Direct synthesis of tricarbonyl(cyclopentadienyl)rhenium and tricarbonyl(cyclopentadienyl)technetium units from ferrocenyl moieties - Preparation of 17α-ethynylestradiol derivatives bearing a tricarbonyl(cyclopentadienyl)technetium group

Article abstract of DOI:10.1002/ejic.200300731

The preparation of new tricarbonyl(cyclopentadienyl)rhenium and tricarbonyl(cyclopentadienyl)technetium derivatives is described, The approach used was applied to a cold target model, 17α-ethynylestradiol substituted at the 17α position by a ketotricarbonyl(cyclopentadienyl)rhenium group. The novel organometallic reaction applied here, when extended to potential radiopharmaceuticals, consists of a cyclopentadienyl-ligand transfer between ketoferrocenes and fac-[^99mTc((H₂O)₃(CO) ₃]⁺ in a water/DMSO 1:1 mixture. This reaction lead to the synthesis of a new estradiol derivative, labeled with ^99mTc. The synthesis of another product was performed by using [⁹⁹TcCl ₃(CO)₃]^2- as the Tc precursor and its X-ray crystal structure was determined. In each case high yields were obtained. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejic.200300731

SHORT COMMUNICATION
Direct Synthesis of Tricarbonyl(cyclopentadienyl)rhenium and
Tricarbonyl(cyclopentadienyl)technetium Units from Ferrocenyl Moieties ؊
Preparation of 17α-Ethynylestradiol Derivatives Bearing a
Tricarbonyl(cyclopentadienyl)technetium Group
[a]
[a]
[a]
[a]
[b]
´
´
Stephane Masi, Siden Top,* Leila Boubekeur, Gerard Jaouen,* Stefan Mundwiler,
Bernhard Spingler,[b] and Roger Alberto*[b]
Keywords: Technetium / Rhenium / Estradiol / Radiopharmaceuticals / Bioorganometallics
The preparation of new tricarbonyl(cyclopentadienyl)rhen-
ium and tricarbonyl(cyclopentadienyl)technetium derivatives action lead to the synthesis of a new estradiol derivative, la-
[
99mTc(H2O)3(CO)3]+ in a water/DMSO 1:1 mixture. This re-
is described. The approach used was applied to a cold target
model, 17α-ethynylestradiol substituted at the 17α position
by a ketotricarbonyl(cyclopentadienyl)rhenium group. The
novel organometallic reaction applied here, when extended
beled with 99mTc. The synthesis of another product was per-
formed by using [99TcCl3(CO)3]2− as the Tc precursor and its
X-ray crystal structure was determined. In each case high
yields were obtained.
to potential radiopharmaceuticals, consists of
pentadienyl-ligand transfer between ketoferrocenes and fac-
a
cyclo-
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
this approach can be easily extended to the preparation of
tricarbonyl(cyclopentadienyl)technetium compounds be-
cause Re and Tc complexes exhibit very similar chemical
behavior.
