Chemoselective Suzuki-Miyaura reactions of 4-bromo-3-O-triflyl-estrone. Synthesis and atropisomerism of arylated estrones

Article abstract of DOI:10.1016/j.tet.2018.02.015

4-Bromo-3-O-triflyl-estrone has been synthesized in 2 steps from estrone and was successfully employed in chemoselective palladium catalysed Suzuki-Miyaura reactions. Mono- and bis-arylations were carried out selectively by variation of ligands and solven

Full text of DOI:10.1016/j.tet.2018.02.015

Accepted Manuscript
Chemoselective Suzuki-Miyaura reactions of 4-bromo-3-O-triflyl-estrone. Synthesis
and atropisomerism of arylated estrones
Stefan Jopp, Tina Wallaschkowski, Peter Ehlers, Eva Frank, Gyula Schneider, János
Wölfling, Erzsébet Mernyák, Alexander Villinger, Peter Langer
PII:
S0040-4020(18)30140-6
10.1016/j.tet.2018.02.015
TET 29286
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 5 December 2017
Revised Date: 1 February 2018
Accepted Date: 5 February 2018
Please cite this article as: Jopp S, Wallaschkowski T, Ehlers P, Frank E, Schneider G, Wölfling Já,
Mernyák Erzsé, Villinger A, Langer P, Chemoselective Suzuki-Miyaura reactions of 4-bromo-3-O-
triflyl-estrone. Synthesis and atropisomerism of arylated estrones, Tetrahedron (2018), doi: 10.1016/
j.tet.2018.02.015.
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1
ACCEPTED MANUSCRIPT
Chemoselective Suzuki-Miyaura Reactions of 4-Bromo-3-O-triflyl-
estrone. Synthesis and Atropisomerism of Arylated Estrones
a
a
a,b
c
c
Stefan Jopp , Tina Wallaschkowski , Peter Ehlers , Eva Frank , Gyula Schneider , János
c
c
a
a,b
Wölfling , Erzsébet Mernyák , Alexander Villinger , Peter Langer*
a
University of Rostock, Institute of Chemistry, Albert-Einstein-Str. 3a, 18059 Rostock,
Germany. E-mail: peter.langer@uni-rostock.de
b
Leibniz Institute for Catalysis at the University of Rostock, Albert-Einstein-Str. 29a, 18059
Rostock, Germany
c
Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged,
Hungary
Graphical abstract:
O
Me
H
H
H
TfO
O
O
Me
H
Br
Me
H
H
H
H
H
Chemoselective Suzuki-Miyaura Reaction
overall 19 examples with 35-99 % yield
TfO
R2
R1
R1
1
2
1
2
step for R = R
1
2
steps for R =/= R
Abstract:
-Bromo-3-O-triflyl-estrone has been synthesized in 2 steps from estrone and was
4
successfully employed in chemoselective palladium catalyzed Suzuki-Miyaura reactions.
Mono- and bis-arylations were carried out selectively by variation of ligands and solvents.
Overall 19 derivatives of mono- and bis-arylated estrones were synthesized under optimized
conditions in high yields. Various products showed atropisomerism which was studied in
detail by NMR spectroscopy.
Keywords: steroids; cross-coupling reactions; palladium; chemoselectivity; palladium

2
ACCEPTED MANUSCRIPT
Introduction
Steroids are wide-spread in nature and play a major role in the regulation of many processes
of the human body. Cholesterol, for example, is an important structural component of the cell
1
membrane. Cortisol has various functions in the lipometabolism and in the metabolism of
2
carbohydrates and furthermore suppresses the immune system. Androgenic and estrogenic
steroids function as sex hormones of human males and females. Estrone, estradiol and
3
estriol are the three major estrogens and their functionalized derivatives have found many
4
applications in pharmaceutical research. These derivatives are widely applied as inhibitors
5
of the estrogenic receptor as well as imaging agents in the treatment of breast cancer.
6
7
We have previously shown that 3-alkynylestrones and 4-arylestrones are potent
phosphatase and lipase inhibitors, respectively. As part of our ongoing interest in the
8
application of palladium catalysed reactions on estrones we thus decided to work on 4-
bromo-3-O-triflyl-estrone as an interesting new starting material in such reactions. Our main
interest in this work was to investigate the chemoselectivity of the coupling reaction. In fact,
to the best of our knowledge, chemoselective palladium catalysed Suzuki-Miyaura reactions
have not been reported on estrones so far.
Results and discussion
Estrone 1 was converted into 4-bromoestrone 2 by a known procedure in a moderate yield of
9
4
4 %. A major side-product of this reaction is 2,4-dibromoestrone, which can be isolated in a
yield of 27 %. 4-Bromoestrone 2 was then converted into its corresponding triflate 3 in 95 %
yield (Scheme 1). The structure of 3 was independently confirmed by X-ray crystal structure
analysis (Figure 1).
O
O
O
Me
H
Me
H
Me
H
i
ii
H
H
H
H
H
H
HO
HO
TfO
Br
2 (44 %)
Br
3 (95 %)
1
Scheme 1. Synthesis of the starting material 3; i: 1 (3.6 mmol), N-bromoacetamide (3.6 mmol), ethanol (50 mL),
r.t., 24 h; ii: 2 (3.0 mmol), DMAP (0.6 mmol), 2,6-lutidine (5.7 mmol), DCM (30 mL), 0 °C , then Tf O (3.6 mmol),
2
r.t., 4 h.

3
ACCEPTED MANUSCRIPT
1
0
Figure 1. ORTEP of starting material 3 (disordered atoms of the triflate group have been omitted for clarity)
With starting material 3 in hand, we studied the chemoselective arylation by palladium
catalysed Suzuki-Miyaura reactions (Table 1). To our delight the initial test reaction using
Pd(PPh ) as catalyst gave the mono-arylated product 4a in very good yield (89 %), even
3
4
though 3 equivalents of arylboronic acid were used. Only 10 % of bis-arylated product 5a
19
was formed under these conditions. The analysis of the products by F-NMR proved that the
bromine atom is substituted first and the triflate group second. We obtained even higher
yields of 92 and 98 % changing the catalyst to Pd(OAc) and using P(Cy) or cataCXium® A
2
3
as ligands, respectively. On the other hand, SPhos proved to be the ligand of choice for bis-
arylation, achieving product 5a in a high yield of 88 % using toluene as the solvent.
Furthermore, a change of the solvent to dioxane gave a nearly quantitative yield of 5a
(
99 %). The different reactivity of cataCXium® A and SPhos might result from steric effects
and interactions between ligand and substrate. While cataCXium® A might be too sterically
encumbered for a second substitution, the aromatic moiety of SPhos is able to rotate out of
plane and can furthermore interact with the phenyl-ring of the mono-substituted substrate.
a
Table 1. Optimization of the chemoselective Suzuki-Miyaura reaction
O
O
Me
H
Me
H
O
Me
H
H
H
B(OH)2
OMe
H
i
H
H
+
+
TfO
H
TfO
MeO
Br
OMe
4a
OMe
5a
3

4
ACCEPTED MANUSCRIPT
Catalyst
mol%]
Pd(PPh ) [5]
Ligand
Equivalents
Yield 4a
[%]
89
Yield 5a
Solvent
[
[mol%]
boronic acid
[%]
10
0
-
3.0
3.0
3.0
1.5
3.0
3.0
toluene
toluene
toluene
toluene
toluene
dioxane
3
4
Pd(OAc) [5]
P(Cy) [10]
92
2
3
Pd(OAc) [5]
cataCXium® A [10]
cataCXium® A [10]
SPhos [10]
98
0
2
Pd(OAc) [5]
98
0
2
Pd(OAc) [5]
12
88
99
2
SPhos [10]
0
Pd(OAc) [5]
2
a
Reaction conditions i: 3 (0.21 mmol), 4-methoxyphenylboronic acid, K
solvent (4 mL), 100 °C , 20 h; isolated yields.
3 4
PO (0.63 mmol), Pd-catalyst, ligand,
With our optimized conditions in hand, we analysed the scope of the mono-fold Suzuki-
Miyaura reaction (Table 2). First, we investigated the impact of steric hindrance. para-
Methoxy substituted product 4a was obtained in a high yield of 98 %, while the meta-product
4b showed a slightly diminished yield of 84 % and was isolated as a mixture of atropisomers
(
vide infra). The ortho-product 4c, however, was not formed at all. In general, all products
were isolated in high yields of 84 to 99 %, including those containing electron-donating and
electron-withdrawing groups, like OMe, tBu and CF , as well as the heterocyclic thienyl
3
group. Only the strongly electron-withdrawing cyano group led to a low yield of 35 % for
product 4g. A vinyl-group was tolerated without the occurrence of a potential Heck reaction
as a side reaction, leading to product 4h in 96 % yield. All reactions showed a high selectivity
towards the mono-arylated products 4a-i. No formation of bis-arylated products was
observed, however, a common side-product is the dehalogenated starting material 3, which
was detected in small amounts in some reactions. For all products 4a-h a rotational
1
13
hindrance was observed by H- and C-NMR (vide infra).
a
Table 2. Synthesis of compounds 4a-i
O
Me
H
O
Me
H
B(OH)2
H
i
H
+
TfO
H
H
R
TfO
Br
R
3
4a-i

