Alkynylation of steroids via Pd-free Sonogashira coupling

Article abstract of DOI:10.1039/c5ob00559k

Cu-catalyzed Pd-free Sonogashira coupling has been proposed as a straightforward and convenient route to valuable steroidal enynes. A biligand catalyst system based on Ph₃P and TMEDA has been designed. The protocol was utilized for the efficient coupling of iodosteroids with diverse terminal alkynes and 1-trimethylsilylalkynes. A possible role of an auxiliary ligand as a phase-transfer catalyst for a sparingly soluble inorganic base (K₂CO₃) was revealed.

Full text of DOI:10.1039/c5ob00559k

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Alkynylation of steroids via Pd-free Sonogashira
coupling
Cite this: DOI: 10.1039/x0xx00000x
Yury N. Kotovshchikov, Gennadij V. Latyshev, Nikolay V. Lukashev* and Irina
P. Beletskaya
Received 00th January 2012,
Accepted 00th January 2012
Cu-catalyzed Pd-free Sonogashira coupling has been proposed as a straightforward and
convenient route to valuable steroidal enynes. A biligand catalyst system based on Ph3P and
TMEDA has been designed. The protocol was utilized for the efficient coupling of
iodosteroids with diverse terminal alkynes and 1-trimethylsilylalkynes. A possible role of
auxiliary ligand as a phase-transfer catalyst for sparingly soluble inorganic base (K2CO3) was
revealed.
DOI: 10.1039/x0xx00000x
www.rsc.org/
for fine-tuning their biological activity.12 Sonogashira coupling
is a convenient approach to steroidal enynes, which are
valuable synthetic intermediates to be easily transformed to
pharmacologically significant 20-ketosteroids13 as well as a
large number of diverse heterocycles14 (Scheme 1).
The conventional Pd-catalyzed Sonogashira coupling of
steroids was successfully applied for the synthesis of new
biologically active compounds exhibiting anticancer15 and
antiviral16 effects, supramolecular structures (such as
dendrimers,17 macrocycles,18 and molecular machines19),
Introduction
The Sonogashira reaction is one of the most efficient and
convenient ways for C(sp2)–C(sp) bond formation by cross-
coupling of aryl or vinyl halides with terminal acetylenes.1 An
important trend in modern development of synthetic methods is
the search for cheaper starting materials, ligands, and catalysts.
Thus, e.g. copper derivatives are replacing very expensive
palladium in the cross-coupling and related processes.2
The Pd-free Cu-catalyzed Sonogashira coupling has been
attracting a significant interest for two last decades since its
discovery.3 A large number of new catalytic systems based on
copper complexes have been proposed. These catalysts involve
not only phosphines,4 but also N- and O-donating ligands,5
some of which are quite simple and readily available.
Following principles of green chemistry, “ligand-free”,6
aqueous,7 and solvent-free8 systems were reported. Efficient
and recyclable heterogeneous catalysts were designed utilizing
metallic copper, copper oxides,9 and immobilized copper
complexes.10 Apart from the synthesis of enynes and
arylacetylenes, Pd-free Sonogashira coupling was applied as a
key step of new cascade processes leading to various
heterocycles such as indoles, benzofurans, isocoumarins, and
other fused systems.11 However, the synthetic potential of this
bioconjugates
with
porphyrins,20
nucleosides,21
and
oligosaccharides.22 The same approach became popular for
introduction of various radioactive,23 electrochemical,24 and
luminescent labels25 into steroid molecules.
So far, all of the catalyst systems proposed for the synthesis of
alkynylsteroids via Sonogashira reaction were based on
palladium complexes. Moreover, in some cases the cross-
coupling could be performed in high yield only with tandem
catalytic effect of palladium and silver.26 Herein, we report a
new protocol for the synthesis of steroidal enynes via Pd-free
Sonogashira coupling.
Results and discussion
method toward the preparation of rather complex molecules, in Preparation of steroidal enynes was performed by Cu-catalyzed
particular, for the derivatization of polyfunctional natural cross-coupling of steroidal vinyl iodides with terminal
products, remains largely unexplored.
acetylenes. The starting iodosteroids were prepared according
The steroids represent an important class of widespread to the previously reported procedures27 from readily available
multirole signalling molecules regulating diverse processes in ketosteroids by Barton’s method, which is the cleavage of
living organisms, such as salt and water balance, metabolism, hydrazones by iodine in the presence of base (Scheme 1).
immune response, reproductive cycle, etc. Modification of
steroidal drugs provides a well-established and efficient route
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Scheme 1 Synthetic routes to steroidal enynes and their post-transformation.
Conditions for the reaction between steroidal vinyl iodides and Therefore, we suspected that the results could be accounted for
terminal acetylenes were optimized by using
as a model not by Cu-catalysis, but rather by trace impurities of Pd.30
substrate (Scheme 2, Table 3). Iodosteroid is known to be However, carrying out the cross-coupling of with 1-hexyne in
1
1
1
challenging compound for cross-couplings and generally the presence of 100 ppb Pd(Ph3P)2Cl2 (10-5 mol%) revealed no
demonstrates poor reactivity due to a steric hindrance. Only effect of palladium. Therefore, we didn’t take into account any
moderate or low yields of the respective coupling products are significant contribution of Pd to catalysis of the reaction under
often accessible under either Cu-27 or even Pd-catalysis.28 It is investigation.
worth mentioning that a strong negative effect of steric bulk for
Ullmann-type chemistry is a well-known feature substantially
limiting the scope of the methods.29
Table 1 Ligand effect on the Cu-catalyzed coupling of 1 with
phenylacetylene
Taking into consideration a large number of ligands proposed
for the Cu-catalyzed Sonogashira coupling,3-5 it was interesting
to compare the performance of different catalytic systems
(Table 1). Although the alkynylation of
1 with phenylacetylene
proceeds in the presence of CuI even under “ligand-free”
conditions (entry 1), an addition of some N- and O-donating
ligands increases the yield significantly (entries 3–5).
Nevertheless, the best ligand was found to be Ph3P (entry 6), in
the presence of which the conversion of
1 within 4 h at 100 °C
Entry
Ligand
Yield
2aa (%)
39
36
52
Entry
Ligand
Yield
2aa (%)
100
0
0
15
in DMSO with K2CO3 as a base was nearly quantitative. In
contrast to Ph3P bidentate phosphines demonstrated an
extremely low activity (entries 7–10), and in the case of BINAP
and dppe the reaction didn’t take place at all. Apparently, the
chelating diphosphines form with copper(I) ions too stable and
inert complexes blocking all coordination sites and thus
quenching the reaction.
1
2
3
4
5
–
6
7
8
9
10
20 % Ph3P
10 % BINAP
10 % dppe
10 % dppp
10 % dppf
20 % DMEDA
20 % L-Pro
20 % L1
63
84
20 % L2
21
a By 1H NMR.
Interestingly, phosphines are rarely used in other Cu-catalyzed
reactions, and always never outperform N- or O-chelators.
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Scheme 2 Cu-catalyzed alkynylation of iodosteroid 1.
Aliphatic 1-alkynes are known to be less reactive than
arylacetylenes requiring a more careful tuning of the catalytic
system. As expected, 1-hexyne reacted with
1 much more
slowly than phenylacetylene (Table 2). Moreover, the
formation of the target coupling product 2b was accomplished
by an undesirable reductive dehalogenation giving product
3.
The decrease in the coupling rate led to a higher yield of , as
3
the dehalogenation rate is believed not to depend on the
acetylene used. Changing solvent from DMSO to DMF doesn’t
affect the yield of the products (cf. entries 1 and 2). The use of
K3PO4 instead of K2CO3 affords practically the same result,
while the use of KOH increases the amount of reduction
Scheme 3 Possible equilibrium of copper acetylides.
product 3, and in the case of Cs2CO3 and pyridine no reaction
Table 3 The effect of additional ligand on the Cu-catalyzed coupling of 1
with 1-hexyne
was observed (entries 3–6). Changing Ph3P to phosphines
bearing donating alkyl substituents leads to a negative effect
(entries 7 and 8). Thus, the initial variation of conditions didn’t
allow us to improve the rate and selectivity in the reaction of
with 1-hexyne.
1
Table 2 The effect of reaction conditions on the Cu-catalyzed coupling of 1
with 1-hexyne
Entry
Ligand
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
–
Additive
–
Yield 2ba (%)
1
2
3
4
5
6
7
8
9
40
41
23
48
50
54
61
89
7
Entry
Ligand
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Cy3P
Base
K2CO3
K2CO3
K3PO4
KOH
Cs2CO3
pyridine
K2CO3
K2CO3
Solvent
DMSO
DMF
DMSO
DMF
DMSO
DMSO
DMSO
DMSO
Yield 2b/3a (%)
40/<5
40/<5
37/4
100 % pyridine
100 % Et3N
10 % DMEDA
10 % dmphen
10 % EDTA
10 % phen
1
2
3
4
5
6
7
8
22/13
0/8
0/0
6/<5
30/0
10 % TMEDA
10 % TMEDA
(t-Bu)3P∙HBF4
a By 1H NMR.
a By 1H NMR.
Thus, we applied a biligand catalyst system comprising Ph3P
and an additional N-donating ligand (Table 3). The use of
pyridine didn’t allow us to improve the result (entry 2),
although it is a common solvent for the coupling of copper(I)
acetylides in non-catalytic Castro-Stephens variant.31 In the
case of Et3N the conversion was even lower (entry 3), thus
confirming an inhibitory effect of amines on the reaction.3b
Since copper acetylides tend to form oligomeric or polymeric
associates, which are often sparingly soluble, we supposed that
an introduction of additional N-donating ligands
L (Scheme 3)
could increase the amount of soluble copper acetylide
complexes. The subsequent ligand exchange with Ph3P should
afford catalytically active monomeric copper(I) complex.