The search for an easy route to CpM(CO)3 complexes
(where M ϭ Re, Tc) bearing a functional substituent on
the Cp ring, with the purpose of being compatible with the
handling of radioactive compounds, has attracted much
interest.[4] Wenzel reported a unique double ligand-transfer
reaction where the technetium source is [99mTcO4]Ϫ.[5] More
recently, Alberto et al. reported the preparation of different
[(R-Cp)99mTc(CO)3] molecules (R ϭ ketone), where the fac-
The synthesis of new radiolabeled estrogen derivatives
has generated much interest during the last decade.[1] The
design of new molecules labeled with technetium, 99mTc, or
rhenium, 188Re, for imaging and therapy of breast tumors,
respectively, is of current interest since most of the com-
pounds prepared have not yet shown enough affinity or sel-
ectivity towards estrogen receptors (ER) and, in addition,
their synthesis is rather circuitous. Many different systems
have been envisaged for the labeling of ligands with tech-
netium or rhenium. One general approach is the coordi-
nation of a TcV moiety through chelation with heteroatom
systems, but the molecules obtained are not always stable
in solution.[1,2] Therefore, we have elaborated an organome-
tallic approach, in which a low-oxidation-state-rhenium
core is tethered to a cyclopentadienyl (Cp) ligand.[3] The
organometallic tether using this ligand seems to be particu-
larly attractive. This group has the advantage of being lipo-
philic, fairly small in size and very robust. Furthermore,
[
99mTc(H2O)3(CO)3]ϩ compound, generated in physiologi-
cal media, is the 99mTc precursor.[6] With regard to rhenium,
Top et al. reported various syntheses of [(RЈ-Cp)Re(CO)3]
molecules (RЈ ϭ organic fragment) based on the use of [Re-
(CO)6][BF4] with particular monosubstituted ferrocene
compounds in DMSO. This method is compatible with
aqueous media as we obtained promising results in a water/
DMSO 1:1 mixture.[7]
[a]
The first step in the transformation of [Re(CO)6][BF4] in
DMSO seems to be the departure of three carbonyl ligands
from the [Re(CO)6]ϩ cation. Thus, we postulated the forma-
tion of the fac-[Re(DMSO)3(CO)3]ϩintermediate. It is be-
lieved that fac-[Re(DMSO)3(CO)3]ϩ may react with the
cyclopentadienyl ligands the same way that fac-
Laboratoire de Chimie et Biochimie des Complexes
´
´
Moleculaires, Ecole Nationale Superieure de Chimie de Paris,
UMR C.N.R.S. 7576,
´
11, rue Pierre et Marie Curie, 75231 Paris Cedex 05, France
Fax: (internat.) ϩ33-1-43-26-00-61
E-mail: Jaouen@ext.jussieu.fr
[b]
Institute of Inorganic Chemistry, University of Zürich
Winterthurerstrasse 190, 8057 Zürich, Switzerland
Fax: (internat.) ϩ41-1-635-68-03
E-mail: ariel@aci.unizh.ch
Supporting information for this article is available on the
WWW under http://www.eurjic.org or from the author.
[
99mTc(H2O)3(CO)3]ϩ does.[6,7] Combining these aspects, we
decided to extend our work with ferrocene derivatives and
the [Re(CO)6]ϩ cation to the preparation of [(R-
Eur. J. Inorg. Chem. 2004, 2013Ϫ2017
DOI: 10.1002/ejic.200300731
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2013

S. Top, G. Jaouen, R. Alberto et al.
SHORT COMMUNICATION
Cp)99mTc(CO)3] from the same ferrocene derivatives and
using fac-[99mTc(H2O)3(CO)3]ϩ as the reagent.
Results and Discussion
The ketoferrocene 1 was first used as a model for the
reaction between [Re(CO)6][BF4] and fac-[99mTc(H2O)3-
(CO)3]ϩ. It was prepared from ferrocene and p-anisoyl chlo-
ride following the procedure described in the literature.[8]
The reaction with [Re(CO)6]ϩ was carried out by heating
the DMSO solution of 1 and [Re(CO)6]ϩ at 160 °C for 30
min and 2 was obtained in 65 % yield (see Scheme 1).
Scheme 3. Deprotection of the ethynyl estradiol derivatives
Scheme 1. Ligand-transfer reaction between ketoferrocene 1 and
the hexacarbonylrhenium cation
Scheme 4. Ligand-transfer reaction between 7 and the rhenium-
hexacarbonyl cation
Since the chemistry of Re is similar to that of Tc, the
above reaction between [Re(CO)6]ϩ and the ferrocenyl de-
rivative may be adapted to Tc analogs. Recently, Alberto
et al. have found a very convenient synthetic method for
In the hormone series, the ferrocenyl-β-estradiol deriva-
tive, 3, was prepared. The amidoferrocene 4, prepared ac-
cording to the Weinreb method,[9] was reacted with the lith-
ium compound generated from 17α-ethynylestradiol, dipro-
tected with methylmethoxy (MOM) to produce 3 (see
Scheme 2). Heating 3 with [Re(CO)6][BF4] in DMSO for
one hour affords the rhenium compound 5 in 41 % yield.
