Synthesis of selenated tetracyclic indoloazulenesviaiodine and diorganyl diselenides

Article abstract of DOI:10.1039/d1ob00268f

Herein, we report an efficient protocol for the synthesis of selenated tetracyclic indoloazulenes. The reaction of diorganyl diselenides with molecular iodine in dichloromethane leads to thein situformation of organo selenenyl iodide. The synthesis of selenylated tetracyclic indoloazulenes through intramolecular cascade cyclization has been achievedviaorgano selenenyl iodide and bisindole at room temperature under metal-free conditions in good yields. All compounds were fully characterized by the FT-IR, HRMS, and¹H,¹³C and⁷⁷Se NMR spectral data.

Full text of DOI:10.1039/d1ob00268f

Organic &
Biomolecular Chemistry
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Synthesis of selenated tetracyclic indoloazulenes
via iodine and diorganyl diselenides†
Cite this: Org. Biomol. Chem., 2021,
9, 3199
1
Khin Myat Noe Win, Amol D. Sonawane
and Mamoru Koketsu
*
Herein, we report an efficient protocol for the synthesis of selenated tetracyclic indoloazulenes. The reac-
tion of diorganyl diselenides with molecular iodine in dichloromethane leads to the in situ formation of
organo selenenyl iodide. The synthesis of selenylated tetracyclic indoloazulenes through intramolecular
cascade cyclization has been achieved via organo selenenyl iodide and bisindole at room temperature
under metal-free conditions in good yields. All compounds were fully characterized by the FT-IR, HRMS,
Received 12th February 2021,
Accepted 14th March 2021
DOI: 10.1039/d1ob00268f
1
13
77
rsc.li/obc
and H, C and Se NMR spectral data.
trifluoroacetic acid (TFA) catalyzed regioselective one-pot
cascade reactions to afford tetracyclic indoles containing a
Introduction
Indole heterocycles have received significant attention in seven-membered ring (Scheme 1, method b). However, these
modern organic synthesis due to their wide variety of biologi- two methods require higher temperatures and the use of an
1
cal activities, and are particularly found in a large array of expensive gold metal catalyst. Among the other synthetic
2
3
14
natural products, pharmaceuticals and bio-related fields.
approaches, in 2013, Yao realized that the intramolecular
Tetracyclic structures derived from indole that contain a seven- electrophilic addition of molecular iodine mediated cyclization
membered ring are used as direct precursors in the synthesis of ortho-substituted arylalkynes leads to the construction of
4
5
6
of anticonvulsant, anticancer, antimicrobial and anti- iodo-substituted tetracyclic indole fused azulene derivatives
7
inflammatory compounds. In a literature survey, the develop- (Scheme 1, method c). The past decade has shown growing
ment of new and efficient protocols for the synthesis of
medium-ring annulated indole derivatives has received sub-
8
stantial attention during the last few decades. The interest in
selenium-containing heterocycles has increased considerably
because of their ability to construct new chemical bonds
9
under mild reaction conditions and promote cyclization. In
addition, the pharmacological properties of selenium-contain-
ing products obtained from cascade cyclization of alkynes via
diorganyl diselenide are likely to be dramatically increased
1
0
when applied to biologically important substrates
and
seleno-heterocycles have raised attention in synthetic chem-
1
1
12
istry. In 2011, Seidel’s group found that aminobenzalde-
hydes react with electron-rich and electron-poor indoles and
diphenyl phosphate (DPP) in toluene under microwave
irradiation through
a redox-neutral cascade reaction to
produce indole annulation products in good to excellent yields
1
3
(Scheme 1, method a). Furthermore, Liu and co-workers
examined the reaction of ortho-phenylethynyl substituted
nitrostyrene and an indole substrate using gold(I) complex and
Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu
University, Gifu 501-1193, Japan. E-mail: koketsu@gifu-u.ac.jp
†
Electronic supplementary information (ESI) available: Experimental pro-
1
13
cedures, characterization data for the new compounds, and copies of H and
NMR spectra.See DOI: 10.1039/d1ob00268f
C
Scheme 1 Strategies for the synthesis of annulated indole derivatives.
