New and efficient synthesis of CpRe(CO)3 substituted steroids

Article abstract of DOI:10.1016/S0040-4020(01)00263-0

Fulvenes generated from steroids have been efficiently engaged in a process implying nucleophilic or basic attack followed by a transmetallation reaction in the presence of BrRe(CO)₅ to afford the corresponding CpRe(CO)₃ substituted compounds. This new strategy is of relevant interest for the synthesis of new potential radiopharmaceuticals.

Full text of DOI:10.1016/S0040-4020(01)00263-0

TETRAHEDRON
Pergamon
Tetrahedron 57 ꢀ2001) 3939±3944
New and ef®cient synthesis of CpReꢀCO) substituted steroids
3
a
Franck Le Bideau, Alejandro P e rez-Luna, J e r oà me Marrot, Marie-No eÈ lle Rager, Elie St e phan,
a
b
a
a
a
Siden Top and G e rard Jaouen
a,p
a
UMR 7576 CNRS, Ecole Nationale Sup e rieure de Chimie de Paris, 11 rue Pierre et Marie Curie, 75231 Paris Cedex05, France
Universit e de Versailles Saint-Quentin-en-Yvelines, IREM, b aà timent Lavoisier, 45 av. des Etats-Unis, 78035 Versailles Cedex, France
b
Received 21 November 2000; revised 12 February 2001; accepted 26 February 2001
AbstractÐFulvenes generated from steroids have been ef®ciently engaged in a process implying nucleophilic or basic attack followed by a
transmetallation reaction in the presence of BrReꢀCO) to afford the corresponding CpReꢀCO) substituted compounds. This new strategy is
of relevant interest for the synthesis of new potential radiopharmaceuticals. q 2001 Elsevier Science Ltd. All rights reserved.
5
3
1
. Introduction
2. Results and discussion
2.1. Fulvene synthesis
There is a growing interest in the study of new bioorgano-
1
,2
metallic materials. In this ®eld and in connection with
studies of new potential radiopharmaceuticals, an ef®cient
route towards CpReꢀCO) substituted steroids is desirable
and we thus focussed our studies in this direction. Taking
into account the cost of the organometallic precursor
BrReꢀCO) and in view of a future introduction of radio-
active nuclides, we needed a general strategy which allows
the introduction of the CpReꢀCO) unit as late as possible in
the synthesis. To this aim, we found that steroids bearing a
fulvene group were very attractive precursors for a one-pot
Only two general methods for the preparation of steroids
substituted by a fulvene group have been reported in the
literature. Knox reported the synthesis and a biological
study ꢀanabolic properties, anti-ovulatory, anti-androgenic
and anti-estrogenic activities) of 3-fulvene androstane,
3
5
4
pregnane or nor-derivatives 2. These compounds were
3
obtained by treating the corresponding 3-keto-androstanes
or pregnanes 1 with a solution of cyclopentadiene and
sodium in ethanol according to Thiele's method ꢀScheme
3
5
synthesis of the desired products. These compounds are
1).
easier to prepare and to characterize and more interesting
than the corresponding cyclopentadienyl species because
they may provide access to a wide variety of products
depending on the conditions ꢀbasic versus nucleophilic).
In this paper, we describe in full detail our synthetic strategy
and efforts to achieve the synthesis of this new generation of
potential radiopharmaceuticals.
6
Erker et al. have recently used the Little and Stone method
to introduce the fulvene part at the C-16 position of a
7
modi®ed estradiol 3 and at the C-3 position of cholestanone
8
5 ꢀScheme 2).
Compounds 4 and 6 are precursors of organometallic
Scheme 1.
Keywords: fulvenes; cyclopentadienyl; rhenium.
Corresponding author. Tel.: 133-01-43-26-9555; fax: 133-01-43-26-00-61; e-mail: jaouen@ext.jussieu.fr
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020ꢀ01)00263-0

3940
F. Le Bideau et al. / Tetrahedron 57 ꢀ2001) 3939±3944
Scheme 2.
species used as homogeneous Ziegler-type catalysts for
stereoselective propene polymerization.
formed in 72% yield starting from 5a-androstan-17b-ol-3-
one 9 ꢀScheme 4).