5
ACCEPTED MANUSCRIPT
O
Me
O
Me
H
H
H
H
H
H
TfO
TfO
4a (98 %)
4b (84 %)
MeO
OMe
O
Me
O
Me
H
H
H
H
H
H
TfO
TfO
TfO
TfO
MeO
4
d (99 %)
4
c (0 %)
tBu
O
O
Me
H
Me
H
H
H
H
H
H
H
TfO
TfO
TfO
4e (85 %)
4f (90 %)
F
CF
3
O
O
Me
H
Me
H
H
H
H
4h (96 %)
4g (35 %)
CN
O
Me
H
H
4i (90 %)
S
a
Reaction conditions i: 3 (0.21 mmol), arylboronic acid (0.32 mmol), K
3
PO
4
(0.63 mmol), Pd(OAc)
2
(5 mol%),
cataCXium® A (10 mol%), toluene (4 mL), 100 °C , 20 h ; isolated yields.
As the next step, we compared the results of the mono-arylation with the synthesis of bis-
arylated products 5a-h (Table 3). The twofold Suzuki-Miyaura reaction of our starting
material 3 works generally in very high yields. All products, independant from the type of
functional group used, were isolated in high yields (91 to 99 %). The only exception in our

6
ACCEPTED MANUSCRIPT
tests was the cyano group as product 5f was not formed, although the mono-arylated product
4g could be isolated in 34 % yield.
a
Table 3. Synthesis of compounds 5a-h
O
Me
H
O
Me
H
B(OH)2
R
H
i
H
+
H
H
TfO
R
Br
R
3
5a-h
O
Me
H
O
Me
H
H
H
H
H
MeO
MeO
5a (99 %)
5b (93 %)
MeO
OMe
O
O
Me
Me
H
H
H
H
H
H
tBu
F
5c (98 %)
5d (99 %)
tBu
F
O
O
Me
Me
H
H
H
H
H
H
F3C
NC
5e (99 %)
5f (0 %)
CF3
CN
O
Me
O
Me
H
H
H
H
H
H
S
5g (96 %)
5h (91 %)
S
a
Reaction conditions i: 3 (0.21 mmol), arylboronic acid (0.63 mmol), K
3 4 2
PO (0.63 mmol), Pd(OAc) (5 mol%),
SPhos (10 mol%), dioxane (4 mL), 100 °C , 20 h; isolat ed yields.

7
ACCEPTED MANUSCRIPT
Similar to the other products, meta-substituted product 5b was isolated as a mixture of
1
atropisomers. In fact, a rotational hindrance was observed for all products (5a-g) in both H-
13
and C-NMR. While the aryl ring in position 3 rotates freely, rotation of the aromatic ring in
position 4 is hampered by the corresponding B-ring protons in position 6 of the steroid
scaffold (Figure 2). The same effect was observed for compounds 4a-h. Hence, we
1
investigated this effect by H-NMR studies in DMF-d7 for compound 5c at elevated
temperatures (Figures 3 and 4). Interestingly, rotational hindrance was not completely
overcome even at 130 °C . However, the transition fro m magnetically inequivalent protons of
the aromatic ring in position 4 into magnetically equivalent protons at higher temperatures is
1
obvious. Furthermore product 5b has been investigated by H-NMR at elevated temperatures
in DMSO-d6 and by HPLC. The atropisomerism was overcome at 80 °C for this compound
(
see supporting information). The HPLC measurement showed one peak, most likely due to
the high similarity of both isomers.
O
O
Me
H
Me
H
H
H
H
H
H
H
H
H
H
H
tBu
OMe
OMe
tBu
5c
5
b
2
Figure 2. Sterical hindrance through interaction of the CH -group in position 6 and the ortho-protons of the
aromatic ring

8
ACCEPTED MANUSCRIPT
Figure 3. 1H-NMR of product 5c in DMF-d7 at 25 °C , the positions of the aromatic protons we re determined via
COSY-, NOESY, HSQC- and HMBC-2D-NMR
Figure 4. 1H-NMR of product 5c in DMF-d7 at 25 °C , 100 °C and 130 °C .
The structure of 5c was also independently confirmed by X-ray crystal structure analysis
(
Figure 5). The structure shows that the phenyl ring in position 4 is twisted in an angle of 90°
from the aromatic A-ring of the estrone, while the phenyl ring in position 3 shows an angle of
around 45°.
Figure 5. ORTEP of bis-arylated product 5c (the disordered atoms of the tert-butyl groups have been omitted for
1
0
clarity)

9
ACCEPTED MANUSCRIPT
Finally, we investigated the synthesis of 3,4-bis-arylated estrones containing two different
aryl groups (Table 4). We used mono-arylated product 4d as starting material, as this
product could be easily obtained in a 500 mg scale, maintaining a high yield of 99 %. 4d was
coupled with four electronically different arylboronic acids, containing a CF , OMe and vinyl
3
group as well as a thienyl ring. In comparison to the direct bis-arylation, the mixed secondary
arylation of 4d showed lower yields of 70 to 97 %. However, mixed bis-arylated products
containing electronically different substituents, such as 6a containing a tert-butyl and a CF3
group, are readily available through this type of reaction. This paves the way to a broad
number of potential products.
a
Table 4. Synthesis of compounds 6a-d
O
O
Me
Me
H
H
H
H
H
H
i
+
R
B(OH)2
TfO
R
tBu
tBu
6a-d
4
d
O
O
Me
Me
H
H
H
H
H
H
F3C
MeO
6a (86 %)
6b (90 %)
tBu
tBu
O
O
Me
Me
H
H
H
H
H
H
S
6
c (70 %)
6d (97 %)
tBu
tBu
a
Reaction conditions i: 4d (0.187 mmol), arylboronic acid (0.281 mmol), K
3 4 2
PO (0.561 mmol), Pd(OAc) (5
mol%), SPhos (10 mol%), dioxane (4 mL), 100 °C , 20 h; isolated yields.
We furthermore applied compound 4d in a Sonogashira reaction, using a procedure of our
6
previous work on estrones (Scheme 2). Product 7 has been synthesized in 58 %. The

10
ACCEPTED MANUSCRIPT
sterical hindrance of the phenyl ring located at position 4 most likely is responsible for the
only moderate yield of 58 %.
O
O
Me
H
Me
H
H
H
H
H
i
+
TfO
tBu
tBu
4d
7 (58 %)
Scheme 2. Sonogashira reaction of 4d; i: 4d (0.42 mmol), phenylacetylene (0.50 mmol), diisopropylamine
1.26 mmol), Pd(PPh (10 mol%), CuI (10 mol%), DMF (6 mL), 100 °C , 20 h ; isolated yield.
(
3 4
)
Conclusion
In conclusion, 4-bromo-3-trifyl-estrone 3 has been successfully employed in chemoselective
palladium catalyzed Suzuki-Miyaura reactions for the first time. The synthesis of mono- and
bis-arylated products is selectively controllable by the choice of ligand. The reaction is
generally applicable for many types of electron-rich, electron-withdrawing and heterocyclic
groups in very high yields. Overall 19 new examples of mono-, bis-, and mixed bis-arylated
products have been synthesized with our optimized conditions, with one further example
showing a mixed Suzuki and Songashira product, paving the way for a high number of
different estrogenic compounds with potential biological activity.
Experimental Section
General. For NMR spectra the substrates were dissolved in CDCl or DMSO-d6 and the
3
spectra were recorded on a Bruker AVANCE 300 III, 250 II or 500. The IR spectra were
measured as ATR experiments with a Nicolet 6700 FT-IR spectrometer and a Nicolet 550
FT-IR spectrometer. MS and HRMS were measured by an Agilent 6890 N/5973 GC-MS and
an Agilent 1200/6210 Time-of-Flight LC-MS. Melting points were determined by a Micro-Hot-
Stage GalenTM III Cambridge Instruments.
4-Bromo-3-hydroxy-13β-estra-1,3,5(10)-trien-17-one [2]
Estrone 1 (3.6 mmol, 973 mg) and N-bromoacetamide (3.6 mmol, 497 mg) were dissolved in
ethanol (50 mL) and stirred at room temperature for 24 hours. The precipitate was filtrated
and dried to yield 2 as a white solid (548 mg, 44 %). 2,4-Dibromo-3-hydroxy-13� -estra-
1,3,5(10)-trien-17-one (421 mg, 27 %) can be isolated as side-product from the filtrate by