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However, the application of N,N-donating chelating ligands led free” conditions (CuI, DMF, 120 °C, Scheme 5). Various Cu(I)
to a significant improvement (entries 4–8). Thus, the addition and Cu(II) complexes ([Cu(MeCN)4]BF4, (CuOTf)2∙C6H6,
of TMEDA not only results in increase of the yield of enyne 2b Cu(OTf)2) were all equally useful in this transformation. It is
from 40 to 89 % (cf. entries 1 and 8), but also suppresses the worth noting that 2m, containing electron-withdrawing nitro-
formation of undesired product
3 almost completely. It is group, did not afford 4d on heating with Cu salts, probably due
noteworthy that the use of TMEDA without Ph3P leads to to a lower nucleophilicity of amino-group.
unsatisfactory result (entry 9).
The potential of the developed biligand catalytic system (CuI :
Ph3P : TMEDA = 10:20:10 mol%) was revealed in the reaction
of iodosteroid
to excellent yields of steroidal enynes
majority of cases despite the above mentioned inertness of
1
with various terminal alkynes (Table 4). Good
were obtained in a
in
2
1
Cu(I)-catalyzed reactions due to steric hindrance. The reaction
proceeds smoothly with arylacetylenes containing electron-
donating (2c) or weak electron-withdrawing (2d) groups.
Substantially lower reactivity of C-Br bond compared to C-I
allow to preserve aryl bromide fragment during the coupling
providing 2d with almost quantitative yield. The obtained aryl
Scheme
ethynylphenol (b).
4 Base-promoted cyclizations of aminoenyne 2m (a) and o-
bromide moiety is
a convenient precursor for further
modifications of the steroid side chain via well-established
palladium-catalyzed chemistry. However, strong electron-
acceptors in arylacetylene lead either to significantly
diminished yields or to the complete suppression of the
coupling (Table 4, entries 5 and 6). This is probably caused by
the high propensity of these alkynes to undergo Michael
addition in basic media leading to the complex mixture of
products. However, such a strongly electron-deficient substrate
as 2-ethynylpyridine afforded a very good yield of the enyne
2g. Almost the same yields were achieved with other electron-
deficient and electron-donating heteroaryl alkynes (2h, 2i).
Good yields were also achieved with less reactive aliphatic
terminal alkynes including 1-hexyne (2b, 86 %) and 3-
diethylaminopropyne (2o, 68 %). However, propargyl alcohol
which is known to be inert in Cu-catalyzed Sonogashira
coupling gave no product 2r under these conditions.
Scheme 5 Cu-catalyzed transformation of o-aminoenynes to indoles 4a-c
.
Since the basic media will favor the cleavage of alkynylsilanes
we investigated tandem desilylation-Sonogashira-type coupling
with readily available trimethylsilylalkynes. Indeed both aryl-
Various o-alkynylanilines were competent substrates in the
coupling, affording o-aminoenynes 2j-m in excellent yields.
Both donor methyl and electron-withdrawing chlorine
substituents were tolerated. The coupling of 4-nitro-2-
ethynylaniline was also very efficient but the product 2m was
isolated as an equimolar mixture with the corresponding indole
4d (Scheme 4a). The observed 5-endo-dig cyclization of 2m to
4d is probably facilitated by increased NH-acidity of 4-
nitroaniline core. In the case of much more acidic o-
ethynylphenol, no coupling product 2n was detected in the
reaction mixture due to fast intramolecular cyclization of the
terminal alkyne to 5-chlorobenzo[b]furan (Scheme 4b). The
other aminoenynes 2j-l are less acidic than 2m, so the
cyclization to indole requires the assistance of Lewis acid
capable of effective coordination with triple bond. Since Ph3P
lowers the Lewis acidity of Cu(I), no cyclization is observed for
2j-l in the reaction media. However, good yields of indoles
were obtained by heating these aminoenynes under “ligand-
(
2a, Table 4, entry 15) and hetarylenynes (2p, entry 16) were
prepared under the optimized conditions in excellent yields.
Accordingly, no coupling product was observed neither with
trimethylsilylacetylene nor with bis(trimethylsilyl)acetylene,
since formation of volatile acetylene should proceed much
faster than the coupling. The other internal alkynes capable to
give terminal alkynes in situ were also considered. Propargyl
alcohols are known to be versatile sources of terminal alkynes
via base-catalyzed retro-Favorsky reaction. While no reaction
was observed with 3-arylpropargyl alcohol (Table 4, entry 19),
a significant amount of coupling product 2c was observed for 3-
aryl-1,1-dimethylpropargyl alcohol (entry 20). The process has
a
well-known counterpart in Pd-catalyzed Sonogashira
coupling,32 though it is not quite efficient to be preparatively
useful.
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Table 4 Yields of alkynylation products in the Cu-catalyzed coupling of 1 with acetylenes
Entry
1
Alkyne
Product
Isolated
yield (%)
100a
Entry
11
Alkyne
Product
Isolated
yield (%)
85
2a
2k, R = CH3
2l, R = Cl
90
2
2b
86
12
2m + 4d
96c
(44:56)
3
4
2c
75
99
13
14
2n
2o
0d
2d
68e
5
6
2e
2f
(34)b
0
15
16
2a
2p
100
92
7
8
2g
2h
85
87
17
18
2q
2r
0
0
9
2i
2j
86
94
19
20
2s
2c
0
10
(59)b
a Reaction for 4 h. b 1H NMR yield in parentheses. c Yield for mixture of 2m and 4d. d Cyclization of starting acetylene to 5-chlorobenzo[b]furan was
observed. e Reaction for 48 h.
The scope of protocol was expanded to testosterone and in 84 % yield. It is noteworthy that this route to steroids
cholestenone-derived steroidal iododienes
Since these dienes are much less sterically encumbered than
the Cu-catalyzed coupling with these substrates was much corresponding vinyl triflate.24a High yields were also achieved
smoother. In fact, we have never detected any traces of for aliphatic alkynes including 3-diethylaminopropyne (7e),
protodeiodinated by-products in these reactions. Arylacetylenes which was expected to poison catalyst due to known
5
and
6
(Table 5). containing electrochemical probe gives almost the same yield
as palladium-catalyzed reaction of ethynylferrocene with the
1
,
with both electron-donating (8c-e), weak (7b, 8b) and even detrimental effect of trialkylamines on Cu-catalyzed
moderate (7c) electron-withdrawing groups were tolerated. The Sonogashira reaction.3b However, the presence of free carboxy
coupling with o-ethynylaniline afforded uncyclized o- group led to slowdown of the coupling, though the product 7f
aminophenylenyne 8d in a good isolated yield. The developed was isolated in 79 % yield after heating the reaction mixture for
method was used to prepare ferrocene-cholesterol conjugate 8e 66 h.
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The rather slow coupling of
5
with 4-(propargyloxy)benzoic
Table 5 Yields of alkynylation products in the Cu-catalyzed coupling of 5
and 6 with acetylenes
acid is much less efficient when Bu4NBr (entry 15) or aliquat-
336 (entry 16) are used instead of TMEDA (entry 14).
Surprisingly, the increase of additive amount led to deceleration
of the reaction rate (cf. entries 3 vs. 4 and 5 vs. 6). Since Bu4NI
inhibits the coupling (entry 11), the observed effect is probably
caused by the formation of tetraalkylammonium iodide due to
anion exchange with iodide anion, which is formed in the
course of the coupling.
Table 6 Effect of phase transfer agents
Entry Substrate
Alkyne
Product
Isolated
yield (%)
100
1
2
3
5
5
5
7a
7b
7c
98
83
Entry
1
2
3
4
5
6
7
8
Additive
–
10 % TMEDA
10 % TEBAC
Product
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2o
Yielda (%)
4
89b
29
19
97
41b
79
9
20 % TEBAC
4
5
5
5
7d
7e
95
97
10 % (n-Bu)4NBr
20 % (n-Bu)4NBr
10 % aliquat-336c
10 % (n-Bu)4NHSO4
10 % 18-crown-6
100 % PEG-1500
10 % (n-Bu)4NI
10 % TMEDA
10 % (n-Bu)4NBr
10 % TMEDA
10 % (n-Bu)4NBr
10 % aliquat-336c
9
23
23
0
6
5
7f
79a
10
11
12
13
14
15
16
66d
66d
53d
33d
17d
7
8
6
6
6
6
8a
8b
8c
8d
90
87
87
80
2o
7f
7f
7f
a By 1H NMR. b Reaction for 4 h. c Me(Oct)3NCl. d Reaction for 17 h.
9
A notable acceleration of the coupling was also observed in the
presence of 18-crown-6 (cf. entries 1 and 9 in Table 6), which is
an excellent ligand for potassium cation. Improving the
solubility of K2CO3, thus increasing an amount of carbonate
anion in a solution should accelerate the formation of copper
acetylide. It prompted us to suppose that the formation of
copper acetylides might be the rate-limiting stage for Cu-
catalyzed Sonogashira coupling. Indeed, an addition of Ph3P to
stoichiometric reaction of CuI with terminal alkyne (2-(4-
nitrophenyloxy)prop-1-yne) in the presence of K2CO3 led to
catastrophic slowdown of Cu acetylide formation with
incomplete conversion of starting alkyne even after 5 h (HPLC
monitoring), whereas in the absence of Ph3P a full conversion
was observed within a few minutes. The addition of TMEDA (1
equiv.) led to partial improvement of alkyne conversion, while
no effect of TMEDA was observed in the reaction of preformed
10
11
6
8e
84
a Reaction for 66 h.
