A novel and mild metal-exchange reaction in the organometallic cyclopentadienyl series: 1,1'-diaryl 2-cymantrenyl 1-butene as an example [13]

Full text of DOI:10.1021/ja991915k

736
J. Am. Chem. Soc. 2000, 122, 736-737
different if during the liberation of Cp-, the intermediate could
be kept in a stable form, for example a cyclopentadiene with four
π electrons.
In fact to achieve the hypothetical result in Scheme 1, it is
important to answer two preliminary questions concerning both
the choice of organometallic and the conditions of decomplex-
ation.
A Novel and Mild Metal-Exchange Reaction in the
Organometallic Cyclopentadienyl Series: 1,1′-Diaryl
2-Cymantrenyl 1-Butene as an Example
Siden Top,* El Bachir Kaloun, and Ge´rard Jaouen*
Laboratoire de Chimie Organome´talliqu
Ecole Nationale Supe´rieure de Chimie de Paris
UMR C.N.R.S. 7576, 11, rue Pierre et Marie Curie
75231 Paris Cedex 05, France
In terms of the initial choice of organometallic, it is clear that
a easily oxidizable carbonylated half-sandwich complex, R-CpM-
(CO)x, is preferred for reasons of ease of bond-breaking and
simplification of the reaction and the purification process
(compared to a R-CpMCp′ sandwich). In addition, this substrate
should demonstrate rich reactivity, and in particular should be
amenable to the Friedel-Crafts reaction and be manipulable with
a minimum of precautions. As for the recovery of the organic
intermediate in the form of a cyclopentadiene, this should be
possible with a mild decomplexation performed in the presence
of a well-chosen protic solvent. These ideas were applied to the
cymantrene complex 1 (Scheme 2).
This type of skeleton, with OH instead of OMe groups,
recognizes the estrogen receptor and shows a strong estrogenic
effect, while with an -O-(CH2)3-NMe2 chain in place of an
OMe group, it becomes an antiestrogenic entity.5b A simple
exchange of metals would thus permit changes in the properties
(structure, cytotoxicity, radiopharmaceutical properties) of this
entity.
ReceiVed June 9, 1999
The (C5H5-) cyclopentadienyl ligand, because of its size,
robustness, and electron count, is one of the most useful
coordinating ligands in organometallic chemistry. Its almost
ubiquitous nature has led to a number of articles on its function-
alization.1 The variety of preparation methods utilized demon-
strates both the absence of a dominant synthetic strategy suitable
for all cases and the necessity of seeking new approaches to deal
with novel problems. Here we describe a new synthetic approach
that gives access, starting from the same substrate, to different
families of cyclopentadienyl organometallic complexes whose
substituents possess a degree of complexity compatible with the
production of fine chemicals.
This approach was dictated by the imperatives inherent in the
new field of bioorganometallic chemistry.2 Our work led us to
attempt to introduce various CpM groups onto complicated
substrates, for example CpRe(CO)3 onto hormones3 and antibod-
ies,4 CpFeCp′, CpCp′TiCl2 onto antitumoral agents,5 or CpW-
(CO)3R onto proteins,6 for therapeutic, analytical or structural
reasons, and we were faced with difficulties in preparation that
needed to be solved.
Scheme 2 shows the synthetic route used.
The approach consists of a McMurry coupling reaction between
2 and dimethoxybenzophenone. Heating an equimolar mixture
of 210 and dimethoxybenzophenone in THF in the presence of
the McMurry reagent Zn/TiCl411 furnishes compound 1 in a yield
of 83% after chromatographic purification.
Compound 1 is a yellow solid, stable in air. It is known that
light causes decomposition of manganese cyclopentadienyls, more
or less rapidly depending on the compound. To our knowledge
the organic products of this decomposition are not normally fully
identified. A derivative of cyclopentadiene would be expected
but, because dimerizations and polymerizations occur easily via
the Diels-Alder reaction, the photochemical decomposition of
manganese complexes leads to an unusable mixture of several
products. To minimize the quantity of polymers, and especially
to trap the liberated cyclopentadiene, the speed of decomplexation
can be accelerated by using a UV irradiating lamp of appropriate
strength in an ethyl ehter/methanol (1:2) ether mixture. With this
Some years ago, we proposed a mild decomplexation method
in the Cr(CO)3 arene series, based on a photochemical oxidation
in air and sunlight, at room temperature, producing quantitative
amounts of substituted aromatics.7 Curiously, this idea was not
extrapolated to the metal cyclopentadienyls, where the breaking
of bonds, either chemically (e.g., with Li on ferrocene)8 or
electrochemically,9 leads to formation of unstable cyclopentadi-
enyls that are difficult to manipulate. It would be altogether
* To whom correspondence should be sent: Prof. G. Jaouen, Laboratoire
de Chimie Organome´tallique, Ecole Nationale Supe´rieure de Chimie de Paris,
UMR C.N.R.S. 7576, 11, rue Pierre et Marie Curie, 75231 Paris Ce´dex 05,
France. Telephone: 33-1 43 26 95 55. Fax: 33-1 43 26 00 61. E-mail:
Jaouen@ext.jussieu.fr.