11
ACCEPTED MANUSCRIPT
1
column chromatography (heptane/ethyl acetate 5:1). mp. 263–265 °C . H NMR (300 MHz,
DMSO-d6): δ = 0.80 (s, 3H, CH ); 1.27–1.58 (m, 6H, CHAlkyl); 1.71–1.75 (m, 1H, CHAlkyl);
3
1.91–2.17 (m, 4H, CHAlkyl); 2.29–2.44 (m, 2H, CHAlkyl); 2.56–2.66 (m, 1H, CHAlkyl); 2.82–2.90
3
3
(
m, 1H, CHAlkyl); 6.75 (d, J = 8.47 Hz, 1H, CH ); 7.10 (d, J = 8.48 Hz, 1H, CH ); 9.84 (s,
Ar Ar
13
1
H, OH). C NMR (75 MHz, DMSO-d6): δ = 13.4 (CH ); 21.1, 25.7, 26.2, 30.7, 31.3, 35.4
3
(
CH ); 37.0, 43.5 (CH); 47.2 (C); 49.4 (CH); 112.5 (C ); 113.2, 124.9 (CH ); 132.2, 136.3,
2 Ar Ar
-1
1
51.9 (C ); 219.6 (C=O). IR (ATR, cm ): ꢀȬ = 3417 (m), 2917 (m), 1728 (s), 1594 (w), 1475
Ar
+
81
(
s), 1407 (m), 1162 (s), 819 (m), 534 (s). MS (EI, 70 eV): m/z (%) = 351 (21), 350 (M , Br,
+
79
1
00), 349 (19), 348 (M , Br, 98), 291 (30), 250 (34), 238 (30), 237 (31), 226 (31), 224 (39),
158 (50), 157 (54), 145 (51), 144 (72), 132 (45), 131 (51), 128 (57), 127 (39), 115 (97), 97
(
39), 91 (42), 79 (33), 77 (45), 67 (48), 55 (61), 41 (67). HRMS (EI, 70 eV): Calculated for
79
+
81
C H BrO ( Br, M ), 348.07194; measured 348.07133. Calculated for C H BrO ( Br,
18
21
2
18 21
2
+
M ), 350.06990; measured 350.06966.
4
-Bromo-3-(trifluoromethylsulfonyloxy)-13β-estra-1,3,5(10)-trien-17-one [3]
(3.0 mmol, 1.048 g), 4-dimethylaminopyridine (DMAP, 0.6 mmol, 0.073 g) and 2,6-lutidine
2
(
(
5.7 mmol, 0.611 g) were dissolved in dichloromethane (30 mL) and cooled to 0 °C . Tf O
2
3.6 mmol, 1.016 g) was added dropwise and the reaction was stirred for 4 h, while warming
up to room temperature. 1M HCl (30mL) was added. The organic phase was washed with
brine, dried with Na SO and filtrated. The crude product was purified by column
2
4
chromatography (heptane/ethyl acetate 5:1) to yield 3 as white solid (1.372 g, 95 %). mp.
1
1
70–171 °C . H NMR (250 MHz, CDCl ): δ = 0.91 (s, 3H, CH ); 1.43–1.65 (m, 6H, CHAlkyl);
3
3
1.96–2.23 (m, 4H, CHAlkyl); 2.33–2.58 (m, 3H, CHAlkyl); 2.79–2.86 (m, 1H, CHAlkyl); 3.01–3.11
3
3
13
(
m, 1H, CHAlkyl); 7.14 (d, J = 8.71 Hz, 1H, CH ); 7.34 (d, J = 8.72 Hz, 1H, CH ). C NMR
Ar Ar
(
63 MHz, CDCl ): δ = 13.7 (CH ); 21.5, 25.9, 26.3, 31.2, 31.4, 35.8 (CH ); 37.0, 44.4 (CH);
3
3
2
1
4
7.7 (C); 50.3 (CH); 118.6 (q, J = 320.6 Hz, CF ); 119.0 (C ); 119.3, 125.6 (CH ); 139.2,
3
Ar
Ar
19
-1
1
42.1, 145.2 (C ); 220.1 (C=O). F NMR (235 MHz, CDCl ): δ = -73.48. IR (ATR, cm ):
Ar
3
ꢀ
6
4
Ȭ = 2934 (w), 1733 (m), 1592 (w), 1403 (m), 1200 (s), 1135 (s), 936 (m), 810 (s), 704 (m),
+
81
+ 79
73 (m), 583 (m). MS (EI, 70 eV): m/z (%) = 482 (M , Br, 100), 481 (16), 480 (M , Br, 96),
38 (30), 436 (29), 425 (17), 423 (23), 331 (40), 329 (39), 305 (34), 303 (28), 293 (47), 291
(
51), 268 (47), 237 (24), 226 (21), 212 (17), 211 (30), 141 (16), 129 (22), 128 (34), 115 (44),
79
+
9
7 (29), 77 (18), 69 (65), 55 (20). HRMS (EI, 70 eV): Calculated for C H BrF O S ( Br, M ),
19 20 3 4
81
+
4
80.02123; measured 480.02060. Calculated for C H BrF O S ( Br, M ), 482.01918;
19 20 3 4
measured 482.01909.

12
ACCEPTED MANUSCRIPT
General procedure A for the onefold Suzuki-Miyaura reaction of 3
3
(0.21 mmol, 100 mg), boronic acid (0.32 mmol), K PO (0.63 mmol, 132 mg), Pd(OAc) (5
3 4 2
mol%, 2.3 mg), cataCXium® A (10 mol%, 7.4 mg) and toluene (4 mL) were heated in a
pressure tube under argon atmosphere at 100 °C for 20 hours. The reaction was quenched
with water (5 mL) and extracted with ethyl acetate (3x 10 mL). The organic phase was dried
with Na SO and filtrated. The crude product was purified by column chromatography
2
4
(
heptane/ethyl acetate) to yield 4a-i.
General procedure B for the twofold Suzuki-Miyaura reaction of 3
(0.21 mmol, 100 mg), boronic acid (0.63 mmol), K PO (0.63 mmol, 132 mg), Pd(OAc) (5
3
3
4
2
mol%, 2.3 mg), SPhos (10 mol%, 8.5 mg) and dioxane (4 mL) were heated in a pressure
tube under argon atmosphere at 100 °C for 20 hours. The reaction was quenched with water
(
5 mL) and extracted with ethyl acetate (3x 10 mL). The organic phase was dried with
Na SO and filtrated. The crude product was purified by column chromatography
2
4
(
heptane/ethyl acetate) to yield 5a-h.
General procedure C for the Suzuki-Miyaura reaction of 4d
d (0.187 mmol, 100 mg), boronic acid (0.281 mmol), K PO (0.561 mmol, 119 mg),
4
3
4
Pd(OAc) (5 mol%, 2.1 mg), SPhos (10 mol%, 7.7 mg) and dioxane (4 mL) were heated in a
2
pressure tube under argon atmosphere at 100 °C for 20 hours. The reaction was quenched
with water (5 mL) and extracted with ethyl acetate (3x 10 mL). The organic phase was dried
with Na SO and filtrated. The crude product was purified by column chromatography
2
4
(
heptane/ethyl acetate) to yield 6a-d.
3-(Trifluoromethylsulfonyloxy)-4-(4-methoxyphenyl)-13β-estra-1,3,5(10)-trien-17-one
[
4a]
4a was synthesized according to general procedure A using 4-methoxyphenylboronic acid
(
0.32 mmol, 48 mg) and was purified via column chromatography (heptane/ethyl acetate 5:1)
1
to yield a yellow oil (104 mg, 98 %). H NMR (250 MHz, CDCl ): δ = 0.93 (s, 3H, CH ); 1.50–
3
3
1.65 (m, 6H, CHAlkyl); 1.90–2.17 (m, 4H, CHAlkyl); 2.31–2.57 (m, 5H, CHAlkyl); 3.85 (s, 3H,
3
OCH ); 6.94–7.01 (m, 2H, CH ); 7.09–7.17 (m, 3H, CH ); 7.37 (d, J = 8.71 Hz, 1H, CH ).
3
Ar
Ar
Ar
13
C NMR (63 MHz, CDCl ): δ = 13.8 (CH ); 21.5, 25.9, 26.2, 28.6, 31.5, 35.8 (CH ); 37.3,
3
3
2

13
ACCEPTED MANUSCRIPT
1
4
4.5 (CH); 47.8 (C); 50.4 (CH); 55.2 (OCH ); 113.7, 118.2 (CH ); 118.3 (q, J = 320.3 Hz,
3 Ar
CF ); 126.0 (CH ); 126.5 (C ); 130.8, 130.9 (CH ); 134.7, 138.5, 140.5, 145.8, 159.3 (C );
3
Ar
Ar
Ar
Ar
19
-1
2
20.4 (C=O). F NMR (235 MHz, CDCl ): δ = -74.39. IR (ATR, cm ): ꢀȬ = 2928 (w), 1737 (m),
3
1515 (m), 1465 (m), 1247 (s), 1202 (s), 1138 (s), 1109 (m), 1031 (m), 920 (s), 935 (s), 787
+
(
m), 733 (m), 601 (s). MS (EI, 70 eV): m/z (%) = 509 (14), 508 (M , 58), 375 (25), 212 (16),
+
2
11 (100). HRMS (EI, 70 eV): Calculated for C H F O S (M ), 508.15258; measured
26
27
3
5
508.15245.
3-(Trifluoromethylsulfonyloxy)-4-(3-methoxyphenyl)-13β-estra-1,3,5(10)-trien-17-one
[
4b]
4b was synthesized according to general procedure A using 3-methoxyphenylboronic acid
(
0.32 mmol, 48 mg) and was purified via column chromatography (heptane/ethyl acetate 5:1)
1
to yield a yellow oil (88 mg, 84 %). H NMR (300 MHz, CDCl ): δ = 0.93 (s, 6H, CH ); 1.49–
3
3
1.65 (m, 12H, CHAlkyl); 1.91–2.17 (m, 8H, CHAlkyl); 2.35–2.60 (m, 10H, CHAlkyl); 3.82 (s, 3H,
OCH ); 3.83 (s, 3H, OCH ); 6.74–6.82 (m, 4H, CH ); 6.93–6.97 (m, 2H, CH ); 7.16 (d,
3
3
Ar
Ar
3
13
J = 8.74 Hz, 2H, CH ); 7.32–7.40 (m, 4H, CH ). C NMR (63 MHz, CDCl ): δ = 13.8 (CH );
Ar
Ar
3
3
2
1.5, 25.9, 26.1, 28.3, 31.5, 35.8 (CH ); 37.2, 44.5 (CH); 47.8 (C); 50.4 (CH); 55.3, 55.3
2
1
(
OCH ); 113.6, 113.8, 115.0, 115.3, 118.2 (CH ); 118.3 (q, J = 320.1 Hz, CF ); 121.8,
3
Ar
3
1
22.0, 126.1, 129.5, 129.6 (CH ); 134.8, 135.7, 138.0, 138.1, 140.5, 145.3, 159.6, 159.6
Ar
1
9
-1
(
(
C ); 220.4 (C=O). F NMR (282 MHz, CDCl ): δ = -74.36, -74.37. IR (ATR, cm ): ꢀȬ = 2929
Ar
3
w), 1737 (m), 1580 (w), 1417 (s), 1289 (m), 1204 (s), 1138 (s), 1012 (m), 923 (s), 909 (m),
+
7
94 (m), 505 (m). MS (EI, 70 eV): m/z (%) = 509 (24), 508 (M , 85), 375 (22), 212 (15), 211
+
(
100), 165 (11). HRMS (EI, 70 eV): Calculated for C H F O S (M ), 508.15258; measured
26
27
3
5
508.15203.
3-(Trifluoromethylsulfonyloxy)-4-(4-tert-butylphenyl)-13β-estra-1,3,5(10)-trien-17-one
[
4d]
4d was synthesized according to general procedure A using 4-tert-butylphenylboronic acid
(
0.32 mmol, 55 mg) and was purified via column chromatography (heptane/ethyl acetate
1
1
0:1) to yield a yellow solid (112 mg, >99 %). mp. 73–74 °C . H NMR (500 MHz, CDCl ):
3
δ = 0.93 (s, 3H, CH ); 1.36 (s, 9H, CH3,tBu); 1.47–1.64 (m, 6H, CHAlkyl); 1.91–2.17 (m, 4H,
3
3
CHAlkyl); 2.33–2.60 (m, 5H, CHAlkyl); 7.11–7.17 (m, 3H, CH ); 7.37 (d, J = 8.38 Hz, 1H, CH );
Ar
Ar
13
7
.43–7.47 (m, 2H, CHAr). C NMR (63 MHz, CDCl ): δ = 13.8 (CH ); 21.5, 25.9, 26.2, 28.6
3 3
(
CH ); 31.3 (CH ); 31.5 (CH ); 34.6 (C ); 35.8 (CH ); 37.3, 44.5 (CH); 47.8 (C); 50.4 (CH);
2 3,tBu 2 tBu 2
1
1
18.2 (CH ); 118.3 (q, J = 320.3 Hz, CF ); 125.2, 125.3, 125.9, 129.2, 129.3 (CH ); 131.3,
Ar 3 Ar
19
1
35.0, 138.3, 140.4, 145.6, 151.0 (C ); 220.5 (C=O). F NMR (282 MHz, CDCl ): δ = -74.49.
Ar
3

