Synthesis of new C60 based phosphines

Article abstract of DOI:10.1016/j.tetlet.2003.09.198

Two series of new phosphine derivatives based on C₆₀ protected by borane have been synthesized and characterized. These phosphines were used for two preliminary complexation trials with [RhCl(COD)]₂ and [Re(S₃CPh)₂(S₂CPh)] to afford, respectively, the corresponding complexes [RhCl(COD)(PRPh₂)] and [Re(S ₂CPh)₃(PRPh₂)].

Full text of DOI:10.1016/j.tetlet.2003.09.198

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8811–8814
Synthesis of new C60 based phosphines
Sandrine Ballot and Nicolas Noiret*
Ecole Nationale Supe´rieure de Chimie de Rennes, Synthe`ses et Activations de Biomole´cules, CNRS UMR 6052,
Institut de Chimie de Rennes, Avenue du Ge´ne´ral Leclerc, F-35700 Rennes, France
Received 22 July 2003; revised 12 September 2003; accepted 24 September 2003
Abstract—Two series of new phosphine derivatives based on C60 protected by borane have been synthesized and characterized.
These phosphines were used for two preliminary complexation trials with [RhCl(COD)]2 and [Re(S3CPh)2(S2CPh)] to afford,
respectively, the corresponding complexes [RhCl(COD)(PRPh2)] and [Re(S2CPh)3(PRPh2)].
© 2003 Elsevier Ltd. All rights reserved.
Fullerenes, especially C60, have received increasing
attention since their discovery in 1985.1 Their deriva-
tives show a large range of promising applications in
many domains due to their remarkable electronic,2
magnetic3 and charge-transfer4 properties. In biomedi-
cal fields, various potential areas of application have
been investigated such as neuroprotection,5 apoptosis,6
inhibition of HIV-protease,7 photodynamic therapy8or
X-ray contrast agents.9 Among potential domains,
radiomedicine and diagnostic purposes appear to be
another interesting field of possible development for
both empty or endohedral metallofullerene derivatives.
characterize, we alternatively used phosphine–borane
complexes which are very stable and not sensitive to
chemical oxidation.14 Finally, the first attempts at
fullerene–phosphine ligand coordination were carried
out on rhodium and rhenium complexes.
The general synthetic pathway for the preparation of
fullerene phosphine ligands is presented in Scheme 1.
Starting from diols 1, monotosylated compounds 2a
and 2c were obtained by treatment with tosyl chloride
and triethylamine in dichloromethane; the monobromi-
nated derivative 2b was prepared by refluxing 1,8-
octanediol 1b with aqueous HBr (48%) in cyclohexane.
Then two routes leading to fullerene adducts were
possible through the key building blocks 5. Derivatives
5b and 5c were obtained in two steps: first, the
triphenylphosphine–borane complex was stirred with
lithium metal in dry THF, then compound 2b or 2c was
added in dry THF to the non-isolated intermediate
[Ph2P(BH3)Li] complex to afford building blocks 5b
and 5c in 43 and 65% yields, respectively.
As part of our work on the synthesis of radiopharma-
ceuticals, we have reported recently the synthesis of
oxorhenium(V) complexes carrying the C60 moiety,10
using a new SNO/SN coordination system around the
metal. Tertiary phosphines are able to stabilize various
transition metals in a variety of oxidation states and
coordination geometries, mainly due to p backbonding.
This approach has been used for the design of various
radiopharmaceuticals. In this paper, we present the
synthesis of phosphine ligands bearing C60. To connect
C60 to phosphine, we chose the well-known cyclopropa-
nation of Bingel11 and 1,3-dipolar addition of azome-
thine ylides12 for fullerene functionalization. Fullerene
derivatives are well known to sensitize the formation of
singlet oxygen through their triplet excited state.13 This
property is discordant with the high sensitivity of
alkylphosphines to oxidation. Thus, with the aim of
making fullerene derivatives easy to handle, purify and
Malonate derivatives 3 and 6 were conveniently avail-
able by esterification reactions between alcohols 2 and 5
and ethyl malonyl chloride in CH2Cl2. Malonates 6
could also be obtained from the corresponding tosyl-
ated derivatives 3 by reaction with [Ph2P(BH3)Li] in dry
THF. Bingel reactions with C60, diiodine, DBU and
malonates 6 led to the first fullerene-protected phos-
phine ligands 7. Fullerene derivative 4a prepared by the
Bingel reaction from 3a did not allow the preparation
of the corresponding phosphine ligand.
Keywords: fullerenes; phosphine ligands; rhenium; rhodium.
* Corresponding author. Tel.: +33-223-238-061; fax: +33-223-238-046;
e-mail: noiret@ensc-rennes.fr
From key building blocks 5, the corresponding alde-
hyde derivatives 8 were prepared through classical PCC
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.09.198

