Enantioselective cycloaddition of Muenchnones onto [60]fullerene: Organocatalysis versus metal catalysis

Article abstract of DOI:10.1021/ja500071k

Novel chiral catalytic systems based on both organic compounds and metal salts have been developed for the enantioselective [3 + 2] cycloaddition of muenchnones onto fullerenes and olefins. These two different approaches proved to be efficient and complem

Full text of DOI:10.1021/ja500071k

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̈
Enantioselective Cycloaddition of Munchnones onto [60]Fullerene:
Organocatalysis versus Metal Catalysis
Juan Marco-Martínez,§ Silvia Reboredo,§ Marta Izquierdo,§ Vanesa Marcos,§ Juan Luis Lopez,§
́
Salvatore Filippone,§ and Nazario Martín*,§,‡
§Departamento de Química Organ
́
ica I, Facultad de Química, Universidad Complutense, E-28040 Madrid, Spain
‡IMDEA−Nanoscience, Campus de Cantoblanco, E-28049 Madrid, Spain
S
* Supporting Information
ABSTRACT: Novel chiral catalytic systems based on both organic
compounds and metal salts have been developed for the
enantioselective [3 + 2] cycloaddition of munchnones onto fullerenes
̈
and olefins. These two different approaches proved to be efficient and
complementary in the synthesis of optically active pyrrolino[3,4:1,2]
[60]fullerenes with high levels of enantiomeric excess and moderate to
good conversions. Further functionalization of the pyrrolinofullerene
carboxylic acid derivatives has been carried out by esterification and
amidation reactions.
by fullerenes thanks to their neutral behavior toward the catalyst in
nucleophilic addition reactions. An illustrative example of this use of
fullerenes has recently been reported by our group.3b
INTRODUCTION
■
Chirality in fullerenes and related carbon nanostructures is
currently a challenging topic of interest for the design and
application of these new optically active compounds in fields
such as medicinal chemistry or materials science.1 Particularly,
in the latter field, where fullerenes find the most promising
applications, chirality has recently proved to play a critical role
in the control of some physical properties.2 On the other hand,
the unavailability of asymmetric synthesis in fullerene science
has strongly limited the use of chiral fullerene derivatives and,
therefore, the development of chiral carbon nanostructures
with enhanced properties. A major breakthrough has been the
introduction of asymmetric metal-catalyzed processes to
prepare optically pure [60] and [70]fullerene derivatives by
cycloaddition reaction of azomethine ylides onto hollow
fullerenes3,4 as well as onto metallofullerenes5 with a full control
of the stereochemical outcome. Furthermore, more recently,
organocatalytic methods have been applied for the first time in
fullerene science affording chiral [60]fullerene derivatives by a
convergent cycloaddition of allenoates onto C60.6
Thus, in the search for new optically active fullerene
derivatives as well as for new chiral induction modes onto no
activated double bonds such as those of fullerenes, we turned
our attention onto oxazol-5-(4H)-ones (oxazolones or
azlactones). These substrates featuring different reactive sites
(acidic, electrophilic, or Lewis acid active site) allow a versatile
chemistry7 and a potentially diverse chiral induction using both
metal catalysts8 and organocatalysts (Scheme 1).9
Scheme 1. General Strategies for the Catalytic Asymmetric
Synthesis of Pyrrolino[3,4:1,2][60]fullerenes
Despite the aforementioned achievements, the difficult
activation and the even more difficult asymmetric induction
of all-carbon cages make the introduction of chirality onto
fullerenes still a challenging and profitable task. Indeed, the
absence of functional groups and the no coordinating polyolefin
nature of fullerenes prevent both the use of metal mediated
processes and the employ of chiral organic molecules to activate
the fullerene double bonds.
On the other hand, what is a drawback in the chiral
functionalization of fullerenes turns into a very useful setting for
the evaluation “a priori” of the employed catalyst, regardless of
the olefin system used. Thus, the efficiency, the sense of the
asymmetric induction, or, in general, the stereochemical
outcome for a chiral metal- or organocatalyst could be benchmarked
Particularly, oxazolones are known to efficiently react as 1,3-
dipoles (the so-called munchnones) with alkenes under Lewis
̈
acidic conditions. A diastereoselective silver mediated reaction
Received: January 4, 2014
Published: January 31, 2014
© 2014 American Chemical Society
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and an enantioselective gold-catalyzed synthesis, reported by
Tepe10 and Toste,11 respectively, are the sole stereoselective
examples reported so far for the preparation of Δ1-pyrrolines.