14
ACCEPTED MANUSCRIPT
-1
IR (ATR, cm ): ꢀȬ = 2957 (w), 1739 (m), 1515 (w), 1465 (m), 1418 (s), 1202 (s), 1185 (s),
1138 (s), 1022 (s), 936 (m), 922 (s), 837 (s), 664 (m), 599 (s). MS (EI, 70 eV): m/z (%) = 534
+
+
(
M , 11), 519 (23), 57 (100). HRMS (EI, 70 eV): Calculated for C H F O S (M ), 534.20462;
29 33 3 4
measured 534.20471.
3
-(Trifluoromethylsulfonyloxy)-4-(4-fluorophenyl)-13β-estra-1,3,5(10)-trien-17-one [4e]
e was synthesized according to general procedure A using 4-fluorophenylboronic acid (0.32
4
mmol, 47 mg) and was purified via column chromatography (heptane/ethyl acetate 5:1) to
1
yield a yellow solid (88 mg, 85 %). mp. 121–122 °C . H NMR (500 MHz, CDCl ): δ = 0.93 (s,
3
3H, CH ); 1.32–1.62 (m, 6H, CHAlkyl); 1.92–2.16 (m, 4H, CHAlkyl); 2.32–2.55 (m, 5H, CHAlkyl);
3
3
13
7
.13–7.20 (m, 5H, CH ); 7.40 (d, J = 8.68 Hz, 1H, CH ). C NMR (125 MHz, CDCl ):
Ar
Ar
3
δ = 13.8 (CH ); 21.5, 25.9, 26.1, 28.5, 31.5, 35.8 (CH ); 37.3, 44.5 (CH); 47.8 (C); 50.4 (CH);
3
2
2
2
1
15.5 (d, J = 21.6 Hz, CH ); 115.6 (d, J = 21.5 Hz, CH ); 118.3 (CH ); 118.3 (q,
Ar Ar Ar
1
4
3
J = 320.1 Hz, CF ); 126.4 (CH ); 130.3 (d, J = 3.48 Hz, C ); 131.4 (d, J = 8.25 Hz, CH );
3
Ar
Ar
Ar
3
1
1
31.5 (d, J = 8.29 Hz, CH ); 134.0, 138.2, 140.7, 145.4 (C ); 162.5 (d, J = 247.5 Hz, C-F);
Ar Ar
19
-1
2
20.3 (C=O). F NMR (282 MHz, CDCl ): δ = -74.37 (CF ), -113.70 (C-F). IR (ATR, cm ):
3
3
ꢀȬ = 2873 (w), 1732 (m), 1512 (m), 1466 (m), 1414 (s), 1202 (s), 1159 (m), 1139 (s), 1057
+
(
(
(
m), 925 (s), 823 (s), 621 (m), 506 (m). MS (EI, 70 eV): m/z (%) = 496 (M , 20), 251 (17), 225
21), 200 (15), 199 (100), 109 (14), 69 (14). HRMS (ESI): Calculated for C H F O S
25
25
4
4
+
M+H ), 497.14042; measured 497.14048.
3-(Trifluoromethylsulfonyloxy)-4-(4-trifluoromethylphenyl)-13β-estra-1,3,5(10)-trien-17-
one [4f]
4f was synthesized according to general procedure A using 4-trifluoromethylphenylboronic
acid (0.32 mmol, 61 mg) and was purified via column chromatography (heptane/ethyl acetate
1
5
:1) to yield a yellow oil (103 mg, 90 %). H NMR (300 MHz, CDCl ): δ = 0.95 (s, 3H, CH );
3
3
1.53–1.67 (m, 6H, CHAlkyl); 1.95–2.09 (m, 4H, CHAlkyl); 2.34–2.57 (m, 5H, CHAlkyl); 7.22 (d,
3
3
J = 8.76 Hz, 1H, CH ); 7.34–7.40 (m, 2H, CH ); 7.45 (d, J = 8.71 Hz, 1H, CH ); 7.71–7.76
Ar
Ar
Ar
13
(
m, 2H, CH ). C NMR (63 MHz, CDCl ): δ = 13.8 (CH ); 21.5, 25.9, 26.0, 28.5, 31.5, 35.7
Ar 3 3
1
(
CH ); 37.2, 44.5 (CH); 47.8 (C); 50.3 (CH); 118.2 (q, J = 320.4 Hz, CF ); 118.5 (CH );
2 3 Ar
1
2
1
24.0 (q, J = 272.3 Hz, C-CF ); 125.4 (m, CH ); 126.8 (CH ); 129.9 (q, J = 32.6 Hz, C-
3 Ar Ar
5
CF ); 130.2, 130.3 (CH ); 133.5, 137.7 (C ); 138.4 (q, J = 1.29 Hz, C ); 140.8, 144.9 (C );
3
Ar
Ar
Ar
Ar
19
-1
2
20.3 (C=O). F NMR (282 MHz, CDCl ): δ = -62.66 (CF ), -74.37 (CF ). IR (ATR, cm ):
3
3
3
ꢀȬ = 2931 (w), 1737 (m), 1618 (w), 1419 (m), 1322 (s), 1207 (s), 1124 (s), 1064 (m), 921 (m),
+
8
44 (m), 734 (w), 607 (m). MS (EI, 70 eV): m/z (%) = 547 (27), 546 (M , 94), 502 (32), 489

15
ACCEPTED MANUSCRIPT
(
19), 395 (43), 393 (16), 303 (17), 301 (46), 299 (18), 289 (17), 287 (19), 275 (47), 250 (15),
2
49 (100), 233 (18), 97 (19), 69 (33), 55 (17). HRMS (EI, 70 eV): Calculated for C H F O S
26
24
6
4
+
(
M ), 546.12940; measured 546.12963.
3
-(Trifluoromethylsulfonyloxy)-4-(4-cyanophenyl)-13β-estra-1,3,5(10)-trien-17-one [4g]
g was synthesized according to general procedure A using 4-cyanophenylboronic acid
4
(
0.32 mmol, 45 mg) and was purified via column chromatography (heptane/ethyl acetate 5:1)
1
to yield a white solid (36 mg, 35 %). mp. 168–169 °C . H NMR (300 MHz, CDCl ): δ = 0.93
3
(
s, 3H, CH ); 1.47–1.65 (m, 5H, CHAlkyl); 1.92–2.28 (m, 5H, CHAlkyl); 2.33–2.55 (m, 5H,
3
3
3
CHAlkyl); 7.20 (d, J = 8.77 Hz, 1H, CH ); 7.33–7.39 (m, 2H, CH ); 7.45 (d, J = 8.71 Hz, 1H,
Ar
Ar
13
CH ); 7.73–7.79 (m, 2H, CH ). C NMR (63 MHz, CDCl ): δ = 13.8 (CH ); 21.5, 25.9, 26.0,
Ar
Ar
3
3
2
8.5, 31.5, 35.7 (CH ); 37.2, 44.4 (CH); 47.8 (C); 50.3 (CH); 112.2 (CN); 118.2 (q,
2
1
J = 320.2 Hz, CF ); 118.5 (C ); 118.6, 127.2, 130.7, 130.8, 132.2, 132.4 (CH ); 133.1,
3
Ar
Ar
1
9
1
37.5, 139.6, 141.0, 144.7 (C ); 220.2 (C=O). F NMR (282 MHz, CDCl ): δ = -74.21. IR
A
r
3
-
1
(
(
(
(
ATR, cm ): ꢀȬ = 2860 (w), 2228 (m), 1735 (m), 1512 (w), 1417 (s), 1205 (s), 1138 (s), 1010
+
m), 923 (s), 842 (s), 620 (m), 599 (s). MS (EI, 70 eV): m/z (%) = 504 (24), 503 (M , 100), 459
30), 446 (16), 352 (29), 258 (23), 206 (34). HRMS (EI, 70 eV): Calculated for C H F NO S
26
24
3
4
+
M ), 503.13727; measured 503.13700.
3
-(Trifluoromethylsulfonyloxy)-4-(4-vinylphenyl)-13β-estra-1,3,5(10)-trien-17-one [4h]
h was synthesized according to general procedure A using 4-vinylphenylboronic acid (0.32
4
mmol, 47 mg) and was purified via column chromatography (heptane/ethyl acetate 5:1) to
1
yield a yellow oil (102 mg, 96 %). H NMR (300 MHz, CDCl ): δ = 0.95 (s, 3H, CH ); 1.48–
3
3
1.71 (m, 6H, CHAlkyl); 1.91–2.24 (m, 4H, CHAlkyl); 2.36–2.61 (m, 5H, CHAlkyl); 5.32 (dd,
2
3
2
3
J = 0.72 Hz, J = 10.90 Hz, 1H, CH=CH2 ); 5.83 (dd, J = 0.78 Hz, J = 17.61 Hz, 1H,
,cis
3
3
CH=CH2,trans); 6.78 (dd, J = 17.62 Hz, J = 10.92 Hz, 1H, CH=CH ); 7.16–7.22 (m, 3H, CH );
2
Ar
3
13
7
.40 (d, J = 8.91 Hz, 1H, CH ); 7.48–7.56 (m, 2H, CH ). C NMR (75 MHz, CDCl ):
Ar Ar 3
δ = 13.8 (CH ); 21.5, 25.9, 26.1, 28.5, 31.5, 35.8 (CH ); 37.2, 44.5 (CH); 47.8 (C); 50.4 (CH);
3
2
1
1
14.4 (CH2,Vinyl); 118.2 (CH ); 118.3 (q, J = 320.3 Hz, CF ); 126.1, 126.2, 126.3, 129.8,
Ar 3
1
29.9 (CH ); 133.9, 134.6 (C ); 136.4 (CH ); 137.2, 138.1, 140.5, 145.4 (C ); 220.3
Ar
Ar
Vinyl
Ar
1
9
-1
(
(
(
C=O). F NMR (282 MHz, CDCl ): δ = -74.31. IR (ATR, cm ): ꢀȬ = 2931 (w), 1737 (m), 1710
3
s), 1417 (m), 1359 (m), 1205 (s), 1139 (s), 921 (m), 842 (m), 603 (m). MS (EI, 70 eV): m/z
+
%) = 504 (M , 25), 259 (10), 233 (10), 208 (17), 207 (100), 69 (13), 55 (10). HRMS (EI,
+
7
0 eV): Calculated for C H F O S (M ), 504.15767; measured 504.15756.
27
27
3
4

