The di-t-butylsilylene protecting group as a bridging unit in linear and macrocyclic bis-malonates for the regioselective multifunctionalization of C60

Article abstract of DOI:10.1016/j.tetlet.2013.09.024

Fullerene equatorial bis-adducts have been prepared with high regioselectivity by a double Bingel reaction between [60]fullerene and di-t-butylsilylene-tethered bis-malonates. Macrocyclic bis-malonates incorporating di-t-butylsilylene moieties have also b

Full text of DOI:10.1016/j.tetlet.2013.09.024

Tetrahedron Letters 54 (2013) 6251–6257
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Tetrahedron Letters
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The di-t-butylsilylene protecting group as a bridging unit in linear
and macrocyclic bis-malonates for the regioselective
multifunctionalization of C60
Sebastiano Guerra, Thi Minh Nguyet Trinh, Franck Schillinger, Lucie Muhlberger, David Sigwalt,
⇑
Michel Holler, Jean-François Nierengarten
Laboratoire de Chimie des Matériaux Moléculaires, Université de Strasbourg et CNRS (UMR 7509), Ecole Européenne de Chimie, Polymères et Matériaux (ECPM), 25 rue
Becquerel, 67087 Strasbourg Cedex 2, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 July 2013
Revised 3 September 2013
Accepted 9 September 2013
Available online 16 September 2013
Fullerene equatorial bis-adducts have been prepared with high regioselectivity by a double Bingel reac-
tion between [60]fullerene and di-t-butylsilylene-tethered bis-malonates. Macrocyclic bis-malonates
incorporating di-t-butylsilylene moieties have also been prepared and used to functionalize C60 in multi-
ple Bingel cyclopropanations. Fullerene bis-adducts with a cis-2 addition pattern and tris-adducts with an
e,e,e addition pattern have been thus obtained. Finally, the bridging di-t-butylsilylene is not only a direct-
ing group for the cyclization step, it is also a protecting group that can be readily cleaved to afford the
corresponding acyclic fullerene polyols.
Keywords:
tButylsilylene
Fullerene
Ó 2013 Elsevier Ltd. All rights reserved.
Malonate
Macrocycle
Regioselectivity
Fullerene chemistry has generated unprecedented stereochem-
ical problems1 and the regioselective polyfunctionalization of C60
through multiple addition reactions remains a major challenge.
Actually, mono-functionalized C60 derivatives possess nine differ-
ent 6–6 bonds (bonds at the junction between two six-membered
rings, see Fig. 1) and mixtures of regioisomers are obtained by
successive reactions at the C60 core.2,3 The synthesis of fullerene
tris-adducts is even more challenging as 46 isomers differing by
the relative position of the three addends on the carbon sphere
are theoretically possible. The first efficient methodologies allow-
ing the regioselective preparation of C60 multi-adducts have been
reported by Diederich and co-workers and are based on cyclization
reactions on the fullerene scaffold.4 These seminal contributions
have inspired most of the research efforts devoted toward the
preparation of fullerene multi-adducts with a well-defined stereo-
chemistry.5–8 As part of this research, we have recently developed
an expeditious synthesis of fullerene tris-adducts based on a three-
fold Bingel reaction between C60 and t-butyl(trialkoxy)silane
derivatives bearing three malonate substituents.8 The silane unit
is at the same time a directing group allowing the control of the
stereochemistry of the tris-addition on the C60 sphere during the
cyclization step and a protecting group that can be readily cleaved
to generate the corresponding acyclic fullerene derivatives. Based
on this finding, we became interested in using the di-t-butylsilyl-
ene protecting group as a bridging unit in linear and macrocyclic
bis-malonates for the regioselective bis-functionalization of C60
.
Upon cyclization, a desilylation reaction provides the correspond-
ing acyclic polyol derivatives. The possibility to easily open the
bridging unit upon cyclization is a clear advantage to generate
new fullerene building blocks with a controlled distribution of
functional groups on their surfaces.
As shown in Scheme 1, the preparation of bis-malonates 2a–b
was first achieved from 1a–b8b to validate the possibility of using
di-t-butylsilylene bridged bis-malonates for the regioselective bis-
functionalization of C60. Treatment of compounds 1a–b (2 equiv)
with di-t-butylsilyl bis(trifluoromethanesulfonate) (tBu2Si(OTf)2, 1
equiv) in DMF in the presence of pyridine (pyr) gave the correspond-
ing bis-malonates 2a–b. Fullerene derivatives 3a–b were then pre-
pared by taking advantage of the versatile regioselective reaction
developed in the group of Diederich,5a which led to macrocyclic
bis-adducts of C60 by a cyclization reaction at the C sphere with
bis-malonate derivatives in a double Bingel9 cyclopropanation.
Reaction of 2a with C60, I2, and 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) in toluene afforded the corresponding cyclization product
3a in 23% yield. Similarly, compound 3b was obtained in 48% yield
from bis-malonate 2b and C60 under the same conditions.
⇑
Corresponding author. Tel.: +33 368 852 763; fax: +33 368 852 774.
E-mail address: nierengarten@unistra.fr (J.-F. Nierengarten).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.09.024

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S. Guerra et al. / Tetrahedron Letters 54 (2013) 6251–6257
cis-1
e,e,e tris-adduct 22
cis-2
cis-3
e-face
!
e-edge
trans-4
trans-3
e bis-adduct 3b
trans-2
trans-1
cis-2 bis-adduct 21
Figure 1. Addition of a second addend to a C2v-symmetrical C60 mono-adduct can
in principle lead to nine different regioisomeric bis-adducts. Relative to the first
addend, the second one can be located either in the same hemisphere (cis), in the
opposite hemisphere (trans) or on the equatorial belt (e). For identical addends, a
second attack onto the e-edge or e-face positions leads to identical products.