8812
S. Ballot, N. Noiret / Tetrahedron Letters 44 (2003) 8811–8814
oxidation in dichloromethane (58 and 82% yields).
Fulleropyrrolidines 9 were finally obtained by 1,3-dipo-
lar addition of azomethine ylides prepared in situ from
N-methylglycine and the latter aldehydes 8 in 18 and
22% yields, respectively. Deprotection of the phos-
phine–borane complexes occurred using tertiary amines
such as diazabicyclooctane (DABCO)15 in dry toluene
for 4 h at 50–60°C under an atmosphere of argon
(Scheme 2). The complex solution was then added and
stirred overnight under an argon atmosphere at room
temperature or 60°C.16
with bis(perthiobenzoato)(dithiobenzoato)rhenium(III)
(Scheme 2).
The spectroscopic data for the novel fullerene phos-
phine ligands (7a, 7c, 9b and 9c) are in agreement with
1
the proposed structures.17 Thus, the H NMR spectra
of the methanofullerene 7a and fulleropyrrolidine 9c
showed the presence of the aromatic protons in the
region between l 7.7 and 7.4 ppm as two multiplets of
4 and 6 protons and the methylene close to phosphorus
as an ill-defined signal between 2.2 and 2.1 ppm. The
1H NMR spectrum of 9c showed the characteristic
signals of a fulleropyrrolidine with the two doublets of
one proton each at 4.8 and 4.1 ppm for the CH2N
group, the triplet of one proton at 3.9 ppm for the
Preliminary complexation experiments with rhodium
utilized chloro(1,5-cyclooctadiene)rhodium(I) dimer,
whereas complexation with rhenium was carried out
Scheme 1. Reagents and conditions: (i) TsCl, Et3N, CH2Cl2, room temperature or HBr, cyclohexane, D; (ii) ethyl malonyl chloride,
Et3N, CH2Cl2, room temperature; (iii) C60, I2, DBU, toluene, room temperature; (iv) [Ph2P(BH3)Li], THF, room temperature; (v)
PCC, CH2Cl2, room temperature; (vi) C60, N-methylglycine, toluene, D.
Scheme 2. Reagents and conditions: (i) DABCO, toluene, 50–60°C; (ii) [Rh(COD)Cl]2, toluene, room temperature; (iii)
[Re(S3CPh)2(S2CPh)], toluene, room temperature.