[
99mTc(H2O)3(CO)3]ϩ starting from 99mTcO4Ϫ [11] Therefore,
.
it would be interesting to use the reagent
99mTc(H2O)3(CO)3]ϩ in the exchange reaction. According
to the procedure already described for the reaction of fac-
99mTc(H2O)3(CO)3]ϩ with NaCp derivatives,[6] an aliquot
of 0.5 mL of an aqueous solution containing
99mTc(H2O)3(CO)3]ϩ (nϪµ range) was mixed with
[
[
[
0.5 mL of a DMSO solution, where an excess of 1 had been
previously dissolved (1.5Ϫ2 µmol). The mixture was heated
at 95 °C and the reaction was monitored by HPLC (high-
pressure liquid chromatography) equipped with a γ radiode-
tector. The expected complex, 8a, was formed in Ͼ 80 %
radiochemical yield after heating for 4 h (see Scheme 5).
The presence of 8a (99mTc) was confirmed by comparing its
HPLC chromatogram, measured by γ-detection, with the
HPLC chromatogram of the analogous cold compound, 2
(Re). Due to the very low concentration of the 99mTc spec-
ies, characterization is only possible by chromatographic
comparison.
Scheme 2. Synthesis of tricarbonyl(cyclopentadienyl)rhenium de-
rivative 5
The removal of the methoxymethyl groups was achieved
by using BCl3 in dichloromethane (see Scheme 3). The rhe-
nium compound 6 and the ferrocenyl derivative 7 were ob-
tained in good yields. Compound 6 had already been pre-
pared by another method.[10] Heating the unprotected
ferrocenyl steroid 7 with [Re(CO)6][BF4] also gives the rhe-
nium complex 6 but in low yield (12 %) (see Scheme 4).
Scheme 5. Synthesis of a cyclopentadienyltechnetium derivative
from the corresponding ferrocene precursor
2014
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Inorg. Chem. 2004, 2013Ϫ2017

Tricarbonyl(cyclopentadienyl)rhenium and -technetium Units
SHORT COMMUNICATION
After the successful formation of 8a from fac-
Conclusion
[
99mTc(H2O)3(CO)3]ϩ, we attempted to synthesize 8 on a
larger scale, in order to identify it with more accuracy.
Starting from [99TcCl3(CO)3]2Ϫ, larger quantities of com-
plex 8 can be produced and handled because the long half-
life of 99Tc results in weak radiation of this isotope. Thus,
1 was treated in 0.5 mL of DMSO at 140 °C with
[99TcCl3(CO)3][Et4N]2. Within 1 h, 8b had formed in about
74 % yield and was crystallized from a diethyl ether/hexane
2:1 solution. The reaction was monitored with HPLC
equipped with a β radiodetector. The retention time of the
isolated 8b (99Tc) is very close to that of 8a (99mTc)
(24.3 min for 8b and 24.4 min for 8a, respectively), thus pro-
ving the identity of 8a. The structure of 8b was elucidated
by an X-ray study. An ORTEP representation of this com-
plex is given in Figure 1.
In summary, we have presented the synthesis of new
complexes bearing tricarbonyl(cyclopentadienyl)rhenium
or tricarbonyl(cyclopentadienyl)technetium functionalities,
where the target molecules belong to the estradiol series. In
addition, the first synthesis of tricarbonyl(cyclopentadienyl)-
technetium derivatives from the organometallic aqua com-
plex fac-[99mTc(H2O)3(CO)3]ϩ and ferrocene-containing
compounds has been successfully investigated. Thanks to
this convenient method, the efficient radiochemical syn-
thesis of a novel 17α-ethynylestradiol derivative can be
achieved in aqueous media under mild conditions, without
protecting the estradiol substituents. On the basis of these
encouraging results, the reaction should be useful in the de-
velopment of a wide variety of radiolabeled compounds in
aqueous media.
Experimental Section
DMSO was used without any purification. TLC chromatography
was performed on silica gel 60-GF254. Infrared spectra were re-
corded on an IR-FT BOMEM Michelson-100 spectrometer. 1H-
and 13C NMR spectra were recorded on 200 MHz and 400 MHz
Bruker spectrometers. Mass spectrometry was performed with a
Nermag R 10Ϫ10C spectrometer. Melting points were measured
with a Kofler device. Elemental analyses were performed by the
´
regional microanalysis department of Universite Pierre et Marie
Curie.