Fullerene bis-adducts 3a–b were characterized by 1H and 13C
NMR, UV–vis, and IR spectroscopies.10 In addition, their structure
was confirmed by MALDI-TOF mass spectrometry showing the ex-
pected pseudo-molecular ion peaks at m/z 1210.2 for 3a ([M+H]+,
calcd for C82H37O10Si: 1210.3) and 1237.3 for 3b ([M+H]+, calcd
for C84H41O10Si: 1237.3). For both 3a and 3b, the molecular sym-
metry (C1) deduced from the 1H and 13C NMR spectra suggests
an equatorial addition pattern. This is also consistent with molecu-
lar modeling studies (see ESI). For fullerene derivatives bearing two
malonate addends, the relative position of the two cyclopropane
rings on the C60 core suggested by the molecular symmetry is con-
veniently confirmed by UV/vis spectroscopy. Effectively, the
absorption spectra of C60 bis-adducts are highly dependent on
the addition pattern and characteristic for each of the regioisom-
ers.5 The absorption spectra of bis-adducts 3a and 3b are similar
thus showing that the relative position of the two cyclopropane
rings on the fullerene core is identical for both compounds. As
shown in Figure 2, the absorption spectrum recorded in CH2Cl2
for compound 3b is broad in the visible region with two shoulders
(398 and 410 nm) and a quite sharp band at ca. 420 nm. Indeed, the
UV/vis spectrum of 3b clearly reveals the diagnostic features
mono-adduct 20
Figure 2. Absorption spectra (CH2Cl2) of fullerene derivatives 3b, 20, 21, and 22
showing significant differences as a function of the number of addends. In the case
of bis-adducts 3b and 21, characteristic features of e (3b) and cis-2 (21) bis-addition
patterns are clearly observed.
previously reported for analogous equatorial C60 bis-adducts.5
Therefore, in addition to the C1 symmetry deduced from their 1H
and 13C NMR spectra, the absorption spectra of 3a and 3b allowed
us to definitively elucidate their stereochemistry. It is worth noting
that the equatorial addition pattern is Cs symmetric but owing to the
macrocyclic structureof compounds 3a–b, the symmetry is reduced.
Finally, different reaction conditions for the cleavage of the con-
necting di-t-butylsilylene protecting group in 3a–b were tested
(Scheme 1). Reaction of 3a–b with HF-pyridine in THF gave diols
4a–b in good yields (80–90%). Desilylation conditions using an ex-
cess of BF3ꢀEt2O (20 equiv) in CH2Cl2/CH3CN were also found to be
effective for the preparation of 4a–b from 3a–b.11 From a practical
point of view, the use of BF3ꢀEt2O is by far more convenient as these
conditions do not require HF-resistant equipment. Furthermore,
traces of pyridine were particularly difficult to remove in samples
of 4a–b prepared by treatment of 3a–b with HF.pyridine.
O
O
(i)
O
O
O
O
(CH2)n OH
O
O
(CH2)n
O
Si(tBu)2
1a n = 2
1b n = 3
2a n = 2
2b n = 3
2
Si
OH
HO
O
O
Following the successful preparation of equatorial C60 bis-ad-
ducts from silylene-tethered bis-malonates, a similar synthetic
strategy was used for the preparation of an equatorial fullerene
bis-adducts substituted with two symmetrically substituted mal-
onate addends (Scheme 2). Compound 6 was obtained in an almost
quantitative yield by heating 3-chloro-1-propanol (5) at 120 °C in
the presence of 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum’s
acid). Treatment of 6 (1 equiv) with an excess of 1,3-propanediol
(4 equiv) under esterification conditions using N-(3-dimethylami-
nopropyl)-N0-ethylcarbodiimide hydrochloride (EDC) and 4-dim-
ethylaminopyridinium tosylate (DPTS) afforded 7 in 50% yield.
Subsequent treatment with tBu2Si(OTf)2/pyr in DMF provided
bis-malonate 8 in 51% yield. The C1-symmetrical macrocyclic
(CH2)n
O
(CH2)n
(CH2)n
(CH2)n
(iii)
(ii)
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
3a n = 2
3b n = 3
4a n = 2
4b n = 3
Scheme 1. Reagents and conditions: (i) tBu2Si(OTf)2, DMF, pyr, rt, 12 h (2a: 43%;
2b: 52%); (ii) C60, DBU, I2, PhMe, ꢁ15 °C, 1 h (3a: 23%, 3b: 48%); (iii) BF3ꢀEt2O,
CH2Cl2, CH3CN, rt 12 h (4a: 91%; 4b: 74%).

S. Guerra et al. / Tetrahedron Letters 54 (2013) 6251–6257
6253
O
O
O
O
The equatorial addition pattern of fullerene bis-adducts 9–12
was confirmed by both their absorption spectra and their symme-
try deduced from their 1H and 13C NMR spectra. Whereas deriva-
tives 9, 10, and 11 bearing unsymmetrically substituted
malonate addends are all C1-symmetrical compounds, bis-adduct
12 with its two C(CO2(CH2)3Cl)2 subunits is Cs symmetric as de-
duced from a careful analysis of its 13C NMR spectrum (Fig. 3).