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interest in developing an efficient and non-metallic protocol intramolecular cascade cyclization under open flask reaction
for the synthesis of azulene annulated indole tetracycles. In conditions at room temperature (Scheme 1, method d).
our ongoing research, recently, our group has successfully
attempted novel cascade cyclizations which resulted in the syn-
thesis of various substituted selenium heteroacenes, such as
1
5
Results and discussion
pyrano[4,3-b]quinolin-1-one, selenophene-fused thieno[2,3-b]
1
6
17
quinolines,
isoquinoline-fused quinazolinone,
seleno-
Our investigations in this direction began with 2-(phenylethy-
nyl)bisindole 2a–2e as intermediate products which were syn-
thesized using 2-(alkylylethynyl)benzaldehyde 1, indole, and
hydrated ferric sulfate in ethanol (5 mL) under reflux con-
pheno[2,3-b]quinoxaline and selenopheno[2,3-b]pyrazine het-
1
8
eroacenes. Herein, we report the use of molecular iodine and
diorganyl diselenide reagents for the successful in situ oxi-
dation reaction of organo selenenyl iodide with 2-(phenylethy-
nyl)bisindole and a new atom-economical protocol for the syn-
thesis of selenylated tetracyclic indole fused azulenes through
19
ditions for 1 h (Scheme 2).
To investigate our assumption, we optimized the synthesis
of selenylated tetracyclic indoloazulene 3a along with several
electrophiles and bases and variation in time and temperature.
The interesting observations are presented in Table 1. We first
reacted I
2
3 2 2
(2.0 equiv.) and NaHCO (2.0 equiv.) in CH Cl
(
5.0 mL) at 0 °C, and the cyclized product 3a was obtained in
35% yield (Table 1, entry 1). Furthermore, upon using different
bases such as Na
2
CO , Cs CO and K PO with iodine at 0 °C,
3
2
3
3
4
the desired product was obtained in poor yields (Table 1,
entries 2–4). Next, we screened the reaction with iodine and
CuI under reflux conditions to obtain 3a in 8% yield (Table 1,
entry 5). The reaction carried out under reflux conditions with
an iodine loading of 1.0 equiv. compared to a loading of I of
Scheme 2 Synthesis of 3,3’-((2-(phenylethynyl)phenyl) methylene)bis
2
(
1H-indole) 2a.
2.0 equiv. showed a slightly higher yield of 62% (Table 1,
Table 1 Optimization conditions for the synthesis of 12-(1H-indol-3-yl)-7-(methylselanyl)-6-phenyl-5,12-dihydrobenzo [4,5]cyclohepta[1,2-b]
indole (3a)
+
Entry
Solvent
E (equiv.)
(MeSe)
2
(equiv.)
Time (h)
Temp. (°C)
Yield (%) 3a
a
1
2
3
4
5
6
7
8
9
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
I
I
I
I
I
I
I
2
2
2
2
2
2
2
, NaHCO
, Na CO
, Cs CO
, K PO
, CuI (2.0)
(2.0)
3
(2.0)
(2.0)
(2.0)
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
0.5
0.7
1.0
1.5
2.0
2.5
2.0
2.0
2.0
2.0
1
1
1
24
1
1
1
24
24
24
24
24
8
5
5
5
5
0
0
0
0
35
31
11
a
2
3
a
2
3
a
3
4
(2.0)
NR
b
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
rt
rt
rt
rt
rt
8
b
53
62
b
(1.0)
b
NIS (1.0)
FeCl
FeCl
NR
b
3
(1.0)
·6H O (1.0)
·2H O (1.0)
NR
b
1
1
1
1
1
1
1
1
1
1
2
2
0
1
2
3
4
5
6
7
8
9
0
1
3
2
NR
b
CuCl
2
2
NRc
I
I
I
I
I
I
I
I
I
I
2
2
2
2
2
2
2
2
2
2
(1.0)
(1.0)
(1.0)
(1.0)
(1.0)
(1.0)
(1.0)
(1.0)
(1.0)
(1.0)
NR
c
6
c
29
51
70
32
c
c
c
rt
rt
rt
rt
c
CHCl
ACN
DMSO
3
5
40
c
24
24
24
NRc
NRc
NR
Dioxane
rt
a
b
c
Reactions were performed at 0 °C. Reflux conditions. Room temperature. NR: no reaction. All reactions are carried out in an open flask.
