Di- And dodeca-mitsunobu reactions on C60 derivatives: Postfunctionalization of fullerene mono- and hexakis-adducts

Article abstract of DOI:10.1002/chem.200902141

A study was conducted to demonstrate the use of the Mitsunobu reaction as an efficient tool for the post-functionalization of fullerene mono- and hexakis-adducts. A C₆₀ mono-adduct bearing 2 hydroxyl groups and a hexakis-adduct with 12 hydroxyl

Full text of DOI:10.1002/chem.200902141

DOI: 10.1002/chem.200902141
Di- and Dodeca-Mitsunobu Reactions on C60 Derivatives: Post-
Functionalization of Fullerene Mono- and Hexakis-Adducts
Philippe Pierrat, Cꢀline Rꢀthorꢀ, Thierry Muller,* and Stefan Brꢁse*[a]
The diverse addition patterns of fullerene adducts make
them attractive molecules, generating widespread applica-
tion.[1] Firstly, in terms of the latter, mono-adducts are ex-
tensively used in opto-electronic devices, owing to the fuller-
ene coreꢀs capacity to accept up to six electrons.[2] A second
important application involves the utilization of fullerene
adducts as structural components in material sciences.[3]
With their octahedral topology,[4] Th-symmetric hexakis-ad-
ducts, are particularly intriguing. Amongst others, the latter
have been used in C60-based star polymers.[5] In the afore-
mentioned contexts, the relatively stable methanofullerene
adducts obtained through Bingel cyclopropanation reactions
are of particular interest. However, this functionalization ap-
proach—primarily developed by A. Hirsch[6] and later opti-
mized by Y.-P. Sun[7]—suffers from two critical weaknesses.
One is its effectively exclusive limitation to malonates; only
a few exceptions are known. The other is a structural con-
cern. In fact, quite often only the use of fairly simple malo-
nates leads to the desired fullerene adducts in reasonable
yields without tedious purifications. In order to overcome
these problems, several groups have developed post-func-
tionalizations of methanofullerene adducts. For instance, J.-
F. Nierengarten adapted the copper-mediated Huisgen 1,3-
dipolar cycloaddition reaction and applied it to the prepara-
tion of complex hexasubstituted fullerenes.[8] A. Hirsch de-
veloped a selective deprotection–functionalization sequence
of fullerene e,e,e-trisadducts.[9] Our own group derivatized
hexakis methanofullerenes by using several organometallic
cross-coupling reactions.[10]
This article outlines the use of the Mitsunobu reaction[11]
as an efficient tool for the post-functionalization of fullerene
mono- and hexakis-adducts. The mild, virtually neutral con-
ditions under which this dehydrative coupling of an alcohol
with a pronucleophile (generally an acid) proceeds, prompt-
ed our group to use this reaction for the derivatization of
fullerene adducts. To this end, we have prepared a C60
mono-adduct bearing 2 hydroxyl groups and a hexakis-
adduct with 12 hydroxyl functions. The preparation of hexa-
kis compound 4 is depicted in Scheme 1.
Ethylene glycol was mono-protected as tert-butyldimethyl-
silyl ether according to a previously reported procedure.[12]
Subsequent diesterification of malonic acid was performed
in the presence of DCC in 97% yield. Hexakis-adduct 3 was
then readily synthesized by using the optimized conditions
[a] Dr. P. Pierrat, Dr. C. Rꢁthorꢁ, Dr. T. Muller, Prof. Dr. S. Brꢂse
Institut fꢃr Organische Chemie and Center
for Functional Nanostructures (CFN)
Karlsruhe Institute of Technology (KIT)
Fritz-Haber-Weg 6, 76131 Karlsruhe (Germany)
Fax : (+49)721 608 8581
E-mail: Stefan.Braese@kit.edu
Scheme 1. i) DCC, MeCN, RT, 2 h (97%); ii) C60 (0.1 equiv), CBr4
(10 equiv), DBU (2 equiv), o-dichlorobenzene, RT, 24 h; iii) HCl/MeOH,
CH2Cl2, RT, 12 h (28% over 2 steps).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902141.
11458
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Chem. Eur. J. 2009, 15, 11458 – 11460