In connection with our interest in new CpReꢀCO) substi-
3
These fulvenes, which are less polar compounds than the
corresponding ketones, are easily puri®ed by ¯ash chroma-
tography and can be stored at room temperature for several
weeks without modi®cation. It should also be emphasized
that since water decreases the yield, reactions have to be
carried out in a ¯ame-dried schlenk tube with anhydrous
solvents and reactants.
tuted steroids, we needed an access to the corresponding
fulvenes. Cholest-4-en-3-one 7a was chosen as a model
substrate and ®rst submitted to the condition reported by
4
Knox to afford traces of the desired fulvene 8a. This poor
amount of desired product led us to test the second method
7
,8
reported by Erker et al. We found that dichloromethane
was as good cosolvent as ether used by these authors to
overcome the lack of solubility of the starting materials in
methanol. These reaction conditions allowed us to obtain
the fulvenes 8a, 8b and 8c in good yields ꢀranging from
2.2. Formation of the CpReꢀCO) unit
3
Having found a highly practical route to access steroids
bearing a fulvene functionality, we turned our attention on
how to have access to the corresponding CpReꢀCO) substi-
6
6 to 76%) ꢀScheme 3).
3
It should be noted that the carbonyl function of the pro-
gesterone 7b in the C-20 position was not transformed
probably because of the steric hindrance of the C-18 methyl
group. This result was reported by Little and Stone for
hindered aldehydes as the major drawback of their method.
Using the same conditions as above, compound 10 was
tuted compounds. The idea of obtaining a cyclopentadienyl
metal unit by reduction of a fulvene through nucleophilic or
basic attack was originally developed by Pauson for the
9
synthesis of ferrocene derivatives and substituted cyclo-
pentadienyl derivatives of nickel, cobalt, molybdenum and
6
1
0
titanium. The method was afterwards explored for the
Scheme 3.
Scheme 4.

F. Le Bideau et al. / Tetrahedron 57 ꢀ2001) 3939±3944
3941
Scheme 5.
Scheme 6.
7
,8,11,12
preparation of various cyclopentadienyl units
but no
The molecular structure ꢀdetermined by X-ray crystallo-
graphic analysis) of the major product 14a showed that
the newly introduced methyl substituent is attached to the
example of the synthesis of CpReꢀCO)3 substituted
compounds was reported. This approach to the desired
compounds had therefore to be attempted. The action of a
base or a nucleophile on the fulvene part of compound 11
could generate intermediate salts, which could be good
precursors of the desired products 12 or 13, through a
transmetallation process in the presence of BrReꢀCO)5
3
a face of the steroid framework.
Fulvenes 8a, 8b and 8c were converted into the correspond-
ing compounds 15a, 15b and 15c in good yields, according
to path b ꢀScheme 5), in the presence of KH and BrReꢀCO)5
at 1108C in a mixture of THF and toluene ꢀScheme 7).
ꢀ
Scheme 5).
According to path a ꢀScheme 5), fulvene 8a was treated
with MeLi in toluene at 2788C and warmed to room
temperature for 3 h. BrReꢀCO) was then added and the
Compound 15a was crystallized from hexane/CH Cl and
2
2
its molecular structure was determined by X-ray crystallo-
graphic analysis ꢀFig. 1). This product was the result of a
proton abstraction in the C-6 position. The structures of 15b
5
reaction mixture was heated to re¯ux for 15 h. Under
these conditions, two diastereomers 14a1/b were
obtained in a 2:1 ratio ꢀaccording to the H NMR
spectra of the mixture) in 39% yield. These diastereo-
mers have different relative con®guration at the newly
formed stereogenic center ꢀScheme 6). In that case no
compound resulting from the reaction of the MeLi as
base was isolated.