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entries 6 and 7). However, the reactions with different bases
like NIS, FeCl , FeCl ·6H O, and CuCl ·2H O failed to give the
3
3
2
2
2
desired product (Table 1, entries 8–11). Then, we used 0.5–2.5
equiv. of (MeSe) loading and 1.0 equiv. of iodine in DCM at
room temperature (Table 1, entries 12–17). The effect of an
MeSe) loading under 2.0 equiv. was insufficient and lower
2
(
2
yields were obtained (Table 1, entries 12–15). Finally, the syn-
thesis of selenylated tetracyclic indoloazulene 3a was carried
out using iodine (1.0 equiv.) and (MeSe) (2.0 equiv.) in DCM
2
at room temperature to afford the desired product 3a in 70%
yield (Table 1, entry 16). The use of 2.5 equiv. of (MeSe) gave
2
3
a in 32% yield (Table 1, entry 17). On the other hand, the
reaction with chloroform solvent was found to be less effective
Table 1, entry 18). Also, the reaction did not proceed with
(
polar solvents such as acetonitrile, dimethyl sulfoxide and
dioxane (Table 1, entries 19–21). It is noteworthy that all the
reactions were carried out under open flask conditions. The
one-pot intramolecular cyclization reaction was found to be
affected by the temperature and equivalents of electrophiles.
Also, it was found that the reaction with diorganyl disulfide
did not proceed to form the sulfenylated cyclized products.
With the optimal reaction conditions in hand, we turned to
investigate the scope of the reaction by using various 2-(pheny-
lethynyl)bisindole derivatives 2 and diorganyl diselenides
under the standard conditions. The effect of different diorga-
Fig. 1 Plausible mechanism.
nyl diselenides was first explored. It was found that diselenide
substrates bearing either a phenyl group or an alkyl group
reacted well to produce the corresponding selenocyclized pro-
ducts 3a–3d in 52–75% yields. The benzaldehyde ring contain-
ing electron-donating 4,5-dimethoxy groups or electron-with-
drawing chloro groups and/or 2-(phenylethynyl) with alkynyl
groups bearing substituents, such as phenyl, 4-methyl and
Table 2 Synthesis of selenylated tetracyclic indoloazulenes 3
4-fluoro, were well tolerated under the present reaction con-
ditions and afforded the desired selenylated tetracyclic indo-
loazulenes 3e–3o with good yields (Table 2). The synthesized
1
compounds 3a–3o were characterized by IR, HRMS, and H,
1
3
77
C and Se NMR spectral analysis.
Based on our previous knowledge and experimental
1
0
results, a plausible reaction mechanism involves the in situ
generation of organo selenenyl iodide and the formation of
selenocyclized tetracyclic indole fused azulene 3 followed by
an iodine-mediated electrophilic cyclization process as shown
in Fig. 1. First, intermediate A is produced by the addition of
molecular iodine to one selenium atom from diorganyl disele-
nides. Next, the reaction of substrate 2 and organo selenenyl
iodide A proceeds to form an acetylene bond to produce a sele-
niranium complex which results in intermediate B. An intra-
molecular nucleophilic attack on activated seleniranium
center B by an indole nucleophile gives rise to the successive
N
aromatization of intermediate C assisted by S 2 displacement
of the iodide ion present in the reaction mixture. Finally, the
electrophilic target product 3 was successfully achieved in
good yields by the removal of HI.
Conclusion
In conclusion, we presented a novel methodology using mole-
cular iodine and diorganyl diselenide mediated selenocycliza-
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tion of 3,3′-((2-(arylethynyl)aryl)methylene)bis(1H-indole) for General procedure for the synthesis of 3,3′-((2-(phenylethynyl)
the synthesis of 12-(1H-indol-3-yl)-7-(arylselanyl)-6-aryl-5,12- phenyl)methylene)bis(1H-indole) 2a–2e
dihydrobenzo[4,5]cyclohepta[1,2-b] indole derivatives
moderate to good yields. This one-pot synthesis strategy fea- To a solution of 2-(phenylethynyl)benzaldehyde 1a (500 mg,
tures an efficient and simple procedure and metal-free and 2.42 mmol, 1.0 equiv.) in dry EtOH (10 mL) was added indole
3 in
2
0
mild reaction conditions for the construction of selenylated (568 mg, 4.85 mmol, 2.0 equiv.) and Fe
2 4 3 2
(SO ) ·xH O (17 mg,
tetracyclic indole fused azulenes. Also, biological evaluations 15 mol%) in a round-bottom flask. The mixture was stirred
1
9
of these novel heterocycles are in progress.