Figure 1. Ortep plot of 8b, ellipsoids drawn with 50 % probability
1: AlCl3 (0.477 g, 3.49 mmol) was added to a 5 mL dichlorometh-
ane solution of ferrocene (0.5 g, 2.69 mmol). p-Anisoyl chloride
(0.305 g, 1.79 mmol) was then added dropwise and the resulting
solution was stirred for 4 h at room temperature. The mixture was
hydrolyzed with water (40 mL) and the aqueous solution was ex-
tracted with diethyl ether (3 ϫ 80 mL). All the organic fractions
were combined, dried over magnesium sulfate, filtered and the sol-
vents evaporated. The compound was purified by a silica-gel plate
(dichloromethane) to give 1 (0.18 g, 31% yield); m.p. 74Ϫ76 °C. 1H
NMR (200 MHz, CDCl3): δ ϭ 3.82 (s, 3 H, -OCH3), 4.13 (s, 5 H,
Cp), 4.49 (s, 2 H, 2,5-H of C5H4), 4.83 (s, 2 H, 3,4-H of C5H4),
6.89 (d, J ϭ 8.0 Hz, 2 H, Ar), 7.88 (d, J ϭ 8.0 Hz, 2 H, Ar) ppm.
13C NMR (50 MHz, CDCl3): δ ϭ 55.4 (-OCH3), 70.1 (CCp), 71.4
(CCp), 72.1 (CCp), 113.4 (CAr), 130.4 (CAr), 162.4 (CAr), 197.3 (CO)
ppm. IR (CH2Cl2): ν˜ ϭ 1635 (νCO) cmϪ1. MS (EI): m/z ϭ 56 [Fe]ϩ,
77, 92, 121, 135 [M Ϫ Fc]ϩ, 171, 277, 320 [M]ϩ.
We next applied the reaction between ketoferrocene com-
pounds and the reagent fac-[99mTc(H2O)3(CO)3]ϩ to steroid
7 and obtained molecule 9 with excellent yields. Thus, using
the conditions described above with 1 and heating for 3 h
30 min, allowed us to form 9 in quantitative yield (Ͼ 90%)
(see Scheme 6). It is remarkable that such a mild and ef-
ficient reaction has never been reported for the synthesis of
molecules belonging to the class of ethynylestradiol. Ad-
ditionally, it is noteworthy that our approach for the labe-
ling of 99mTc on (bio)organic molecules constitutes a real
improvement, with regard to the transformations of ferro-
cene derivatives into corresponding tricarbonyl(cyclopenta-
dienyl)technetium derivatives, described in the litera-
ture.[5,12]
2: [Re(CO)6][BF4] (0.073 g, 0.166 mmol) was dissolved in DMSO
(1 mL) in a 5 mL round-bottomed flask equipped with a magnetic
stirring bar. Compound 1 (0.166 g, 0.518 mmol) was added and the
solution was heated for 30 min at 160 °C. The mixture was allowed
to warm to room temperature and then water (10 mL) was added.
The product was extracted with dichloromethane (2 ϫ 50 mL). The
organic phase was washed, dried (MgSO4), filtered and concen-
trated. The mixture was purified by chromatography on a silica-gel
plate (ethyl acetate/petroleum ether 1:7) to give 2 (0.051 g, 65 %
yield); m.p. 186 °C. 1H NMR (200 MHz, CDCl3): δ ϭ 3.88 (s, 3
H, -OCH3), 5.45 (t, J ϭ 2.2 Hz, 2 H, 3,4-H of C5H4), 6.05 (t, J ϭ
2.2 Hz, 2 H, 2,5-H of C5H4), 6.95 (d, J ϭ 8.0 Hz, 2 H, Ar), 7.83
(d, J ϭ 8.0 Hz, 2 H, Ar) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ
55.4 (-OCH3), 85.1 (2 CCp), 89.4 (2 CCp), 113.8 (2 CAr), 130.8 (2
Scheme 6. Synthesis of a novel 17α-ethynyl estradiol derivative
labeled with 99mTc, in a water/DMSO 1:1 mixture at atmospheric
pressure
Eur. J. Inorg. Chem. 2004, 2013Ϫ2017
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2015

S. Top, G. Jaouen, R. Alberto et al.
SHORT COMMUNICATION
CAr) ppm. IR (CH2Cl2): ν˜ ϭ 2030 s, 1938 s, 1652 w (νCO) cmϪ1
.