Out of the 32 expected fullerene resonances, three are observed
at d = 70.1, 71.3, and 71.4 ppm (sp3 C atoms) and 28 between d =
138.7 and 147.4 ppm (sp2 C atoms). It is also worth noting that
two of the resonances seen in the sp2 region show half intensity
as well as two of the three resonances observed for the fullerene
sp3 C atoms. Actually, the latter observations are unambiguous
proofs for the Cs symmetry of compound 12. Effectively, for such
a fullerene derivative, there are 28 pairs of equivalent C atoms
and four unique ones. Furthermore, out of the three possible Cs-
symmetrical addition patterns (cis-2, e and trans-4), the only one
for which 3 resonances are expected for the sp3 fullerene C atoms
is the equatorial bis-adduct. This is further confirmed by the obser-
vation of three resonances for the carbonyl C atoms (d = 163.4,
163.35 and 163.25 ppm). Therefore, the preparation of compound
12 provided definitive and non-ambiguous conclusions about the
stereochemistry of fullerene derivatives 9, 10, and 11. With their
e fullerene addition pattern, these compounds are ideally suited
for the preparation of fullerene hexa-adducts with an octahedral
addition pattern.12 This new methodology will be therefore very
useful to produce new fullerene scaffolds bearing different malon-
ate addends in a 4:2 ratio.
OH
(i)
(ii)
O
OH
(iv)
O
O
Cl
5
6
7
Cl
Cl
OH
Si
Si
O
O
O
O
(iii)
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
Cl
Cl
Cl
Cl
8
9
R
R
O
O
O
O
O
O
O
Cl
Cl
O
(v)
10 R = OH
11 R = OTs
12 R = Cl
(vi)
(vii)
Scheme 2. Reagents and conditions: (i) Meldrum’s acid, 120 °C, 3 h (99%); (ii) 1,3-
propanediol, EDC, DPTS, CH2Cl2, 0 °C to rt, 12 h (50%); (iii) tBu2Si(OTf)2, DMF, pyr, rt,
4 h (51%); (iv) C60, DBU, I2, PhMe, ꢁ15 °C, 1 h (40%); (v) BF3.Et2O, CH2Cl2, CH3CN, rt
12 h (95%); (vi) TsCl, pyr, CH2Cl2, 0 °C to rt, 48 h (77%); (vii) nBu4NCl, THF, rt, 4 h
(95%).
The concept of using cleavable di-t-butylsilylene-tethered bis-
malonates for the regioselective functionalization of C60 was then
extended to cyclo-oligomalonates (Scheme 3). The selective
mono-protection of 1,3-propanediol (13) was carried out by treat-
ment with Ag2O and p-methoxybenzyl chloride (PMBCl) according
to the conditions reported by Bouzide and Sauvé.13 Treatment of
the resulting mono-protected derivative 14 with tBu2Si(OTf)2 and
imidazole in DMF provided 15 in 68% yield. The PMB protecting
groups in 15 were conveniently removed by treatment with
fullerene e-bis-adduct 9 was then obtained in 40% yield by reaction
of 8 with C60 in the presence of DBU and I2. Desilylation with BF3-
ꢀEt2O followed by reaction of the resulting 10 with p-toluenesulfo-
nyl chloride (TsCl) in the presence of pyridine gave 11. Finally,
treatment of bis-tosylate 11 with an excess of tetra-n-butylammo-
nium chloride (nBu4NCl) in THF yielded 12 in 95% yield.
(2C)
2
7
7’
a/b
c
*
*
Cl
Cl
10
4/9/9’
9
8
O
7
O
6
O
O
5/10/10’
9'
4
1
3/8/8’
O
Cl
Cl
O
b
2
7'
8' 10'
5
3
a
O
O
c
sp2 C60
C=O
1/6
a/b/c
Figure 3. 13C NMR spectrum (CDCl3, 100 MHz) of compound 12. Inset: detailed views showing the resonances of the carbonyl groups (left), the fullerene sp2 C atoms (center)
⁄
and the fullerene sp3 C atoms (right); indicates the two sp2 fullerene C atoms showing half intensity signals.

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S. Guerra et al. / Tetrahedron Letters 54 (2013) 6251–6257
2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in CH2Cl2 containing
a small amount of water. The di-t-butylsilylene remained un-
changed and key building block 16 was thus obtained in good
yields (86%). Reaction of diol 16 with malonyl chloride in the pres-
ence of 4-dimethylaminopyridine (DMAP) under pseudo high dilu-
tion conditions afforded a mixture of cyclooligomers and polymers.
Macrocycles 17, 18, and 19 were isolated in a pure form in 24%,
15%, and 3% yield, respectively, by repeated chromatographic sep-
arations.14 While the 1H and 13C NMR spectra of 17, 18, and 19
were in full agreement with their cyclooligomeric structures, it
was not possible to conclude about their ring-size based on the
NMR data. In the case of 18 and 19, the proposed structures were
confirmed by MALDI-TOF mass spectrometry. For the smallest
member, high level of fragmentation prevented the detection of
the molecular ion peak. However, based on the elution order of
the compounds and on their relative yields, compound 17 is likely
the cyclomonomeric derivative. To gain further evidence about the
proposed structure for 17, a Bingel reaction was performed to gen-
erate the C2v symmetrical fullerene mono-adduct 20. The structure
of 20 was confirmed by MALDI-TOF mass spectrometry as well as by
1H and 13C NMR, IR, and UV/vis (Fig. 2) spectroscopies thus showing
that compound 17 was effectively the cyclomonomalonate.
bis-adduct 21 with an excellent regioselectivity.15 Indeed, the only
isolable by-product was a bis-fullerene derivative resulting from
the reaction of 18 with two molecules of C60 but no regioisomeric
bis-adducts of 21 could be isolated from the reaction mixture. The
13C NMR spectrum of compound 21 is shown in Figure 4. As dis-
cussed in the case of 12, the presence of half intensity signals for
some of the resonances of the fullerene C atoms seen in the sp2 re-
gion is an unambiguous signature for a Cs symmetrical structure. In
addition, the presence of only two resonances for the fullerene sp3
C atoms suggests that this bis-adduct 21 could be either a cis-2 or a
trans-4 regioisomer. The UV–vis spectrum of 21 is indeed fully con-
sistent with a cis-2 C60 bis-adduct (Fig. 2). The stereochemistry of
compound 21 was thus elucidated. To further support this struc-
tural assignment, computational studies were also performed.