under reflux conditions for 1 h. After completion of the reac-
tion, the solvent was evaporated under reduced pressure. The
residue was extracted with ethyl acetate and the organic phase
was washed successively with water and brine. The organic
Experimental: general
2 4
layer was dried over Na SO . The resulting crude product was
purified by column chromatography using n-hexane : ethyl
acetate (70 : 30) as the eluent to afford 2a as a red solid. Yield:
All solvents and reagents were purchased from suppliers and
used without further purification. IR spectra were recorded on
a JASCO FT/IR-460 Plus spectrophotometer. Reactions were
monitored by thin-layer chromatography (TLC) performed on
silica plates using UV-light or an iodine chamber for visualiza-
tion. Column chromatography was performed on silica gel
8
1
7
4%; melting point: 82–84 °C; IR (neat): 3418, 3059, 3009,
703, 1676, 1598, 1492, 1457, 1418, 1338, 1216, 1093, 1010,
53, 690, 667, 600 cm−
1
; H-NMR (400 MHz, CDCl ) δ 7.85
3
1
(
(
(
2H, s), 7.59 (1H, s), 7.47 (2H, s), 7.33 (2H, s), 7.24 (2H, s), 7.19
6H, t, J = 3.1 Hz), 7.01 (2H, d, J = 7.2 Hz), 6.64 (2H, s), 6.52
(60–120 mesh) using n-hexane and ethyl acetate as eluents.
1
3
1H, s); C-NMR (100 MHz, CDCl ) δ 146.1, 136.8, 132.3,
3
Evaporation and condensation were carried out in vacuo. NMR
spectra were recorded with JEOL JNM-ECS 400 spectrometers
with tetramethylsilane as an internal standard. Chemical
shifts δ and coupling constants J are given in ppm (parts per
million) and Hz (hertz), respectively. The following abbrevi-
ations are used: s: singlet, d: doublet, t: triplet, m: multiplet.
Additionally, unknown compounds were characterized by
HRMS analysis. The data of all known compounds are consist-
ent with the given literature reports. Scale-up reactions were
also performed as per the given general procedure without any
modification. Melting points were measured using a Yanaco
micromelting point apparatus.
1
1
31.6, 128.7, 128.4, 128.5, 128.1, 127.3, 126.2, 123.8, 123.4,
22.9, 122.0, 120.0, 119.3, 119.3, 111.1, 94.0, 88.4, 38.0; HRMS
(
ESI): m/z = 423.1861 calcd for C H N , found 423.1837 [M +
31 23 2
+
H] .
,3′-((4,5-Dimethoxy-2-(phenylethynyl)phenyl)methylene)bis
3
(
1H-indole) (2b). Yield: 62%; melting point: 105–107 °C; IR
(
1
neat): 3411, 3007, 1648, 1596, 1509, 1457, 1338, 1247, 1205,
183, 1086, 1040, 855, 804, 743, 691 cm− ; H-NMR (400 MHz,
1
1
CDCl ) δ 7.91 (2H, s), 7.49 (2H, d, J = 7.6 Hz), 7.34 (2H, d, J =
3
8
6
.1 Hz), 7.15–7.22 (5H, m), 7.09 (1H, s), 7.01 (2H, t, J = 7.2 Hz),
.82 (1H, s), 6.73 (2H, s), 6.48 (1H, s), 3.90 (3H, s), 3.62 (3H, s);
1
3
C-NMR (100 MHz, CDCl ) δ 149.4, 147.1, 139.7, 136.8, 131.4,
3
1
1
28.5, 127.9, 127.3, 123.6, 123.5, 122.0, 120.1, 119.5, 119.4,
Diselenide preparation
14.5, 111.9, 111.0, 92.7, 88.5, 56.1, 55.9, 37.9; HRMS (ESI):
+
Preparation of 1,2-dibutyldiselenide. Selenium (200 mg, m/z = 483.2073 calcd for C H N O , found 483.2056 [M + H] .