product was extracted with dichloromethane (2 ϫ 150 mL). The
MS (EI): m/z ϭ 386 [M Ϫ 3 CO]ϩ, 412, 442 [M Ϫ CO]ϩ, 469 organic phase was washed, dried (MgSO4), filtered and concen-
[M]ϩ. C16H11O5Re (469.46): calcd. C 40.93, H 2.36; found C 40.97,
H 2.29.
trated. The mixture was purified by chromatography on a silica-gel
plate (ethyl acetate/petroleum ether 1:5) to give 5 (0.331 g, 41 %
yield); m.p. 119 °C. 1H NMR (400 MHz, CDCl3): δ ϭ 0.94 (s, 3
H, CH3-18), 2.85 (m, 2 H, H-6), 3.43 (s, 3 H, -OCH3), 3.47 (s, 3
H, -OCH3), 4.84 (d, J ϭ 7.2 Hz, 1 H, -OCH2O-17), 4.99 (d, J ϭ
7.2 Hz, 1 H, -OCH2O-17), 5.15 (s, 2 H, -OCH2O-3), 5.41 (m, 2 H,
3,4-H of C5H4), 6.21 (m, 2 H, 2,5-H of C5H4), 6.78 (d, 1 H, 4-H),
6.83 (dd, J ϭ 8.4 Hz, 1 H, 2-H), 7.20 (d, J ϭ 8.4 Hz, 1 H, 1-H)
ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 13.2 (C-18), 29.8 (C-6),
23.1, 26.3, 27.2, 33.7 and 37.4 (C-7, C-11, C-12, C-15 and C-16),
39.1, 43.5 and 49.5 (C-8, 9 and C-14), 48.8 (C-13), 56.0 (2 CH3O),
85.1 and 85.4 (CCp and C-17), 85.5, 89.2 and 89.3 (CCp), 94.0 (-
OCH2O-17), 94.5 (-OCH2O-3), 94.3 and 96.5 (C-19 and C-20),
113.8, 116.3 and 126.5 (C-1, C-2, and C-4), 133.4 (C-10), 138.0 (C-
5), 155.1 (C-3), 171.3 (CO, ketone), 191.4 (Re-CO) ppm. IR
4: The synthesis of 4 was performed using the procedure for the
preparation of N-methoxy-N-methylamides (see reference [9]). Oxa-
lyl chloride (7.250 g, 57 mmol) was added to ferrocenecarboxylic
acid (0.550 g, 2.39 mmol) placed in a Schlenk tube and cooled in
an ice bath. The mixture was stirred for 3 h, then the excess oxalyl
chloride was removed under vacuum. Chloroform (20 mL) was ad-
ded, followed by addition of N,O-dimethylhydroxyamine hydro-
chloride (0.260 g, 2.63 mmol). Anhydrous pyridine (0.420 g, 5.26
mmol) was added dropwise to the mixture, cooled in an ice bath.
The mixture was stirred for 2 h 30 min to allow the temperature
to rise to room temperature. Then, dichloromethane (200 mL) was
added and the solution obtained was washed with a saturated
K2CO3 solution, dried over magnesium sulfate, filtered and the sol-
vents were evaporated. The compound obtained was crystallized in
pentane to give 4 (0.524 g, 83 % yield); m.p. 28 °C. 1H NMR
(200 MHz, CDCl3): δ ϭ 3.31 (s, 3 H, -NCH3), 3.74 (s, 3 H, -
NOCH3), 4.22 (s, 5 H, Cp), 4.39 (t, J ϭ 1.8 Hz, 2 H, 3,4-H of
C5H4), 4.91 (t, J ϭ 1.8 Hz, 2 H, 2,5-H of C5H4) ppm. 13C NMR
(50 MHz, CDCl3): δ ϭ 33.4 (-NCH3), 61.0 (-NOCH3), 69.5 (CCp),
70.6 (CCp), 71.0 (CCp), 73.0 (CCp), 171.0 (CO) ppm. IR (CH2Cl2):
ν˜ ϭ 1616 s (νCO) cmϪ1. MS (EI): m/z ϭ 56 [Fe]ϩ, 65 [Cp]ϩ, 121
[FeCp]ϩ, 129, 185 [Fc]ϩ, 213 [FcCO]ϩ, 273 [M]ϩ·. C13H15FeNO2
(273.05): calcd. C 57.17, H 5.54, N 5.13; found C 57.02, H 5.73,
N 5.15.