These nitrogen-containing heterocyclic systems are extensively
found in nature as biosynthetic intermediates and as part of
pheromones, alkaloids, steroids, hemes, and chlorophylls.12
Recently, the first organocatalytic [3 + 2] cycloaddition of
munchnones to a double bond was achieved by the
̈
employment of a bifunctional catalyst endowed with a basic
site (chiral amine) and thiourea moiety able to activate the
double bond. However, these results were limited to the highly
activated dipolarophiles methyleneindolinones.13
Herein, we report two different asymmetric activations of
azlactones (Scheme 1), able to induce a cycloaddition to the
“singular” fullerene dipolarophile affording optically active
pyrrolino[3,4:1,2][60]fullerenes, a new class of chiral fullerene
derivatives. For the first time, catalysts based on nonprecious
metals14 and on an organocatalytic methodology are described
and evaluated onto fullerenes as well as conventional double
bonds.
RESULTS AND DISCUSSION
■
Figure 1. Cinchona-type catalysts tested for the organocatalytic [3 + 2]-
Screening of Chiral Organic Catalysts. As none of the
organocatalytic activation modes known so far15 enable the
asymmetric activation of fullerenes double bonds, the organo-
catalytic chiral induction on these all-carbon compounds has to
be necessarily introduced through the partner starting material.
Thus, thanks to the presence of a highly acidic proton in the
oxazolone ring, we guessed the use of a chiral base could be a
suitable method to trigger the enantioselective cycloaddition
onto [60]fullerene.
cycloaddition of munchnones onto [60]fullerene.
̈
onto methyleneindolinone (Figure 1).13 However, and not
surprisingly, they did not display any enantioselectivity. Indeed,
these catalysts can only activate azlactones by means of the
nitrogen base, while the LUMO activation by hydrogen bond
with thiourea does not take place in fullerenes.
The use of phase transfer catalysts 7a−h (PTC, Figure 2) in
On the other hand, since base-catalyzed reactions of
azlactones with electron-poor olefins give rise to nucleophilic
addition with different regioselectivity at C-2 or C-4 carbon
atom,16 we started to verify the feasibility of the [3 + 2]
cycloaddition onto [60]fullerene by the use of a common base.
Thus, Et3N promoted the [3 + 2] cycloaddition of azlactone 1a
to [60]fullerene affording a 5-carboxypyrroline (26% conver-
sion). The different chemoselectivity with respect to other
olefins, and therefore the pyrroline formation, is probably due to
the high electron-withdrawing nature of fullerene. Thus, after the
nucleophilic addition of the azlactone, the stability of the
fullerene anion allows the further cyclization by nucleophilic
attack on the C-2 followed by ring-opening of the oxazolone ring
(Scheme 1, path b). The efficiency of this reaction as well as the
stereoselectivity of the chiral catalysts screened were evaluated
through the easily isolated and stable N-acyl urea derivative 2a
that results from a typical rearrangement of carbodiimides.17
Based on the previous organocatalytic reports of [3 + 2]
cycloaddition of iminoesters onto different activated double
bonds,18 we decided to start our screening focusing on the
noncovalent catalysis, in particular, in cinchona alkaloid
derivatives16 for their easy availability and their excellent results
in a large number of stereoselective nucleophilic additions to
activated double bonds.
toluene/basic water achieved the formation of no racemic
Figure 2. PTCs tested for the organocatalytic [3 + 2] cycloaddition of
munchnones onto [60]fullerene.
̈
mixtures of 2a. However, the enantioselectivities obtained were
poor even at low temperature, once again in contrast to that
previously reported in the literature.19
Despite the ability of organic bases to promote such
cycloaddition was confirmed, catalysts 3a−d and 4a,b, featuring
one or two quinuclidine skeletons, respectively, were unable to
afford any significant enantiomeric excesses of pyrrolino[60]-
fullerene 2a (Figure 1).