It is known that diamines in Cu-catalyzed amination can act not
only as ligands for copper but as mass-transfer agents for
sparingly soluble inorganic base.33 To clarify the effect of
TMEDA addition on the reaction rate we carried out the
coupling of 1-hexyne with iodosteroid
1 in the presence of
various phase-transfer catalysts (Table 6). The acceleration of
the coupling was observed for all additives except Bu4NI (entry
11), which completely inhibited the reaction. The most
prominent acceleration was observed with Bu4NBr and aliquat-
336 (entries 5 and 7), which were even more efficient than
TMEDA (entry 2). However, the increase of the reaction rate
proved to be very dependent on the nature of the substrate. For
instance, Bu4NBr and TMEDA led to the same yield in the
copper acetylide with iodosteroid 1. Therefore, we believe that
the addition of co-ligands in Cu-catalyzed Sonogashira
coupling improves the solubility of inorganic base leading to
the increased amount of catalytically active acetylide copper
complexes (Scheme 6).
reaction of
1 with 3-diethylaminopropyne (entries 12 and 13).
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corresponding ketones according to previously reported
procedures.27
Copper-catalyzed Sonogashira coupling of iodosteroids and
terminal acetylenes
General Procedure
In a vial with a screw cap, iodosteroid 1, 5 or 6 (0.150 mmol),
terminal acetylene (0.180 mmol), anhydrous K2CO3 (41.5 mg,
0.300 mmol), CuI (2.9 mg, 15 μmol, 10 mol%),
triphenylphosphine (7.9 mg, 30 μmol, 20 mol%), and
N,N,N’,N’-tetramethylethylenediamine (TMEDA) (2.2 μL, 15
μmol, 10 mol%) were mixed under an Ar atmosphere in DMSO
(0.5 mL). The reaction mixture was stirred at 100 °C for 4–66
h, then diluted with CH2Cl2 (25 mL) and washed with water (4
× 25 mL). The organic layer was dried with anhydrous Na2SO4,
and the solvents were evaporated in vacuo. The residue was
purified by column chromatography.
Scheme 6 Plausible mechanism of the Cu-catalyzed Sonogashira coupling.
Conclusions
We developed a new synthetic approach to important steroidal
enynes based on Pd-free Sonogashira reaction. The introduction
of additives, acting as phase-transfer agents for sparingly
soluble inorganic base, was found to considerably improve
catalytic performance of CuI/Ph3P system. Though Cu-
catalyzed protocols in Sonogashira reaction are generally less
effective and versatile than the classical Pd-catalyzed methods,
a wide range of aryl- and hetarylacetylenes as well as aliphatic
1-alkynes can be efficiently coupled with steroidal vinyl iodides
affording the corresponding enynes in up to quantitative yields.
Trimethylsilylalkynes can also be viable substitutes for terminal
alkynes in this protocol due to the in situ desilylation. The
limitations of the procedure are mainly imposed by relatively
basic media which induces side reactions with strongly
electron-deficient acetylenes, propargyl alcohols, and some
base-sensitive o-ethynylanilines and phenols. Notwithstanding,
the protocol appeared highly efficient in coupling of o-
ethynylanilines, which can be easily transformed to steroid-
anchored indoles.
Copper-catalyzed synthesis of indoles from o-ethynylanilines
General Procedure
In a vial with a screw cap, steroidal aniline 2j-l (0.150 mmol)
and CuI (5.7 mg, 30 μmol, 20 mol%) were mixed under an Ar
atmosphere in DMF (0.5 mL). The reaction mixture was stirred
at 100 °C for 24 h, then diluted with CH2Cl2 (25 mL) and
washed with water (4 × 25 mL). The organic layer was dried
with anhydrous Na2SO4, and the solvents were evaporated in
vacuo. The residue was purified by column chromatography.
17-(phenylethynyl)androsta-4,16-dien-3-one (2a). Prepared
from
0.18 mmol) without addition of TMEDA; heating 4 h. Yield
55.8 mg (100 %). Prepared from (59.4 mg, 0.15 mmol) and
1 (59.4 mg, 0.15 mmol) and phenylacetylene (19.8 μL,
1
(trimethylsilyl)phenylacetylene (0.18 mmol, 35.4 μL); heating
24 h; eluent: CH2Cl2–MeOH = 100 : 1. Yield 55.8 mg (100 %).
Light-brown solid; mp 209–210 °C; 1H NMR (400 MHz,
CDCl3) δ 7.44–7.39 [m, 2H, 2,6-CH(Ph)], 7.32–7.23 [m, 3H,
3,4,5-CH(Ph)], 6.07 (m, 1H, 16-CH), 5.72 (s, 1H, 4-CH), 2.48–
2.20 (m, 5H), 2.11–1.36 (m, 10H), 1.20 (s, 3H, 19-CH3), 1.18–
0.97 (m, 2H), 0.94 (s, 3H, 18-CH3); 13C NMR (100.6 MHz,
CDCl3) δ 199.3 [C(3)=O], 170.8 (5-C), 137.0 (17-C), 135.5
(16-CH), 131.5 [2C, 2,6-CH(Ph)], 128.2 [2C, 3,5-CH(Ph)],
127.9 [4-CH(Ph)], 123.9 (4-CH), 123.5 [1-C(Ph)], 92.9 (C≡C),
84.8 (C≡C), 55.4, 54.1, 47.9 (quat.), 38.7 (quat.), 35.5, 34.33,
34.30, 33.9, 32.7, 32.0, 31.7, 20.8, 17.2, 16.2; IR (KBr) ν =
2195 (C≡C), 1668 (C=O), 760 (Ph) cm-1; HRMS (MALDI-
TOF) calcd for C27H31O [M+H]+ 371.2375; found 371.2373;
Anal. calcd for C27H30O: C, 87.52; H, 8.16; found C, 87.12; H,
8.07.
Experimental
General information
NMR spectra were recorded with a Bruker Avance 400 and an
Agilent 400MR spectrometers (1H 400 MHz, 13C 100.6 MHz)
at ambient temperature in CDCl3 or in CDCl3–DMSO-d6 and
CDCl3–CD3OD mixtures for compounds with low solubility in
CDCl3. Chemical shifts are presented in ppm (δ scale) and
1
referenced to hexamethyldisiloxane (δ = 0.05 ppm) in the H
NMR spectra and to the solvent signal in the 13C NMR spectra.
IR spectra were recorded with a Thermo Nicolet 200 FT-IR
instrument in KBr pellets. MALDI-TOF spectra were recorded
with a Bruker Daltonics UltraFlex instrument in a dithranol
matrix using PEG 400 or PEG 600 as the internal standard.
Elemental analyses were performed with an Elementar Vario
MICRO cube apparatus. Column chromatography was carried
out on Macherey–Nagel silica gel 60 (0.040–0.063 mm).
17-(hex-1-yn-1-yl)androsta-4,16-dien-3-one (2b). Prepared
from
1 (59.4 mg, 0.15 mmol) and hex-1-yne (0.18 mmol, 20.7
μL); heating 17 h; eluent: CH2Cl2–MeOH = 100 : 1. Yield 45.1
1
mg (86 %). Light-yellow oil; H NMR (400 MHz, CDCl3) δ
5.86 (m, 1H, 16-CH), 5.72 (s, 1H, 4-CH), 2.47–2.24 (m, 6H),
2.17 (ddd, J = 15.9, 6.6, 3.5 Hz, 1H), 2.04–1.93 (m, 2H), 1.89–
Steroidal vinyl iodides
1, 5 and 6 were prepared from the
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J. Name., 2012, 00, 1-3 | 7

Organic & Biomolecular Chemistry
View ArticlPe Oanglinee 8 of 13
DOI: 10.1039/C5OB00559K
ARTICLE
Journal Name
1.80 (m, 2H), 1.78–1.22 (m, 10H), 1.20 (s, 3H, 19-CH3), 1.16– HRMS (MALDI-TOF) calcd for C26H30NO [M+H]+ 372.2327;
0.95 (m, 2H), 0.91 (t, J = 7.3 Hz, 3H, CH2CH3), 0.86 (s, 3H, found 372.2318.
18-CH3); 13C NMR (100.6 MHz, CDCl3) δ 199.4 [C(3)=O], 17-[(quinolin-3-yl)ethynyl]androsta-4,16-dien-3-one
(2h).
1 (59.4 mg, 0.15 mmol) and 3-ethynylquinoline
171.1 (5-C), 137.6 (17-C), 133.3 (16-CH), 123.9 (4-CH), 93.9 Prepared from
(C≡C), 75.6 (C≡C), 55.3, 54.1, 47.6 (quat.), 38.7 (quat.), 35.5, (27.6 mg, 0.18 mmol); heating 24 h; eluent: hexanes–EtOAc =
34.33, 34.26, 33.9, 32.7, 31.74, 31.68, 30.9, 21.8, 20.8, 19.2, 2 : 1. Yield 55.1 mg (87 %). Off-white solid; mp 170–173 °C;
17.2, 16.0, 13.6 (CH2CH3); HRMS (MALDI-TOF) calcd for 1H NMR (400 MHz, CDCl3)
δ 8.90 [br. s, 1H, 2-
C25H35O [M+H]+ 351.2688; found 351.2697.