16
ACCEPTED MANUSCRIPT
3-(Trifluoromethylsulfonyloxy)-4-(3-thienyl)-13β-estra-1,3,5(10)-trien-17-one [4i]
4i was synthesized according to general procedure A using 3-thienylboronic acid (0.32 mmol,
47 mg) and was purified via column chromatography (heptane/ethyl acetate 5:1) to yield a
1
yellow oil (90 mg, 90 %). H NMR (300 MHz, CDCl ): δ = 0.93 (s, 3H, CH ); 1.47–1.73 (m,
3
3
3
6
H, CHAlkyl); 1.94–2.17 (m, 4H, CHAlkyl); 2.33–2.63 (m, 5H, CHAlkyl); 6.99 (dd, J = 4.93 Hz,
4
3
4
J = 1.25 Hz, 1H, CHHetAr); 7.15 (d, J = 8.76 Hz, 1H, CHHetAr); 7.21 (dd, J = 2.94 Hz,
4
3
3
J = 1.25 Hz, 1H, CHHetAr); 7.38 (d, J = 8.73 Hz, 1H, CHHetAr); 7.43 (dd, J = 4.95 Hz,
4
13
J = 2.95 Hz, 1H, CH ). C NMR (63 MHz, CDCl ): δ = 13.7 (CH ); 21.5, 25.9, 26.1, 28.4,
Ar
3
3
1
3
1.5, 35.8 (CH ); 37.2, 44.5 (CH); 47.8 (C); 50.4 (CH); 118.3 (CH ); 118.3 (q, J = 320.3 Hz,
2
A
r
CF ); 124.9, 125.7, 126.3, 128.7 (CH ); 130.3, 133.7, 138.9, 140.5, 145.8 (C ); 220.3 (C=O).
3
Ar
Ar
19
-1
F NMR (235 MHz, CDCl ): δ = -74.23. IR (ATR, cm ): ꢀȬ = 2860 (w), 1737 (m), 1418 (s),
3
1250 (m), 1204 (s), 1138 (s), 1013 (m), 922 (s), 829 (m), 605 (m). MS (EI, 70 eV): m/z
+
(
%) = 485 (20), 484 (M , 75), 351 (100), 187 (40). HRMS (EI, 70 eV): Calculated for
+
C H F O S (M ), 484.09844; measured 484.09770.
23
23
3
4
2
3,4-Bis-(4-methoxyphenyl)-13β-estra-1,3,5(10)-trien-17-one [5a]
5a was synthesized according to general procedure B using 4-methoxyphenylboronic acid
(
0.63 mmol, 96 mg) and was purified via column chromatography (heptane/ethyl acetate 5:1)
1
to yield a brown solid (99 mg, >99 %). mp. 168–169 °C . H NMR (250 MHz, CDCl ): δ = 0.95
3
(
s, 3H, CH ); 1.53–1.69 (m, 6H, CHAlkyl); 1.92–2.18 (m, 4H, CHAlkyl); 2.42–2.64 (m, 5H,
3
3
CHAlkyl); 3.73 (s, 3H, OCH ); 3.78 (s, 3H, OCH ); 6.68 (d, J = 8.61 Hz, 2H, CH ); 6.72–6.77
3
3
Ar
3
(
m, 1H, CH ); 6.79–6.89 (m, 2H, CH ); 6.98 (d, J = 8.60 Hz, 2H, CH ); 7.04 (dd,
Ar
Ar
Ar
3
4
3
3
J = 8.32 Hz, J = 1.97 Hz, 1H, CH ); 7.24 (d, J = 8.02 Hz, 1H, CH ); 7.39 (d, J = 8.13 Hz,
Ar
Ar
1
3
1
H, CH ). C NMR (63 MHz, CDCl ): δ = 13.8 (CH ); 21.5, 26.0, 26.6, 29.0, 31.7, 35.8
Ar 3 3
(
CH ); 37.5, 44.8 (CH); 47.9 (C); 50.6 (CH); 55.0, 55.0 (OCH ); 112.9 (2xCH ); 113.2, 113.3,
2 3 Ar
1
1
1
4
24.4, 127.4 (CH ); 130.7 (2xCH ); 131.2, 131.3 (CH ); 132.7, 134.3, 135.3, 138.8, 139.1,
Ar Ar Ar
-1
40.0, 157.7, 157.9 (C ); 220.8 (C=O). IR (ATR, cm ): ꢀȬ = 2924 (m), 1737 (s), 1608 (m),
Ar
510 (m), 1241 (s), 1107 (m), 1028 (s), 819 (s), 583 (m). MS (EI, 70 eV): m/z (%) = 468 (21),
+
67 (89), 466 (M , 100), 464 (9), 356 (5), 355 (5), 342 (8), 303 (6), 301 (7), 287 (5), 121 (7).
+
HRMS (EI, 70 eV): Calculated for C H O (M ), 466.25025; measured 466.25053.
32
34
3
3,4-Bis-(3-methoxyphenyl)-13β-estra-1,3,5(10)-trien-17-one [5b]