3
3
27 2 2
2
.53 mmol) was added to a stirred solution of sodium boro-
3,3′-((5-Chloro-2-(phenylethynyl)phenyl)methylene)bis(1H-
hydride (191 mg, 5.07 mmol) in ethanol (20 mL) at 0 °C. indole) (2c). Yield: 71%; melting point: 123–125 °C; IR (neat):
Stirring was continued for 30 min at this temperature. Then, 3417, 3059, 3016, 2400, 1705, 1619, 1588, 1554, 1493, 1472,
selenium (200 mg, 2.53 mmol) was added to the reaction 1457, 1418, 1338, 1216, 1178, 1094, 1040, 1011, 906, 823, 754,
mixture and stirred for 30 min at 0 °C. Finally, iodobutane 690, 667, 590 cm− ; H-NMR (400 MHz, CDCl
(
1
1
) δ 7.86 (2H, s),
1.01 mL, 8.87 mmol) was added over a period of 5 min. After 7.48 (3H, dd, J = 17.6, 8.0 Hz), 7.32 (2H, d, J = 8.2 Hz),
stirring for a further hour at room temperature, the reaction 7.15–7.19 (7H, m), 7.02 (2H, t, J = 7.3 Hz), 6.63 (2H, s), 6.49
3
1
3
mixture was extracted with hexane and washed with water, (1H, s); C-NMR (100 MHz, CDCl
3
) δ 148.0, 136.8, 134.3,
dried over Na SO , and concentrated in vacuo. The crude 133.4, 131.6, 128.8, 128.3, 127.1, 126.7, 123.8, 123.1, 122.2,
2
4
product was purified by silica gel column chromatography 121.5, 119.8, 119.5, 118.6, 111.2, 94.9, 87.3, 37.9; HRMS (ESI):
SiO , n-hexane/toluene = 20/1) to afford dibutyl diselenides as m/z = 479.1291 calcd for C33 21ClNaN , found 479.1288 [M +
an orange coloured liquid. Yield: 72%; orange coloured liquid; Na] .
(
2
H
2
+
1
H-NMR (400 MHz, CDCl
3
) δ 2.92 (4H, t, J = 7.6 Hz), 1.68–1.75
3,3′-((2-(p-Tolylethynyl)phenyl)methylene)bis(1H-indole) (2d).
(
4H, m), 1.42 (4H, q, J = 7.5 Hz), 0.93 (6H, t, J = 7.3 Hz); Yield: 79%; melting point: 98–100 °C; IR (neat): 3416, 3057,
1
3
77
C-NMR (100 MHz, CDCl ) δ 33.2, 30.0, 22.7, 13.7; Se-NMR 1691, 1604, 1510, 1457, 1419, 1338, 1217, 1178, 1095, 818,
3
743 cm− ; H-NMR (400 MHz, CDCl
1
1
) δ 7.89 (2H, s), 7.56–7.58
(
75 MHz, CDCl
3
) δ 307.8.
3
Preparation of 1,2-dipropyldiselenide. Yield: 68%; orange (1H, m), 7.47 (2H, d, J = 8.2 Hz), 7.34 (2H, d, J = 8.2 Hz),
1
coloured liquid; H-NMR (400 MHz, CDCl ) δ 2.86–2.94 (4H, 7.16–7.19 (4H, m), 7.09 (2H, d, J = 8.2 Hz), 7.01 (3H, d, J = 6.9
3
1
3
13
m), 1.72–1.81 (4H, m), 1.00 (6H, t, J = 7.3 Hz); C-NMR Hz), 6.68 (2H, s), 6.52 (1H, s), 2.29 (3H, s); C-NMR (100 MHz,
7
7
(
3 3
100 MHz, CDCl ) δ 32.4, 24.3, 14.2; Se-NMR (75 MHz, CDCl ) δ 146.0, 138.3, 136.8, 132.2, 131.5, 129.1, 128.7, 128.2,
CDCl ) δ 303.4.
127.3, 126.2, 123.8, 123.1, 122.0, 120.3, 120.1, 119.3, 111.1,
3
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9
4.3, 87.8, 38.0, 21.56; HRMS (ESI): m/z = 437.2018 calcd for δ 323.4; HRMS (ESI): m/z = 545.1496 calcd for C34H N Se,
29 2
+
+
C H N , found 437.2006 [M + H] .
found 545.1505 [M + H] .
