A new synthesis of fullerenyl ketones catalyzed by Ti(Oi-Pr)4

Article abstract of DOI:10.1016/j.tetlet.2013.04.034

The reaction of fullerene C₆₀ with aryl carboxylates and EtMgBr in the presence of Ti(Oi-Pr)₄ as the catalyst leads to the formation of novel fullerenyl ketones.

Full text of DOI:10.1016/j.tetlet.2013.04.034

Tetrahedron Letters 54 (2013) 3260–3262
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A new synthesis of fullerenyl ketones catalyzed by Ti(Oi-Pr)4
⇑
Usein M. Dzhemilev, Marina A. Famutdinova, Natal’ya R. Popod’ko, Airat R. Tuktarov
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of fullerene C60 with aryl carboxylates and EtMgBr in the presence of Ti(Oi-Pr)4 as the
catalyst leads to the formation of novel fullerenyl ketones.
Received 17 January 2013
Revised 11 March 2013
Accepted 9 April 2013
Available online 15 April 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
[60]Fullerene
Carboxylates
Organomagnesiums
Metal complex catalysis
1,2-Addition
Fullerenyl ketones
Functionalized fullerenes are very attractive systems from a
practical point of view, with most examples being fulleropyridines
and methanofullerenes.
which allows the synthesis of cyclopropanols in high yields from
olefins, carboxylates, and EtMgBr in the presence of Ti
complexes.
While the synthesis of fulleropyridines is mainly carried out
under the Prato reaction conditions,1 methods for synthesizing
methanofullerenes are based predominantly upon two processes:
the reaction between fullerenes and in situ generated
a-halo-
geno-carbanions (the Bingel–Hirsch reaction),2–4 or the cycloaddi-
tion of diazo compounds to these carbon clusters.5
The Bingel–Hirsch reaction is widely used as a preparative
method for the synthesis of methanofullerenes as promising sub-
stances of high value.6,7 On the other hand, the reactions of fuller-
enes with diazo compounds have wide synthetic potential leading
to not only methanofullerenes, but also homo- and
pyrazolinofullerenes.8–16
In our search for a new and effective method to functionalize
fullerenes, we focused on the known Kulinkovich reaction,17–20
H
O
O
O
0 oC, 0−5 min
Ph
+
Ti(Oi-Pr) , EtMgBr
tolu4ene
Ph
Me
[H]+
1
Scheme 1. Synthesis of fullerenyl ketone 1 via the Ti(Oi-Pr)4-catalyzed reaction of
fullerene C60 with methyl benzoate and ethylmagnesium bromide in toluene.
Figure 1. The HMBC spectrum of compound 1 (400.13 MHz for 1H, 100.62 MHz for
⇑
Corresponding author. Tel./fax: +7 347 2842750.
E-mail address: tuktarovar@gmail.com (A.R. Tuktarov).
13C, solvent = CS2–CDCl3, 5:1).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.04.034

U. M. Dzhemilev et al. / Tetrahedron Letters 54 (2013) 3260–3262
3261
We hypothesized that the use of fullerene in this reaction,
instead of an olefin, would simplify the preparation of
methanofullerenes with different functional groups at the bridge
carbon atom, the synthesis of which usually requires multi-step
procedures.
However, the reaction between fullerene C60 and aryl carboxyl-
ates under the Kulinkovich reaction conditions did not lead to the
target [2+1] cycloadducts. In each case, instead of the desired met-
hanofullerene, we obtained the previously undescribed fullerenyl
ketones.
These unexpected results prompted us to study this reaction in
detail focusing on the reaction between fullerene C60 and methyl
benzoate in the presence of EtMgBr and a Ti-containing complex
catalyst. Our preliminary experiments revealed that the best
results were achieved while using Ti(Oi-Pr)4 as the catalyst and
EtMgBr under mild reaction conditions (0 °C, 5–10 min, toluene).
Thus, fullerene C60, under an argon atmosphere, underwent a
reaction with methyl benzoate and EtMgBr in the presence of
Ti(Oi-Pr)4 (1:10:40:10 molar ratio) in toluene at 0 °C21 to give pre-
dominantly phenyl fullerenyl ketone 122 in 57% yield after hydro-
lysis of the reaction mixture with 5% aqueous HCl (Scheme 1). An
increase in temperature (20 °C) contributed to the formation, along
with the target adduct 1, of by-products, namely, 1,2-dihydroful-
lerene and 1-ethyl-1,2-dihydrofullerene in a 3:3:1 ratio and a total
yield of 63%.