CH(quinoline)], 8.20 [s, 1H, 4-CH(quinoline)], 8.07 [d, J = 7.8
Hz, 1H, 5- or 8-CH(quinoline)], 7.76 [d, J = 7.8 Hz, 1H, 5- or
17-[(4-methoxyphenyl)ethynyl]androsta-4,16-dien-3-one
(2c). Prepared from
1 (59.4 mg, 0.15 mmol) and (4- 8-CH(quinoline)], 7.70 [t, J = 7.8 Hz, 1H, 6- or 7-
methoxyphenyl)acetylene (23.3 μL, 0.18 mmol); heating 24 h; CH(quinoline)], 7.54 [t, J = 7.8 Hz, 1H, 6- or 7-CH(quinoline)],
eluent: CH2Cl2–MeOH = 100 : 1. Yield 44.8 mg (75 %). White 6.19 (m, 1H, 16-CH), 5.74 (s, 1H, 4-CH), 2.49–2.25 (m, 5H),
solid; mp 221–223 °C; 1H NMR (400 MHz, CDCl3) δ 7.36 [d, J 2.16–1.40 (m, 10H), 1.22 (s, 3H, 19-CH3), 1.20–1.00 (m, 2H),
= 8.6 Hz, 2H, 2,6-CH(Ar)], 6.82 [d, J = 8.6 Hz, 2H, 3,5- 0.98 (s, 3H, 18-CH3); 13C NMR (100.6 MHz, CDCl3) δ 199.3
CH(Ar)], 6.03 (m, 1H, 16-CH), 5.73 (s, 1H, 4-CH), 3.79 (s, 3H, [C(3)=O], 170.7 (5-C), 152.2 [2-CH(quinoline)], 146.7 [8a-
CH3O), 2.48–2.20 (m, 5H), 2.11–1.35 (m, 10H), 1.21 (s, 3H, C(quinoline)], 137.9 [16-CH or 4-CH(quinoline)], 137.2 [16-
19-CH3), 1.18–0.98 (m, 2H), 0.93 (s, 3H, 18-CH3); 13C NMR CH or 4-CH(quinoline)], 136.6 (17-C), 129.9, 129.4, 127.5,
(100.6 MHz, CDCl3) δ 199.4 [C(3)=O], 171.0 (5-C), 159.4 [4- 127.2 [2C, CH(quinoline) + 4a-C(quinoline)], 124.0 (4-CH),
C(Ar)], 137.2 (17-C), 134.7 (16-CH), 132.9 [2C, 2,6-CH(Ar)], 117.7 [3-C(quinoline)], 90.2 (C≡C), 88.2 (C≡C), 55.5, 54.1,
123.9 (4-CH), 115.6 [1-C(Ar)], 113.8 [2C, 3,5-CH(Ar)], 92.9 48.1 (quat.), 38.7 (quat.), 35.6, 34.4 (2C), 33.9, 32.7, 32.2, 31.8,
(C≡C), 83.4 (C≡C), 55.4, 55.2 (CH3O), 54.1, 47.9 (quat.), 38.7 20.8, 17.2, 16.3; HRMS (MALDI-TOF) calcd for C30H32NO
(quat.), 35.5, 34.3 (2C), 33.9, 32.7, 32.0, 31.7, 20.8, 17.2, 16.2; [M+H]+ 422.2484; found 422.2486.
HRMS (MALDI-TOF) calcd for C28H33O2 [M+H]+ 401.2481; 17-[(1,3,5-trimethyl-1H-pyrazol-4-yl)ethynyl]androsta-4,16-
found 401.2482.
17-[(4-bromophenyl)ethynyl]androsta-4,16-dien-3-one (2d). ethynyl-1,3,5-trimethyl-1H-pyrazole (24.2 mg, 0.18 mmol);
Prepared from (59.4 mg, 0.15 mmol) and (4- heating 24 h; eluent: hexanes–EtOAc = 1 : 1. Yield 51.7 mg (86
dien-3-one (2i). Prepared from 1 (59.4 mg, 0.15 mmol) and 4-
1
1
bromophenyl)acetylene (32.6 mg, 0.18 mmol); heating 17 h; %). White solid; mp 190–193 °C; H NMR (400 MHz, CDCl3)
eluent: CH2Cl2–MeOH = 100 : 1. Yield 67.0 mg (99 %). White δ 5.95 (m, 1H, 16-CH), 5.72 (s, 1H, 4-CH), 3.68 (s, 3H, CH3N),
solid; mp 219–222 °C (dec.); H NMR (400 MHz, CDCl3) δ 2.48–2.18 (m, 5H), 2.26 [s, 3H, CH3C(pyrazole)], 2.23 [s, 3H,
1
7.44–7.40 [m, 2H, CH(Ar)], 7.30–7.26 [m, 2H, CH(Ar)], 6.10 CH3C(pyrazole)], 2.09–1.35 (m, 10H), 1.21 (s, 3H, 19-CH3),
(dd, J = 3.0, 2.0 Hz, 1H, 16-CH), 5.73 (s, 1H, 4-CH), 2.48–2.21 1.18–0.96 (m, 2H), 0.93 (s, 3H, 18-CH3); 13C NMR (100.6
(m, 5H), 2.11–1.37 (m, 10H), 1.21 (s, 3H, 19-CH3), 1.19–0.97 MHz, CDCl3) δ 199.3 [C(3)=O], 170.9 (5-C), 149.2 [3-
(m, 2H), 0.93 (s, 3H, 18-CH3); 13C NMR (100.6 MHz, CDCl3) C(pyrazole)], 141.4 [5-C(pyrazole)], 137.4 (17-C), 133.1 (16-
δ 199.4 [C(3)=O], 170.8 (5-C), 136.8 (17-C), 136.3 (16-CH), CH), 123.9 (4-CH), 102.0 [4-C(pyrazole)], 87.9 (C≡C), 84.9
132.9 [2C, CH(Ar)], 131.5 [2C, CH(Ar)], 124.0 (4-CH), 122.5 (C≡C), 55.4, 54.1, 47.8 (quat.), 38.7 (quat.), 36.0 (CH3N), 35.5,
[1- or 4-C(Ar)], 122.1 [1- or 4-C(Ar)], 91.9 (C≡C), 86.0 (C≡C), 34.3 (2C), 33.9, 32.7, 31.9, 31.7, 20.8, 17.1, 16.2, 12.3
55.5, 54.1, 48.0 (quat.), 38.7 (quat.), 35.5, 34.3 (2C), 33.9, 32.7, [CH3C(pyrazole)], 10.4 [CH3C(pyrazole)]; HRMS (MALDI-
32.1, 31.7, 20.8, 17.2, 16.3; HRMS (MALDI-TOF) calcd for TOF) calcd for C27H35N2O [M+H]+ 403.2749; found 403.2757;
C27H30BrO [M+H]+ 449.1480; found 449.1494.
Anal. calcd for C27H34N2O: C, 80.55; H, 8.51; N, 6.96; found
17-[(pyridin-2-yl)ethynyl]androsta-4,16-dien-3-one
(2g). C, 80.26; H, 8.65; N, 6.71.
Prepared from
1
(59.4 mg, 0.15 mmol) and 2-ethynylpyridine 17-[(2-aminophenyl)ethynyl]androsta-4,16-dien-3-one (2j).
(118.8 mg, 0.30 mmol) and 2-ethynylaniline
(18.6 mg, 0.18 mmol); heating 20 h; eluent: hexanes–EtOAc = Prepared from
2 : 1. Yield 47.2 mg (85 %). White solid; mp 204–205 °C; H (41.0 μL, 0.36 mmol); heating 24 h; eluent: CH2Cl2–MeOH =
NMR (400 MHz, CDCl3) δ 8.57 [d, J = 4.6 Hz, 1H, 6- 200 : 1. Yield 108.3 mg (94 %). Off-white solid; mp 217–219
1
1
1
CH(pyridine)], 7.62 [td, J = 7.7, 1.8 Hz, 1H, 4-CH(pyridine)], °C; H NMR (400 MHz, CDCl3) δ 7.27 [dd, J = 7.6, 1.1 Hz,
7.41 [d, J = 7.7 Hz, 1H, 3-CH(pyridine)], 7.18 [dd, J = 7.7, 4.6 1H, 6-CH(Ar)], 7.13–7.06 [m, 1H, 4-CH(Ar)], 6.74–6.65 [m,
Hz, 1H, 5-CH(pyridine)], 6.22 (m, 1H, 16-CH), 5.73 (s, 1H, 4- 2H, 3- and 5-CH(Ar)], 6.07 (dd, J = 2.8, 2.0 Hz, 1H, 16-CH),
CH), 2.49–2.23 (m, 5H), 2.14–1.39 (m, 10H), 1.21 (s, 3H, 19- 5.73 (s, 1H, 4-CH), 4.36 (br. s, 2H, NH2), 2.49–2.21 (m, 5H),
CH3), 1.19–0.98 (m, 2H), 0.96 (s, 3H, 18-CH3); 13C NMR 2.13–1.38 (m, 10H), 1.21 (s, 3H, 19-CH3), 1.19–0.97 (m, 2H),
(100.6 MHz, CDCl3) δ 199.3 [C(3)=O], 170.8 (5-C), 150.0 [6- 0.95 (s, 3H, 18-CH3); 13C NMR (100.6 MHz, CDCl3) δ 199.5
CH(pyridine)], 143.7 [2-C(pyridine)], 138.1 [16-CH or 4- [C(3)=O], 171.0 (5-C), 147.4 [2-C(Ar)], 136.9 (17-C), 135.1
CH(pyridine)], 136.3 (17-C), 135.9 [16-CH or 4-CH(pyridine)], (16-CH), 132.0 [4- or 6-CH(Ar)], 129.4 [4- or 6-CH(Ar)],
127.1 [3-CH(pyridine)], 124.0 (4-CH), 122.4 [5-CH(pyridine)], 124.0 (4-CH), 117.9 [3- or 5-CH(Ar)], 114.2 [3- or 5-CH(Ar)],
92.2 (C≡C), 84.9 (C≡C), 55.5, 54.1, 48.1 (quat.), 38.7 (quat.), 108.3 [1-C(Ar)], 90.1 (C≡C), 89.3 (C≡C), 55.4, 54.1, 47.9
35.5, 34.33, 34.27, 33.9, 32.7, 32.2, 31.7, 20.7, 17.2, 16.2; (quat.), 38.7 (quat.), 35.5, 34.4, 34.3, 33.9, 32.7, 32.1, 31.7,
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

View Article Online
DOI: 10.1039/C5OB00559K
Page 9 of 13
Journal Name
Organic & Biomolecular Chemistry
ARTICLE
20.8, 17.2, 16.3; HRMS (MALDI-TOF) calcd for C27H32NO 48.0 (quat.), 38.7 (quat.), 35.5, 34.4, 34.3, 33.9, 32.7, 32.2,
[M+H]+ 386.2484; found 386.2479.