The molecular geometry of the various regioisomers (cis-2, cis-3,
e, trans-3 and trans-4) was optimized with Spartan’10 Macintosh
Parallel Edition (Wavefunction Inc., USA) at the AM1 semi-empiri-
cal level. The cis-2 isomer was effectively found to be noticeably
lower in energy when compared to all the other regioisomers
(D
E >75 kJ/mol).
The reaction of the cyclo-tris-malonate 19 with C60 was also car-
ried out. The reaction was highly regioselective and only the fuller-
ene tris-adduct with an e,e,e-addition pattern was thus obtained.
Compound 22 was isolated with a remarkable 61% yield. The relative
Reaction of the 28-membered ring macrocyclic bis-malonate 18
with C60 in the presence of iodine and DBU gave the cis-2 C60
OH
OPMB
Si
(i)
(ii)
(iv)
O
O
HO
HO
13
14
OR
RO
15 R = PMB
(iii)
16 R = H
Si
Si
O
O
O
O
Si
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
+
+
O
O
O
O
O
O
O
O
17
Si
Si
Si
O
O
O
O
(v)
O
O
18
19
(v)
O
Si
(v)
O
O
O
O
Si
Si
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
Si
O
O
20
Si
Si
O
O
O
O
21
O
O
22
Scheme 3. Reagents and conditions: (i) PMBCl, Ag2O, CH2Cl2, 48 h (80%); (ii) tBu2Si(OTf)2, DMF, imidazole, rt, 12 h (68%); (iii) DDQ, CH2Cl2, H2O, rt, 6 h (86%); (iv) malonyl
chloride, DMAP, CH2Cl2, rt, 48 h (17: 24%; 18: 15%; 19: 3%); (v) C60, DBU, I2, PhMe, rt, 1 h (20: 46%; 21: 27%; 22: 61%).

S. Guerra et al. / Tetrahedron Letters 54 (2013) 6251–6257
6255
(A)
(B)
Figure 4. (A) 13C NMR spectrum (CDCl3, 100 MHz) of compound 21 (Ç: cyclohexane); inset: detailed view showing the resonances of the fullerene sp2 C atoms; ⁄ indicates the
sp2 fullerene C atoms showing half intensity signals. (B) 13C NMR spectrum (CDCl3, 100 MHz) of compound 22 showing its threefold symmetry (Ç: cyclohexane); inset:
detailed view showing the resonances of the fullerene sp2 C atoms.
position of the three cyclopropane rings on the C60 core were deter-
mined based on the symmetry (C3) deduced from the 1H and 13C
NMR spectra.16 As shown in Figure 4, the number of resonances ob-
served in the 13C NMR spectrum of 22 is fully consistent with a three-
fold symmetrical compound. The cherry-red color and the UV/vis
spectrum of 22 (Fig. 2) are also in complete agreement with the pro-
posed e,e,e-addition pattern for compound 22.8
As shown in Scheme 4, the preparation of macrocylic oligo-mal-
onates was also carried out from 1,4-butanediol (23) by following
the synthetic route developed for the preparation of compounds
17–19. Mono-protection of 23 by treatment with Ag2O/PMBCl
followed by silylation (tBu2Si(OTf)2/imidazole) and deprotection
(DDQ) afforded diol 26. Reaction of 26 with malonyl chloride in
the presence of DMAP gave the cyclomonomalonate 27 as the main
product. Its structure was confirmed by MALDI-TOF mass spec-
trometry. Higher cyclooligomers were also obtained but in very
low yields. This result prompted us to develop a stepwise synthetic
route that will prevent the formation of cyclomonomalonates
(Scheme 4). Treatment of 25 with 1 equiv of DDQ provided the
mono-protected derivative 28 in 47% yield. Subsequent reaction
with malonyl chloride in the presence of DMAP gave malonate
29. The choice of the appropriate protecting groups for the two ter-
minal alcohol functions of 29 was the key to this synthesis. The
deprotection conditions must not be acidic to preserve the bridging
di-t-butylsilylene groups and may not be basic to preserve the es-
ter functions.17 The PMB protecting groups being removed under

6256
S. Guerra et al. / Tetrahedron Letters 54 (2013) 6251–6257
Si
Si
OR
O
O
O
O
(ii)
(iv)
HO
OR
(iii)
RO
O
O
23 R = H
25 R = PMB
26 R = H
O
O
(i)
27
24 R = PMB
(v)
Si
Si
O
O
O
O
OR
OR
O
O
O
O
Si
O
O
O
(vi)
(viii)
O
O
O
O
O
O
O
OPMB
HO
28
O
O
O
O
Si
Si
29 R = PMB
30 R = H
31
(vii)
Si
HO
OH
O
O
HO
OH
O
O
O
O
O
O
O
O
O
(ix)
O
O
O
(x)
O
O
O
O
O
O
Si
32
33
Scheme 4. Reagents and conditions: (i) PMBCl, Ag2O, CH2Cl2, 48 h (95%); (ii) tBu2Si(OTf)2, DMF, imidazole, rt, 12 h (60%); (iii) DDQ, CH2Cl2, H2O, rt, 6 h (91%); (iv) malonyl
chloride, DMAP, CH2Cl2, rt, 48 h (51%); (v) DDQ (1 equiv), CH2Cl2, H2O, rt, 6 h (from 25: 47%); (vi) malonyl chloride, DMAP, CH2Cl2, rt, 12 h (67%); (vii) DDQ, CH2Cl2, rt, 2 h
(68%); (viii) malonyl chloride, DMAP, CH2Cl2, rt, 48 h (51%); (ix) C60, DBU, I2, PhMe, rt, 1 h (39%); (x) BF3ꢀEt2O, CH2Cl2, CH3CN, rt, 12 h (88%).
