J. Am. Chem. Soc. 2001, 123, 4093-4094
4093
Scheme 1. Comparison of Reactivity of Rhenium Sources
One-Pot Formation of Substituted Cyclopentadienyl
and Indenyltricarbonyl Rhenium Complexes through
in Situ Generation of Cyclopentadienyl- and
Indenyltributylstannanes
a solution of 1 in MeCN was treated with a THF solution of
CpTBT at room temperature, formation of CpRe(CO)3 was
complete within 5 min, and this material could be obtained in 80%
yield, after isolation and chromatography (Scheme 1). The
corresponding reaction with BrRe(CO)5 required 6 h at reflux in
THF to achieve a similar yield. It should be noted that under
analogous conditions, neither of the other Cp donors, nickelocene
nor trimethylsilyl-cyclopentadiene, produced any significant
amount of CpRe(CO)3.
With this promising result in hand, we attempted to prepare a
variety of substituted cyclopentadienyl- and indenyltributyltin
compounds. Unfortunately, we were unable to isolate most of
these compounds, because of the facility with which they under-
went protonolysis (destannylation). To circumvent this hydrolysis
problem, we chose not to isolate the tributyltin species, but rather
to generate them in situ, and use them directly in the reaction
with the addition of the metal precursor 1.
Recently, tin-amines have been used in palladium-catalyzed
amination reactions of aryl halides.8 However, the tin-amines have
long been known for their ability to react with protic solvents,
such as alcohols, thiols, and other amines, to form the corre-
sponding tin-alkoxides, sulfides, or amines under mild conditions.9
They also are known to react with the relatively acidic protons
of cyclopentadiene and indene to form the corresponding enyl-
tin species.6b,10
Our initial attempt to utilize the tin-amines was in the prepa-
ration of unsubstituted CpRe(CO)3. When we treated a THF
solution of freshly cracked cyclopentadiene with diethylamino-
tributyltin at room temperature for 2 h, added this mixture to a
solution of 1 in a minimal amount of MeCN, and refluxed the
resulting solution, we indeed saw formation of CpRe(CO)3 by
TLC analysis. After 1 h, CpRe(CO)3 was isolated, as above, in
81% yield.
Richard R. Cesati III and John A. Katzenellenbogen*
Department of Chemistry
UniVersity of Illinois at Urbana-Champaign
Urbana, Illinois 61801
ReceiVed September 6, 2000
The extensive use of metallic radionuclides in nuclear medicine
is dominated by technetium-99m (γ, t1/2 ) 6 h), and radiophar-
maceuticals labeled with this isotope are used in approximately
80% of all diagnostic imaging procedures.1 For tumor radiothera-
peutic purposes, rhenium-186 (â, t1/2 ) 91 h) and rhenium-188
(â, t1/2 ) 17 h) have shown great promise.2 Recently, a large
number of publications have appeared describing the synthesis
of low-valent technetium and rhenium (i.e., M(CO)3+) and their
use for the preparation of new radiopharmaceuticals.3 Our own
interest has been focused on the development of novel methods
for the generation of stable substituted η5-cyclopentadienyltri-
carbonyl rhenium and technetium (CpRe(CO)3 and CpTc(CO)3)
complexes for radiolabeling biologically interesting molecules,
especially small molecule ligands for receptors.4 However, until
recently, the preparation of these organometallic species has
required harsh conditions and multistep procedures.5 Herein we
describe the utility of trialkyltin-substituted cyclopentadienes in
the efficient synthesis of substituted CpRe(CO)3 complexes.
Reactions of trialkylstannylcyclopentadienes with Group VII
pentacarbonyl halides [MX(CO)5] for the preparation of unsub-
stituted CpRe(CO)3 complexes have been reported.6 Most reac-
tions utilized the trimethyltin derivative and were complete within
3-7 h, with manganese, as expected, exhibiting a higher rate of
reaction than rhenium. However, for this chemistry to be useful
for radiolabeling receptor ligands, we needed to be able to include
additional functionality in the cyclopentadienyl ring.