31.7, 20.8, 17.2, 16.3.
17-[(2-amino-5-methylphenyl)ethynyl]androsta-4,16-dien-3- 17-(5-nitro-1H-indol-2-yl)androsta-4,16-dien-3-one (4d). 1H
one (2k). Prepared from (118.8 mg, 0.30 mmol) and 2- NMR (400 MHz, CDCl3) δ 9.11 (br. s, 1H, NH), 8.48 [d, J =
1
ethynyl-4-methylaniline (47.2 mg, 0.36 mmol); heating 24 h; 2.2 Hz, 1H, 4-CH(indole)], 8.03 [dd, J = 8.9, 2.2 Hz, 1H, 6-
eluent: CH2Cl2–MeOH = 200 : 1. Yield 101.6 mg (85 %). Off- CH(indole)], 7.32 [d, J = 8.9 Hz, 1H, 7-CH(indole)], 6.62 [d, J
1
white solid; mp 160–163 °C; H NMR (400 MHz, CDCl3) δ = 1.1 Hz, 1H, 3-CH(indole)], 6.13 (dd, J = 3.0, 1.8 Hz, 1H, 16-
7.07 [d, J = 2.4 Hz, 1H, 6-CH(Ar)], 6.89 [dd, J = 8.2, 2.4 Hz, CH), 5.74 (s, 1H, 4-CH), 2.51–2.25 (m, 6H), 2.16–1.38 (m,
1H, 4-CH(Ar)], 6.59 [d, J = 8.2 Hz, 1H, 3-CH(Ar)], 6.03 (dd, J 9H), 1.24 (s, 3H, 19-CH3), 1.17–0.98 (m, 2H), 1.08 (s, 3H, 18-
= 3.1, 2.0 Hz, 1H, 16-CH), 5.72 (s, 1H, 4-CH), 4.08 (br. s, 2H, CH3); 13C NMR (100.6 MHz, CDCl3) δ 199.7 [C(3)=O], 171.1
NH2), 2.47–2.19 (m, 5H), 2.18 [s, 3H, CH3C(Ar)], 2.10–1.36 (5-C), 145.4 (quat.), 141.7 (quat.), 139.3 (quat.), 137.1 (quat.),
(m, 10H), 1.19 (s, 3H, 19-CH3), 1.16–0.96 (m, 2H), 0.93 (s, 3H, 128.3 (quat.), 127.3, 123.9 (4-CH), 117.8, 117.4, 110.2 [7-
18-CH3); 13C NMR (100.6 MHz, CDCl3) δ 199.3 [C(3)=O], CH(indole)], 101.3 [3-CH(indole)], 56.3, 54.0, 46.9 (quat.),
170.9 (5-C), 145.1 [2-C(Ar)], 136.9 (17-C), 134.8 (16-CH), 38.7 (quat.), 35.5, 35.3, 33.9 (2C), 32.7, 31.7, 31.6, 20.9, 17.2,
132.0 [4- or 6-CH(Ar)], 130.2 [4- or 6-CH(Ar)], 127.0 [5- 16.6.
C(Ar)], 123.9 (4-CH), 114.3 [3-CH(Ar)], 108.2 [1-C(Ar)], 89.8 17-[3-(diethylamino)prop-1-yn-1-yl]androsta-4,16-dien-3-
(C≡C), 89.5 (C≡C), 55.3, 54.0, 47.8 (quat.), 38.6 (quat.), 35.4, one (2o). Prepared from
1 (59.4 mg, 0.15 mmol) and
34.4, 34.3, 33.9, 32.7, 32.0, 31.7, 20.8, 20.2 [CH3C(Ar)], 17.1, diethylpropargylamine (25.0 μL, 0.18 mmol); heating 48 h;
16.2; HRMS (MALDI-TOF) calcd for C28H34NO [M+H]+ eluent: CH2Cl2–MeOH = 20 : 1. Yield 38.8 mg (68 %). Yellow
1
400.2640; found 400.2632.
oil; H NMR (400 MHz, CDCl3) δ 5.93 (m, 1H, 16-CH), 5.73
(s, 1H, 4-CH), 3.60 (s, 2H, CH2NEt2), 2.55 [q, J = 7.2 Hz, 4H,
17-[(2-amino-5-chlorophenyl)ethynyl]androsta-4,16-dien-3-
one (2l). Prepared from
1 (118.8 mg, 0.30 mmol) and 2- N(CH2CH3)2], 2.47–2.25 (m, 4H), 2.20 (ddd, J = 16.0, 6.6, 3.4
ethynyl-4-chloroaniline (54.6 mg, 0.36 mmol); heating 24 h; Hz, 1H), 2.06–1.96 (m, 2H), 1.90–1.81 (m, 2H), 1.79–1.61 (m,
eluent: CH2Cl2–MeOH = 200 : 1. Yield 113.0 mg (90 %). Off- 3H), 1.52 (qd, J = 12.8, 4.3 Hz, 1H), 1.42–1.31 (m, 2H), 1.20
1
white solid; mp 148–150 °C; H NMR (400 MHz, CDCl3) δ (s, 3H, 19-CH3), 1.17–0.95 (m, 2H), 1.08 [t, J = 7.2 Hz, 6H,
7.21 [d, J = 2.5 Hz, 1H, 6-CH(Ar)], 7.02 [dd, J = 8.6, 2.5 Hz, N(CH2CH3)2], 0.88 (s, 3H, 18-CH3); 13C NMR (100.6 MHz,
1H, 4-CH(Ar)], 6.60 [d, J = 8.6 Hz, 1H, 3-CH(Ar)], 6.08 (dd, J CDCl3) δ 199.4 [C(3)=O], 170.9 (5-C), 136.9 (17-C), 134.5
= 3.1, 2.0 Hz, 1H, 16-CH), 5.72 (s, 1H, 4-CH), 4.23 (br. s, 2H, (16-CH), 123.9 (4-CH), 87.1 (C≡C), 80.3 (C≡C), 55.3, 54.1,
NH2), 2.47–2.21 (m, 5H), 2.12–1.36 (m, 10H), 1.20 (s, 3H, 19- 47.6 (quat.), 47.2 [2C, N(CH2CH3)2], 41.2 (CH2NEt2), 38.7
CH3), 1.17–0.96 (m, 2H), 0.93 (s, 3H, 18-CH3); 13C NMR (quat.), 35.5, 34.3 (2C), 33.9, 32.7, 31.8, 31.7, 20.8, 17.1, 16.1,
(100.6 MHz, CDCl3) δ 199.4 [C(3)=O], 170.8 (5-C), 146.0 [2- 12.6 [2C, N(CH2CH3)2]; HRMS (MALDI-TOF) calcd for
C(Ar)], 136.5 (17-C), 136.0 (16-CH), 131.1 [4- or 6-CH(Ar)], C26H38NO [M+H]+ 380.2953; found 380.2970.
129.3 [4- or 6-CH(Ar)], 123.9 (4-CH), 122.0 [5-CCl(Ar)], 17-[(pyridin-3-yl)ethynyl]androsta-4,16-dien-3-one
(2p).
115.2 [3-CH(Ar)], 109.5 [1-C(Ar)], 91.1 (C≡C), 88.0 (C≡C), Prepared from (59.4 mg, 0.15 mmol) and 3-
1
55.4, 54.0, 47.9 (quat.), 38.6 (quat.), 35.4, 34.3, 34.2, 33.9, [(trimethylsilyl)ethynyl]pyridine (34.2 μL, 0.18 mmol); heating
32.6, 32.1, 31.6, 20.7, 17.1, 16.2; HRMS (MALDI-TOF) calcd 24 h; eluent: hexanes–EtOAc = 2 : 1. Yield 51.1 mg (92 %).
for C27H31ClNO [M+H]+ 420.2094; found 420.2102.
17-[(2-amino-5-nitrophenyl)ethynyl]androsta-4,16-dien-3-
Colorless crystals; mp 214–215 °C; 1H NMR (400 MHz,
CDCl3) δ 8.66 [br. s, 1H, 2-CH(pyridine)], 8.50 [br. d, J = 5.0
one (2m) and 17-(5-nitro-1H-indol-2-yl)androsta-4,16-dien- Hz, 1H, 6-CH(pyridine)], 7.70 [d, J = 7.6 Hz, 1H, 4-
3-one (4d). Prepared from (118.8 mg, 0.30 mmol) and 2- CH(pyridine)], 7.23 [dd, J = 7.6, 5.0 Hz, 1H, 5-CH(pyridine)],
1
ethynyl-4-nitroaniline (58.4 mg, 0.36 mmol); heating 24 h; 6.15 (m, 1H, 16-CH), 5.73 (s, 1H, 4-CH), 2.49–2.23 (m, 5H),
eluent: CH2Cl2–MeOH = 50 : 1. A 46 : 54 inseparable mixture 2.15–1.38 (m, 10H), 1.22 (s, 3H, 19-CH3), 1.19–0.98 (m, 2H),
of 2m and 4d was obtained. Yield 124.5 mg (96 %). Yellow oil. 0.95 (s, 3H, 18-CH3); 13C NMR (100.6 MHz, CDCl3) δ 199.3
HRMS (MALDI-TOF) calcd for C27H31N2O3 [M+H]+ [C(3)=O], 170.7 (5-C), 152.1 [2-CH(pyridine)], 148.2 [6-
431.2335; found 431.2342.