The thioureas 5a−c and squaramide 6 are also bifunctional
catalysts featuring a chiral base and a thiourea moiety very
similar to the catalysts used for the cycloaddition of azlactones
Finally, we turn our attention into chiral N-heterocyclic
carbenes (NHCs). These compounds have been widely
employed as ligands in metal catalysis,20 while more recently
have experienced a great interest in organocatalysis.21 In this
regard, NHCs have been used as Brønsted base catalysts
capable to generate alkoxides and enolates in transesterification
reactions22 or Claisen condensations,23 respectively. With this
in mind, we tested several commercially available chiral
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triazolium salts (8−11) as NHC precursors by reaction with 10
equiv of NaH in anhydrous toluene (Figure 3 and Table 1).
Under these reaction conditions, we were able to isolate the
desirable adduct 2a in variable conversions (Table 1, entries 1−4)
but in excellent enantiomeric excess (ee) when 1 equiv of the
triazolium salt 8a was used (entry 1). Several bases with variable
basicity were evaluated (entries 5−10) demonstrating that
stronger bases such as KOH (entry 10) worked better in terms
of conversion and enantioselectivity than weaker ones like
Na2CO3 (entry 6). However, when DBU, widely used with this
type of NHCs, was employed, the reaction did not take place
(entry 9). The quantity of base was also studied in the reaction
(entries 11−14), and we could observe that the optimal
enantioselectivity was achieved with 10 equiv of NaH. Afterward,
the solvent study revealed a preference for toluene (entries 15−18).
In addition, and with the aim of finding the better conditions
for an efficient enantioselective cycloaddition, we also screened
the temperature of the process; nevertheless, neither the lower
temperatures (entries 19−20) nor the higher ones (entry 21)
improved the previous obtained results. Fortunately, we
were also able to isolate the corresponding enantiomer of
pyrrolinofullerene 2a by using the commercially available NHC
opposite enantiomer 8b with also high ee and conversion values
(entry 22). Finally, the catalytic version of the process has also
been tested (10 mol %), giving rise to a decrease in the
conversion as well as in the enantioselectivity (entry 23).
Therefore, after many attempts, we eventually succeeded in
inducing and controlling the chirality on [60]fullerene
derivatives by using an NHC-organocatalyst. It is worth noting
that the process takes place without the previous activation of
the dipolarophile under mild reaction conditions and with
moderate to good levels of conversion and enantioselectivity.
Screening of Chiral Metal−Ligand Complexes. In the
search for an alternative methodology for the asymmetric
synthesis of pyrrolinofullerenes, we explored the combination
of non precious metals with easily available chiral phosphines.
Racemic ( )-BINAP along with silver acetate salt was found
efficient to afford, after N-N′-dicyclohexylcarbodiimide (DCC)
addition, the racemic mixture of 5-carbamoyl pyrrolino[3,4:1,2]
[60]fullerene derivative 2b in moderate conversion (45%)
(entry 1, Table 2). As (R)-BINAP afforded poor ee values
(20%) (see Supporting Information), we decided to use those
chiral metal complexes that previously gave us better results in
the cycloaddition of iminoesters to fullerenes.3 Thus, chiral
complex AgOAc/(R,R)-BPE (12) induced the cycloaddition of
the azlactone 1b with good conversion but with a modest 50%
ee (entry 2, Table 2). On the other hand, Cu(OAc)2, while
gave rise to poor conversion and ee with (R)-FeSulPhos (13),
proved to be a suitable metal for this transformation (entry 3,
Table 2). Neither the complex (R)-DTBM-SegPhos-gold
benzoate was able to reproduce the same high enantioselective
level reported previously.11 Thus, the cycloaddition occurs in
high conversion though only 40% of ee was achieved (entry 4,
Table 2). This result is probably due to the no coordinating
nature of [60]fullerene that needs different conditions to those
used for typical electron poor coordinating olefins. However, it
is noteworthy that the absolute configuration of the new chiral
center (S) in 2b, inferred by CD spectra, is the same as the
nonfullerenic analogue obtained with the same catalyst,11 and it
is consistent with an electrophilic attack of the [60]fullerene to
Figure 3. NHCs tested for the organocatalytic [3 + 2] cycloaddition of
munchnones onto [60]fullerene.