To extend this reaction to other ring systems, we attempted to
carry out the analogous reaction using indene rather than
cyclopentadiene. In this experiment, a THF solution of indene
was treated with diethylamino-tributyltin at reflux for 1 h. TLC
showed complete consumption of the indene starting material and
formation of a new, higher Rf, compound. However, upon addition
of the MeCN solution of 1 at room temperature, TLC analysis
showed the rapid reappearance of free indene, with no detectable
formation of the desired indenyltricarbonyl rhenium (InTR)
complex. It is unlikely that adventitious water can account for
this complete protonolysis. Rather, because the pKa values of
indene and the solvent MeCN are comparable, it is more likely
that the indene anion is being protonated by this solvent, although
it is not clear why this same protonation would not happen with
the more basic Cp-tin species. In any case, we developed as an
alternative a strictly aprotic system in THF solvent.
Our initial studies focused on the reaction of tributylstannyl-
cyclopentadiene (CpTBT) with (Et4N)2[ReBr3(CO)3] (1)3a as the
source of Re(CO)3+, an approach analogous to that which we
used in a related three-component condensation.7 Because the
metal precursor 1 is insoluble in THF, it was dissolved in
acetonitrile (MeCN). CpTBT, being insoluble in MeCN, was
dissolved in THF, which was used as reaction cosolvent. When
(1) Schwochau, K. Angew. Chem., Int. Ed. Engl. 1994, 33, 2258.
(2) (a) John, E.; Thakur, M. L.; DeFulvio, J.; McDevitt, M. R.; Damjanov,
I. J. Nucl. Med. 1993, 34, 260. (b) Lisic, E. C.; Mirzadeh, S.; Knapp, F. F.,
Jr. J. Labelled Compd. Radiopharm. 1993, 33, 65.
(3) (a) Alberto, R.; Egli, A.; Abram, U.; Hegetschweiler, K.; Gramlich J.
Chem. Soc., Dalton Trans. 1994, 2815. (b) Alberto, R.; Schibli, R.; Egli, A.;
Schubiger, A. P.; Abram, U. J. Am. Chem. Soc. 1998, 120, 7987. (c) Alberto,
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G.; Baldwin, R. M.; Zoghbi, S. S.; Innis, R. B.; Katzenellenbogen, J. A. J.
Labelled Compd. Radiopharm. 1999, 42, S1, 150-152
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(6) The following citations contain several examples of reactions involving
silyl-substituted compounds as well as one example of a methyl-substituted
compound. (a) Abel, E. W.; Moorhouse, S. J. Organomet. Chem. 1971, 28,
211. (b) Abel, E. W.; Moorhouse, S. J. Chem. Soc., Dalton Trans. 1973, 1706.
(7) (a) Minutolo, F.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1998, 120,
4514. (b) Minutolo, F.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1998, 120,
13264. (c) Minutolo, F.; Katzenellenbogen, J. A. Organometallics 1998, 18,
13, 2519.
(8) (a) Buchwald, S. L.; Guram, A., Process and catalysts for the preparation
of arylamines. U.S. Patent 5576460, 19961119, 1996. (b) Guram, A. S.;
Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 7901. (c) Hartwig, J. F.;
Richards, S.; Baranano, D.; Paul, F. J. Am. Chem. Soc. 1996, 118, 3626. (d)
Louie, J.; Hartwig, J. F. J. Am. Chem. Soc. 1995, 117, 11598. (e) Louie, J.;
Paul, F.; Hartwig, J. F. Organometallics 1996, 15, 2794. (f) Paul, F.; Patt, J.;
Hartwig, J. F. J. Am. Chem. Soc. 1994, 116, 5969. (g) Yamamoto, T.;
Nishiyama, S.; Koie, Y., Preparation of N-arylamines. Japanese Patent
11100355, 19990413, 1999.
(9) (a) Anderson, J. W.; Barker, G. K.; Drake, J. E.; Rodger, M. In J. Chem.
Soc., Dalton Trans. 1973, 1716. (b) George, T. A.; Lappert, M. F. J. Chem.
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10.1021/ja005585b CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/04/2001