A short route to cyclopentadienyltricarbonylrhenium substituted derivatives

Article abstract of DOI:10.1016/S0022-328X(02)02090-9

CpRe(CO)₃ substituted derivatives were obtained in good yields (44-96%) from fulvenes and Re2(CO)₁₀ in boiling mesitylene. This new methodology was applied to the synthesis of CpRe(CO)₃ substituted steroids with success.

Full text of DOI:10.1016/S0022-328X(02)02090-9

Journal of Organometallic Chemistry 668 (2003) 140ꢀ144
/
www.elsevier.com/locate/jorganchem
Note
A short route to cyclopentadienyltricarbonylrhenium substituted
derivatives
F. Le Bideau, J. He´nique, P. Pigeon, J.-M. Joerger, S. Top, G. Jaouen *
UMR 7576 CNRS, Ecole Nationale Supe´rieure de Chimie de Paris, 11 rue Pierre et Marie Curie, F-75231 Paris Cedex 05, France
Received 29 July 2002
Abstract
CpRe(CO)3 substituted derivatives were obtained in good yields (44ꢀ
This new methodology was applied to the synthesis of CpRe(CO)3 substituted steroids with success.
/
96%) from fulvenes and Re2(CO)10 in boiling mesitylene.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: Bioorganometallic chemistry; Cyclopentadienyl ligands; Rhenium; Fulvene
1. Introduction
tions used. Even though the reaction occured at 128 8C
(run 1), the yields increased upon raising the tempera-
ture (runs 2, 3 and 5). The best result was obtained in
boiling mesitylene under reflux (run 5). The solvent-free
reaction (run 4) gave only 40% yield in comparison with
the 62% yield obtained at the same temperature (run 3).
Increasing the number of equivalents of 1 relative to 2
(run 6) did not alter significantly the yield while a
smaller amount of 1 gave only 60% of 3 and 4 (run 7).
The last experiment (run 8) showed that doubling the
dilution led to a decrease of the yield. These results can
be explained by the relative instability of the fulvene
under the conditions used, the best choice thus appear-
ing to be a delicate balance between the formation of the
products and degradation of the fulvene 1. Finally,
varying the reaction conditions did not allow us to direct
the reaction towards the formation of a sole product, the
ratios being quite identical from run 2 to 8.
The access to compounds for use in bioorganometallic
chemistry is not always readily achieved by adopting
synthetic methods used in classical organometallic
chemistry. Our interest in CpRe(CO)3 substituted bio-
molecules [1] as potential radiopharmaceuticals led us to
explore efficient synthesis of these species in the ‘cold
series’. We thus recently reported a one-pot synthesis of
CpRe(CO)3 substituted steroids from the corresponding
fulvenes and BrRe(CO)5 under basic conditions [2]. We
now present a new procedure using Re2(CO)10 (a
precursor of BrRe(CO)5) as the rhenium source which
allows direct access to cyclopentadienyltricarbonylrhe-
nium substituted derivatives from fulvenes under neutral
conditions.
2. Results and discussion
On the basis of these results and apart from the
reaction time, the conditions described in run 5 were
used for the synthesis of other cyclopentadienyltricar-
bonylrhenium derivatives (Scheme 2). A longer reaction
The commercially available fulvene 1 was chosen as a
model substrate for the optimisation process (Scheme 1,
Table 1). Mixtures of 1 and 2 (0.2 mmol) were heated at
different temperatures, with varying amounts of solvent
for 2 h. In these reactions, a relatively small portion of
the reduced compound 4 was formed under the condi-
* Corresponding author. Fax: ꢁ
/
33-1-43260061
E-mail address: jaouen@ext.jussieu.fr (G. Jaouen).
Scheme 1.