7-(Butylselanyl)-12-(1H-indol-3-yl)-6-phenyl-5,12-dihydrobenzo
indole) (2e). Yield: 64%; melting point: 89–91 °C; IR (neat): [4,5]cyclohepta[1,2-b]indole (3c). Yield: 63%; melting point:
3
2
25 2
3
,3′-((2-((4-Fluorophenyl)ethynyl)phenyl)methylene)bis(1H-
3
1
7
415, 3060, 1694, 1598, 1508, 1457, 1418, 1338, 1221, 1156, 131–133 °C; IR (neat): 3420, 3057, 2956, 1456, 1443, 1354,
−
1
1
−1
1
093, 1011, 836, 793, 743 cm ; H-NMR (400 MHz, CDCl
3
) δ 1314, 1218, 1091, 1057, 905, 742, 702, 667 cm
; H-NMR
.88 (2H, s), 7.55–7.58 (1H, m), 7.45 (2H, d, J = 7.8 Hz), 7.33 (400 MHz, CDCl
3
) δ 8.09 (1H, d, J = 7.8 Hz), 7.84 (1H, d, J = 6.9
(2H, d, J = 7.8 Hz), 7.14–7.19 (3H, m), 7.09 (2H, dd, J = 8.9, 5.3 Hz), 7.79 (1H, s), 7.71 (1H, d, J = 7.8 Hz), 7.50 (1H, s), 7.42 (4H,
Hz), 7.01 (2H, d, J = 7.3 Hz), 6.86 (2H, t, J = 8.7 Hz), 6.64 (2H, d, J = 7.8 Hz), 7.28 (1H, d, J = 8.2 Hz), 7.16–7.22 (5H, m), 7.04
1
3
s), 6.48 (1H, s); C-NMR (100 MHz, CDCl
1
1
3
) δ 146.1, 136.8, (1H, d, J = 7.8 Hz), 6.87 (1H, t, J = 7.6 Hz), 6.69 (1H, s), 6.02
33.5, 133.4, 132.2, 128.7, 128.5, 127.3, 126.2, 123.8, 122.8, (1H, s), 1.71–1.76 (1H, m), 1.32 (1H, t, J = 5.7 Hz), 0.77 (1H, d, J
22.0, 120.0, 119.4, 119.3, 116.0, 115.4, 111.1, 93.0, 88.0, 38.0; = 8.7 Hz), 0.67 (3H, t, J = 6.6 Hz), 0.46 (3H, t, J = 6.9 Hz);
1
3
HRMS (ESI): m/z = 441.1767 calcd for C31
H
22
N
2
F, found
3
C-NMR (100 MHz, CDCl ) δ 144.1, 141.1, 136.8, 136.7, 136.7,
+
4
41.1764 [M + H] .
135.7, 134.3, 133.4, 132.6, 129.0, 128.6, 128.5, 127.4, 126.6,
1
1
25.8, 122.9, 122.5, 121.6, 120.0, 119.9, 119.8, 119.3, 118.3,
15.1, 111.1, 111.0, 40.6, 31.0, 28.7, 22.6, 13.3; Se-NMR
General procedure for the synthesis of 12-(1H-indol-3-yl)-7-
77
(
[
methylselanyl)-6-phenyl-5,12-dihydrobenzo[4,5]cyclohepta
1,2-b]indole 3a–3o
(
75 MHz, CDCl ) δ 323.9; HRMS (ESI): m/z = 559.1652 calcd for
3
+
C
35
H
31
N
2
Se, found 559.1651 [M + H] .