̈
Table 1. Screening of NHCs in the Cycloaddition of
a
Azlactone 1a with [60]Fullerene
b
b
T
(°C)
conv.
(%)
ee (%)
c
entry NHC base (equiv)
solvent
product
1
2
8a
9
NaH (10)
NaH (10)
NaH (10)
NaH (10)
KI (10)
toluene
toluene
toluene
toluene
toluene
toluene
rt
rt
>99
10
98
11
4
88 (S)-2a
16 (S)-2a
16 (R)-2a
22 (R)-2a
0
3
10
11
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8b
8a
rt
4
rt
5
rt
6
Na2CO3 (10)
rt
33
37
−
34 (S)-2a
4 (S)-2a
−
7
NaHCO3 (10) toluene
rt
8
KHDMS (10)
DBU (10)
KOH (10)
NaH (1)
toluene
toluene
toluene
toluene
toluene
toluene
toluene
CS2
rt
9
rt
−
−
10
11
12
13
14
15
16
17
18
19
20
21
22
rt
96
98
45
78
37
−
74 (S)-2a
72 (S)-2a
72 (S)-2a
76 (S)-2a
80 (S)-2a
−
rt
NaH (5)
rt
NaH (100)
NaH (1000)
NaH (10)
NaH (10)
NaH (10)
NaH (10)
NaH (10)
NaH (10)
NaH (10)
NaH (10)
NaH (10)
rt
rt
rt
CH3CN
o-DCB
PhCl
rt
−
−
rt
89
85
8
68 (S)-2a
36 (S)-2a
84 (S)-2a
34 (S)-2a
54 (S)-2a
84 (R)-2a
64 (S)-2a
rt
toluene
toluene
toluene
toluene
toluene
0
−30
50
rt
10
>99
99
28
the Re face of the munchnone.
̈
d
The next step was to skip from the acetate to a less
coordinating no basic counterion in an attempt to obtain a
tighter interaction between metals and the monodentate azlactone.
In sharp contrast to what happened in the cycloaddition of the
iminoesters,3 the use of SbF6− as counterion of the complex silver-
(R,R)-BPE (12) along with Et3N as a base, afforded pyrroline 2a
with 87% ee (entry 5, Table 2). This behavior was also observed
when we employed the pair (R)-FeSulPhos (13)-Cu(I) but using
23
rt
a
General reaction conditions: A mixture of the triazolium salt (NHC,
1 equiv), [60]fullerene (1 equiv), and the base (10 equiv) in 1 mL of
solvent is stirred for 10 min at rt, then 0.016 mmol of azlactone 1a
(2 equiv) is added. After 30 min of reaction, excess of DCC is added.
b
Conversion and ee have been determined by HPLC analysis.
c
Absolute configuration has been assigned on the base of CD
d
measurements. 10 mol % of 8a is used.
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a
Table 2. Metal-Catalyzed 1,3-Dipolar Cycloaddition of Azlactone 1b with [60]Fullerene
b
b
c
entry
metal salt/ligand
solvent (base)
T (°C)
conv. (%)
ee (%) product
1
2
3
4
5
6
7
AgOAc/( )-BINAP
AgOAc/(R,R)-BPE
toluene (/)
toluene (/)
toluene (/)
PhF/THF (/)
PhF (Et3N)
PhCl (Et3N)
PhCl (Et3N)
25
0
45
88
23
95
33
25
25
−
50 (S)-2b
5 (R)-2b
40 (S)-2b
87 (S)-2b
70 (R)-2b
90 (S)-2b
Cu(OAc)2/(R)-FeSulPhos
(R)-DTBM-SegPhos(AuOBz)2
AgSbF6/(R,R)-BPE
25
−30
0
d
CuI(OTf) /(R)-FeSulPhos
25
0
d
CuI(OTf) /(S)-Me-f-KetalPhos
a
General reaction conditions: A mixture of 0.01 mmol azlactone 1b, [60]fullerene (1 equiv), metal salt (20 mol%), ligand (20 mol%), and base
b
(1 equiv) in 1.5−2 mL of indicated solvent is stirred for one hour at indicated temperature, then excess of DCC is added. Conversion and ee have
c
d
been determined by HPLC analysis. Absolute configuration has been assigned on the base of CD measurements. CuI(OTf)-benzene complex.