(CH2Cl2): ν˜ ϭ 2205 w (νCϵC), 2032 s, 1940 vs, 1642 w (νCO) cmϪ1
.
MS (EI): 187Re m/z ϭ 45 [CH2OCH3]ϩ, 746 [M]ϩ. MS (IC, DCI/
NH3): 187Re m/z ϭ 747 [M ϩ H]ϩ, 764 [M ϩ NH4]ϩ. C33H35O8Re
(746.19): calcd. C 53.14, H 4.73; found C 53.07, H 5.00.
6: The deprotection of 5 was carried out according to a procedure
described in the literature.[13] Under an inert atmosphere, 5
(0.070 g, 0.094 mmol) was dissolved in 8 mL of dichloromethane.
The solution was cooled to Ϫ90 °C and BCl3 (1 mL, 1  in CH2Cl2)
was added dropwise. A rapid evolution of the color from beige
to orange was observed. The solution was stirred for 30 min, the
temperature of the cooling bath was thus Ϫ30 °C. The bath was
removed and dichloromethane (150 mL) was poured into the mix-
ture. This organic phase was washed with water (50 mL) and neu-
tralized with 50 mL of K2CO3 (10 %). The organic phase was
washed, dried (MgSO4), filtered and concentrated. The mixture was
purified by silica-gel chromatography (diethyl ether/petroleum
ether 2:1) to give 6 (0.051 g, 83% yield); m.p. 156 °C. 1H NMR
(200 MHz, CDCl3): δ ϭ 0.95 (s, 3 H, CH3-18), 2.75 (m, 2 H, 6-H),
5.78 (m, 2 H, 3,4-H of C5H4), 6.34 (m, 2 H, 2,5-H of C5H4), 6.53
(d, 1 H, 4-H), 6.59 (dd, 1 H, 2-H), 7.09 (d, 1 H, 1-H) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 12.8 (C-18), 23.1 (C-15), 26.3, 27.1
(C-7 and C-11), 29.6 (C-6), 33.3 (C-16), 39.0 and 39.4 (C-12 and
C-8), 43.5 (C-9), 48.1 (C-13), 50.3 (C-14), 80.4 (C-17), 85.5 and
89.4 (4 CCp), 83.0, 96.3 and 96.6 (1 CCp and CϵC), 112.8 (C-2),
115.3 (C-4), 126.7 (C-1), 132.3 (C-10), 138.3 (C-5), 153.5 (C-3),
171.4 (CO), 191.5 (Re-CO) ppm. IR (CH2Cl2): ν˜ ϭ 2033 s, 1943
vs, 1653 w (νCO) cmϪ1. MS (IC, DCI/NH3): 187Re m/z ϭ 659 [M
ϩ H]ϩ, 676 [M ϩ NH4]ϩ. C29H27O6Re ϩ 1 Et2O (732.21): calcd.
C 54.16, H 5.10; found C 54.35, H 5.01.