(1) (a) Macomber, D. W.; Hart, W. P.; Rausch, M. D. AdV. Organomet.
Chem. 1982, 21, 1. (b) Janiak, C.; Schumann, H. AdV. Organomet. Chem.
1991, 33, 291. (c) Okuda, J. Comments Inorg. Chem. 1994, 16, 185. (d)
Coville, N. J.; du Plooy, K. E.; Pikl, W. Coord. Chem. ReV. 1992, 116, 1. (e)
Jutzi, P.; Dahlhauss, J. Coord. Chem. ReV. 1994, 137, 179. (f) Herberhold,
M. In Ferrocenes; Togni, A., Hayashi, T., Eds.; VCH: Weinheim, Germany,
1995. (g) Plenio, H.; Warnecke, A. Organometallics 1996, 15, 5066. (h)
Takahashi, T.; Sun, W.-H.; Xi, C.; Kotora, M. Chem. Commun. 1997, 2069.
i) de Azevedo, C. G.; Boese, R.; Newman, D. A.; Vollhardt, K. P. C.
Organometallics 1995, 14, 4980.
(2) (a) Jaouen, G.; Vessie`res, A.; Butler, I. S. Accounts Chem. Res. 1993,
26, 361. (b) Severin, K.; Bergs, R.; Beck, W. Angew. Chem., Int. Ed. 1998,
37, 1634.
(3) Top, S.; El Hafa, H.; Vessie`res, A.; Quivy, J.; Vessermann, J.; Hughes,
D. W. McGlinchey, M. J.; Mornon, J.-P.; Thoreau, E.; Jaouen, G. J. Am Chem
Soc. 1995, 117, 8372.
(4) Salmain, M.; Gunn, M.; Gorfti, A.; Top, S.; Jaouen, G. Bioconjugate
Chem. 1993, 4, 424.
(5) (a) Top, S.; Tang, J.; Vessie`res, A.; Carrez, D.; Provot, C.; Jaouen, G.
J. C. S. Chem. Commun. 1996, 955. (b) Top, S.; Vessie`res, A.; Jin, L.; Quivy,
J.; Leclercq, G.; Croisy, A.; Jaouen, G., 1999, manuscript submitted for
publication.
(6) Salmain, M.; Gorfti, A. Jaouen, G. Eur. J. Biochem. 1998, 258, 192.
(7) (a) Jaouen, G.; Dabard, R. Tetrahedron. Lett. 1971, 1015. (b) Jaouen,
G. Arene Complexes in Organic Synthesis. In Transition Metal Organome-
tallics in Organic Synthesis; Alper, H., Ed.; Acad. Press: 1978; Vol. 2, pp
65, Chapter 2. (c) Top, S.; Jaouen, G. J. Org. Chem. 1981, 46, 18.
(8) Osgerby, J. M.; Pauson, P. L. J. Chem. Soc. 1961, 4605.
(9) Chaloyard, A.; El Murr, N. Inorg. Chem. 1980, 19, 3217.
(10) Fischer, E. O.; Fellmann, W. J. Organomet. Chem. 1963, 1, 191.
(11) McMurry, J. E. Acc. Chem. Res. 1983, 16, 405.
(12) Synthesis of 3 and 1. 1.71 g (9 mmol) of TiCl4 was added dropwise
to a suspension of 1.17 g (12 mmol) of zinc powder in 30 mL THF at 0 °C.
The blue mixture obtained was heated at reflux for 2 h, the solution became
black. The oil bath was removed. A second solution was prepared by dissolving
0.882 g (3 mmol) of 4, 4′-dimethoxybenzophenone and 0.780 g (3 mmol)
propionylcymantrene, 2, in 15 mL THF. The latter solution was added
dropwise to the first solution, and the resulting mixture was then heated again
for 2 h. After cooling to room temperature, the mixture was hydrolyzed with
100 mL of a 10% Na2CO3 solution. After ether extraction and solvent removal,
the crude product, 2.12 g, was chromatographed on silica gel plates (TLC)
with ethyl ether/pentane 1/5 as eluent to give 1.25 g of 1 (83% yield). 1 was
1
crystallized from ethyl ether/pentane to give yellow crystals, mp 91 °C. H
RMN (200 MHz, CDCl3) δ 7.10, d, 7.01, d 6.84, d, 6.80, d (8H, aromatic
ring), 4.54, t, 4.47, t (4H, C5H4), 3.81, s, 3.80, s (6H, 2 MeO), 2.31, q (2H,
CH2CH3), 1.05, t (CH2CH3). Anal. (C26H23O5Mn): calcd, C, 66.38, H, 4.93;
found, C, 66.45, H, 5.00. 0.402 g of 1 were dissolved in 15 mL of technical
grade ethyl ether and 30 mL of methanol. The long tube containing the solution
was placed in front of the UV lamp (TQ150) for irradiation. Significant gas
evolution was observed. After 1 h irradiation, a brown powder precipitated
from the solution. The solution was filtered through a filter funnel filled with
0.5 mm thick silica gel and then removed by evaporation. Silica gel TLC
with ethyl ether/pentane 1/6 as eluent gave 0.228 g of 3 as a beige oil (81%
yield). 1H RMN (200 MHz, CDCl3) δ 7.14-6.67, m (8 H, aromatic ring),
6.40-5.94 (m, 3H of C5H5 ring), 3.83, s, 3.82, s, 3.78, s, 3.77, s (6H, 2 MeO),
3.01, m, 2.66, m (2H, CH2 of C5H5 ring), 2.42, q, 2.41, q (2H, CH2CH3),
1.02, t, 1.01, t (CH2CH3) (mixture of two isomers).
