 MHz, CDCl3): δ
2.70 (t, J ) 6.1 Hz, 2H), 2.33 (t, J ) 6.1 Hz, 2H), 1.64 (m, 4H).
Syn th esis of Glycin e N-(5-Cya n op en tyl)-1,1-d im eth yl-
eth yl Ester (19). To a cold solution of 18 (250 mg, 2.55 mmol)
and TEA (530 µL, 3.8 mmol) in 5 mL of diethyl ether tert-
butyl bromoacetate (188 µL, 1.28 mmol) was dropped in 2 h.
The mixture was stirred at room temperature for 20 h. The
J O000076D