neutral conditions by treatment with DDQ, both the ester functions
and the di-t-butylsilylene groups remained effectively intact and
diol 30 was obtained in a good yield (68%). Reaction of 30 with
malonyl chloride under pseudo high dilution conditions gave
cyclobismalonate 31 in 51% yield. Macrocycle 31, which has a ring
size of 32 atoms, was characterized by NMR spectroscopy and mass
spectrometry.
malonate subunits to the di-t-butylsilylene moieties, fullerene bis-
adducts with different addition patterns should become easily
accessible thus opening new perspectives in the chemistry of mul-
tifunctionalized fullerene derivatives.
Acknowledgments
Reaction of C60 with macrocyclic bis-malonate 31, I2, and DBU
afforded 32 in 39% yield. As discussed for 21, the relative position
of the two cyclopropane rings on the fullerene core was deter-
mined based on the Cs molecular symmetry deduced from the
NMR spectra15 and on the diagnostic features of a cis-2 bis-addition
pattern seen in the absorption spectrum of 32. Finally, treatment of
compound 32 with an excess of BF3.Et2O gave the Cs-symmetrical
fullerene cis-2 bis-adduct 33 in 88% yield. With its four alcohol
functions, compound 33 is a valuable building block for further
chemical modifications.
In conclusion, the reaction of linear and macrocyclic di-t-butyl-
silylene-tethered bis-malonate with C60 gave access to fullerene
bis-adducts with an excellent regioselectivity. The bridging di-t-
butylsilylene is not only a directing group during the cyclization
step, it is also a protecting group that can be readily cleaved to af-
ford the corresponding acyclic fullerene polyols. By systematically
changing the length and the rigidity of the spacer units linking the
This research was supported by the CNRS, the University of
Strasbourg, and the Agence Nationale de la Recherche (ANR,
Programme Blanc 2011, Sweet60s). S.G. gratefully thanks the Swiss
National Science Foundation and TMNT the University of
Strasbourg (IdEx 2013) for their post-doctoral fellowships. We
further thank M. Schmitt for the high field NMR measurements.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.09.
024.
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3. For representative examples, see: (a) Nakamura, Y.; Takano, N.; Nishimura, T.;
Yashima, E.; Sato, M.; Kudo, T.; Nishimura, J. Org. Lett. 2001, 3, 1193–1196; (b)
Kordatos, K.; Bosi, S.; Da Ros, T.; Zambon, A.; Lucchini, V.; Prato, M. J. Org. Chem.
2001, 66, 2802–2808.
resulting mixture was stirred overnight at room temperature. A saturated
NaHCO3 aqueous solution was added and the aqueous layer extracted with
CH2Cl2. The organic layer was washed with water, dried (MgSO4) and
concentrated. Column chromatography (SiO2, CH2Cl2/MeOH 96:4) gave 4a–b.
Compound 4a (36 mg, 91%): brown solid; IR (neat): 3443 (br, OH), 1737 (C@O);
UV/vis (CH2Cl2): 251 (20040), 309 (sh, 7600), 399 (1300), 410 (sh, 830), 422
(790), 479 (980); 1H NMR (400 MHz, CDCl3): 4.60–4.49 (m, 8H), 3.97 (m, 4H),
2.26 (br s, 1H), 2.09 (br s, 1H), 1.47 (t, J = 7 Hz, 6H). MALDI-TOF-MS: 1091.5 (8%,
[M+Na]+, calcd for C74H20O10Na: 1091.1), 1068.5 (100%, [M]+, calcd for
4. (a) Isaacs, L.; Haldiman, R. F.; Diederich, F. Angew. Chem., Int. Ed. Engl. 1994, 33,
2339–2342; (b) Boudon, C.; Gisselbrecht, J.-P.; Gross, M.; Isaacs, L.; Anderson,
H. L.; Faust, R.; Diederich, F. Helv. Chim. Acta 1995, 78, 1334–1344; (c) Isaacs, L.;
Seiler, P.; Diederich, F. Angew. Chem., Int. Ed. Engl. 1995, 34, 1466–1469.
5. For examples of regioselective preparations of fullerene bis-adducts based on
cyclization reactions, see: (a) Nierengarten, J.-F.; Gramlich, V.; Cardullo, F.;
Diederich, F. Angew. Chem., Int. Ed. 1996, 35, 2101–2103; (b) Nierengarten, J.-F.;
Habicher, T.; Kessinger, R.; Cardullo, F.; Diederich, F.; Gramlich, V.;
Gisselbrecht, J.-P.; Boudon, C.; Gross, M. Helv. Chim. Acta 1997, 80, 2238–
2276; (c) Ashton, P. R.; Diederich, F.; Gómez-López, M.; Nierengarten, J.-F.;
Preece, J. A.; Raymo, F. M.; Stoddart, J. F. Angew. Chem., Int. Ed. 1997, 36, 1448–
1451; (d) Isobe, H.; Tokuyama, H.; Sawamura, M.; Nakamura, E. J. Org. Chem.