0022-328X/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 3 2 8 X ( 0 2 ) 0 2 0 9 0 - 9

F. Le Bideau et al. / Journal of Organometallic Chemistry 668 (2003) 140ꢀ
/144
141
Table 1
Reaction of compound 1 with 2 (0.2 mmol) under selected conditions
studied 10 years ago [4,5]. In particular 2-(cyclopenta-
dienyltricarbonylrhenium)propene (3) was prepared in a
four-step procedure from cyclopentadiene with an over-
all yield of 32%. Our one-pot synthesis gave the same
product in 61% yield. We also showed that the
corresponding reduced forms of these compounds were
easily obtained in good yields through ionic hydrogena-
tion. In future work, we hope to exploit this method for
the discovery of new potential radiopharmaceutical (in
the cold series) bearing a CpRe(CO)3 substituted group.
a
b
Run 1 (mmol)
Solvent (ml)
T (8C) Yield (%) (3/4)
1
2
3
4
5
6
7
8
0.8
0.8
0.8
0.8
0.8
1.6
0.4
0.8
1
1
1
0
1
1
1
2
128
141
155
155
163
163
163
163
7 (100/0)
34 (89/11)
62 (89/11)
40 (87/13)
76 (81/19)
72 (82/18)
60 (82/18)
67 (85/15)
a
Yields are based on rhenium (0.4 mmol).
The ratios were determined on the 1H-NMR spectra of the
mixture of compounds 3 and 4 obtained after filtration on silica gel.
b
4. Experimental
time was needed with these fulvenes 5 to give satisfac-
tory yields. The modified steroids 8 were also converted
into the corresponding compounds 9 in yields compar-
able to those obtained by our previous procedure
(Scheme 3) [2] based on the use of BrRe(CO)5 and
KH. These products are the result of a proton abstrac-
tion in the C-6 position. Neither the isomeric products
(resulting from the deprotonation of the C-2 position)
nor products resulting from reduction of the double
bond were isolated.
As can be seen from these examples, different func-
tional groups were found to be compatible with the
reaction conditions, including ether, alcohol, ketone,
amine, chloride and thioether.
Compounds 7 were synthesized from 6 using an ionic
hydrogenation [3] in the presence of triethylsilane and
trifluoroacetic acid in nearly quantitative yields (Scheme
4). The amino compound 6a led to an inseparable
mixture of 7a and a by-product derived from the silane.
This reaction thus provides access to the reduced
compounds in good yields.
4.1. General
1H- and 13C-NMR spectra were taken on 200 MHz
Bruker AC 200 spectrometer. Chemical shifts are
reported in ppm and referenced to the residual proton
resonances of the solvents. IR spectra were recorded by
using a BOMEN MB spectrometer. Mass spectra were
obtained on NERMAG R1010C apparatus. HRMS
were measured at the Service de Spectrome´trie de Masse
of the Ecole Normale Supe´rieure (Paris, France). Melt-
ing points were measured on a Buchi B-510 apparatus
¨
and were uncorrected. Thin-layer chromatography
(TLC) was performed on Merck silica gel 60 F 254.
Silica gel Merck Gerudan SI (40ꢀ63 mm) was used for
/
column chromatography using the Still method [6].
Elemental analyses were measured at the microanalysis
laboratory of the Pierre et Marie Curie University
(Paris, France) or of the CNRS (Gif sur Yvette, France).
Anhydrous MeOH (99.8%) was purchased from Al-
drich. Reactions were carried out in flame-dried Schlenk
glassware under an inert atmosphere (Ar). 6,6-Di-
methylfulvene
(98%),
4?-methylthioacetophenone
(97%), and 4?-methoxyacetophenone (98%) were pur-
chased from Aldrich; 4?-aminoacetophenone (98%) was
purchased from Avocado; 4?-chloroacetophenone was
purchased from Fluka; Rhenium carbonyl (98%) was
purchased from Strem Chemicals; Mesitylene (99%) and
pyrrolidine (99%) were purchased from Acros. These
reactants and solvent were used as received.
3. Conclusion
In conclusion, we have provided a short and efficient
synthesis of several organometallic species bearing a
conjugated side chain from fulvenes and Re2(CO)10 as
the metallic source. The synthesis of similar species was
Scheme 2.

142
F. Le Bideau et al. / Journal of Organometallic Chemistry 668 (2003) 140ꢀ144
/
Scheme 3.
4.2. General method for the fulvene synthesis
Anal. Calc. for C14H14S (214.3): C, 78.45; H, 6.58.
Found: C, 78.21; H, 6.59%.