1
and 15c were assigned by comparison of their H NMR
spectra with that of 15a, which exhibit similar patterns. It
is worth noting that no isomeric product resulting from the
deprotonation at the C-2 position was isolated after puri®ca-
tion by ¯ash chromatography, although the NMR spectra of
the crude reaction mixtures showed small amounts of these
species in the case of 15b and of 15c.
Scheme 7.

3942
F. Le Bideau et al. / Tetrahedron 57 ꢀ2001) 3939±3944
Figure 1. ORTEP structure of 15a obtained by X-ray crystallographic analysis.
Scheme 8.
Finally, fulvene 10 was transformed under the same condi-
tions into a mixture of isomers 16 ꢀ16a/16b 4:1), which
could not be separated ꢀScheme 8). The position of the
double bond in the major product 16a was assigned on the
basis of ꢀH,H)- and ꢀH,C)-correlated NMR spectroscopy.
on Merck silica gel 60 F 254. Silica gel Merck Gerudan
SI ꢀ40±63 mm) was used for column chromatography
1
3
using the Still method. Elemental analyses were measured
at the microanalysis laboratory of the Pierre et Marie Curie
University ꢀParis, France). Optical rotations were measured
with a JASCO P-1010 polarimeter. All solvents and
reagents were puri®ed when necessary using standard
procedures. Anhydrous methanol ꢀ99.8%) was purchased
from Aldrich and used as received. Reactions were carried
out in ¯ame-dried schlenk glassware under inert atmosphere
ꢀargon). 4-Cholesten-3-one, pregnenolone and adrenoster-
one ꢀAldrich); testosterone, pyrrolidine and progesterone
1
The H NMR spectra of these conjugated CpReꢀCO)3
substituted steroids exhibit three multiplets between 5.6
and 5.2 ppm due to the cyclopentadienyl protons as against
three multiplets between 6.7 and 6.4 ppm for the corre-
sponding fulvenes.
ꢀAcros); 5a-androstan-17b-ol-3-one ꢀSigma) were used as
received.
3. Conclusions
The results presented above describe a new route to
CpReꢀCO) substituted steroids. Although organic solvents
4.1. General method for the fulvene synthesis
3
are not the ideal media for the synthesis of radiopharma-
ceuticals, this ef®cient method may lead to discovery of new
targets of relevant interest in the ®eld of medicinal
chemistry. The introduction of the metal carbonyl unit on
a steroid in the last step of the synthesis describe here is a
crucial point for future developments of potential radio-
pharmaceuticals. For this reason, fulvenes could be more
interesting than the corresponding cyclopentadienes
because of the great number of products accessible accord-
ing to the condition used ꢀbasic versus nucleophilic) and
their higher stability.
To a solution of steroid ꢀ5 mmol) and cyclopentadiene
1 mL, 12 mmol) in 8 mL of MeOH/CH Cl ꢀ1/1), freshly
ꢀ
2
2
distilled pyrrolidine ꢀ2 mL, 24 mmol) was added. The
mixture was stirred at room temperature for 20 h, diluted
with AcOEt ꢀ50 mL), washed with brine ꢀ3£25 mL), dried
over MgSO and concentrated. The obtained residue was
4
puri®ed via ¯ash chromatography.
4
4
8
.1.1. 4-Cholesten-3-ꢀ2,4-cyclopentadien-1-ylidene) 8a.