17-[(2-amino-5-nitrophenyl)ethynyl]androsta-4,16-dien-3-
CH(pyridine)], 138.3 [16-CH or 4-CH(pyridine)], 137.1 [16-
CH or 4-CH(pyridine)], 136.5 (17-C), 124.0 (4-CH), 122.9 [5-
one (2m). 1H NMR (400 MHz, CDCl3) δ 8.18 [d, J = 2.6 Hz, CH(pyridine)], 120.7 [3-C(pyridine)], 89.4 (C≡C), 88.2 (C≡C),
1H, 6-CH(Ar)], 7.98 [dd, J = 9.0, 2.6 Hz, 1H, 4-CH(Ar)], 6.67 55.4, 54.1, 48.0 (quat.), 38.7 (quat.), 35.5, 34.32, 34.28, 33.9,
[d, J = 9.0 Hz, 1H, 3-CH(Ar)], 6.15 (dd, J = 3.3, 2.0 Hz, 1H, 32.7, 32.2, 31.7, 20.8, 17.2, 16.2; HRMS (MALDI-TOF) calcd
16-CH), 5.74 (s, 1H, 4-CH), 5.04 (br. s, 2H, NH2), 2.50–2.25 for C26H30NO [M+H]+ 372.2327; found 372.2330.
(m, 5H), 2.15–1.38 (m, 10H), 1.22 (s, 3H, 19-CH3), 1.17–0.98 17-(1H-indol-2-yl)androsta-4,16-dien-3-one (4a). Prepared
(m, 2H), 0.95 (s, 3H, 18-CH3); 13C NMR (100.6 MHz, CDCl3) from 2j (57.8 mg, 0.15 mmol); heating 24 h; eluent: CH2Cl2–
δ 199.6 [C(3)=O], 171.1 (5-C), 152.7 [2-C(Ar)], 138.3 [17-C or MeOH = 100 : 1. Yield 52.2 mg (90 %). Off-white solid; mp
1
5-C(Ar)], 137.2, 136.1 [17-C or 5-C(Ar)], 128.5 [4- or 6- 195–198 °C; H NMR (400 MHz, CDCl3) δ 8.88 (br. s, 1H,
CH(Ar)], 125.7 [4- or 6-CH(Ar)], 123.9 (4-CH), 112.7 [3- NH), 7.52 [d, J = 7.7 Hz, 1H, 4- or 7-CH(indole)], 7.31–7.27
CH(Ar)], 107.5 [1-C(Ar)], 91.8 (C≡C), 86.8 (C≡C), 55.4, 54.1, [m, 1H, 4- or 7-CH(indole)], 7.13–7.07 [m, 1H, 5- or 6-
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DOI: 10.1039/C5OB00559K
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CH(indole)], 7.05–6.99 [m, 1H, 5- or 6-CH(indole)], 6.48 [d, J (5-C), 135.5 (4-CH), 131.4 [2C, 2,6-CH(Ph)], 128.2 [2C, 3,5-
= 1.5 Hz, 1H, 3-CH(indole)], 6.01 (dd, J = 3.0, 1.9 Hz, 1H, 16- CH(Ph)], 127.8 [4-CH(Ph)], 126.1 (6-CH), 123.7 [1-C(Ph)],
CH), 5.73 (s, 1H, 4-CH), 2.48–2.23 (m, 6H), 2.11–1.48 (m, 117.2 (3-C), 91.5 (C≡C), 89.3 (C≡C), 81.8 (17-CHOH), 51.4,
9H), 1.21 (s, 3H, 19-CH3), 1.17–0.97 (m, 2H), 1.06 (s, 3H, 18- 48.2, 42.8 (quat.), 36.5, 34.6 (quat.), 33.6, 31.8, 31.6, 30.5,
CH3); 13C NMR (100.6 MHz, CDCl3) δ 199.5 [C(3)=O], 171.2 27.0, 23.3, 20.6, 19.1, 11.0; HRMS (MALDI-TOF) calcd for
(5-C), 146.1 (quat.), 136.1 (quat.), 133.8 (quat.), 128.7 [3a- C27H32O [M]+ 372.2453; found 372.2446; Anal. calcd for
C(indole)], 124.7, 123.7, 121.8, 120.1, 119.4, 110.3 [7- C27H32O: C, 87.05; H, 8.66; found C, 87.27; H, 8.66.
CH(indole)], 99.5 [3-CH(indole)], 56.1, 53.8, 46.7 (quat.), 38.5 3-[(4-bromophenyl)ethynyl]androsta-3,5-dien-17β-ol (7b).
(quat.), 35.30, 35.28, 33.8 (2C), 32.6, 31.6, 31.3, 20.8, 17.0, Prepared from
16.5; HRMS (MALDI-TOF) calcd for C27H31NO [M]+ bromophenyl)acetylene (32.6 mg, 0.18 mmol); heating 17 h;
385.2406; found 385.2397. eluent: CH2Cl2–MeOH = 100 : 1. Yield 66.4 mg (98 %). White
5
(59.7 mg, 0.15 mmol) and (4-
1
17-(5-methyl-1H-indol-2-yl)androsta-4,16-dien-3-one (4b). solid; mp 109–113 °C; H NMR (400 MHz, CDCl3) δ 7.44–
Prepared from 2k (59.9 mg, 0.15 mmol); heating 24 h; eluent: 7.38 [m, 2H, CH(Ar)], 7.29–7.23 [m, 2H, CH(Ar)], 6.36 (s, 1H,
CH2Cl2–MeOH = 100 : 1. Yield 44.3 mg (74 %). Yellowish oil; 4-CH), 5.53 (m, 1H, 6-CH), 3.64 (t, J = 8.5 Hz, 1H, 17-
1H NMR (400 MHz, CDCl3) δ 8.08 (br. s, 1H, NH), 7.31 [s, CHOH), 2.45–2.17 (m, 3H), 2.06 (m, 1H), 1.90–1.79 (m, 2H),
1H, 4-CH(indole)], 7.17 [d, J = 7.9 Hz, 1H, 6- or 7- 1.76–0.93 (m, 12H), 0.96 (s, 3H, 19-CH3), 0.77 (s, 3H, 18-
CH(indole)], 6.94 [d, J = 7.9 Hz, 1H, 6- or 7-CH(indole)], 6.41 CH3); 13C NMR (100.6 MHz, CDCl3) δ 141.4 (5-C), 135.9 (4-
[s, 1H, 3-CH(indole)], 5.91 (m, 1H, 16-CH), 5.73 (s, 1H, 4- CH), 132.8 [2C, CH(Ar)], 131.5 [2C, CH(Ar)], 126.5 (6-CH),
CH), 2.51–2.19 (m, 6H), 2.39 [s, 3H, CH3C(indole)], 2.11–1.46 122.7 [1- or 4-C(Ar)], 121.9 [1- or 4-C(Ar)], 116.9 (3-C), 92.7
(m, 9H), 1.21 (s, 3H, 19-CH3), 1.17–0.96 (m, 2H), 1.05 (s, 3H, (C≡C), 88.3 (C≡C), 81.8 (17-CHOH), 51.4, 48.2, 42.9 (quat.),
18-CH3); 13C NMR (100.6 MHz, CDCl3) δ 199.6 [C(3)=O], 36.5, 34.6 (quat.), 33.5, 31.8, 31.7, 30.5, 26.8, 23.3, 20.6, 19.1,
171.1 (5-C), 146.4 (quat.), 134.4 (quat.), 133.9 (quat.), 129.1 11.0; HRMS (MALDI-TOF) calcd for C27H32BrO [M+H]+
[3a- or 5-C(indole)], 128.9 [3a- or 5-C(indole)], 124.3, 123.9, 451.1637; found 451.1676.
123.8, 120.0, 110.0 [7-CH(indole)], 99.6 [3-CH(indole)], 56.2, 3-{[2-(methoxycarbonyl)phenyl]ethynyl}androsta-3,5-dien-
54.0, 46.9 (quat.), 38.7 (quat.), 35.5, 35.4, 34.0, 33.9, 32.7, 17β-ol (7c). Prepared from
5 (59.7 mg, 0.15 mmol) and methyl
31.7, 31.4, 21.4 [CH3C(indole)], 21.0, 17.2, 16.6; HRMS 2-ethynylbenzoate (28.8 mg, 0.18 mmol); heating 24 h; eluent:
(MALDI-TOF) calcd for C28H34NO [M+H]+ 400.2640; found CH2Cl2–MeOH = 50 : 1. Yield 53.6 mg (83 %). White solid;
400.2651.
mp 149–151 °C; 1H NMR (400 MHz, CDCl3) δ 7.91 [d, J = 7.8
17-(5-chloro-1H-indol-2-yl)androsta-4,16-dien-3-one
(4c). Hz, 1H, 3-CH(Ar)], 7.52 [d, J = 7.6 Hz, 1H, 6-CH(Ar)], 7.46–
Prepared from 2l (63.0 mg, 0.15 mmol); heating 24 h; eluent: 7.38 [m, 1H, 4- or 5-CH(Ar)], 7.34–7.28 [m, 1H, 4- or 5-
CH2Cl2–MeOH = 100 : 1. Yield 54.2 mg (86 %). Yellowish oil; CH(Ar)], 6.41 (s, 1H, 4-CH), 5.55 (m, 1H, 6-CH), 3.92 (s, 3H,
1H NMR (400 MHz, CDCl3–DMSO-d6) δ 10.10 (br. s, 1H, CH3O), 3.65 (t, J = 8.4 Hz, 1H, 17-CHOH), 2.49–2.17 (m, 3H),
NH), 7.44 [d, J = 2.0 Hz, 1H, 4-CH(indole)], 7.24 [d, J = 8.5 2.06 (m, 1H), 1.90–1.81 (m, 2H), 1.76–0.95 (m, 12H), 0.98 (s,
Hz, 1H, 7-CH(indole)], 7.01 [dd, J = 8.5, 2.0 Hz, 1H, 6- 3H, 19-CH3), 0.77 (s, 3H, 18-CH3); 13C NMR (100.6 MHz,
CH(indole)], 6.39 [d, J = 1.5 Hz, 1H, 3-CH(indole)], 6.16 (dd, J CDCl3) δ 166.8 (CO2Me), 141.5 (5-C), 136.2, 133.8, 131.53,
= 3.1, 2.0 Hz, 1H, 16-CH), 5.71 (s, 1H, 4-CH), 2.51–2.22 (m, 131.46 [2-C(Ar)], 130.4, 127.3, 126.5, 124.2 [1-C(Ar)], 117.4
6H), 2.12–1.98 (m, 2H), 1.94–1.86 (m, 1H), 1.81 (qd, J = 11.1, (3-C), 96.7 (C≡C), 88.3 (C≡C), 81.8 (17-CHOH), 52.0 (CH3O),
3.2 Hz, 1H), 1.74–1.47 (m, 5H), 1.23 (s, 3H, 19-CH3), 1.20– 51.5, 48.2, 42.9 (quat.), 36.5, 34.6 (quat.), 33.6, 31.8, 31.7,
0.97 (m, 2H), 1.05 (s, 3H, 18-CH3); 13C NMR (100.6 MHz, 30.5, 26.8, 23.3, 20.6, 19.1, 11.0; HRMS (MALDI-TOF) calcd
CDCl3–DMSO-d6) δ 198.8 [C(3)=O], 170.7 (5-C), 145.5 for C29H35O3 [M+H]+ 431.2586; found 431.2593.