Adduct 1 was separated from the reaction mixture by prepara-
tive HPLC. The structure of fullerenyl ketone 1 was confirmed by
one-dimensional (1H, 13C) and two-dimensional (HHCOSY, HSQC,
and HMBC) NMR experiments.
The 1H NMR spectrum of 1 contained high frequency resonance
signals (dH 7.73, 7.79, and 8.72) characteristic of protons of a phe-
nyl group, as well as a singlet (dH 7.39) due to the hydrogen atom
H
0 oC, 30 min
MeO2C
+
Ti(Oi-Pr) , EtMgBr
tolu4ene
O
[H]+
2
Scheme 2. The synthesis of fullerenyl ketone 2 via catalytic addition of the methyl ester of 1,10-biphenyl-2-carboxylic acid to fullerene C60
.
H
0 oC, 0-5 min
CO2Me
MeO2C
CO2Me
+
Ti(Oi-Pr) , EtMgBr
tolu4ene
[H]+
O
3
Scheme 3. Ti(Oi-Pr)4-catalyzed reaction of fullerene C60 with dimethyl terephthalate and EtMgBr.
Ti(Oi-Pr)4
MgBr
Ar
H
O
[H]+
2 EtMgBr
C2H6
Oi-Pr
Ar
O
1
Ti
9
Oi-Pr
4
2 EtMgBr
Oi-Pr
Oi-Pr
Oi-Pr
Ti
i-PrO
OMe
Ti
Oi-Pr
Oi-Pr
Ti
O
5
Ar
8
Oi-Pr
Oi-Pr
Ti
Oi-Pr
i-PrO
O
O
Ti
Ar
O
Me
OMe
Ar
Oi-Pr
Oi-Pr
7
Ti
Ar
O
Me
O
6
Scheme 4. A plausible mechanism for the formation of fullerenyl ketone 1.

3262
U. M. Dzhemilev et al. / Tetrahedron Letters 54 (2013) 3260–3262
attached directly to the fullerene core (dC 57.15). This proton signal
(dH 7.39) in the HMBC experiment had cross-peaks with the carbon
atoms of the fullerene sphere (dC 152.06 and 77.35), the quaternary
carbon atom of the phenyl substituent (dC 136.48), as well as the
carbonyl group (dC 197.60) (Fig. 1).
The MALDI TOF mass spectrum of 1 (negative ion mode using
elemental sulfur as a matrix) contained an intense molecular ion
peak [M]ꢀ at m/z 826.037 (ca. 826.041 for C67H6O), which also sup-
ported the proposed structure.
Similar results were obtained with the methyl ester of
1,10-biphenyl-2-carboxylic acid. Under selected reaction conditions
(0 °C, 30 min, toluene), this methyl ester entered into the reaction
with fullerene C60 and EtMgBr in the presence of the Ti(Oi-Pr)4 cat-
alyst giving rise to biphenyl fullerenyl ketone 223 in 45% yield after
hydrolysis of the reaction mixture (Scheme 2).
tific-pedagogical personnel of innovative Russia’ for 2009–2013
(Agreement No. 8584).
References and notes
1. Prato, M.; Maggini, M.; Giacometti, C.; Scorrano, G.; Sandona, G.; Farnia, G.
Tetrahedron 1996, 52, 5221.
2. Bingel, C. Chem. Ber. 1957, 1993, 126.
3. Camps, X.; Hirsch, A. J. Chem. Soc., Perkin Trans. 1 1997, 1595.
4. Hirsch, A. Synthesis 1995, 895.
5. Tuktarov, A. R.; Dzhemilev, U. M. Russ. Chem. Rev. 2010, 79, 585.
6. Troshin, P. A.; Lyubovskaya, R. N.; Razumov, V. F. Nanotechnol. Russ. 2008, 3,
242.
7. Cataldo, F.; Da Ros, T. Medicinal Chemistry and Pharmacological Potential of
Fullerenes and Carbon Nanotubes; Springer, 2008.
8. Tuktarov, A. R.; Korolev, V. V.; Sabirov, D. Sh.; Dzhemilev, U. M. Russ. J. Org.
Chem. 2011, 47, 41.