10.1021/ja991915k CCC: $19.00 © 2000 American Chemical Society
Published on Web 01/15/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 4, 2000 737
Scheme 1
Scheme 3
Scheme 2
the cymantrene complex 1 is a stable and unique source for several
series of organometallic complexes of varied interest. In this
respect the strategy recalls and complements the fixation onto a
substrate by using a hydroxylated cyclopentene as a masked
cyclopentadiene1i, a strategy which was not successful in our case.
In special cases, nitroferrocenyl compounds,14 nickelocene15 and
manganocene16 can also produce free substituted cyclopentadiene.
A complex of Re similar to 6 could be used, in radioactive form,
as a radiopharmaceutical. There is a current revival of interest in
the rapid fixation of isotopes 186 and 188 of Re, and even of
99mTc, onto bioligands.3,17 A compound such as 7 containing a
heavy metal could find an application in the X-ray structural
determination of the receptor protein.6 However although 6 and
7 are obtainable by other routes, the same cannot be said for 5.
Access to this molecule requires the formation of Cp′CpTiCl2 in
the last step of the synthesis, which is permitted by the strategy
described here. A biological study of the products derived from
5, 6, and 7 is underway. We are also studying the potential and
limits of this new decomplexation-recomplexation reaction for
a variety of applications.
approach we were able to obtain in 1 h the cyclopentadiene 3 in
81% yield after purification.12 Once pure, 3 proves relatively stable
against polymerization, and it can be kept several days under
refrigeration. The 1H NMR spectrum showed that 3 is a mixture
of at least two diene positional isomers. However, separation is
not essential for the rest of the procedure.
The organo-lithium reagent 4 reacts with CpTiCl3, BrRe(CO)5,
W(CO)6, and FeCl2 to form compounds 5, 6, 7, and 8, respec-
tively, in yields ranging from 45 to 64%.13
Scheme 3 calls for several comments. It illustrates the fact that
Acknowledgment. We thank the “Centre National de la Recherche
Scientifique” and DeBiopharm company for their financial support, and
Barbara McGlinchey for translating the manuscript.
(13) 1H RMN of 5 (200 MHz, CDCl3) 7.20, 7.00, 6.88, 6.81 (4d, 8H, 2
C6H4); 6.49 (s, 5H, C5H5); 6.27, 6.15 (2m, 4H, C5H4); 3.82, 3.81 (2s, 6H,
2MeO); 2.44 (q, 2H, CH2CH3); 1.00 (t, 3H, CH2CH3). Mass spectrum (DCI)
JA991915K
1
m/z: 532 (M + NH4)+, 333. H RMN of 6 (200 MHz, CDCl3) δ 7.08, 7.03,
6.85, and 6.80 (4d, 8H, 2 C6H4), 5.11, 5.07 (2t, 4H, C5H4), 3.80, and 3.79
(2s, 6H, 2 MeO), 2.27, q (2H, CH2CH3), 1.07, t (CH2CH3). MS (70 eV) m/z:
602 [M+], 518 [M+ - 3CO]. 1H RMN of 7 (200 MHz, CDCl3) δ 7.11, 7.03,
6.87, 6.81 (4d, 8H, 2 C6H4), 5.14, 4.96 (2t, 4H, C5H4), 3.81, s, 3.80, s (6H, 2
MeO), 2.32, q (2H, CH2CH3), 1.05, t (CH2CH3). MS (70 eV) m/z: 614 [M+],
529, 515 [M+ - 3CO - Me], 484.1H RMN of 8 (200 MHz, CDCl3) δ 7.07,
6.94, 6.85, 6.76 (4d, 8H, 2 C6H4), 4.05 and 3.80 (2m, 4H, C5H4), 3. 81 and
3.80 (2s, 6H, 2 MeO), 2.59 (q, 2H, CH2CH3), 1.02 (t, 3H, CH2CH3). MS (70
eV) m/z: 718 [M+], 387.
(14) Salter, R.; Pickett, T. E.; Richards, C. J. Tetrahedron Asymmetry 1998,
9, 4239.
(15) Moberg, C. J. Organomet. Chem. 1976, 108, 125.
(16) Unseld, D.; Krivykh, V. V.; Heinze, K.; Wild, F.; Artus, G.; Schmalle,
U.; Berke, H. Organometallics 1999, 18, 1525.
(17) (a) Alberto, R.; Schibli, R.; Egli, A.; Schubiger, P. A.; Abram, U.;
Kaden, T. A. J. Am. Chem Soc. 1998, 120, 7987. (b) Minutolo, F.;
Katzenellenbogen, J. A. Organometallics 1999, 18, 2519.