17
ACCEPTED MANUSCRIPT
5b was synthesized according to general procedure B using 3-methoxyphenylboronic acid
(
0.63 mmol, 96 mg) and was purified via column chromatography (heptane/ethyl acetate 5:1)
1
to yield a yellow oil (91 mg, 93 %). H NMR (300 MHz, CDCl ): δ = 0.96 (s, 6H, 2xCH );
3
3
1
.51–1.71 (m, 14H, CHAlkyl); 1.93–2.24 (m, 8H, CHAlkyl); 2.44–2.66 (m, 8H, CHAlkyl); 3.60 (s,
H, OCH ); 3.61 (s, 3H, OCH ); 3.63 (s, 3H, OCH ); 3.73 (s, 3H, OCH ); 6.53–6.54 (m, 1H,
3
3
3
3
3
CH ); 6.60–6.63 (m, 3H, CH ); 6.65–6.69 (m, 2H, CH ); 6.71–6.80 (m, 6H, CH ); 7.04–7.22
Ar
Ar
Ar
Ar
3
3
13
(
(
(
m, 4H,CH ); 7.30 (d, J = 8.10 Hz, 2H, CH ); 7.43 (d, J = 8.20 Hz, 2H, CH ). C NMR
Ar Ar Ar
75 MHz, CDCl ): δ = 13.8 (CH ); 21.5, 26.0, 26.6, 28.8, 31.7, 35.8 (CH ); 37.6, 44.8, 44.9
3
3
2
CH); 47.9 (C); 50.6 (CH); 55.0, 55.1, 55.1, 55.3 (OCH ); 111.9, 112.2, 122.3, 112.4, 114.9,
3
1
1
1
15.7, 116.0, 122.1, 122.2, 122.8, 122.9, 124.6, 127.3, 128.3, 128.4, 128.6, 128.9 (CHAr);
34.9, 134.9, 139.0, 139.0, 139.3, 140.1, 140.1, 141.7, 141.7, 143.1, 143.1, 158.6, 159.1,
-1
59.2 (C ); 220.7 (C=O). IR (ATR, cm ): ꢀȬ = 2927 (m), 1735 (s), 1577 (m), 1465 (m), 1207
Ar
+
(
s), 1039 (s), 908 (m), 777 (s), 729 (s). MS (EI, 70 eV): m/z (%) = 467 (31), 466 (M , 100),
+
2
71 (11), 67 (11), 55 (13). HRMS (EI, 70 eV): Calculated for C H O (M ), 466.25025;
32
34
3
measured 466.24979.
3
,4-Bis-(4-tert-butylphenyl)-13β-estra-1,3,5(10)-trien-17-one [5c]
c was synthesized according to general procedure B using 4-tert-butylphenylboronic acid
5
(
0.63 mmol, 112 mg) and was purified via column chromatography (heptane/ethyl acetate
1
1
0:1) to yield a white solid (107 mg, 98 %). mp. 226–227 °C . H NMR (300 MHz, CDCl ):
3
δ = 0.96 (s, 3H, CH ); 1.24 (s, 9H, CH3,tBu); 1.28 (s, 9H, CH3,tBu); 1.53–1.71 (m, 6H, CHAlkyl);
3
1.94–2.18 (m, 4H, CHAlkyl); 2.40–2.56 (m, 3H, CHAlkyl); 2.64–2.70 (m, 2H, CHAlkyl); 6.85 (dd,
3
4
3
3
J = 8.04 Hz, J = 1.86 Hz, 1H, CH ); 6.94 (d, J = 8.34 Hz, 2H, CH ); 7.04 (dd, J = 8.02 Hz,
Ar
Ar
4
3
3
4
J = 1.84 Hz, 1H, CH ); 7.10 (d, J = 8.38 Hz, 2H, CH ); 7.17 (dd, J = 8.06 Hz, J = 2.04 Hz,
Ar
Ar
3
4
3
1
7
2
4
H, CH ); 7.24 (dd, J = 8.11 Hz, J = 2.04 Hz, 1H, CH ); 7.30 (d, J = 8.08 Hz, 1H, CH );
Ar
Ar
Ar
3
13
.41 (d, J = 8.15 Hz, 1H, CH ). C NMR (75 MHz, CDCl ): δ = 13.9 (CH ); 21.5, 26.0, 26.7,
Ar
3
3
9.0 (CH ); 31.2, 31.3 (CH ); 31.7 (CH ); 34.2, 34.4 (C ); 35.9 (CH ); 37.6, 44.9 (CH);
2
3,tBu
2
tBu
2
8.0 (C); 50.6 (CH); 124.1 (2xCH ); 124.3, 124.4, 124.5, 127.2 (CH ); 129.4, 130.0
Ar
Ar
(
2xCH ); 135.0, 137.3, 138.8, 138.9, 139.6, 140.6, 148.5, 149.0 (C ); 220.9 (C=O). IR (ATR,
Ar Ar
-1
cm ): ꢀȬ = 2865 (m), 1745 (s), 1467 (m), 1391 (m), 1267 (m), 1114 (m), 837 (m), 598 (m). MS
+
(
EI, 70 eV): m/z (%) = 519 (16), 518 (M , 53), 503 (23), 207 (10), 73 (10), 67 (11), 57 (100),
+
5
5 (23), 41 (25), 29 (13). HRMS (EI, 70 eV): Calculated for C H O (M ), 518.35432;
38
46
measured 518.35407.
3,4-Bis-(4-fluorophenyl)-13β-estra-1,3,5(10)-trien-17-one [5d]

18
ACCEPTED MANUSCRIPT
5d was synthesized according to general procedure B using 4-fluorophenylboronic acid (0.63
mmol, 88 mg) and was purified via column chromatography (heptane/ethyl acetate 5:1) to
1
yield a white solid (92 mg, >99 %). mp. 55–56 °C . H NMR (300 MHz, CDCl ): δ = 0.95 (s,
3
3
6
1
H, CH ); 1.54–1.69 (m, 6H, CHAlkyl); 1.92–2.18 (m, 4H, CHAlkyl); 2.41–2.61 (m, 5H, CHAlkyl);
3
.79–6.85 (m, 2H, CH ); 6.88–6.92 (m, 2H, CH ); 6.95–7.00 (m, 3H, CH ); 7.04–7.09 (m,
Ar
Ar
Ar
3
3
13
H, CH ); 7.23 (d, J = 8.10 Hz, 1H, CH ); 7.42 (d, J = 8.09 Hz, 1H, CH ). C NMR
Ar
Ar
Ar
(
125 MHz, CDCl ): δ = 13.8 (CH ); 21.5, 26.0, 26.6, 29.0, 31.7, 35.8 (CH ); 37.5, 44.8 (CH);
3 3 2
2
2
4
7.9 (C); 50.6 (CH); 114.4 (d, J = 21.2 Hz, 2xCH ); 114.8 (d, J = 21.5 Hz, CH ); 115.0 (d,
Ar
Ar
2
3
3
J = 21.5 Hz, CH ); 124.8, 127.3 (CH ); 131.2 (d, J = 7.9 Hz, 2xCH ); 131.8 (d, J = 7.8 Hz,
Ar
Ar
Ar
4
4
2
xCH ); 135.2 (C ); 136.0 (d, J = 3.4 Hz, C ); 137.6 (d, J = 3.4 Hz, C ); 138.5, 139.4,
Ar Ar Ar Ar
1
1
19
1
39.5 (C ); 161.4 (d, J = 245.5 Hz, C-F); 161.5 (d, J = 245.8 Hz, C-F); 220.6 (C=O).
F
Ar
-1
NMR (282 MHz, CDCl ): δ = -116.66, -115.94. IR (ATR, cm ): ꢀȬ = 2925 (m), 1735 (s), 1602
3
(
m), 1508 (s), 1467 (m), 1218 (s), 1157 (s), 1006 (m), 819 (s), 592 (m). MS (EI, 70 eV): m/z
+
+
(
%) = 443 (45), 442 (M , 100), 277 (8). HRMS (EI, 70 eV): Calculated for C H OF (M ),
30 28 2
442.21027; measured 442.21000.
3,4-Bis-(4-trifluoromethylphenyl)-13β-estra-1,3,5(10)-trien-17-one [5e]
5e was synthesized according to general procedure B using 4-trifluoromethylphenylboronic
acid (0.63 mmol, 119 mg) and was purified via column chromatography (heptane/ethyl
1
acetate 5:1) to yield a yellow oil (114 mg, >99 %). H NMR (300 MHz, CDCl ): δ = 0.97 (s,
3
3
H, CH ); 1.55–1.71 (m, 6H, CHAlkyl); 1.96–2.19 (m, 4H, CHAlkyl); 2.44–2.60 (m, 5H, CHAlkyl);
3
3
3
3
7
.10 (d, J = 8.06 Hz, 1H, CH ); 7.14 (d, J = 7.99 Hz, 2H, CH ); 7.27 (dd, J = 7.94 Hz,
Ar Ar
4
3
3
J = 3.41 Hz, 2H, CH ); 7.40 (d, J = 8.11 Hz, 2H, CH ); 7.49 (d, J = 8.08 Hz, 2H, CH );
Ar
Ar
Ar
3
13
7
2
1
.55 (d, J = 8.01 Hz, 1H, CH ). C NMR (75 MHz, CDCl ): δ = 13.8 (CH ); 21.5, 26.0, 26.5,
Ar 3 3
1
8.9, 31.6, 35.8 (CH ); 37.5, 44.8 (CH); 47.9 (C); 50.5 (CH); 124.1 (q, J = 272.0 Hz, CF );
2
3
1
3
3
24.1 (q, J = 272.1 Hz, CF ); 124.6 (q, J = 3.70 Hz, 2xCH ); 124.9 (q, J = 3.79 Hz, CH );
3
Ar
Ar
3
2
1
25.1 (q, J = 3.83 Hz, CH ); 125.4, 127.4 (CH ); 128.5 (q, J = 32.4 Hz, C-CF ); 128.9 (q,
Ar Ar 3
2
J = 32.5 Hz, C-CF ); 129.9 (2xCH ); 130.5, 130.6 (CH ); 134.9, 137.7, 138.8, 140.2 (C );
3
Ar
Ar
Ar
5
5
19
1
43.8 (q, J = 1.18 Hz, C ); 145.0 (q, J = 1.17 Hz, C ); 220.6 (C=O). F NMR (282 MHz,
Ar Ar
-1
CDCl ): δ = -62.47. IR (ATR, cm ): ꢀȬ = 2930 (m), 1736 (m), 1616 (m), 1320 (s), 1119 (s),
3
+
1
063 (s), 1017 (m), 821 (m), 731 (m). MS (EI, 70 eV): m/z (%) = 543 (45), 542 (M , 100), 498
(
31), 485 (24), 432 (18), 429 (24), 377 (22), 359 (15), 270 (19), 79 (18), 69 (18), 68 (15), 67
+
(
16), 55 (43), 43 (19), 41 (23). HRMS (EI, 70 eV): Calculated for C H OF (M ), 542.20389;
32
28
6
measured 542.20447.