-Cholesten-3-one ꢀ185 mg, 0.5 mmol) was converted into
a according to the general procedure. Puri®cation by ¯ash
chromatography ꢀpentane) afforded 8a as a red solid
ꢀ137 mg, 66%). H NMR ꢀ200 MHz, CDCl ) d 6.65 ꢀm,
1
4. Experimental
3
1
H), 6.55 ꢀm, 2H), 6.5 ꢀm, 2H), 3.00 ꢀdt, Jˆ13.4, 3.8 Hz,
1
13
H and C NMR spectra were recorded on a 200 MHz
1H), 2.8±0.6 ꢀm, 42H), 1.12 ꢀs, 3H), 0.94 ꢀd, Jˆ6.6 Hz,3H),
1
3
Bruker AC 200 spectrometer. Chemical shifts are reported
in ppm and referenced to the residual proton resonances of
the solvent used. Infrared ꢀIR) spectra were recorded by
using a BOMEN MB spectrometer. Mass spectra were
obtained on NERMAG R1010C apparatus. Melting points
were measured on a B uÈ chi B-510 apparatus and are uncor-
rected. Thin-layer chromatography ꢀTLC) was performed
0,90 ꢀd, Jˆ6.6 Hz, 6H), 0.71 ꢀs, 3H) ppm; C NMR
ꢀ50 MHz, CDCl ) d 159.3, 147.2, 138.7, 130.1, 129.6,
3
121.1, 119.9, 118.8, 56.0, 55.9, 54.1, 42.3, 39.7, 39.4,
38.3, 36.0, 35.7, 33.4, 32.6, 28.1, 27.9, 25.1, 24.1, 23.7,
22.7, 22.5, 21.2, 18.6, 18.0, 11.9 ppm; IR ꢀCH Cl ) 2934,
1601, 1454, 1377, 1367, 1083 cm ; MS ꢀm/z) 432, 417,
281, 207, 170, 156, 144, 130, 91, 83; Anal. Calcd for
2
2
2
1

F. Le Bideau et al. / Tetrahedron 57 ꢀ2001) 3939±3944
3943
C H ꢀ432.6): C 88.82, H 11.18. Found C 86.65, H 11.22;
3
by ¯ash chromatography ꢀpentane) afforded a mixture of
14a and 14b ꢀ54 mg, 39%) as a white solid. A sample of
2
48
2
0
mp 1308C; [a]D ˆ1228.3 ꢀ0.60, CH Cl ).
2
2
14 was obtained from the mixture by crystallisation
ꢀCH Cl /hexane) for further analysis.
4
8
.1.2. 4-Pregnene-3-ꢀ2,4-cyclopentadien-1-ylidene)-20-one
b. 4-Pregnene-3,20-dione ꢀ1.570 g, 5 mmol) was
2
2
1
14a: H NMR ꢀ200 MHz, CDCl ) d 5.3±5.1 ꢀm, 4H), 5.02
converted into 8b according to the general procedure. Puri-
cation by ¯ash chromatography ꢀdichloromethane)
3
®
ꢀbs, 1H), 2.2±0.6 ꢀm, 31H), 1.23 ꢀs, 3H), 1.05 ꢀs, 3H), 0.91
ꢀs, 3H) 0.89 ꢀs, 3H), 0.71 ꢀs, 3H) ppm; C NMR ꢀ50 MHz,
1
13
afforded 8b as an orange solid ꢀ1.390 g, 76%). H NMR
200 MHz, CDCl ) d 6.7±6.6 ꢀm, 1H), 6.6±6.5 ꢀm, 2H),
ꢀ
CDCl ) d 194.6, 145.0, 126.7, 122.1, 84.2, 82.8, 81.6, 56.2,
3
3
6
.5±6.4 ꢀm, 2H), 3.00 ꢀdt, Jˆ16.2, 4.0 Hz, 1H), 2.8±0.6
54.3, 42.5, 39.9, 39.5, 37.1, 36.2, 35.9, 35.8, 35.4, 35.0,
34.5, 33.0, 32.5, 29.7, 28.4, 28.2, 28.0, 24.2, 23.8, 22.8,
22.5, 21.5, 19.2, 18.6, 12.0 ppm; IR ꢀKBr) 2932, 2012,
ꢀ
m, 28H), 2.14 ꢀs, 3H), 1.13 ꢀs, 3H), 0.67 ꢀs, 3H) ppm;
C NMR ꢀ50 MHz, CDCl ) d 209.5, 158.4, 146.6, 139.0,
1
3
3
2
1
1
3
2
1
1
8
30.2, 129.7, 121.3, 119.9, 118.8, 63.5, 56.1, 53.9, 43.9,
8.7, 38.3, 36.1, 35.6, 33.2, 32.5, 31.4, 29.6, 25.1, 24.3,
2.7, 21.2, 18.0, 13.2 ppm; IR ꢀKBr) 2927, 2848, 1701,
616, 1456, 1389 cm ; MS ꢀm/z) 362, 347, 319, 170,
56, 144, 129, 91; Anal. Calcd for C H O ꢀ362.5): C
6.13, H 9.45. Found C 85.89, H 9.32; mp 1618C;
1929, 1467, 1381 cm ; MS ꢀm/z) 718, 703, 690, 661,
628, 427, 415, 119; Anal. Calcd for C H O Re ꢀ718.0):
C 60.22, H 7.16. Found C 60.25, H 7.10; mp 1958C.