triflate instead of acetate and Et3N as base. Similarly to the
azomethine ylides addition onto [60]fullerene, this chiral ligand
gave rise to the opposite pyrroline enantiomer with 25%
conversion and −70% ee (entry 6, Table 2). The enantioselectivity
was found higher by using (S)-Me-f-KetalPhos (14) as chiral
ligand of Cu(I)triflate-benzene complex since the pyrroline 2b is
formed with 25% conversion and 90% ee (entry 7, Table 2). It is
worthy to note that these results represent the first example of
chiral complexes (entries 1, 2, and 9, Table 3). Furthermore,
excellent enantiomeric excesses were observed for the
pyrrolinofullerenes 2b and 2c (90% and 96%, entries 2 and
3, Table 3) with CuI(OTf)-benzene complex/(S)-Me-f-
KetalPhos (14)/Et3N for the (S)-2 products. It is worth
mentioning that in the latter case, the presence of three large
alkoxy chains in the aromatic moiety of 2c provided enough
solubility to allow the direct isolation of the free carboxylic acid
pyrrolinofullerene derivative without the need of using DCC
for the further esterification (see SI).
enantioselective cycloaddition of munchnones catalyzed by a
̈
copper salt (Figure 4).
When CuI(OTf)-benzene complex/(S)-Me-f-KetalPhos
(14)/Et3N system is employed, the enantioselectivity of
cycloaddition of azlactone 1d, endowed with a more hindered
benzyl group, onto [60]fullerene is still high with 88% of ee
(entry 4, Table 3). The complex silver-(R,R)-BPE (12) gave
rise to slightly lower enantioselectivity (68%). Interestingly, its
chiral induction sense resulted substrate dependent, and it
reverted when the phenylalanine-substituted azlactone 1d was
used (entry 4, Table 3). Thus, such cycloaddition afforded the
opposite enantiomer of pyrroline 2d.
Figure 4. Chiral ligands: (R,R)-BPE ((−)-1,2-bis[(2R,5R)-2,5-diphenyl-
phospholano]ethane), (12), (R)-FeSulPhos ((Rp)-2-(tert-butylthio)-1-
(diphenylphosphino)ferrocene), (13), (S)-Me-f-KetalPhos (1,1-bis-
[(2S,3S,4S,5S)-2,5-dimethyl-3,4-O-isopropylidene-3,4-dihydroxyphospholanyl]-
ferrocene), (14).
Azlactones based on glycine, 1e,f, showed moderate
conversions probably due to a less stability of the final products
(also the trapping of the more acidic second proton affords side
products and/or racemization processes).
Moreover, the pair CuI(OTf)-benzene complex/(R)-FeSul-
Phos (13) leads always to the (R)-2 products. In the case of
pyrrolinofullerene 2g, this copper system with (R)-FeSulPhos
(13) performed even better in terms of ee than (S)-Me-f-
KetalPhos (14), 96% (R-2g) vs 90% (S-2g), respectively
(entry 7, Table 3). Therefore, copper chiral systems allow the
efficient switching on the enantioselectivity of the formed
pyrrolino[3,4:1,2][60]fullerenes and with better conversion
and ee values than the silver chiral system.
Finally, different substitution on the aryl ring of the
oxazolone with donating or electron-withdrawing groups did
not modify the behavior of these substrates. Thus, products
2h−j were obtained with excellent ee values (82−94%) when
CuI(OTf)-benzene complex/(S)-Me-f-KetalPhos (14)/Et3N
system was employed (entries 8−10, Table 3).
On the other hand, organocatalysis also provides good to
excellent conversion and enantiomeric excesses. However, better
results on enantioselectivity were obtained for less hindered
Scope of the Catalytic Processes with Different
Oxazolones. Once optimized the conditions for the organo-
catalytic and for the metal-catalyzed [3 + 2] cycloaddition of
oxazolones onto [60]fullerene, we studied the scope of the
reaction. The different oxazolones used were prepared from
amino acids such as glycine, alanine, and phenylalanine and
benzoic acid or derivatives endowed with one or three
hydrocarbon chains. The results obtained for both method-
ologies, using different azlactones 1a−j as 1,3-dipoles are shown
in Table 3.