To a solution of ketone (5 mmol) and cyclopentadiene
(1 ml, 12 mmol) in 8 ml of MeOH, pyrrolidine (2 ml, 24
mmol) was added. The mixture was stirred at room
temperature (r.t.) for the appropriate time (60 h for 5a,
5c, and 5d; 24 h for 5b) and diluted with AcOEt/AcOH
(50:0.5 ml except for 5a, the purification being processed
on the crude reaction mixture). After stirring for 15 min,
4.3. General method for the CpRe(CO)3 substituted
compounds synthesis
The mesitylene was degassed under a stream of Ar (15
min) prior to use. Dirhenium decacarbonyl (0.2 mmol)
was added to a solution (or a suspension) of fulvene (0.8
mmol) in mesitylene (1 ml). The reaction mixture was
quickly immersed in an oil bath heated to 180 8C and
boiled under reflux for 2 or 3 h. After cooling to r.t., the
mesitylene was removed under vacuum and the residue
was purified via flash chromatography. The spectra of
compounds 9a, 9b and 9c are in accord with those
previously reported [2].
the organic layer was washed with brine (3ꢂ25 ml),
/
dried over MgSO4 and concentrated. The residue thus
obtained was purified via flash chromatography (5a:
petroleum etherꢀ/CH2Cl2, 50:50; 5b: C5H12; 5c and 5d:
petroleum etherꢀ
/
CH2Cl2, 80:20). Compounds 5a, 5b
and 5c are known, and their 13C-NMR spectra are in
accord with those reported in the literature [7]. Com-
pounds 8a, 8b and 8c were prepared as previously
described [2].
4.3.1. 2-(Cyclopentadienyltricarbonylrhenium)propene
(3) and 2-(cyclopentadienyltricarbonylrhenium)propane
(4)
4.2.1. 6-Methyl-6-(4?-aminophenyl)fulvene (5a) (25%,
orange oil), 6-Methyl-6-(4?-chlorophenyl)fulvene (5b)
(50%, orange oil), 6-Methyl-6-(4?-methoxy)fulvene (5c)
(48%, orange solid), 6-Methyl-6-(4?-methylthio)fulvene
(5d) (56%, orange oil)
Purification by filtration (petroleum etherꢀCH2Cl2,
/
95:5) afforded a mixture of 3 and 4 as a colorless oil
(76%). The 1H-NMR spectrum of the mixture shows the
presence of 3 according to Ref. [5]. Compound 4 was
obtained by reduction of 3 (vide infra).
1
4.2.1.1. Compound Sd. H-NMR (200 MHz, CDCl3): d
7.4ꢀ
/
7.2 (m, 4H), 6.7ꢀ
/
6.4 (m, 3H), 6.3ꢀ6.2 (m, 1H), 2.55
/
(s, 3H), 2.53 (s, 3H); 13C-NMR (50 MHz, CDCl3): d
149.1, 143.2, 139.2, 138.5, 131.6, 131.4, 129.8, 125.4,
123.4, 121.0, 22.3, 15.4; IR (CDCl3): 3072, 2995, 2925,
2246, 1609, 1592, 1490, 1364; MS (m/z): 214, 199, 167;
1
4.3.1.1. Compound 4. H-NMR (200 MHz, CDCl3): d
5.3ꢀ
/
5.2 (m, 4H), 2.68 (sept, Jꢃ
/
6.8 Hz, 1H), 1.17 (s, Jꢃ
/
6.8 Hz, 6H); 13C-NMR (50 MHz, CDCl3): d 194.5,
118.4, 82.7, 82.4, 26.8, 23.9; IR (KBr): 2019, 1911.
Scheme 4.

F. Le Bideau et al. / Journal of Organometallic Chemistry 668 (2003) 140ꢀ
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143
4.3.2. 1-Cyclopentadienyltricarbonylrhenium-1-
(4?-aminophenyl)ethene (6a) and 1-cyclopenta-
dienyltricarbonylrhenium-1-(4?-aminophenyl)ethane (7a)
Purification by flash chromatography (petroleum
4.3.4. 1-Cyclopentadienyltricarbonylrhenium-1-
(4?-methoxyphenyl)ethene (6c) and 1-
cyclopentadienyltricarbonylrhenium-1-
(4?-methoxyphenyl)ethane (7c)
etherꢀ/CH2Cl2, 50:50).
Purification by flash chromatography (C5H12ꢀ
/
CH2Cl2, 85:15).