S. Ballot, N. Noiret / Tetrahedron Letters 44 (2003) 8811–8814
8813
Table 1. Selected 31P NMR (CDCl3, 161.98 MHz) data for free ligands and complexes
Acknowledgements
CHN group and the singlet of three protons at 3 ppm
for NCH3. The 13C NMR spectra of the two fullerene
derivatives were also in agreement with the proposed
structures. The CH2–CH2–P group was characterized by
two doublets: at 20.6 and 31.2 ppm for CH2–CH2–P and
25.7 and 25.6 ppm for CH2–CH2–P in the
methanofullerene and fulleropyrrolidine, respectively
with coupling constants of 14 and 37 Hz for CH2–CH2–P
and CH2–CH2–P, respectively. Finally, all the protected
ligands were characterized by 31P NMR with a singlet at
about 17 ppm. This signal was very broad due to borane
complexation.
This research was financially supported by the French
Ministry of Science/Research and Technology. We thank
A. Roucoux (ENSCR) for helpful discussions.
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complex [Re(S3CPh)2(S2CPh)] to the corresponding
[Re(S2CPh)3(PRPh2)] complexes.18 31P NMR spectra of
the reaction media showed three different sets of signals:
the complex as a singlet at −5.8 ppm, the phosphine oxide
as a singlet at 33.7 ppm and a major signal (singlet) at
43.9 ppm corresponding to the phosphine thiooxide
(PꢀS). The latter signal is due to the reduction of two
perthiobenzoates of the [Re(S3CPh)2(S2CPh)] complex,
establishing again that complex 11 had been synthesized.
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for two preliminary complexation trials with [RhCl-
(COD)]2 and [Re(S3CPh)2(S2CPh)] to afford, respec-
tively, the corresponding complexes, [RhCl(COD)-
(PRPh2)] and [Re(S2CPh)3(PRPh2)].
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2.52%. Found: C, 87.0; H 2.7%
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1
Compound 9c: H NMR (CDCl3, 400 MHz) l 7.69–7.59
(m, 4H, arom), 7.50–7.38 (m, 6H, arom), 4.80 (d, J=9.6
Hz, 1H, CH2N), 4.15 (d, J=9.6 Hz, 1H, CH2N), 3.88 (t,
J=5.2 Hz, 1H, CHN), 2.97 (s, 3H, NCH3), 2.56–2.47 (m,
1H, NCH–CH2), 2.40–2.31 (m, 1H, NCH–CH2), 2.20–
2.13 (m, 2H, CH2P), 1.95–1.82 (m, 2H, CH2), 1.54–1.11
(m, 16H, 8 CH2); 13C NMR (CDCl3, 100.62 MHz) l
156.57, 154.58, 154.49, 153.57, 147.29, 147.25, 146.88,
146.62, 146.46, 146.35, 146.30, 146.23, 146.21, 146.14,
146.10, 146.02, 146.00, 145.87, 145.63, 145.57, 145.46,
145.37, 145.35, 145.28, 145.23, 144.80, 144.63, 144.47,
144.40, 143.25, 143.10, 142.74, 142.70, 142.69, 142.66,
142.25, 142.23, 142.21, 142.12, 141.87, 141.79, 141.72,
140.32, 140.24, 139.80, 139.65, 137.23, 136.31, 135.92,
135.60 (C C60), 132.22, 132.13, 131.15, 131.12, 129.99,
129.44, 128.89, 128.79 (C arom), 78.24 (NCH), 76.35
(Csp3 C60), 70.48, 70.18 (CH2N, Csp3 C60), 40.16
(NCH3), 31.32, 31.19 (CH2CH2P, J=13.6 Hz), 31.11
(NCHCH2), 30.25, 29.53, 29.50, 29.43, 29.10, 27.49, 23.03
(CH2), 25.86, 25.50 (CH2P, J=36.9 Hz); 31P NMR
(CDCl3, 161.98 MHz) l 16.96 (broad s). Anal. calcd for
C89H42O4BP (1217.10): C, 87.83; H, 3.48%. Found: C,
87.6; H 3.5%.
16. General procedure: Under an argon atmosphere, pro-
tected phosphine (4 equiv.) and DABCO (4 equiv.) were
refluxed in dry toluene for 4 h. After cooling to room
temperature, the rhenium or rhodium complex (1 equiv.)
dissolved in dry toluene was added under an Ar atmo-
sphere and the mixture was stirred overnight (at room
temperature or 60°C). After evaporation of solvent under
vacuum, NMR spectroscopy was carried out under
argon.
1
17. Selected spectroscopic data for compound 7a: H NMR
(CDCl3, 400 MHz) l 7.69–7.64 (m, 4H, arom), 7.49–7.42
(m, 6H, arom), 4.54 (q, J=7.1 Hz, 2H, CH2OCO), 4.46
(t, J=6.5 Hz, 2H, COOCH2), 2.24–2.17 (m, 2H, CH2P),
1.86–1.80 (m, 2H, CH2), 1.66–1.52 (m, 4H, 2CH2), 1.47
(t, J=7.1 Hz, 3H, CH3CH2); 13C NMR (CDCl3, 100.62
MHz) l 163.70, 163.61 (COO), 145.46, 145.33, 145.26,
145.23, 145.19, 144.95, 144.76, 144.74, 144.68, 143.95,
143.93, 143.15, 143.09, 143.00, 142.27, 142.24, 141.96,
141.91, 141.02, 141.00, 139.24, 138.84, 137.94 (C C60),
132.21, 132.12, 131.32, 131.30, 129.67, 129.12, 129.10,
129.00, 128.90, 128.29, 125.36 (C arom), 77.30, 71.62
(Csp3 C60), 67.00 (COOCH2), 63.55 (CH2COO), 52.28
(COC–CO), 28.21 (CH2), 27.70, 27.55 (CH2CH2P, J=14
Hz), 25.93, 25.57 (CH2P, J=37 Hz), 22.73 (CH2), 14.27
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