(quat.), 135.2 (quat.), 134.5 (quat.), 129.4 [3a-C(indole)], 3-(hex-1-yn-1-yl)androsta-3,5-dien-17β-ol (7d). Prepared
125.6, 124.0 [5-C(indole)], 123.3, 121.2, 118.8, 111.2 [7- from
5 (59.7 mg, 0.15 mmol) and hex-1-yne (20.7 μL, 0.18
CH(indole)], 98.2 [3-CH(indole)], 55.8, 53.4, 46.3 (quat.), 38.2 mmol); heating 17 h; eluent: CH2Cl2–MeOH = 100 : 1. Yield
(quat.), 35.0, 34.9, 33.44, 33.41, 32.2, 31.2, 31.0, 20.5, 16.7, 50.1 mg (95 %). Light-yellow oil; 1H NMR (400 MHz, CDCl3)
16.1; HRMS (MALDI-TOF) calcd for C27H30ClNO [M]+ δ 6.16 (c, 1H, 4-CH), 5.42 (m, 1H, 6-CH), 3.63 (t, J = 8.5 Hz,
419.2016; found 419.2028.
1H, 17-CHOH), 2.31 (t, J = 6.9 Hz, 2H, CH2Pr), 2.28–2.00 (m,
3-(phenylethynyl)androsta-3,5-dien-17β-ol (7a). Prepared 4H), 1.86–1.75 (m, 2H), 1.72–0.94 (m, 16H), 0.93 (s, 3H, 19-
from
5 (59.7 mg, 0.15 mmol) and phenylacetylene (19.8 μL, CH3), 0.90 (t, J = 7.1 Hz, 3H, CH2CH3), 0.76 (s, 3H, 18-CH3);
0.18 mmol) without addition of TMEDA; heating 14 h; eluent: 13C NMR (100.6 MHz, CDCl3) δ 141.4 (5-C), 133.9 (4-CH),
CH2Cl2–MeOH = 100 : 1. Yield 55.8 mg (100 %). White solid; 124.6 (6-CH), 117.9 (3-C), 90.1 (C≡C), 82.4 (C≡C), 81.8 (17-
1
mp 192–193 °C; H NMR (400 MHz, CDCl3) δ 7.44–7.38 [m, CHOH), 51.5, 48.2, 42.9 (quat.), 36.5, 34.6 (quat.), 33.7, 31.8,
2H, 2,6-CH(Ph)], 7.32–7.22 [m, 3H, 3,4,5-CH(Ph)], 6.36 (s, 31.5, 31.0, 30.5, 27.4, 23.3, 21.9, 20.6, 19.2, 19.0, 13.6
1H, 4-CH), 5.52 (m, 1H, 6-CH), 3.64 (t, J = 8.4 Hz, 1H, 17- (CH2CH3), 11.0; HRMS (MALDI-TOF) calcd for C25H36O
CHOH), 2.45–2.16 (m, 3H), 2.06 (m, 1H), 1.89–1.79 (m, 2H), [M]+ 352.2766; found 352.2760.
1.75–1.55 (m, 4H), 1.50–0.92 (m, 8H), 0.97 (s, 3H, 19-CH3), 3-[3-(diethylamino)prop-1-yn-1-yl]androsta-3,5-dien-17β-ol
0.77 (s, 3H, 18-CH3); 13C NMR (100.6 MHz, CDCl3) δ 141.4 (7e). Prepared from
5
(59.7 mg, 0.15 mmol) and
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Organic & Biomolecular Chemistry
ARTICLE
diethylpropargylamine (25.0 μL, 0.18 mmol); heating 24 h; 7.43–7.37 [m, 2H, CH(Ar)], 7.29–7.23 [m, 2H, CH(Ar)], 6.36
eluent: CH2Cl2–MeOH = 20 : 1. Yield 55.7 mg (97 %). Light- (s, 1H, 4-CH), 5.54 (m, 1H, 6-CH), 2.43–2.16 (m, 3H), 2.01 (m,
1
yellow solid; mp 151–153 °C; H NMR (400 MHz, CDCl3) δ 1H), 1.89–1.77 (m, 2H), 1.75–0.80 (m, 20H), 0.94 (s, 3H, 19-
6.21 (s, 1H, 4-CH), 5.45 (m, 1H, 6-CH), 3.63 (t, J = 8.5 Hz, 1H, CH3), 0.91 (d, J = 6.6 Hz, 3H, 21-CH3), 0.854 (d, J = 6.6 Hz,
17-CHOH), 3.56 (s, 2H, CH2NEt2), 2.57 [q, J = 7.1 Hz, 4H, 3H, 26- or 27-CH3), 0.850 (d, J = 6.6 Hz, 3H, 26- or 27-CH3),
N(CH2CH3)2], 2.35–2.12 (m, 3H), 2.05 (m, 1H), 1.87–1.76 (m, 0.69 (s, 3H, 18-CH3); 13C NMR (100.6 MHz, CDCl3) δ 141.3
2H), 1.73–1.54 (m, 4H), 1.50–0.91 (m, 8H), 1.08 [t, J = 7.1 Hz, (5-C), 136.1 (4-CH), 132.8 [2C, CH(Ar)], 131.5 [2C, CH(Ar)],
6H, N(CH2CH3)2], 0.93 (s, 3H, 19-CH3), 0.77 (s, 3H, 18-CH3); 127.0 (6-CH), 122.8 [1- or 4-C(Ar)], 121.8 [1- or 4-C(Ar)],
13C NMR (100.6 MHz, CDCl3) δ 141.3 (5-C), 134.7 (4-CH), 116.8 (3-C), 92.8 (C≡C), 88.1 (C≡C), 56.8, 56.1, 48.1, 42.4
125.3 (6-CH), 117.2 (3-C), 87.1 (C≡C), 83.5 (C≡C), 81.7 (17- (quat.), 39.7, 39.5, 36.2, 35.8, 34.5 (quat.), 33.5, 32.1, 31.7,
CHOH), 51.4, 48.2, 47.2 [2C, N(CH2CH3)2], 42.8 (quat.), 41.4 28.2, 28.0, 26.9, 24.2, 23.9, 22.8, 22.6, 21.0, 19.1, 18.7, 12.0;
(CH2NEt2), 36.5, 34.5 (quat.), 33.6, 31.7, 31.5, 30.5, 27.2, 23.3, HRMS (MALDI-TOF) calcd for C35H48Br [M+H]+ 547.2939;
20.6, 19.0, 12.4 [2C, N(CH2CH3)2], 11.0; HRMS (MALDI- found 547.2944; Anal. calcd for C35H47Br: C, 76.76; H, 8.65;
TOF) calcd for C26H40NO [M+H]+ 382.3110; found 382.3104.
found C, 76.38; H, 8.52.