In general, metal-based chiral catalysts gave rise to the desired
pyrrolinofullerene derivatives 2a−j with moderate to good
conversions and high enantiomeric excesses. The asymmetric
induction sense is fully controlled by suitable choice of the metal
complex, and enantioselectivity is unaffected, or little influenced,
by the substitution of the starting oxazolone.
Thus, azlactones 1a, 1b, or 1i lead to the formation of 2a, 2b,
and 2i with high enantioselectivities both with silver or copper
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Table 3. Scope of the Enantioselective 1,3-Dipolar Cycloaddition of Azlactones 1a−j with [60]Fullerene
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Table 3. continued
a
General reaction conditions: A mixture of the triazolium salt (1 equiv), [60]fullerene (1 equiv), and the base (10 equiv) in 1 mL of solvent is stirred
b
for 10 min at rt, then 0.016 mmol of azlactone 1a−j (2 equiv) is added. After 30 min reaction, excess of DCC is added. General reaction conditions:
A mixture of 0.01 mmol azlactone 1a−j, [60]fullerene (1 equiv), metal salt (20 mol%), ligand (20 mol%), and Et3N (1 equiv) in 1.5 mL of
c
chlorobenzene is stirred for 1 h at 0 °C, then excess of DCC is added. Conversion and ee have been determined by HPLC analysis. Isolated yields
d
have only been determined for the racemic mixture (see SI). As a general trend, higher conversions correspond to higher yields. Absolute
e
configuration has been assigned on the base of CD measurements. CuI(OTf)-benzene complex.
oxazolones such as 1a, 1h, or 1j, in which also an efficient
switching on the enantioselectivity is achieved depending on the
triazolium salt-NHC used (84−88% ee with 8a and 74−84% ee
with 8b; entries 1, 8 and 10, Table 3). Unfortunately, this
methodology seems to be much more substrate dependent than
the metallic one (see, for instance, entries 4 or 7, Table 3). All in
all, milder reaction conditions and higher conversion values make
the organocatalytic methodology an efficient tool for the synthesis
of this kind of fullerene derivatives in larger amounts.
Scheme 2. Silver-Catalyzed Enantioselective 1,3-Dipolar
Cycloaddition of Azlactone 1a with Nonfullerenic Alkenes
In summary, the aforementioned results reveal that the
metal-catalyzed and the organocatalytic procedures have a
different behavior depending upon the substitution pattern.
Thus, whereas the metal-catalyzed procedure afforded better
enantioselectivities with a larger scope of oxazolones, the
organocatalytic methodology showed the best enantiocontrol
with less hindered oxazolones and with better conversion
values. Therefore, we can conclude that both methodologies
nicely complement to each other in the synthesis of new
enantiopure pyrrolinofullerene derivatives.
when the reaction crude from azlactone 1b (entry 1, Table 2) is
reacted with MeOH (under acidic conditions), resulting
pyrrolinofullerene is esterificated affording 16. In the same way,
treatment with glycine methyl ester hydrochloride leads to 17 in
an amidation reaction (Figure 5, for experimental details see SI).
[3 + 2] Cycloaddition onto N-phenylmaleimide. The
efforts to promote the 1,3-dipolar cycloaddition reaction onto
nonfullerenic olefins by using NHC methodology were
unsuccessful. Thus, analogously to other previous described
organic catalyst,7b,24 it promoted a Michael addition but with
poor or no stereoselectivity.
Figure 5. Ester (16) and amido (17) functionalized pyrrolino[3,4:1,2]-
[60]fullerenes.
On the other hand, we have demonstrated that silver-based
chiral catalyst is able to trigger efficiently the cycloaddition onto
nonfullerenic alkenes. Thus, catalytic system AgSbF6/(R,R)-
BPE (12)/Et3N induced the addition of the azlactone 1a onto
N-phenylmaleimide as dipolarophile with high ee (94%, 97:3)
for the exo adduct (15) after 10 h at rt and treatment with
(trimethylsilyl)diazomethane solution (TMSCHN2, 2.0 M in
hexanes) with 67% yield (Scheme 2).
Moreover, controlled formation of pyrrolino[3,4:1,2][60]-
fullerene carboxylic acid derivatives allows new and straightfor-
ward ways for the further functionalization of the [60]fullerene.