3
6
51
3
2
1
1
14b: H NMR ꢀ200 MHz, CDCl ) d 5.4±5.2 ꢀm, 2H), 5.2±
2
6
34
3
1
5.1 ꢀm, 2H), 4.94 ꢀbs, 1H), 2.2±0.6 ꢀm, 46H) ppm; C NMR
3
2
0
[
a]D ˆ1444.1 ꢀ0.76, CH Cl ).
ꢀ50 MHz, CDCl ) d 194.7, 145.8, 125.5, 118.8, 86.7, 83.5,
3
2
2
82.3, 82.0, 56.1, 55.1, 39.9, 39.5, 37.1, 36.0, 35.7, 35.5,
4
1
0
.1.3. Androstan-3-ꢀ2,4-cyclopentadien-1-ylidene)-4-ene-
7b-ol 8c. Androstan-4-ene-17b-ol-3-one ꢀ146 mg,
.5 mmol) was converted into 8c according to the general
35.3, 35.0, 33.9, 33.0, 32.5, 29.3, 28.4, 28.2, 24.2, 23.8,
22.8, 22.5, 21.6, 19.3, 18.6, 12.0 ppm.
procedure. Puri®cation by ¯ash chromatography ꢀdichloro-
methane) afforded 8c as a red solid ꢀ130 mg, 76%). H NMR
4.2. General procedure for the preparation of the
CpReꢀCO) substituted steroids
1
3
ꢀ
200 MHz, CDCl ) d 6.64 ꢀm, 1H), 6.54 ꢀm, 2H), 6.47 ꢀm,
3
2
0
H), 3.64 ꢀt, Jˆ8.1 Hz; 1H), 3.02 ꢀdt, Jˆ16.3, 3.7 Hz, 1H),
Fulvene ꢀ0.25 mmol), KH ꢀ12 mg, 0.3 mmol) washed twice
with pentane and BrReꢀCO) ꢀ122 mg, 0.3 mmol) in THF/
1
.8±2.7 ꢀm, 18H), 1.14 ꢀs, 3H), 0.80 ꢀs, 3H) ppm; C NMR
3
5
ꢀ
50 MHz, CDCl ) d 158.9, 147.1, 140.0, 130.3, 129.8,
3
toluene ꢀ2 mL/2 mL) were re¯uxed for 2 h. The reaction
mixture was cooled to room temperature and diluted in
CH Cl ꢀ20 mL). The organic layer was washed with brine
1
3
1
1
1
21.4, 120.0, 118.9, 81.8, 54.3, 50.6, 42.9, 38.5, 36.6,
6.2, 35.9, 33.3, 32.2, 30.5, 25.2, 23.4, 20.9, 18.1,
1.1 ppm; IR ꢀCH Cl ) 3608, 3054, 2850±2950, 1606,
2
2
2
2
ꢀ2£20 mL), dried ꢀMgSO ), ®ltered and concentrated.
4
2
1
455, 1422, 1370, 895 cm ; MS ꢀm/z) 336, 170, 156,
44, 129, 115, 105, 84; Anal. Calcd for C H O ꢀ336.5):
2
4
32
4.2.1. Cholestan-3-cyclopentadienyletricarbonylerhenium-
3,5-diene
C 85.66, H 9.59. Found C 85.30, H 9.74; mp 2028C;
[
15a.