1997, 62, 5034–5041; (e) Nierengarten, J.-F.; Schall, C.; Nicoud, J.-F.; Heinrich,
B.; Guillon, D. Tetrahedron Lett. 1998, 39, 5747–5750; (f) Nierengarten, J.-F.;
Felder, D.; Nicoud, J.-F. Tetrahedron Lett. 1998, 39, 2747–2750; (g) Dietel, E.;
Hirsch, A.; Eichhorn, E.; Rieker, A.; Hackbarth, S.; Röder, B. Chem. Commun.
1998, 1981–1982; (h) Schick, G.; Jarrosson, T.; Rubin, Y. Angew. Chem., Int. Ed.
1999, 38, 2360–2363; (i) Quian, W.; Rubin, Y. Angew. Chem., Int. Ed. 1999, 38,
2356–2360; (j) Nakamura, Y.; Asami, A.; Inokuma, S.; Ogawa, T.; Kikuyama, M.;
Nishimura, J. Tetrahedron Lett. 2000, 41, 2193–2197; (k) Da Ros, T.; Prato, M.;
Lucchini, V. J. Org. Chem. 2000, 65, 4289–4297; (l) Zhang, S.; Rio, Y.; Cardinali,
F.; Bourgogne, C.; Gallani, J.-L.; Nierengarten, J.-F. J. Org. Chem. 2003, 68, 9787–
9797; (m) Chaker, L.; Ball, G. E.; Williams, J. R.; Burley, G. A.; Hawkins, B. C.;
Keller, P. A.; Pyne, S. G. Eur. J. Org. Chem. 2005, 5158–5162; (n) Sergeyev, S.;
Shär, M.; Seiler, P.; Lukoyanova, O.; Echegoyen, L.; Diederich, F. Chem. Eur. J.
2005, 11, 2284–2294; (o) Figueira-Duarte, T. M.; Gégout, A.; Olivier, J.;
Cardinali, F.; Nierengarten, J.-F. Eur. J. Org. Chem. 2009, 3879–3884.
6. For examples of regioselective synthesis of bis- and tris-adducts from
macrocyclic oligomalonates, see: (a) Reuther, U.; Brandmüller, T.;
Donaubauer, W.; Hampel, F.; Hirsch, A. Chem. Eur. J. 2002, 8, 2261–2273; (b)
Chronakis, N.; Hirsch, A. Chem. Commun. 2005, 3709–3711; (c) Riala, M.;
Chronakis, N. Org. Lett. 2011, 13, 2844–2847; (d) Sigwalt, D.; Holler, M.;
Nierengarten, J.-F. Tetrahedron Lett. 2013, 54, 3160–3163.
C
74H20O10: 1068.1). Compound 4b (61 mg, 74%): brown solid; IR (neat): 3450
(br, OH), 1740 (C@O). UV/vis (CH2Cl2): 306 (sh, 21900), 331 (sh, 7400), 397 (sh,
2350), 409 (sh, 1550), 421 (1450), 478 (sh, 1600). 1H NMR (400 MHz, CDCl3):
4.61–4.48 (m, 8H), 3.80 (m, 4H), 2.04 (m, 4H), 1.94 (br s, 2H), 1.46 (t, J = 7 Hz,
3H), 1.45 (t, J = 7 Hz, 3H); MALDI-TOF-MS: 1096.1 ([M]+, calcd for C76H24O10
:
1096.1).
12. (a) Iehl, J.; Pereira de Freitas, R.; Delavaux-Nico, B.; Nierengarten, J.-F. Chem.
Commun. 2008, 2450–2452; (b) Iehl, J.; Nierengarten, J.-F. Chem. Eur. J. 2009, 15,
7306–7309; (c) Iehl, J.; Nierengarten, J.-F. Chem. Commun. 2010, 46, 4160–
4162; (d) Nierengarten, J.-F.; Iehl, J.; Oerthel, V.; Holler, M.; Illescas, B. M.;
Muñoz, A.; Martín, N.; Rojo, J.; Sánchez-Navarro, M.; Cecioni, S.; Vidal, S.;
Buffet, K.; Durka, M.; Vincent, S. P. Chem. Commun. 2010, 46, 3860–3862; (e)
Sigwalt, D.; Holler, M.; Iehl, J.; Nierengarten, J.-F.; Nothisen, M.; Morin, E.;
Remy, J.-S. Chem. Commun. 2011, 47, 4640–4642; (f) Fortgang, P.; Maisonhaute,
E.; Amatore, C.; Delavaux-Nicot, B.; Iehl, J.; Nierengarten, J.-F. Angew. Chem., Int.
Ed. 2011, 50, 2364–2367; (g) Iehl, J.; Nierengarten, J.-F.; Harriman, A.; Bura, T.;
Ziessel, R. J. Am. Chem. Soc. 2012, 134, 988–998; (h) Iehl, J.; Frasconi, M.; Jacquot
de Rouville, H.-P.; Renaud, N.; Dyar, S. M.; Strutt, N. L.; Carmieli, R.;
Wasielewski, M. R.; Ratner, M. A.; Nierengarten, J.-F.; Stoddart, J. F. Chem. Sci.
2013, 4, 1462–1469.
13. Bouzide, A.; Sauvé, G. Tetrahedron Lett. 1997, 38, 5945–5948.
14. A solution of DMAP (1.42 g, 11.60 mmol) in anhydrous CH2Cl2 (100 mL) was
added dropwise within 3 h to a stirred solution of 16 (1.56 g, 5.30 mmol) and
malonyl chloride (0.57 mL, 5.83 mmol) in anhydrous CH2Cl2 (480 mL). After
18 h, the mixture was filtered on a plug of SiO2 (CH2Cl2) and evaporated.