19
ACCEPTED MANUSCRIPT
3,4-Bis-(4-vinylphenyl)-13β-estra-1,3,5(10)-trien-17-one [5g]
5g was synthesized according to general procedure B using 4-vinylphenylboronic acid (0.63
mmol, 93 mg) and was purified via column chromatography (heptane/ethyl acetate 5:1) to
1
yield a white solid (92 mg, 96 %). mp. 72–73 °C . H NMR (300 MHz, CDCl ): δ = 0.97 (s, 3H,
3
CH ); 1.51–1.71 (m, 6H, CHAlkyl); 1.92–2.22 (m, 4H, CHAlkyl); 2.39–2.65 (m, 5H, CHAlkyl); 5.17–
3
5.25 (m, 2H, CHVinyl); 5.65–5.75 (m, 2H, CHVinyl); 6.59–6.74 (m, 2H, CHVinyl); 6.95 (dd,
3
4
3
3
J = 7.87 Hz, J = 1.71 Hz, 1H, CH ); 7.04 (d, J = 8.28 Hz, 2H, CH ); 7.13 (dd, J = 7.80 Hz,
Ar
Ar
4
3
J = 1.53 Hz, 1H, CH ); 7.20 (d, J = 8.19 Hz, 2H, CH ); 7.26–7.29 (m, 2H, CH ); 7.34 (dd,
Ar
Ar
Ar
3
4
3
13
J = 7.91 Hz, J = 1.79 Hz, 1H, CH ); 7.44 (d, J = 8.09 Hz, 1H, CH ). C NMR (75 MHz,
Ar
Ar
CDCl ): δ = 13.8 (CH ); 21.5, 26.0, 26.6, 28.9, 31.7, 35.8 (CH ); 37.5, 44.9 (CH); 47.9 (C);
3
3
2
5
1
1
0.6 (CH); 113.3, 113.4 (CH2,Vinyl); 124.7 (CH ); 125.4 (2xCH ); 125.7, 125.9, 127.5 (CH );
Ar Ar Ar
29.9 (2xCH ); 130.4, 130.5 (CH ); 135.1, 135.2, 135.5 (C ); 136.5, 136.6 (CHVinyl); 138.8,
Ar
Ar
Ar
-1
39.2, 139.9, 140.0, 141.3 (C ); 220.8 (C=O). IR (ATR, cm ): ꢀȬ = 2925 (m), 1735 (s), 1627
Ar
(
w), 1467 (m), 1255 (m), 1006 (m), 987 (m), 848 (m), 821 (s). MS (EI, 70 eV): m/z (%) = 459
+
+
(
40), 458 (M , 100), 291 (11), 55 (12). HRMS (EI, 70 eV): Calculated for C H O (M ),
34 34
458.26042; measured 458.26005.
3,4-Bis-(3-thienyl)-13β-estra-1,3,5(10)-trien-17-one [5h]
5h was synthesized according to general procedure B using 3-thienylboronic acid (0.63
mmol, 93 mg) and was purified via column chromatography (heptane/ethyl acetate 5:1) to
1
yield a brown solid (80 mg, 91 %). mp. 195–196 °C . H NMR (250 MHz, CDCl ): δ = 0.94 (s,
3
3H, CH ); 1.53–1.67 (m, 6H, CHAlkyl); 1.95–2.19 (m, 4H, CHAlkyl); 2.35–2.57 (m, 3H, CHAlkyl);
3
3
4
2
.64–2.69 (m, 2H, CHAlkyl); 6.72 (dd, J = 4.97 Hz, J = 1.19 Hz, 1H, CH ); 6.85–6.90 (m, 3H,
Ar
3
4
3
4
CH ); 7.08 (dd, J = 4.97 Hz, J = 2.99 Hz, 1H, CH ); 7.29 (dd, J = 4.86 Hz, J = 2.95 Hz,
Ar
Ar
1
3
1
2
1
H, CH ); 7.36–7.38 (m, 2H, CH ). C NMR (63 MHz, CDCl ): δ = 13.8 (CH ); 21.5, 26.0,
Ar Ar 3 3
6.6, 28.7, 31.6, 35.8 (CH ); 37.6, 44.8 (CH); 47.9 (C); 50.5 (CH); 122.4, 123.2, 124.0, 124.9,
2
26.9, 128.7, 129.5 (CH ); 134.5, 135.2, 136.0, 139.3, 140.3, 142.0 (C ); 220.7 (C=O). IR
Ar
Ar
-
1
(
(
ATR, cm ): ꢀȬ = 2929 (m), 1729 (s), 1471 (w), 1259 (m), 1076 (m), 1010 (m), 850 (m), 788
+
s), 765 (s), 678 (m). MS (EI, 70 eV): m/z (%) = 419 (22), 418 (M , 100), 260 (16), 259 (16),
258 (19), 254 (16), 247 (23), 222 (15), 221 (25), 79 (36), 77 (17), 67 (35), 55 (67), 45 (21), 43
+
(
15), 41 (50), 39 (19), 29 (35). HRMS (EI, 70 eV): Calculated for C H OS (M ), 418.14196;
26
26
2
measured 418.14117.
3-(4-Trifluoromethylphenyl)-4-(4-tert-butylphenyl)-13β-estra-1,3,5(10)-trien-17-one [6a]

20
ACCEPTED MANUSCRIPT
6a was synthesized according to general procedure C using 4-trifluoromethylphenylboronic
acid (0.281 mmol, 53 mg) and was purified via column chromatography (heptane/ethyl
1
acetate 10:1) to yield a white solid (85 mg, 86 %). mp. 176–177 °C . H NMR (300 MHz,
CDCl ): δ = 0.96 (s, 3H, CH ); 1.29 (s, 9H, CH3,tBu); 1.50–1.71 (m, 6H, CHAlkyl); 1.94–2.18 (m,
3
3
3
4
4
H, CHAlkyl); 2.43–2.68 (m, 5H, CHAlkyl); 6.84 (dd, J = 8.03 Hz, J = 1.73 Hz, 1H, CH ); 7.04
Ar
3
4
3
(
dd, J = 8.02 Hz, J = 1.69 Hz, 1H, CH ); 7.14 (d, J = 8.00 Hz, 2H, CH ); 7.20 (dd,
Ar Ar
3
4
3
J = 8.06 Hz, J = 1.89 Hz, 1H, CH ); 7.24–7.29 (m, 2H, CH ); 7.35 (d, J = 8.11 Hz, 2H,
Ar
Ar
3
13
CH ); 7.44 (d, J = 8.04 Hz, 1H, CH ). C NMR (75 MHz, CDCl ): δ = 13.8 (CH ); 21.5,
Ar
Ar
3
3
2
4
1
6.0, 26.6, 28.9 (CH ); 31.3 (CH ); 31.7 (CH ); 34.4 (C ); 35.8 (CH ); 38.0, 44.9 (CH);
2 3,tBu 2 tBu 2
3
1
7.9 (C); 50.6 (CH); 124.2 (q, J = 3.70 Hz, 2xCH ); 124.3 (q, J = 271.9 Hz, CF ); 124.6,
Ar
3
2
24.7, 124.9, 127.1 (CH ); 127.9 (q, J = 32.2 Hz, C-CF ); 129.8, 129.9 (CH ); 130.0
Ar
3
Ar
5
(
2xCH ); 135.5, 136.6, 138.1, 140.0, 140.4 (C ); 145.7 (q, J = 1.21 Hz, C ); 149.8 (C );
Ar Ar Ar Ar
19
-1
2
20.7 (C=O). F NMR (282 MHz, CDCl ): δ = -62.43. IR (ATR, cm ): ꢀȬ = 2951 (w), 1739 (s),
3
1454 (w), 1322 (s), 1159 (s), 1107 (s), 1063 (m), 815 (m), 618 (m). MS (EI, 70 eV): m/z
+
(
%) = 531 (37), 530 (M , 100), 516 (36), 515 (100), 57 (21). HRMS (EI, 70 eV): Calculated for
+
C H F O (M ), 530.27910; measured 530.27937.
35
37 3
3-(4-Methoxyphenyl)-4-(4-tert-butylphenyl)-13β-estra-1,3,5(10)-trien-17-one [6b]
6b was synthesized according to general procedure C using 4-methoxyphenylboronic acid
(
0.281 mmol, 43 mg) and was purified via column chromatography (heptane/ethyl acetate
1
1
0:1) to yield a white solid (82 mg, 90 %). mp. 164–165 °C . H NMR (250 MHz, CDCl ):
3
δ = 0.95 (s, 3H, CH ); 1.30 (s, 9H, CH3,tBu); 1.54–1.68 (m, 6H, CHAlkyl); 1.91–2.18 (m, 4H,
3
3
CHAlkyl); 2.43–2.66 (m, 5H, CHAlkyl); 3.73 (s, 3H, OCH ); 6.65 (d, J = 8.84 Hz, 2H, CH ); 6.87
3
Ar
3
4
3
(
dd, J = 8.01 Hz, J = 1.70 Hz, 1H, CH ); 6.96 (d, J = 8.84 Hz, 2H, CH ); 7.05 (dd,
Ar Ar
3
4
3
4
J = 8.00 Hz, J = 1.65 Hz, 1H, CH ); 7.21 (dd, J = 8.02 Hz, J = 1.87 Hz, 1H, CH ); 7.25–
Ar
Ar
3
13
7
.30 (m, 2H, CH ); 7.40 (d, J = 8.31 Hz, 1H, CH ). C NMR (63 MHz, CDCl ): δ = 13.8
Ar Ar 3
(
CH ); 21.5, 26.0, 26.7, 29.0 (CH ); 31.4 (CH ); 31.7 (CH ); 34.4 (C ); 35.9 (CH ); 38.0,
3 2 3,tBu 2 tBu 2
44.9 (CH); 47.9 (C); 50.6 (CH); 55.1 (OCH ); 112.8 (2xCH ); 124.4, 124.5, 124.7, 127.4,
3 Ar
1
29.8, 130.0 (CH ); 130.8 (2xCH ); 134.3, 135.2, 137.3, 138.8, 138.9, 140.4, 149.1, 157.7
Ar
Ar
-1
(
C ); 220.9 (C=O). IR (ATR, cm ): ꢀȬ = 2933 (m), 1736 (s), 1608 (m), 1515 (m), 1465 (m),
Ar
+
1
1
4
244 (s), 1178 (m), 926 (m), 819 (s), 597 (s). MS (EI, 70 eV): m/z (%) = 493 (39), 492 (M ,
+
00), 57 (12). HRMS (EI, 70 eV): Calculated for C H O (M ), 492.30228; measured
35
40
2
92.30225.
3-(3-Thienyl)-4-(4-tert-butylphenyl)-13β-estra-1,3,5(10)-trien-17-one [6c]