9. Tuktarov, A. R.; Korolev, V. V.; Tulyabaev, A. R.; Yanybin, V. M.; Khalilov, L. M.;
Dzhemilev, U. M. Russ. Chem. Bull. 2010, 59, 977.
To further study this reaction, involving two carboxylic groups
simultaneously, we reacted fullerene C60 and the dimethyl ester
of terephthalic acid. Our experiments revealed that only one car-
boxylic group underwent the reaction to give adduct 324 in 53%
isolated yield (Scheme 3). Increasing the duration and temperature
of the reaction as well as altering the ratio of the reactants relative
to fullerene did not favor the reaction at both ester groups.
Based on our previous results and literature data,20 we propose
a plausible mechanism for the formation of fullerenyl ketones from
aryl carboxylates using the model reaction of fullerene C60 with
methyl benzoate and EtMgBr in the presence of Ti(Oi-Pr)4 as the
catalyst (Scheme 4).
Initially, the reaction between Ti(Oi-Pr)4 and EtMgBr affords the
dialkoxytitanocyclopropane intermediate 4 in equilibrium with
the ethylene complex. Displacement of an ethylene molecule from
4 by fullerene C60 results in fullero[60]titanacyclopropane 5 as the
key intermediate. (Treatment of the latter with 5% aqueous HCl
leads to the formation of dihydrofullerene as evidence for the
structure 5).
Subsequent reaction between intermediate 5 and methyl ben-
zoate leads to the formation of fullero[60]oxatitanacyclopentane
7 via the intermediate complex 6. Intramolecular methoxy group
migration across the oxatitanacyclopentane ring of 7 transforms
this molecule into b-titanoketone intermediate 8, which can react
with two equivalents of EtMgBr to give organomagnesium com-
pound (OMC) 9 and regenerate 4, thus completing the catalytic
cycle. Finally, hydrolysis of OMC 9 provides fullerenyl ketone 1.
The absence of the corresponding methanofullerenes among
the reaction products is probably due to thermodynamic factors,
which hinder the intramolecular transformation of intermediate
8 into fullerocyclopropane. In accord with literature data,20 these
transformations are limiting in the Kulinkovich reaction.
In conclusion, we have developed a convenient and efficient
one-pot synthesis of fullerenyl ketones via the reaction between
fullerene C60, methyl arylcarboxylates, and ethylmagnesium bro-
mide in the presence of Ti(Oi-Pr)4 as the catalyst.
10. Tuktarov, A. R.; Korolev, V. V.; Tulyabaev, A. R.; Popod’ko, N. R.; Khalilov, L. M.;
Dzhemilev, U. M. Tetrahedron Lett. 2011, 52, 834.
11. Pellicciari, R.; Annibali, D.; Constantino, G.; Marinozzi, M.; Natalini, B. Synlett
1997, 1196.
12. Tuktarov, A. R.; Akhmetov, A. R.; Sabirov, D. Sh.; Khalilov, L. M.; Ibragimov, A.
G.; Dzhemilev, U. M. Russ. Chem. Bull. 2009, 58, 1724.
13. Pellicciari, R.; Natalini, B.; Potolokova, T. V.; Marinozzi, M.; Nefedova, M. N.;
Peregudov, A. S.; Sokolov, V. I. Synth. Commun. 2003, 33, 903.
14. Tuktarov, A. R.; Akhmetov, A. R.; Khalilov, L. M.; Dzhemilev, U. M. Russ. Chem.
Bull. 2010, 59, 611.
15. Tuktarov, A. R.; Khuzina, L. L.; Dzhemilev, U. M. Russ. Chem. Bull. 2011, 60, 662.
16. Tuktarov, A. R.; Khuzin, A. A.; Popod’ko, N. R.; Dzhemilev, U. M. Tetrahedron
Lett. 2012, 53, 3123.
17. Kulinkovich, O. G.; Sviridov, S. V.; Vasilevskii, D. A.; Pritytskaya, T. S. Russ. J. Org.
Chem. 1989, 25, 2027.
18. Kulinkovich, O. G.; Savchenko, A. I.; Sviridov, S. V.; Vasilevski, D. A. Mendeleev
Commun. 1993, 230.