In contrast to the pyrrolidino[3,4:1,2][60]fullerenes, which
undergo retrocycloaddition processes, pyrrolino[3,4:1,2][60]-
fullerenes are more stable and could be functionalized either on
the imino double bond or the carboxylic acid moiety. Thus,
As expected, both enantiomers of all pyrrolinofullerenes gave
rise to mirror pairs of circular dichroism (CD) spectra
characterized by a strong Cotton effect at around 430 nm
(Figure 6). This peak, which is associated to the UV−vis band
typical of all fullerene monoadducts, has been used as an
empirical way to assign the absolute configuration of chiral
fullerene derivatives.25 According to the corrected sector rule,6
since all pyrrolinofullerenes formed by CuI(OTf)-benzene
complex/(14) and AgSbF6/(12) (except 2d) feature a negative
Cotton effect (red line, Figure 6 and SI), an S configuration in
the C-5 of the heterocyclic ring is assigned. Instead an R
configuration could be assigned to the derivative stemming
from the use of CuI(OTf)-benzene complex/(13) catalyst
(see SI).
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ez,
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ez, M.;
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Figure 6. CD spectra for both enantiomers of 2c (concentration, 4 ×
Chem. Soc. 2014, 136, 705.
10−4 M in dichloromethane).26
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ar, A.; Filippone, S.; Martín-Domenech, A.;
́
CONCLUSIONS
■
In summary, we describe two complementary enantioselective
synthetic methods to obtain new, stable, and versatile
pyrrolino[60]fullerene derivatives with good enantiomeric ex-
cesses. For the first time, and in sharp contrast to conventional
olefins, we have described an organocatalytic methodology able to
promote [3 + 2]cycloaddition of azlactones onto [60]fullerene.
This represents the first organocatalytic example where the
oxazolones are used as 1,3-dipoles with fullerenes.
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́
ault, F.;
[60]Fullerene has also been successfully used as a benchmark
to develop novel chiral catalytic systems based, for the first time,
on silver and copper salts able to promote the enantioselective
́
cycloaddition of munchnones both on [60]fullerene and
̈
́
N-phenylmaleimide. Furthermore, this new synthetic approach
to enantiomerically pure fullerene derivatives affords in situ
preparation of compounds endowed with different chemical
functionality, thus enhancing the scope and versatility of these
new compounds.
The aforementioned results pave the way for the application
of fullerenes in fields where chirality is a key issue such as in
biomedical applications as well as in the thus far less explored
materials science, where chirality has recently been shown to
impact some physical properties.2
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details for the preparation of the azlactones,
pyrrolino[3,4:1,2][60]fullerenes, and functionalized derivatives;
spectroscopic and chromatographic data for characterization of
compounds and CD measurements. This material is available
free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
nazmar@ucm.es
■
(13) Sun, W.; Zhu, G.; Wu, C.; Li, G.; Hong, L.; Wang, R. Angew.
Chem., Int. Ed. 2013, 52, 8633.
(14) Catalysis Without Precious Metals; Bullock, R. M., Ed.; Wiley-
VCH Verlag GmbH & Co. KGaA: Weinheim, 2010.
(15) (a) Special issue on organocatalysis (no. 12) Chem. Rev. 2007,
107. (b) MacMillan, D. W. C. Nature 2008, 455, 304. (c) Bertelsen, B.;
Jørgensen, K. A. Chem. Soc. Rev. 2009, 38, 2178. (d) Jacobsen, E. N.;
MacMillan, D. W. C. Proc. Natl. Acad. Sci.USA 2010, 107, 20618.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the European Research Council
ERC-2012-ADG_20120216 (Chirallcarbon), Ministerio de
Economía y Competitividad (MINECO) of Spain (project
CTQ2011-24652; Consolider-Ingenio CSD2007-00010), and
the CAM (MADRISOLAR-2 project S2009/PPQ-1533). N.M.
thanks to Alexander von Humboldt Foundation.
́
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(17) There are many examples reported in the literature where O-
acylisourea intermediate formed after carbodiimide addition rearrange
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145. (b) Detar, D. F.; Silverstein, R. J. Am. Chem. Soc. 1966, 88, 1013.
(c) Detar, D. F.; Silverstein, R. J. Am. Chem. Soc. 1966, 88, 1020.
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