4-Cholesten-3-ꢀ2,4-cyclopentadien-1-
2
0
a]D ˆ1329.6 ꢀ0.54, CH Cl ).
ylidene) 8a ꢀ108 mg, 0.25 mmol) was converted into 15a
according to the general procedure. Puri®cation by ¯ash
chromatography ꢀdichloromethane/pentaneˆ95:5) afforded
15a as a white solid ꢀ118 mg, 67%).
2
2
4
.1.4. 5a-Androstan-3-ꢀ2,4-cyclopentadien-1-ylidene)-
7b-ol 10. 5a-Androstan-17b-ol-3-one ꢀ1.162 g, 4 mmol)
1
was converted into 10 according to the general procedure.
Puri®cation by ¯ash chromatography ꢀdichloromethane)
afforded 10 as a yellow solid ꢀ1.010 g, 72%). H NMR
Crystal data for C H O Re: Mˆ701.93, orthorhombic,
3
5
47
3
1
aˆ10.525 ꢀ2), bˆ11.477 ꢀ2), cˆ26.102 ꢀ2) AÊ , Uˆ3152.81
3
ꢀ
200 MHz, CDCl ) d 6.58 ꢀm, 2H), 6.50 ꢀm, 2H), 3.63 ꢀt,
3
ꢀ8) AÊ , Tˆ296 K, space group P2 2 2 , Zˆ4, mˆ
1 1 1
2
3.886 mm , 21,696 re¯ections measured, 8160 unique
1
Jˆ7.9 Hz, 1H), 2.98 ꢀbd, Jˆ14.3 Hz, 1H), 2.58 ꢀbd,
Jˆ14.0 Hz, 1H), 0.7±2.5 ꢀm, 20H), 0.99 ꢀs, 3H), 0.76 ꢀs,
ꢀR ˆ0.0413) which were used in all calculations. The
int
1
H) ppm; C NMR ꢀ200 MHz, CDCl ) d 157.9, 139.1,
3
2
3
1
3
1
1
3
®nal wRꢀF ) is 0.0511 ꢀall data), R ˆ0.0293.
3
1
30.5ꢀ2), 119.9, 119.7, 81.8, 54.3, 50.8, 48.3, 42.9, 40.2,
6.6, 36.5, 36.1, 35.4, 31.4, 30.4, 29.4, 28.8, 23.3, 20.7,
2.0, 11.1 ppm; IR ꢀCH Cl ) 3405, 2850±2950, 1635,
1
H NMR ꢀ200 MHz, CDCl ) d 6.26 ꢀsl, 1H), 5.5±5.6 ꢀm,
3
2
2
3H), 5.3±5.2 ꢀm, 2H), 0.9±2.4 ꢀm, 29H), 0.95 ꢀs, 3H), 0.91
ꢀs, 3H), 0.87 ꢀs, 3H), 0.73 ꢀs, 3H) ppm; C NMR ꢀ50 MHz,
2
1
13
467, 1447, 1370, 1047, 767 cm ; MS ꢀm/z) 338, 323,
10, 171, 157, 145, 131, 117, 105, 91; Anal. Calcd for
CDCl ) d 194.4, 141.1, 126.7, 126.6, 124.8, 110.7, 84.4,
3
C H O ꢀ338.5): C 85.15, H 10.12; found C 80.34, H
34
83.2, 79.8, 79.4, 56.8, 56.1, 48.1, 42.4, 39.7, 39.5, 36.2,
35.8, 34.9, 33.4, 32.0, 31.7, 28.2, 28.0, 24.6, 24.1, 23.8,
2
4
2
0
9
.81; mp 1958C; [a]D ˆ118.5 ꢀ0.27,CH Cl ).
2
2
22.8, 22.5, 21.0, 19.0, 18.7, 12.0 ppm; IR ꢀKBr) 2850±
2950, 2020, 1900, 1466, 822 cm ; MS ꢀm/z) 702, 614,
2
1
4
.1.5.