4.3.4.1. Compound 6c (63%, slightly yellow oil). 1H-
NMR (200 MHz, CDCl3): d 7.30 (d, Jꢃ8.8 Hz, 2H),
6.89 (d, Jꢃ8.8 Hz, 2H), 5.49 (s, 1H), 5.47 (t, Jꢃ2.3 Hz,
2H), 5.31 (t, Jꢃ2.3 Hz, 2H), 5.20 (s, 1H), 3.84 (s, 3H);
4.3.2.1. Compound 6a (55%, white solid). 1H-NMR (200
MHz, CDCl3): d 7.17 (d, Jꢃ8.5 Hz, 2H), 6.66 (d, Jꢃ
8.5 Hz, 2H), 5.48 (t, Jꢃ2.2 Hz, 2H), 5.43 (s, 1H), 5.30
(t, Jꢃ
2.2 Hz, 2H), 5.18 (s, 1H), 3.74 (bs, 2H); 13C-
NMR (50 MHz, CDCl3): d 194.2, 146.4, 140.3, 129.9,
129.1, 114.6, 114.2, 107.7, 83.9, 83.6; IR (CDCl3): 2023,
1931; HRMS Calc. for C16H13NO1385Re: 452.0425.
Found: 452.0428; HRMS Calc. for C16H13NO1387Re:
452.0453. Found: 452.0442.
/
/
/
/
/
/
/
/
13C-NMR (50 MHz, CDCl3): d 194.0, 159.5, 140.1,
132.1, 129.2, 114.9, 113.6, 107.3, 83.8, 55.2; IR (CDCl3):
2031, 1928; Anal. Calc. for C17H13O4Re (467.5): C,
43.68; H: 2.80. Found: C, 43.60; H, 2.92%.
4.3.4.2. Compound 7c (28%, slightly yellow oil). 1H-
NMR (200 MHz, CDCl3): d 7.14 (d, Jꢃ
6.86 (d, Jꢃ8.5 Hz, 2H), 5.4ꢀ5.1 (m, 4H), 3.81 (q, Jꢃ
7.2 Hz, 1H), 3.80 (s, 3H), 1.49 (d, Jꢃ
7.2 Hz, 3H); 13C-
NMR (50 MHz, CDCl3): d 194.4, 158.5, 136.9, 128.0,
116.2, 114.0, 84.1, 83.9, 83.6, 81.8, 55.3, 37.6, 22.8; IR
(KBr): 2018, 1917; HRMS Calc. for C17H16O1485Re:
469.0578. Found: 469.0581; HRMS Calc. for
C17H16O1487Re: 471.0607. Found: 471.0600.
/
8.5 Hz, 2H),
/
/
/
4.3.2.2. Compound 7a (25%, white solid). 1H-NMR (200
/
MHz, CDCl3): d 7.00 (d, Jꢃ
8.4 Hz, 2H), 5.4ꢀ5.1 (m, 4H), 3.75 (q, Jꢃ
3.63 (bs, 2H), 1.47 (d, Jꢃ
7.2 Hz, 3H); 13C-NMR (50
/
8.4 Hz, 2H), 6.65 (d, Jꢃ
/
/
/7.2 Hz, 1H),
/
MHz, CDCl3): d 194.5, 145.1, 134.7, 127.8, 116.5, 115.1,
84.0, 83.8, 83.6, 81.6, 37.5, 22.7; IR (KBr): 2017, 1910;
HRMS Calc. for C16H15NO1387Re: 456.0611. Found:
456.0610.
4.3.5. 1-Cyclopentadienyltricarbonylrhenium-1-
(4?-methylthiophenyl)ethene (6d) and 1-
cyclopentadienyltricarbonylrhenium-1-
(4?-methylthiophenyl)ethane (7d)
Purification by flash chromatography (petroleum
4.3.3. 1-Cyclopentadienyltricarbonylrhenium-1-
(4?-chlorophenyl)ethene (6b) and 1-
cyclopentadienyltricarbonylrhenium-1-
etherꢀ/CH2Cl2, 85:15).
(4?-chlorophenyl)ethane (7b)
Purification by flash chromatography (petroleum
4.3.5.1. Compound 6d (54%, white solid). 1H-NMR (200
etherꢀCH2Cl2, 96:4).