Column chromatography (SiO2, CH2Cl2/cyclohexane 80:20 to CH2Cl2) gave 17
(450 mg, 24%), 18 (290 mg, 15%) and 19 (60 mg, 3%). Compound 17: colorless
oil; IR (neat): 1735 (C@O); 1H NMR (400 MHz, CDCl3): 4.29 (t, J = 6 Hz, 4H),
3.86 (t, J = 6 Hz, 4H), 3.37 (s, 2H), 1.91 (m, 4H), 1.01 (s, 18H); 13C NMR
(100 MHz, CDCl3): 166.2, 61.6, 59.3, 42.5, 31.7, 27.8, 20.8. Compound 18:
colorless oil; IR (neat): 1736 (C@O); 1H NMR (400 MHz, CDCl3): 4.29 (t, J = 6 Hz,
8H), 3.90 (t, J = 6 Hz, 8H), 3.37 (s, 4H), 1.89 (m, 8H), 1.00 (s, 36H); 13C NMR
(100 MHz, CDCl3): 166.6, 62.4, 60.0, 41.6, 31.7, 27.8, 21.1; MALDI-TOF-MS:
720.9 ([M]+, calcd for C34H64O12Si2: 720.4). Compound 19: colorless oil. 1H
NMR (400 MHz, CDCl3): 4.22 (m, 12H), 3.84 (t, J = 6 Hz, 12H), 3.30 (s, 6H), 1.83
(m, 12H), 0.93 (s, 54H); 13C NMR (100 MHz, CDCl3): 166.6, 62.5, 60.1, 41.5,
31.7, 27.8, 21.1; MALDI-TOF-MS: 1103.5 (100%, [M+Na]+, calcd for
7. For examples of regioselective synthesis of fullerene tris-adducts, see: (a)
Rapenne, G.; Crassous, J.; Collet, A.; Echegoyen, L.; Diederich, F. Chem. Commun.
1999, 1121–1122; (b) Beuerle, F.; Chronakis, N.; Hirsch, A. Chem. Commun.
2005, 3676–3678; (c) Beuerle, F.; Hirsch, A. Chem. Eur. J. 2009, 15, 7434–7446;
(d) Gmehling, A.; Donaubauer, W.; Hampel, F.; Heinemann, F. W.; Hirsch, A.
Angew. Chem., Int. Ed. 2013, 52, 3521–3524.
C
51H96O18Si3Na: 1103.6), 1081.5 (47%, [M+H]+, calcd for C51H97O18Si3: 1081.6).
8. (a) Guerra, S.; Schillinger, F.; Sigwalt, D.; Holler, M.; Nierengarten, J.-F. Chem.
Commun. 2013, 49, 4752–4954; (b) Sigwalt, D.; Schillinger, F.; Guerra, S.;
Holler, M.; Berville, M.; Nierengarten, J.-F. Tetrahedron Lett. 2013, 54, 4241–
4244.
15. DBU (5 equiv) was added to a solution of C60 (1 equiv), appropriate bis-
malonate (18 or 31, 1 equiv), and I2 (2.5 equiv) in toluene (2 mL/mg of C60).
After 1 h at room temperature, the resulting mixture was directly filtered on a
plug of SiO2 (toluene then CH2Cl2) and concentrated. Column chromatography
(SiO2, CH2Cl2/cyclohexane 50:50 to CH2Cl2) gave the corresponding fullerene
bis-adduct (21 or 32). Compound 21 (115 mg, 27%): brown glassy solid; IR
(neat): 1748 (C@O); UV/vis (CH2Cl2): 259 (84200), 323 (sh, 24700), 439 (2500),
476 (2100), 622 (sh, 250); 1H NMR (400 MHz, CDCl3): 4.71–4.62 (m, 4H), 4.50–
4.41 (m, 4H), 4.03 (m, 4H), 3.88 (m, 4H), 2.10 (m, 4H), 1.98 (m, 4H), 1.11 (s, 9H),
1.04 (s, 18H), 0.87 (s, 9H). 13C NMR (100 MHz, CDCl3): see Figure 4. MALDI-
TOF-MS: 1438.4 ([M+H]+, calcd for C94H61O12Si2: 1438.4). Compound 32
(212 mg, 39%): brown glassy solid; IR (neat): 1743 (C@O); UV/vis (CH2Cl2): 259
(88000), 323 (sh, 26200), 439 (2700), 476 (1300), 622 (sh, 280); 1H NMR
(400 MHz, CDCl3): 4.57 (m, 2H), 4.50 (m, 2H), 4.39 (m, 2H), 4.26 (m, 2H), 1.99
(m, 4H), 1.84 (m, 4H), 1.75 (m, 4H), 1.63 (m, 4H), 1.07 (s, 9H), 1.04 (s, 9H), 1.03
(s, 9H), 0.95 (s, 9H); 13C NMR (100 MHz, CDCl3): 146.3, 146.1, 145.8, 145.7,
145.5, 145.3, 145.0 (2C), 144.7, 144.6, 144.4 (2C), 144.2, 143.6 (2C), 143.5 (2C),
142.4, 141.3, 141.1, 140.1, 137.2, 136.4, 136.1, 135.7, 70.6, 67.7, 66.7, 63.2,
62.8, 50.3, 28.8, 28.5, 27.9, 27.8, 26.9, 25.5, 25.0, 21.4. MALDI-TOF-MS: 1493.3
([M+H]+, calcd for C98H69O12Si2: 1493.4).