4-Cholesten-3b-cyclopentadienyletricarbonyl-
erhenium-3a-methyl 14. MeLi ꢀ1.6 M, 150 mL,
441; Anal. Calcd for C H O Re: C 59.89, H 6.75. Found
3
5
47
3
2
0
0
0
.25 mmol) was added to a solution of fulvene 8a ꢀ80 mg,
.2 mmol) in toluene ꢀ1 mL) at 2788C. The solution was
C 59.76, H 6.89; mp 1808C; [a]D ˆ279.3 ꢀ0.58, CH Cl ).
2
2
slowly warmed to room temperature ꢀ2.5 h) and BrReꢀCO)5
162 mg, 0.4 mmol) was added. The resulting reaction
4.2.2. Pregnan-3-cyclopentadienyletricarbonylerhenium-
3,5-diene-20-one 15b. 8b ꢀ326 mg, 0.9 mmol) was
converted into 15b according the general procedure. Puri®-
cation by ¯ash chromatography ꢀpentane/etherˆ80:20)
ꢀ
mixture was heated to re¯ux for 15 h, cooled to room
temperature, diluted in CH Cl ꢀ5 mL), washed with brine
2
2
1
ꢀ
3£5 mL), dried over MgSO and concentrated. Puri®cation
afforded 15b ꢀ45%) as a white solid H NMR ꢀ200 MHz,
4

3944
F. Le Bideau et al. / Tetrahedron 57 ꢀ2001) 3939±3944
1
3
CDCl ) d 6.23 ꢀbs, 1H), 5.6±5.4 ꢀm, 3H), 5.4±5.2 ꢀm, 2H),
3
Jˆ8.1 Hz, 1H), 0.6±2.2 ꢀm, 20H), 0.75 ꢀs, 6H) ppm;
C
NMR ꢀ50 MHz, CDCl ) d 194.4, 126.6, 124.4, 110.9, 84.0,
2
ꢀ
.55 ꢀt, Jˆ8.8 Hz, 1H), 2.4±0.6 ꢀm, 17H); 2.13 ꢀs, 3H), 0.92
3
1
3
s, 3H), 0.57 ꢀs, 3H) ppm; C NMR ꢀ50 MHz, CDCl ) d
83.1, 81.2, 79.4, 79.1, 53.7, 50.8, 42.7, 41.2, 39.9, 36.5,
35.4, 34.5, 31.7, 31.1, 30.3, 28.3, 23.2, 20.5, 11.7, 10.9 ppm.
3
2
7
3
2
10.0, 194.4, 141.0, 126.5, 126.1, 125.0, 110.5, 84.5, 83.4,
9.8, 79.5, 63.7, 57.0, 47.9, 44.1, 38.8, 34.9, 33.4, 31.9,
1.7, 31.6, 24.6, 24.4, 22.8, 21.0, 13.4 ppm; IR ꢀKBr)
Minor isomer: 5a-Androstan-3-cyclopentadienyle tri-
carbonyle rhenium-3-ene-17b-ol. C NMR ꢀ50 MHz,
CDCl ) d 129.9, 126.3, 110.5, 82.9, 80.1, 53.2, 46.3, 43.1,
3
2
1
13
942±2840, 2013, 1931, 1703 cm ; [a] ˆ235.5 ꢀ0.60,
D
CH Cl ).
2
2
35.3, 34.0, 31.5, 27.3, 25.1, 20.7, 12.2, 11.2 ppm.
4
.2.3.
Androstan-3-cyclopentadienyle
tricarbonyle
rhenium-3,5-diene-17b-ol 15c. FLB11 ꢀ84 mg, 0.25
mmol) was converted into 15e according to the general
procedure. Puri®cation by ¯ash chromatography ꢀpentane/
References
1
. Jaouen, G.; Top, S.; Vessi eÁ res, A.; Alberto, R. J. Organomet.
Chem. 2000, 600, 23±36.
etherˆ70:30) afforded 15c as a white solid ꢀ70 mg, 46%).