3: In a Schlenk tube, 17α-ethynylestradiol diprotected with a meth-
oxymethyl group (0.665 g, 1.73 mmol) was dissolved in THF
(6 mL) and cooled to Ϫ78 °C. nBuLi (0.8 mL, 2.05 mmol, 2.5 
solution in hexane) was added dropwise and the mixture was stirred
for 1 h. By that time the temperature had risen to Ϫ50 °C. Then,
a solution of 4 (0.429 g, 1.57 mmol) in THF (4 mL) was added
dropwise. After 15 min of stirring, the ice bath was removed and
the stirring was maintained for two more hours . Then, dichloro-
methane (200 mL) was added and the solution obtained was
washed with water, dried over magnesium sulfate, filtered and the
solvents were evaporated. The crude product was purified by chro-
matography on a silica-gel plate (diethyl ether/petroleum ether 1:1)
1
to give 3 (77 %); m.p. 102 °C. H NMR (200 MHz, CDCl3): δ ϭ
0.99 (s, 3 H, CH3-18), 2.88 (m, 2 H, H-6), 3.47 (s, 3 H, -OCH3),
3.48 (s, 3 H, -OCH3), 4.28 (s, 5 H, Cp), 4.61 (t, J ϭ 2 Hz, 2 H, 3,4-
H of C5H4), 4.90 (d, J ϭ 6.6 Hz, 1 H, -OCH2O-17), 4.94 (t, J ϭ
2 Hz, 2 H, 3,4-H of C5H4), 5.13 (d, J ϭ 6.6 Hz, 1 H, -OCH2O-17),
5.16 (s, 2 H, -OCH2O-3), 6.79 (d, J ϭ 2.6 Hz, 1 H, H-4), 6.84 (dd,
J ϭ 8.4, 2.6 Hz, 1 H, 2-H), 7.24 (d, J ϭ 8.4 Hz, 1 H, 1-H) ppm.
13C NMR (50 MHz, CDCl3): δ ϭ 13.0 (C-18), 29.6 (C-6), 23.1,
26.3, 27.3, 33.5 and 37.3 (C-7, C-11, C-12, C-15 and C-16), 39.1,
43.7, 49.3 (C-8, C-9 and C-14), 48.5 (C-13), 55.8 and 56.0 (2 MeO-
3), 70.3 and 73.3 (CCp), 85.4 and 87.4 (CCp and C-17), 91.0, 93.9
and 94.4 (C-19, C-20, and -OCH2O-), 113.7 (C-2), 116.2 (C-4),
126.3 (C-1), 133.5 (C-10), 137.9 (C-5), 155.1 (C-3) ppm. IR
(CH2Cl2): ν˜ ϭ 2207 w (νCϵC), 1623 s (νCO) cmϪ1. MS (EI): m/z ϭ
45 [CH2OCH3]ϩ, 596 [M]ϩ·. MS (IC, DCI/NH3): m/z ϭ 597 [M ϩ
H]ϩ. C35H40FeO5 (596.22): calcd. C 70.47, H 6.76; found C 70.17,
H 7.17.
7: The deprotection of 3 was carried out according to the procedure
described above for the deprotection of 5. The crude material was
purified by silica-gel chromatography (diethyl ether/petroleum
ether 1:1) to give 7 (0.081 g, 95% yield); m.p. 143 °C. 1H NMR
(200 MHz, CDCl3): δ ϭ 0.97 (s, 3 H, CH3-18), 2.84 (m, 2 H, 6-H),
4.28 (s, 5 H, Cp), 4.63 (t, 2 H, 3,4-H of C5H4), 4.93 (t, 2 H, 2,5-H
of C5H4), 6.59 (d, 1 H, 4-H), 6.64 (dd, J ϭ 8.4 Hz, 1 H, 2-H), 7.17
(d, J ϭ 8.4 Hz, 1 H, 1-H) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ
12.8 (C-18), 23.0 (C-15), 26.3, 27.3 (C-7 and C-11), 29.6 (C-6), 33.2
(C-16), 39.0 and 39.3 (C-12 and C-8), 43.5 (C-9), 47.9 (C-13), 50.2
(C-14), 70.6 (Ccp and 2 CcpЈ), 73.7 (2 CcpЈ), 80.1 (C-17), 84.9 and
94.8 (1 CCpЈ and CϵC), 112.8 (C-2), 115.3 (C-4), 126.5 (C-1), 131.8
(C-10), 137.9 (C-5), 153.9 (C-3), 181.7 (CO) ppm. IR (CH2Cl2):
5: [Re(CO)6][BF4] (0.540 g, 1.22 mmol) was dissolved in DMSO
(1 mL) in a 5 mL round-bottomed flask equipped with a magnetic
stirring bar. Compound 3 (0.640 g, 1.07 mmol) was added and the ν˜ ϭ 1623 s (νCO) cmϪ1. MS (EI): m/z ϭ 43, 73, 147, 207, 221, 281,
solution was heated for 1 h at 130 °C. The mixture was allowed to
508 [M]ϩ·. C31H32FeO3 ϩ H2O (526.43): calcd. C 70.72, H 6.52;
warm to room temperature and then water (10 mL) was added. The
found C 71.33, H 6.78.