/
MHz, CDCl3): d 7.4ꢀ7.2 (m, 4H), 5.53 (s, 1H), 5.47 (t,
/
Jꢃ2.1 Hz, 2H), 5.32 (t, Jꢃ2.1 Hz, 2H), 5.23 (s, 1H),
/
/
2.51 (s, 3H); 13C-NMR (50 MHz, CDCl3): d 194.0,
140.2, 138.8, 136.4, 128.5, 126.2, 115.5, 106.8, 83.8, 15.6;
IR (CDCl3): 2022, 1940; Anal. Calc. for C17H13O3ReS
(483.6): C, 42.23; H, 2.71. Found: C, 42.85; H, 2.91%.
4.3.3.1. Compound 6b (63%, colorless oil). 1H-NMR
(200 MHz, CDCl3): d 7.4ꢀ7.3 (m, 4H), 5.57 (s, 1H), 5.45
(t, Jꢃ2.3 Hz, 2H), 5.32 (t, Jꢃ2.3 Hz, 2H), 5.22 (s, 1H);
/
/
/
13C-NMR (50 MHz, CDCl3): d 193.8, 139.8, 138.2,
134.1, 129.5, 128.6, 116.0, 106.1, 84.0, 83.7; IR (CDCl3):
2021, 1939; HRMS Calc. for C16H11ClO1385Re:
470.9926. Found: 470.9914; HRMS Calc. for
C16H11ClO13 87Re: 472.9946. Found: 472.9957.
4.3.5.2. Compound 7d (35%, white solid). 1H-NMR (200
MHz, CDCl3): d 7.4ꢀ
/
7.1 (m, 4H), 5.4ꢀ/5.1 (m, 4H), 3.84
(q, Jꢃ
/
7.2 Hz, 1H), 2.50 (s, 3H), 1.52 (d, Jꢃ
/
7.2 Hz,
3H); 13C-NMR (50 MHz, CDCl3): d 194.3, 141.6, 136.8,
127.5, 126.9, 115.4, 84.2, 83.9, 83.6, 81.8, 37.9, 22.6,
15.8; IR (KBr): 2014, 1912.
4.3.3.2. Compound 7b (25%, colorless oil). 1H-NMR
(200 MHz, CDCl3): d 7.30 (d, Jꢃ
Jꢃ8.4 Hz, 2H), 5.4ꢀ5.1 (m, 4H), 3.84 (q, Jꢃ
1H), 1.50 (d, Jꢃ
7.1 Hz, 3H); 13C-NMR (50 MHz,
CDCl3): d 194.1, 143.1, 132.6, 128.7, 128.3, 114.8, 84.2,
83.9, 83.6, 81.9, 37.8, 22.6; IR (KBr): 2020, 1913; HRMS
Calc. for C16H13ClO1385Re: 473.0083. Found: 473.0082;
HRMS Calc. for C16H13ClO1387Re: 475.0102. Found:
475.0106.
/
8.4 Hz, 2H), 7.15 (d,
4.4. General method for the reduction of compounds 6
/
/
/
7.1 Hz,
/
To a solution of 6 (1 mmol) and Et3SiH (232 mg, 2
mmol) in CH2Cl2, trifluoroacetic acid (2 ml) was added.
After stirring at r.t. for 24 h, the mixture was diluted in
CH2Cl2 (100 ml) and poured in a saturated solution of
NaHCO3 (100 ml). The organic layer was dried over
MgSO4, concentrated and flash chromatographied ac-

144
F. Le Bideau et al. / Journal of Organometallic Chemistry 668 (2003) 140ꢀ144
/
[2] F. Le Bideau, A. Pe´rez-Luna, J. Marrot, M.-N. Rager, E. Ste´phan,
S. Top, G. Jaouen, Tetrahedron 57 (2001) 3939.
cording to the conditions previously used (vide supra).
Yields are given in Scheme 4.
[3] D.N. Kursanov, Z.N. Parnes, N.M. Loim, Synthesis (1974) 603.
[4] E.J. Miller, C.A. weigelt, J.A. Serth, R. Rusyid, J. Brenner, L.A.
Luck, M. Godlewski, J. Organomet. Chem. 440 (1992) 91.
[5] T.E. Bitterwolf, X. Dai, J. Organomet. Chem. 440 (1992) 103.
[6] W.C. Still, M. Khan, A.J. Mitra, J. Org. Chem. 43 (1978) 2923.
[7] D.J. Sardella, C.M. Keane, P. Lemonias, J. Am. Chem. Soc. 106
(1984) 4962.
References
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(2001) 2289.