3-[3-(4-carboxyphenoxy)prop-1-yn-1-yl]androsta-3,5-dien-
3-{[4-(dimethylamino)phenyl]ethynyl}cholesta-3,5-diene
17β-ol (7f). Prepared from
5 (29.9 mg, 0.075 mmol) and 4- (8c). Prepared from 6 (74.2 mg, 0.15 mmol) and [4-
(prop-2-yn-1-yloxy)benzoic acid (15.9 mg, 0.090 mmol) in the (dimethylamino)phenyl]acetylene (26.1 mg, 0.18 mmol);
presence of 3 equiv. K2CO3 (31.1 mg, 0.225 mmol); heating 66 heating 21 h; eluent: hexanes–EtOAc = 4 : 1. Yield 67.0 mg (87
1
h; eluent: CH2Cl2–MeOH = 10 : 1. Yield 26.4 mg (79 %). %). White solid; mp 217–220 °C; H NMR (400 MHz, CDCl3)
1
White solid; mp 205–208 °C; H NMR (400 MHz, CDCl3– δ 7.32–7.27 [m, 2H, 2,6-CH(Ar)], 6.65–6.58 [m, 2H, 3,5-
CD3OD) δ 8.03–7.97 [m, 2H, 3,5-CH(Ar)], 7.02–6.96 [m, 2H, CH(Ar)], 6.29 (s, 1H, 4-CH), 5.48 (m, 1H, 6-CH), 2.95 [c, 6H,
2,6-CH(Ar)], 6.26 (s, 1H, 4-CH), 5.49 (m, 1H, 6-CH), 4.87 (s, N(CH3)2], 2.43–2.14 (m, 3H), 2.01 (m, 1H), 1.87–1.77 (m, 2H),
2H, CH2O), 3.64 (t, J = 8.6 Hz, 1H, 17-CHOH), 2.46 (br. s, 2H, 1.75–0.77 (m, 20H), 0.95 (s, 3H, 19-CH3), 0.91 (d, J = 6.5 Hz,
OH), 2.33–1.94 (m, 4H), 1.86–1.75 (m, 2H), 1.72–0.93 (m, 3H, 21-CH3), 0.854 (d, J = 6.6 Hz, 3H, 26- or 27-CH3), 0.850
11H), 0.91 (s, 3H, 19-CH3), 0.75 (s, 3H, 18-CH3); 13C NMR (d, J = 6.6 Hz, 3H, 26- or 27-CH3), 0.69 (s, 3H, 18-CH3); 13C
(100.6 MHz, CDCl3–CD3OD) δ 168.7 (CO2H), 161.6 [1- NMR (100.6 MHz, CDCl3) δ 149.7 [4-C(Ar)], 141.6 (5-C),
C(Ar)], 141.0 (5-C), 136.5 (4-CH), 131.8 [2C, 3,5-CH(Ar)], 134.1 (4-CH), 132.5 [2C, 2,6-CH(Ar)], 125.4 (6-CH), 117.8 (3-
126.7 (6-CH), 123.1 [4-C(Ar)], 116.0 (3-C), 114.5 [2C, 2,6- C), 111.9 [2C, 3,5-CH(Ar)], 110.7 [1-C(Ar)], 90.3 (C≡C), 89.5
CH(Ar)], 89.7 (C≡C), 82.6 (C≡C), 81.5 (17-CHOH), 56.8 (C≡C), 56.9, 56.2, 48.1, 42.5 (quat.), 40.2 [2C, N(CH3)2], 39.8,
(CH2O), 51.4, 48.1, 42.8 (quat.), 36.4, 34.5 (quat.), 33.4, 31.7, 39.5, 36.2, 35.8, 34.6 (quat.), 33.7, 32.1, 31.8, 28.2, 28.0, 27.2,
31.5, 30.1, 26.6, 23.2, 20.5, 19.0, 11.0; HRMS (MALDI-TOF) 24.2, 23.9, 22.8, 22.6, 21.0, 19.1, 18.7, 12.0; HRMS (MALDI-
calcd for C29H33Na2O4 [M-H+2Na]+ 491.2180; found 491.2158. TOF) calcd for C37H53N [M]+ 511.4178; found 511.4117; Anal.
3-(phenylethynyl)cholesta-3,5-diene (8a). Prepared from
6
calcd for C37H53N: C, 86.83; H, 10.44; N, 2.74; found C, 86.47;
(74.2 mg, 0.15 mmol) and phenylacetylene (19.8 μL, 0.18 H, 10.35; N, 2.53.
mmol) without addition of TMEDA; heating 20 h; eluent: 3-[(2-aminophenyl)ethynyl)]cholesta-3,5-diene
(8d).
hexanes–EtOAc = 50 : 1. Yield 63.5 mg (90 %). Light-yellow Prepared from
6 (74.2 mg, 0.15 mmol) and 2-ethynylaniline
solid; mp 147–148 °C (lit.,34 150–152 °C); 1H NMR (400 MHz, (20.5 μL, 0.18 mmol); heating 24 h; eluent: hexanes–EtOAc =
CDCl3) δ 7.45–7.37 [m, 2H, 2,6-CH(Ph)], 7.31–7.21 [m, 3H, 15 : 1. Yield 58.3 mg (80 %). White solid; mp 203–205 °C
3,4,5-CH(Ph)], 6.36 (s, 1H, 4-CH), 5.53 (m, 1H, 6-CH), 2.45– (lit.,35 207–209 °C); H NMR (400 MHz, CDCl3) δ 7.25 [dd, J
1
2.15 (m, 3H), 2.01 (m, 1H), 1.89–1.77 (m, 2H), 1.76–0.79 (m, = 7.6, 1.5 Hz, 1H, 6-CH(Ar)], 7.25 [ddd, J = 8.2, 7.4, 1.5 Hz,
20H), 0.95 (s, 3H, 19-CH3), 0.91 (d, J = 6.4 Hz, 3H, 21-CH3), 1H, 4-CH(Ar)], 6.72–6.64 [m, 2H, 3- and 5-CH(Ar)], 6.35 (m,
0.854 (d, J = 6.6 Hz, 3H, 26- or 27-CH3), 0.851 (d, J = 6.6 Hz, 1H, 4-CH), 5.52 (m, 1H, 6-CH), 4.30 (br. s, 2H, NH2), 2.46–
3H, 26- or 27-CH3), 0.69 (s, 3H, 18-CH3); 13C NMR (100.6 2.15 (m, 3H), 2.01 (m, 1H), 1.88–1.77 (m, 2H), 1.75–0.81 (m,
MHz, CDCl3) δ 141.4 (5-C), 135.6 (4-CH), 131.4 [2C, 2,6- 20H), 0.95 (s, 3H, 19-CH3), 0.91 (d, J = 6.5 Hz, 3H, 21-CH3),
CH(Ph)], 128.2 [2C, 3,5-CH(Ph)], 127.7 [4-CH(Ph)], 126.6 (6- 0.855 (d, J = 6.7 Hz, 3H, 26- or 27-CH3), 0.851 (d, J = 6.7 Hz,
CH), 123.8 [1-C(Ph)], 117.1 (3-C), 91.7 (C≡C), 89.2 (C≡C), 3H, 26- or 27-CH3), 0.69 (s, 3H, 18-CH3); 13C NMR (100.6
56.8, 56.1, 48.1, 42.5 (quat.), 39.7, 39.5, 36.2, 35.8, 34.5 MHz, CDCl3) δ 146.9 [2-C(Ar)], 141.3 (5-C), 135.1 (4-CH),
(quat.), 33.6, 32.1, 31.7, 28.2, 28.0, 27.0, 24.2, 23.8, 22.8, 22.6, 131.8 [4- or 6-CH(Ar)], 129.1 [4- or 6-CH(Ar)], 126.4 (6-CH),
21.0, 19.1, 18.7, 12.0; HRMS (MALDI-TOF) calcd for C35H48 118.1 [3- or 5-CH(Ar)], 117.0 (3-C), 114.3 [3- or 5-CH(Ar)],
[M]+ 468.3756; found 468.3769; Anal. calcd for C35H48: C, 108.8 [1-C(Ar)], 97.0 (C≡C), 85.4 (C≡C), 56.8, 56.0, 48.0, 42.4
89.68; H, 10.32; found C, 89.78; H, 10.16.
(quat.), 39.6, 39.4, 36.1, 35.7, 34.4 (quat.), 33.5, 32.0, 31.6,
3-[(4-bromophenyl)ethynyl)]cholesta-3,5-diene
(8b). 28.1, 27.9, 27.1, 24.1, 23.8, 22.7, 22.5, 20.9, 19.0, 18.6, 11.9;
Prepared from
6
(74.2 mg, 0.15 mmol) and (4- HRMS (MALDI-TOF) calcd for C35H49N [M]+ 483.3865;
bromophenyl)acetylene (32.6 mg, 0.18 mmol); heating 24 h; found 483.3856.
eluent: hexanes–EtOAc = 50 : 1. Yield 71.5 mg (87 %). Light- 3-(ferrocenylethynyl)cholesta-3,5-diene (8e). Prepared from
yellow solid; mp 146–148 °C; H NMR (400 MHz, CDCl3) δ (74.2 mg, 0.15 mmol) and ethynylferrocene (37.8 mg, 0.18
6
1
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DOI: 10.1039/C5OB00559K
Organic & Biomolecular Chemistry
Page 12 of 13
ARTICLE
Journal Name
mmol); heating 24 h; eluent: hexanes–EtOAc = 50 : 1. Yield
72.5 mg (84 %). Orange solid; mp 136–138 °C (lit.,24a 134–136
°C); H NMR (400 MHz, CDCl3) δ 6.29 (s, 1H, 4-CH), 5.49
Org. Biomol. Chem., 2011,
9
, 6938; (d) J.-H. Li, B.-X. Tang, L.-M.
Tao, Y.-X. Xie, Y. Liang and M.-B. Zhang, J. Org. Chem., 2006, 71
7488.
,
1
(m, 1H, 6-CH), 4.41–4.37 (m, 2H, C5H4), 4.22–4.14 (m, 7H, 5H
C5H5 + 2H C5H4), 2.42–2.12 (m, 3H), 2.01 (m, 1H), 1.88–1.76
(m, 2H), 1.73–0.78 (m, 20H), 0.95 (s, 3H, 19-CH3), 0.91 (d, J =
6.4 Hz, 3H, 21-CH3), 0.854 (d, J = 6.6 Hz, 3H, 26- or 27-CH3),
0.850 (d, J = 6.6 Hz, 3H, 26- or 27-CH3), 0.69 (s, 3H, 18-CH3);
13C NMR (100.6 MHz, CDCl3) δ 141.5 (5-C), 134.5 (4-CH),
125.7 (6-CH), 117.7 (3-C), 87.9 (C≡C), 87.7 (C≡C), 71.22 (1C,
C5H4), 71.20 (1C, C5H4), 69.9 (5C, C5H5), 68.5 (2C, C5H4),
66.0 (quat., C5H4), 56.9, 56.2, 48.2, 42.5 (quat.), 39.8, 39.5,
36.2, 35.8, 34.5 (quat.), 33.7, 32.1, 31.8, 28.2, 28.0, 27.2, 24.2,
23.9, 22.8, 22.6, 21.0, 19.1, 18.7, 12.0; HRMS (MALDI-TOF)
calcd for C39H52Fe [M]+ 576.3418; found 576.3407; Anal. calcd
for C39H52Fe: C, 81.23; H, 9.09; found C, 81.58; H, 9.17.
5
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Chemistry Department, M. V. Lomonosov Moscow State University, 1/3
Leninskiye
nvluk@org.chem.msu.ru. Fax: +7 (495) 422-32-97
Electronic Supplementary Information (ESI) available: [copies of the
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