16. DBU (0.15 mL, 1.00 mmol) was added to a solution of C60 (108 mg, 0.15 mmol),
19 (58 mg, 0.15 mmol), and I2 (131 mg, 0.52 mmol) in toluene (400 mL). After
1 h at room temperature, the resulting mixture was filtered on a plug of SiO2
(toluene then CH2Cl2) and concentrated. Column chromatography (SiO2,
CH2Cl2/cyclohexane 50:50 to CH2Cl2) gave 22 (55 mg, 61%) as a cherry-red
glassy solid; IR (neat): 1751 (C@O); UV/vis (CH2Cl2): 252 (169115), 281
(107581), 304 (sh, 86077), 482 (6208), 564 (sh, 1819); 1H NMR (400 MHz,
CDCl3): 4.70 (m, 3H), 4.60 (m, 3H), 4.36 (m, 6H), 3.95–3.77 (m, 12H), 1.94 (m,
12H), 0.98 (s, 36H), 0.90 (s, 36H); 13C NMR (100 MHz, CDCl3): see Figure 4;
MALDI-TOF-MS: 1797.0 ([M+H]+, calcd for C111H91O18Si3: 1796.5).
9. Bingel, C. Chem. Ber. 1993, 126, 1957–1959.
10. DBU (5 equiv) was added to a solution of C60 (1 equiv), appropriate bis-
malonate (2a or 2b; 1 equiv) and I2 (2.5 equiv) in toluene (2 mL/mg of C60) at
ꢁ15 °C. After 1 h at ꢁ15 °C, the resulting mixture was directly filtered on a plug
of SiO2 (first eluted with toluene to eliminate the unreacted C60 then with
CH2Cl2) and concentrated. Column chromatography (SiO2, CH2Cl2/cyclohexane
3:2) gave the corresponding fullerene bis-adduct (3a or 3b). Compound 3a
(59 mg, 23%): dark brown solid; IR (neat): 1744 (C@O); UV/vis (CH2Cl2): 310
(sh, 34800), 368 (sh, 9900), 398 (sh, 3900), 410 (sh, 2500), 421 (2400), 479
(2700); 1H NMR (300 MHz, CDCl3): 4.77 (m, 1H), 4.58–3.99 (m, 10H), 3.89 (m,
1H), 1.44 (t, J = 7 Hz, 6H), 1.09 (s, 9H) 0.94 (s, 9H). 13C NMR (75 MHz, CDCl3):
164.0, 163.6, 163.5, 163.1, 148.7, 147.4, 146.6, 146.5, 146.4, 146.3, 146.2, 145.8,
145.6, 145.5, 145.4, 145.3, 145.1, 145.0, 144.9, 144.8, 144.7, 144.6, 144.4, 144.2,
144.1, 143.9, 143.8, 143.7, 143.6, 143.5, 143.2, 143.1, 142.2, 142.1, 142.0, 141.8,
141.6, 141.5, 140.6, 140.4, 140.0, 139.8, 139.0, 138.6, 71.1, 70.4, 68.1, 66.7, 63.6,
63.5, 62.4, 60.8, 53.8, 51.2, 28.1, 27.7, 21.8, 21.4, 14.3; MALDI-TOF-MS: 1210.2
(100%, [M+H]+, calcd for C82H37O10Si: 1210.3), 1164.7 (21%, [MꢁOEt]+, calcd for
C
80H32O9Si: 1165.2). Compound 3b (332 mg, 48%): dark brown solid; IR (neat):
1751 (C@O); UV/vis (CH2Cl2): 310 (sh, 38670), 361 (sh, 13450), 398 (sh, 3850),
409 (sh, 2410), 421 (2260), 479 (sh, 2740); 1H NMR (300 MHz, CD2Cl2): 4.81–
4.71 (m, 2H), 4.57–4.36 (m, 6H), 3.98–3.84 (m, 4H), 2.06–1.96 (m, 4H), 1.44 (t,
J = 7 Hz, 6H), 1.06 (s, 9H), 0.94 (s, 9H); 13C NMR (75 MHz, CDCl3): 164.1, 163.6,
163.3 (2C), 148.8, 147.3, 147.0, 146.5, 146.4, 146.2, 146.1, 145.8, 145.5, 145.4,
145.3, 145.2, 145.1, 145.0, 144.9, 144.8, 144.7, 144.6, 144.5, 144.3, 144.1, 143.9,
143.7, 143.6, 143.5, 143.2, 143.1, 142.5, 142.0, 141.9, 141.8, 141.7, 141.5, 141.2,
140.5, 139.7, 138.8, 138.6, 71.7, 70.5, 64.2, 63.5, 63.4, 63.3, 60.4, 59.8, 54.0,
51.6, 32.2, 31.7, 27.8, 27.0, 21.3, 14.3; MALDI-TOF-MS: 1237.3 ([M+H]+, calcd
for C84H41O10Si: 1237.3).
17. (a) Nierengarten, J.-F.; Felder, D.; Nicoud, J.-F. Tetrahedron Lett. 2000, 41, 41–44;
(b) Felder, D.; Nierengarten, H.; Gisselbrecht, J.-P.; Boudon, C.; Leize, E.; Nicoud,
J.-F.; Gross, M.; Van Dorsselaer, A.; Nierengarten, J.-F. J. New Chem. 2000, 24,
687–695.
11. BF3ꢀEt2O (20 equiv) was added to
a solution of the appropriate fullerene
derivative (3a–b; 1 equiv) in CH2Cl2/CH3CN (2:1) at room temperature. The