21
ACCEPTED MANUSCRIPT
6c was synthesized according to general procedure C using 3-thienylboronic acid (0.281
mmol, 36 mg) and was purified via column chromatography (heptane/ethyl acetate 10:1) to
1
yield a yellow solid (61 mg, 70 %). mp. 76–77 °C . H NMR (250 MHz, CDCl ): δ = 0.94 (s,
3
3
H, CH ); 1.33 (s, 9H, CH3,tBu); 1.53–1.63 (m, 6H, CHAlkyl); 1.93–2.18 (m, 4H, CHAlkyl); 2.46–
3
3
4
4
2
.61 (m, 5H, CHAlkyl); 6.69 (dd, J = 4.97 Hz, J = 1.12 Hz, 1H, CH ); 6.76 (dd, J = 2.87 Hz,
Ar
4
3
4
J = 1.12 Hz, 1H, CH ); 6.95 (dd, J = 7.92 Hz, J = 1.75 Hz, 1H, CH ); 7.01 (dd,
Ar
Ar
3
4
3
4
J = 4.94 Hz, J = 3.03 Hz, 1H, CH ); 7.07 (dd, J = 7.89 Hz, J = 1.86 Hz, 1H, CH ); 7.30–
Ar
Ar
13
7
.34 (m, 2H, CH ); 7.37–7.38 (m, 2H, CH ). C NMR (63 MHz, CDCl ): δ = 13.8 (CH );
Ar Ar 3 3
2
1.5, 26.0, 26.6, 29.0 (CH ); 31.4 (CH ); 31.7 (CH ); 34.5 (C ); 35.8 (CH ); 38.0, 44.8
2
3,tBu
2
tBu
2
(
(
CH); 47.9 (C); 50.6 (CH); 122.7, 123.6, 124.5, 124.8, 125.0, 126.9, 129.1, 129.4, 129.5
-1
CH ); 133.9, 135.4, 137.5, 139.2, 140.2, 142.9, 149.5 (C ); 220.8 (C=O). IR (ATR, cm ):
Ar
Ar
ꢀȬ = 2925 (m), 1737 (s), 1511 (w), 1463 (m), 1361 (m), 1257 (m), 1006 (m), 829 (s), 790 (s),
+
6
49 (m). MS (EI, 70 eV): m/z (%) = 469 (35), 468 (M , 100), 453 (22), 247 (19), 57 (20).
+
HRMS (EI, 70 eV): Calculated for C H OS (M ), 468.24814; measured 468.24721.
32
36
3-(4-Vinylphenyl)-4-(4-tert-butylphenyl)-13β-estra-1,3,5(10)-trien-17-one [6d]
6c was synthesized according to general procedure C using 4-vinylphenylborinic acid (0.281
mmol, 42 mg) and was purified via column chromatography (heptane/ethyl acetate 10:1) to
1
yield a colourless oil (88 mg, 97 %). H NMR (300 MHz, CDCl ): δ = 0.95 (s, 3H, CH ); 1.29
3
3
(
s, 9H, CH3,tBu); 1.52–1.70 (m, 6H, CHAlkyl); 1.92–2.18 (m, 5H, CHAlkyl); 2.43–2.66 (m, 4H,
3
2
3
CHAlkyl); 5.17 (dd, J = 10.90 Hz, J = 0.74 Hz, 1H, CH=CH ); 5.66 (dd, J = 17.61 Hz,
2,cis
2
3
3
J = 0.81 Hz, 1H, CH=CH2,trans); 6.63 (dd, J = 17.62 Hz, J = 10.90 Hz, 1H, CH=CH ); 6.88
2
3
4
3
(
dd, J = 8.03 Hz, J = 1.89 Hz, 1H, CH ); 7.01 (d, J = 8.26 Hz, 2H, CH ); 7.06 (dd,
Ar Ar
3
4
3
J = 8.05 Hz, J = 1.87 Hz, 1H, CH ); 7.14–7.22 (m, 3H, CH ); 7.27 (d, J = 8.70 Hz, 2H,
Ar
Ar
3
13
CH ); 7.42 (d, J = 8.20 Hz, 1H, CH ). C NMR (75 MHz, CDCl ): δ = 13.8 (CH ); 21.5,
Ar
Ar
3
3
2
4
1
1
1
6.0, 26.7, 29.0 (CH ); 31.4 (CH ); 31.7 (CH ); 34.4 (C ); 35.8 (CH ); 38.0, 44.9 (CH);
2 3,tBu 2 tBu 2
7.9 (C); 50.6 (CH); 113.2 (CH2,Vinyl); 124.5, 124.5, 124.8 (CH ); 125.2 (2xCH ); 127.4,
Ar
Ar
29.8 (CH ); 129.9 (2xCH ); 135.0, 135.3 (C ); 136.6 (CHVinyl); 137.1 138.9, 139.2, 140.3,
Ar
Ar
Ar
-1
41.5, 149.2 (C ); 220.8 (C=O). IR (ATR, cm ): ꢀȬ = 2940 (m), 1737 (s), 1511 (w), 1464 (m),
Ar
+
257 (m), 1006 (m), 905 (m), 820 (s). MS (EI, 70 eV): m/z (%) = 489 (38), 488 (M , 100), 474
+
(
10), 473 (27), 57 (11). HRMS (EI, 70 eV): Calculated for C H O (M ), 488.30737;
36
40
measured 488.30708.
3-(Phenylethynyl)-4-(4-tert-butylphenyl)-13β-estra-1,3,5(10)-trien-17-one [7]

22
ACCEPTED MANUSCRIPT
4d (0.42 mmol, 225 mg), phenylacetylene (0.50 mmol, 51 mg), diisopropylamine (1.26 mmol,
1
27 mg), Pd(PPh ) (10 mol%, 48 mg), CuI (10 mol%, 8 mg) and DMF (6 mL) were heated in
3
4
a pressure tube under argon atmosphere at 100 °C fo r 20 hours. The reaction was quenched
with water (10 mL) and extracted with ethyl acetate (3x 20 mL). The organic phase was dried
with Na SO and filtrated. The crude product was purified by column chromatography
2
4
1
(
heptane/ethyl acetate 10:1) to yield a yellow solid (119 mg, 58 %). mp. 186–187 °C . H
NMR (300 MHz, CDCl ): δ = 0.95 (s, 3H, CH ); 1.43 (s, 9H, CH3,tBu); 1.52–1.64 (m, 6H,
3
3
CHAlkyl); 1.92–2.21 (m, 4H, CHAlkyl); 2.39–2.67 (m, 5H, CHAlkyl); 6.97–7.01 (m, 2H, CHAr);
1
3
7
.17–7.34 (m, 6H, CH ); 7.42–7.52 (m, 3H, CH ). C NMR (75 MHz, CDCl ): δ = 13.8
Ar Ar 3
(
CH ); 21.5, 25.9, 26.4, 28.6 (CH ); 31.5 (CH ); 31.6 (CH ); 34.6 (C ); 35.8 (CH ); 37.5,
3 2 3,tBu 2 tBu 2
4
1
1
1
3
4.9 (CH); 47.9 (C); 50.6 (CH); 89.9, 92.5 (C≡C); 121.1, 123.6 (C ); 124.2, 124.8, 124.9,
Ar
27.6 (CH ); 127.9 (2xCH ); 128.4, 129.0, 129.3 (CH ); 131.2 (2xCH ); 134.9, 137.6 140.5,
Ar
Ar
Ar
Ar
-1
44.7, 149.6 (C ); 220.7 (C=O). IR (ATR, cm ): ꢀȬ = 2939 (m), 1738 (s), 1493 (w), 1257 (w),
Ar
+
112 (w), 1007 (m), 834 (m), 757 (s), 691 (s). MS (EI, 70 eV): m/z (%) = 487 (16), 485 (M ,
9), 430 (100), 429 (66), 307 (10), 303 (12), 291 (12), 289 (13), 266 (22), 265 (58), 57 (24).
+
HRMS (EI, 70 eV): Calculated for C H O (M ), 486.29172; measured 486.29159.
36
38
Acknowledgement
Financial support by the BMBF (Response – Zwanzig20) and by the project GINOP-2.3.2-15-
016-00038 is greatly acknowledged.
2
References
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2
. K. Hoehn K, E. N. Marieb Human Anatomy and Physiology, San Francisco: Benjamin
Cummings, 2010.
3. H. Kuhl Climacteric 2005, 8, 3–63.
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. (a) B. Kleine, W. G. Rossmanith Hormone und Hormonsystem 3, Springer, 2014; (b)
O. A. Akanni, B. A. Marples Steroids 1993, 58, 234-238; (c) A. Takadate, J. Fishman
J. Org. Chem. 1979, 44, 67-71; (d) E. R. Clark, A. M. E. Omar J. Med. Chem. 1977,
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2765-2771; (f) V. Jeyachandran, S. V. Kumar, R. R. Kumar Steroids 2014, 82, 29-37.
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1
982, 40, 171–187; (b) A. C. Stalford, J. L. Maggs, T. L. Gilchrist, K. Park Steroids
997, 62, 750–761; (c) S. D. Jonson, D. A. d’Avignon, J. A. Katzenellenbogen, M. J.
1

23
ACCEPTED MANUSCRIPT
Welch Steroids 1998, 63, 470–478; (d) V. Perron, D. Rabouin, E. Asselin, S. Parent,
R. C.-Gaudreault, G. Bérubé Bioorg. Chem. 2005, 33, 1–15; (e) S. A. Sadek, S. M.
Shaw, W. V. Kessler, G. C. Wolf J. Org. Chem. 1981, 46, 3259–3262; (f) T. L. Fevig,
J. A. Katzenellenbogen J. Org. Chem. 1987, 52, 247–251.
6
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1
0. CCDC 1815969 and 1815970 contain supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.