1
H NMR ꢀ200 MHz, CDCl ) d 6.25 ꢀs, 1H), 5.53 ꢀm, 3H),
3
2
3
. Special issue dedicated to bioorganometallic chemistry:
J. Organomet. Chem. 1999, 589.
5
ꢀ
.34 ꢀm, 1H), 5.30 ꢀm, 1H), 3.67 ꢀt, Jˆ8.0 Hz, 1H), 0.8±2.3
1
m, 17H), 0.95 ꢀs, 3H), 0.80 ꢀs, 3H) ppm; C NMR
3
. Le Bideau, F.; El Kaloun, B.; Haquette, P.; Kernbach, U.;
Marr oà t, J.; Stephan, E.; Top, S.; Vessi eÁ res, A.; Jaouen, G.
J. Chem. Soc., Chem. Commun. 2000, 211±212.
ꢀ
50 MHz, CDCl ) d 194.3, 141.1, 126.5, 126.1, 124.9,
3
1
3
05.3, 84.4, 83.2, 81.7, 79.7, 79.4, 51.4, 48.1, 42.8, 36.4,
4.9, 33.4, 31.7, 31.5, 30.4, 24.5, 23.2, 20.6, 18.9, 11.0 ppm;
2
1
4. Knox, L. H. US Patent 3066155 ꢀCL. 260-397.3).
IR ꢀCH Cl ) 3615, 2850±2945, 2020, 1930 cm ; MS ꢀm/z)
2
2
5
6
7
. Thiele, J. Chem. Ber. 1900, 33, 666±672.
6
06, 591, 574, 223, 205, 149, 97; Anal. Calcd for C H O
27 31 4
. Stone, K. J.; Little, R. D. J. Org. Chem. 1984, 49, 1849±1853.
. Erker, G.; Mollenkopf, C.; Grehl, M.; Sch oÈ necker, B. Chem.
Ber. 1994, 127, 2341±2345.
ꢀ
[
605.8): C 53.53, H 5.16. Found C 53.24, H 5.56; mp 1958C;
a] 295.8 ꢀ0.43, CH Cl ).
D
2
2
8
. Erker, G.; Mollenkopf, C. J. Organomet. Chem. 1994, 483,
4
0
.2.4. Compounds 16a and 16b. Compound 10 ꢀ85 mg,
.25 mmol) was converted into 16a and 16b according to
1
. Knox, G. R.; Pauson, P. L. J. Chem. Soc. 1961, 4610±4615.
73±181.
9
the general procedure. Puri®cation by ¯ash chromatography
pentane/etherˆ60:40) afforded 16a and 16b as a mixture of
diastereomers ꢀwhite solid) ꢀ52 mg, 34%). IR ꢀCH Cl )
1
0. Knox, G. R.; Munro, J. D.; Pauson, P. L.; Smith, G. H.; Watts,
W. E. J. Chem. Soc. 1961, 4619±4624.
ꢀ
2
2
2
1
11. Macomber, D. W.; Hart, W. P.; Raush, J. J. Am. Chem. Soc.
982, 104, 884±886.
3
357, 2809±2975, 2026, 1959, 1909, 1443 cm ; MS
m/z) 608, 518, 388, 360, 330, 149, 81; Anal. Calcd for
C H O ꢀ607.76): C 53.36, H 5.47. Found C 52.75, H 5.57
1
2. Abbenhuis, H. C. L.; Burckhardt, V.; Gramlich, V.; Togni, A.;
Albinati, A.; M uÈ ller, B. Organometallics 1994, 13, 4481±
ꢀ
1
2
7
33
4
4
493.
13. Still, W. C.; Khan, M.; Mitra, A. J. J. Org. Chem. 1978, 43,
923±2925.
Major isomer: 5a-Androstan-3-cyclopentadienyle tri-
carbonyle rhenium-2-ene-17b-ol 16a.
1
H
NMR
2
ꢀ
200 MHz, CDCl ) d 5.98 ꢀdl, Jˆ5.27, 1H), 5.45 ꢀm, 2H),
3
5
.31 ꢀq, Jˆ2.2 Hz, 1H), 5.26 ꢀq, Jˆ2.2 Hz, 1H), 3.64 ꢀt,