2016
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Inorg. Chem. 2004, 2013Ϫ2017

Tricarbonyl(cyclopentadienyl)rhenium and -technetium Units
SHORT COMMUNICATION
6 from 7: The compound 6 was also prepared according to the
procedure described above for the synthesis of 2 or 5 (see also
Scheme 4). 12 % yield of 6 was obtained.
Compound 7 (0.8 mg, 1.6 µmol) in 0.5 mL of DMSO was added
to the aqueous solution. Subsequent heating at 95 °C for 3 h 30 min
afforded 9 in an overall yield of Ͼ 90%.
8a: 0.5 mL of an aqueous solution containing the starting material
[
Compound 1 (0.6 mg, 1.9 µmol) in 0.5 mL of DMSO was added
to the aqueous solution. Subsequent heating at 95 °C for 4 h af-
forded 8a in an overall yield of Ͼ 80%.
99mTc(H2O)3(CO)3]ϩ was prepared as described in the literature.[11]
Acknowledgments
Financial support from the Ministry of Research (S. M. grant), the
Centre National de la Recherche Scientifique, and COST D20
(WG, 007) is gratefully ackowledged. Part of this study is financi-
ally supported by the Bundesamt für Bildung und Wissenschaft
(COST 99.0055) and gratefully acknowledged.
8b: Compound 1 (0.0170 g, 0.053 mmol) in 0.5 mL of DMSO was
added to [NEt4]2[TcCl3(CO)3] (0.0225 g, 0.041 mmol) in a Schlenk
tube equipped with a magnetic stirring bar. The mixture was heated
for 1 h at 140 °C, yielding a brownish precipitate containing the
product, as shown by HPLC analysis. The crude product was puri-
fied by column chromatography on a silica-gel plate (ethyl acetate/
petroleum ether 1:7). Yield: 74 %. The product was dissolved in a
diethyl ether/hexane 2:1 solution, slow evaporation of the solvents
gave crystals suitable for an X-ray study. 1H NMR (200 MHz,
CDCl3): δ ϭ 3.89 (s, 3 H, -OCH3), 5.37 (t, J ϭ 2.4 Hz, 2 H, 3,4-H
of C5H4), 6.01 (t, J ϭ 2.4 Hz, 2 H, 2,5-H of C5H4), 6.96 (d, J ϭ
9.0 Hz, 2 H, Ar), 7.84 (d, J ϭ 9.0 Hz, 2 H, Ar) ppm. 13C NMR
(50 MHz, CDCl3): δ ϭ 55.5 (-OCH3), 87.0 (2 CCp), 91.85 (2 CCp),
113.8 (2 CAr), 130.7 (2CAr), 163.2 (CO, ketone) ppm. 99Tc NMR
(740 Hz, CDCl3): δ ϭ Ϫ2478 ppm. IR (KBr): ν˜ ϭ 2040 s, 1957 vs,
1930 vs, 1631 w (νCO) cmϪ1. MS (FAB): m/z ϭ 382 [M]ϩ.
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[5]
[6]
[7]
˚
0.71073 A, ϕ oscillation scan, monoclinic, space group P21/c, a ϭ
˚
18.2751(5), b ϭ 13.1242(8), c ϭ 6.1913(17) A, β ϭ 90.380(11)°,
3
V ϭ 1484.9(4) A , Z ϭ 4, Dcalcd. ϭ 1.634 g cmϪ3, R1(I Ն 2σ(I)] ϭ
˚
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200 parameters, refinement with SHELXL-97[14] against F2, calcu-
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0.981 mmϪ1. CCDC-209247 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12 Union Road, Cam-
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deposit@ccdc.cam.ac.uk].
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9: 0.5 mL of an aqueous solution containing the starting material
[
99mTc(H2O)3(CO)3]ϩ was prepared as described in the literature.[11]
Received October 14, 2003
Eur. J. Inorg. Chem. 2004, 2013Ϫ2017
www.eurjic.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2017