19. Kulinkovich, O. G.; De Meijere, A. Chem. Rev. 2000, 100, 2789.
20. Wolan, A.; Six, Y. Tetrahedron 2010, 66, 15.
21. General procedure:
A 50 mL glass reactor was charged with C60 (20 mg,
0.0278 mmol) in dry toluene (20 mL), the methyl ester benzoic acid
(0.03 mL, 0.278 mmol), and Ti(Oi-Pr)4 (0.08 mL, 0.278 mmol) under an
anhydrous argon atmosphere at 0 °C. Next, EtMgBr (1 M solution in Et2O,
1.112 mmol) was added dropwise over 2–3 min. The resulting solution was
allowed to warm to rt and stirred for 5–30 min. The mixture was quenched
with an 8–10% (aq) solution of HCl. The layers were separated and the organic
layer was passed through a column containing a small amount of silica gel (ca.
2 g). The reaction products 1–3 and the starting fullerene C60 were separated
by semi-preparative HPLC using toluene as the eluent.
22. Phenyl(C60-Ih)[5,6]fullerene-1(9H)-yl ketone (1). IR: 526, 692, 869, 1009, 1181,
1225, 1428, 1672 cmꢀ1 nm: 255, 327, 432. 1H NMR
. UV (CHCl3), kmax,
(400 MHz, CDCl3): d 7.39 (s, 1H, C60-H), 7.73 (t, 2H, 2CH, J = 7 Hz), 7.79 (t,
1H, CH, J = 7 Hz), 8.72 (d, 2H, 2CH, J = 7 Hz). 13C NMR (100 MHz, CDCl3): d
57.15, 77.35, 129.10, 129.64, 133.39, 136.00, 136.05, 136.48, 140.19, 140.76,
141.69, 141.73, 141.88, 142.21, 142.27, 142.76, 142.85, 143.16, 143.39, 144.50,
144.78, 145.51, 145.57, 145.59, 145.82, 146.33, 146.34, 146.50, 146.52, 147.03,
147.34, 147.49, 150.68, 152.06, 197.60. MALDI TOF, m/z 826.037 [M]ꢀ
(C67H6O).
23. 20-(10,100-Biphenyl)(C60-Ih)[5,6]fullerene-1(9H)-yl ketone (2). IR: 526, 663, 742,
1107, 1260, 1431, 1699 cmꢀ1. UV (CHCl3), kmax, nm: 255, 328, 434. 1H NMR
(400 MHz, CDCl3): d 7.4–7.64 (m, 9H, 9CH), 7.71 (s, 1H, C60-H). 13C NMR
(100 MHz, CDCl3): d 55.99, 79.36, 127.14, 128.53, 128.99, 129.45, 129.58,
129.88, 130.73, 135.33, 135.99, 138.13, 139.32, 139.56, 140.44, 140.73, 141.21,
141.49, 141.74, 142.04, 142.18, 142.54, 142.71, 143.16, 144.14, 144.71, 145.24,
145.32, 145.51, 145.78, 146.14, 146.27, 146.46, 147.05, 147.28, 147.36, 149.05,
153.39, 197.77. MALDI TOF, m/z 902.075 [M]ꢀ (C73H10O).
24. Methyl 4-[(C60-Ih)[5,6]fullerene-1(9H)-ylcarbonyl]benzoate (3). IR: 526, 749, 805,
1019, 1107, 1280, 1434, 1457, 1630, 1724 cmꢀ1. UV (CHCl3), kmax, nm: 253,
319, 430. 1H NMR (400 MHz, CDCl3): d 4.03 (s, 3H, CH3), 7.48 (s, 1H, C60-H),
8.35 (d, 2H, 2CH, J = 8 Hz), 8.63 (d, 2H, 2CH, J = 8 Hz). 13C NMR (100 MHz,
CDCl3): d 52.47, 57.12, 79.20, 129.21, 130.08, 135.61, 136.23, 136.40, 141.72,
142.24, 142.85, 143.16, 143.41, 144.40, 144.79, 145.49, 145.55, 145.64, 145.87,
146.49, 146.97, 147.49, 147.93, 148.25, 152.03, 165.67, 196.24. MALDI TOF, m/z
884.043 [M]ꢀ (C69H8O3).
Acknowledgements
This work was supported by the Russian Foundation for Basic
Research (Grant No. 12-03-31021n12) and the RF Ministry of Edu-
cation and Science under the Federal Program ‘Scientific and scien-