COMMUNICATION
described by Y.-P. Sun.[7] The resulting crude mixture was
purified on silica-gel column to afford an inseparable mix-
ture of pentakis- and hexakis-adduct. The mixture of both
isomers was subjected to desilylation using an excess of hy-
drogen chloride as a methanolic solution. At this stage, pen-
takis and hexakis derivatives could be easily separated
through a silica gel column chromatography using acetone/
EtOH (90/10) as eluent. The chemical structure of com-
1
pound 4 was confirmed by H- and 13C NMR analysis. As
shown in Figure 1, the 13C NMR spectrum of fullerene hexa-
Scheme 2. i) RCO2H (or NuH) (3 equiv), DEAD (3 equiv), PPh3
(3 equiv), THF, RT, 15–18 h; ii) RCO2H (or NuH) (20 equiv), DEAD
(20 equiv), PPh3 (20 equiv), THF, RT, 15–18 h.
Table 1. Pronucleophiles used in the Mitsunobu reaction.
Entry
RCO2H (or NuH)
Product 6
Product 7
[yield in%][a]
[yield in %][a]
1
2
3
4-nitrobenzoic acid
4-cyanobenzoic acid
1-phenyl-1H-tetrazole
-5-thiol[b]
6a [53 (73)]
6b [69 (83)]
6c [52 (72)]
7a [70 (97)]
7b [21 (88)]
7c [70 (97)]
4
4-iodo-2-nitrobenzoic
acid
6d [62 (79)]
7d [21 (88)]
5
6
4-iodobenzoic acid
4-methyl-N-(prop-2-ynyl)
benzenesulfonamide[b]
isoindoline-1,3-dione[b]
6e [3 (17)]
6 f [0]
7e [10 (83)]
7 f [0]
Figure 1. 13C NMR spectra ([D6]DMSO, 125 MHz) of dodeca alcohol 4.
7
6g [0]
7g [0]
[a] In parentheses: Calculated yield per alcohol function. [b] Pronucleo-
phile NuH containing an acidic hydrogen atom.
kis-adduct 4 is in complete agreement with its Th-symmetri-
cal structure and shows the three expected fullerene reso-
nances (d=68.6 ppm for the sp3 C atoms; 140.5 and
144.9 ppm for the two different sp2 C atoms), a signal for
the bridgehead C atoms (d=45.3 ppm), a signal for the car-
bonyl groups (d=162.7 ppm), and two signals for the (CH2)2
linkers (d=58.5 and 68.5 ppm). The corresponding mono-
adduct 5 was obtained following the same strategy in an
overall yield of 36% over 4 steps (see the Supporting Infor-
mation).
With polyalcohol 4 and diol 5 in hand, we started investi-
gating the Mitsunobu reaction (Scheme 2, Table 1). We were
pleased to note that the classic Mitsunobu conditions using
a combination of diethyl azodicarboxylate (DEAD) as oxi-
dizing azo reagent and triphenylphosphine (TPP) as reduc-
ing agent delivered the desired di- and dodeca-esters in
moderate to good yields (Table 1, entries 1–5). Yields per al-
cohol function are however corresponding to yields previ-
ously reported in the literature. To the best of our knowl-
edge, this is the first time that a twelvefold Mitsunobu reac-
tion has been undertaken.
rivative 4 than with mono-adduct 5 (entries 1–5). A possible
explanation for this result involves unidentified side prod-
ucts generated through the reaction of the fullerene core of
mono-adduct 5. In contrast, for hexakis-adduct 4, the core is
completely shielded by the malonates and cannot react any-
more. No reaction took place with known Mitsunobu sub-
strates 4-methyl-N-(prop-2-ynyl)benzenesulfonamide and
isoindoline-1,3-dione (entries 6, 7).
Even the use of 1,1’-(azodicarbonyl)dipiperidine (ADDP)
and tributylphosphine (TBP)—an alternative redox system
specifically developed for inactivated pronucleophiles
having a pKa higher than 11[13]—did not generate better re-
sults (data not shown).
Subsequently, we explored some of the possible applica-
tions of our Mitsunobu approach. Two particularly promis-
ing results are shown in Scheme 3. The first involves a cycli-
zation by a twofold Mitsunobu reaction using 5-nitroisoph-
thalic acid and diol 5 opening up the road to novel fuller-
ene-cyclic malonate derivatives. The second example dem-
onstrates that the Mitsunobu products of both mono- and
hexakis-adducts can be further functionalized by means of
Sonogashira cross coupling reactions in good yield for 9d
(52%, 95% per iodide). Although the yield of mono-adduct
With activated Mitsunobu pronucleophiles (pKa ꢀ11, en-
tries 1–4), the reaction proceeds properly. However, if inac-
tivated substrates are used, the yields drop significantly for
both fullerene adducts (entry 5). Better yields per alcohol
function are consistently attained with hexakis fullerene de-
Chem. Eur. J. 2009, 15, 11458 – 11460
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www.chemeurj.org
11459

T. Muller, S. Brꢂse et al.
Acknowledgements
We gratefully acknowledge the financial support of the Alexander von
Humboldt foundation (grants to P.P. and C.R.) and of the DFG Center
for Functional Nanostructures (CFN, Project C5.2).
Keywords: condensation reaction · fullerenes · Mitsunobu
reaction · post-functionalization · synthetic methods
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2A(PPh3)2
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tually a rare example in which an organometallic cross cou-
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Palladium-mediated cross couplings on lower fullerene ad-
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the catalyst or leading to side reactions.
In conclusion the Mitsunobu condensation between alco-
hols and acids has been successfully applied to the derivati-
zation of methanofullerene mono- and hexakis-adducts. Al-
though results obtained thus far suggest that this approach
is limited to activated Mitsunobu substrates, further investi-
gations are being undertaken to enable the use of a larger
substrate spectrum. This approach enables for third genera-
tion derivatization of the fullerene substrates, which, if com-
bined with existing methods, is a very interesting route yet
to be explored. Within our group, efforts are currently being
made to determine the scope and limitations of this
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Received: August 1, 2009
Published online: October 9, 2009
ACHTUNGTRENNUNGapproach.
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