12-(1H-Indol-3-yl)-6-phenyl-7-(phenylselanyl)-5,12-dihydro-
dimethyl diselenides (45 mg, 0.24 mmol, 2.0 equiv.) in CH Cl2 benzo[4,5]cyclohepta[1,2-b]indole (3d). Yield: 75%; melting
2
To a stirred solution of I (30 mg, 0.12 mmol, 1.0 equiv.) and
2
(
5 mL) was added the corresponding 3,3′-((2-(phenylethynyl) point: 119–121 °C; IR (neat): 3429, 3055, 1931, 1867, 1792,
2
0
phenyl)methylene)bis(1H-indole) 2a (50 mg, 0.12 mmol, 1.0 1576, 1532, 1476, 1456, 1441, 1273, 1317, 1246, 1189, 1117,
equiv.) at rt. The reaction was monitored by TLC. After com- 1046, 982, 912, 848, 760, 738, 703 cm− ; H-NMR (400 MHz,
pletion, the reaction was quenched with saturated aqueous CDCl ) δ 7.95 (1H, d, J = 6.9 Hz), 7.89 (1H, s), 7.81 (1H, d, J =
Na and water. The resulting solution was extracted using 7.8 Hz), 7.68 (1H, d, J = 6.9 Hz), 7.50–7.53 (5H, m), 7.28–7.34
dichloromethane. The organic layer was dried over Na SO . (2H, m), 7.13–7.22 (4H, m), 7.00 (2H, dt, J = 18.2, 7.6 Hz), 6.81
1 1
3
2 2 3
S O
2
4
The crude product was purified by column chromatography (1H, s), 6.64 (1H, t, J = 7.3 Hz), 6.18 (2H, d, J = 6.9 Hz), 6.09
1
3
using n-hexane : ethyl acetate (70 : 30) as the eluent to afford 3a (3H, t, J = 7.6 Hz); C-NMR (100 MHz, CDCl
as a yellow solid. Yield: 70%; melting point: 142–144 °C; IR 137.0, 136.9, 135.9, 135.5, 134.7, 133.8, 132.6, 132.3, 131.8,
neat): 3420, 3056, 1487, 1456, 1443, 1316, 1271, 1218, 1151, 129.2, 129.0, 129.0, 128.2, 127.5, 126.6, 126.2, 125.5, 123.2,
3
) δ 143.2, 140.9,
(
137, 1011, 908, 743, 703, 667 cm−1
; H-NMR (400 MHz, 122.7, 122.0, 120.2, 120.0, 119.7, 118.9, 118.5, 114.3, 111.3,
CDCl ) δ 8.03 (1H, d, J = 7.8 Hz), 7.87 (1H, d, J = 8.7 Hz), 7.78 110.9, 40.9; Se-NMR (75 MHz, CDCl ) δ 448.3; HRMS (ESI):
1
1
7
7
3
3
+
(
27 2
1H, s), 7.69 (1H, d, J = 6.4 Hz), 7.52 (1H, s), 7.42 (4H, t, J = 6.9 m/z = 579.1339 calcd for C37H N Se, found 579.1332 [M + H] .
Hz), 7.30 (1H, d, J = 6.4 Hz), 7.18 (4H, dt, J = 9.2, 3.8 Hz), 7.08
12-(1H-Indol-3-yl)-9,10-dimethoxy-7-(methylselanyl)-6-phenyl-
(
1H, d, J = 8.2 Hz), 7.02 (1H, d, J = 8.2 Hz), 6.84 (1H, t, J = 7.6 5,12-dihydrobenzo[4,5]cyclohepta[1,2-b]indole (3e). Yield: 51%;
1
3
Hz), 6.65 (1H, s), 6.01 (1H, s), 0.99 (3H, t, J = 6.4 Hz); C-NMR melting point: 153–155 °C; IR (neat): 3411, 3056, 3005, 2930,
100 MHz, CDCl ) δ 144.5, 140.9, 136.7, 136.6, 136.0, 135.6, 2843, 1572, 1509, 1461, 1441, 1390, 1342, 1215, 1209, 1246,
(
3
−
1
1
1
1
34.2, 133.2, 132.4, 129.0, 128.7, 128.5, 127.3, 126.6, 126.0, 1215, 1117, 1101, 1031, 1007, 858, 808, 747, 704, 665 cm ;
23.0, 122.5, 121.6, 120.3, 120.1, 119.9, 119.2, 118.3, 115.3,
1
H-NMR (400 MHz, CDCl
3
) δ 7.90 (1H, s), 7.80 (1H, d, J = 7.8
7
7
11.1, 111.0, 40.5, 8.9; Se-NMR (75 MHz, CDCl
3
) δ 245.6; Hz), 7.52 (6H, dd, J = 13.5, 5.3 Hz), 7.33 (1H, d, J = 7.8 Hz),
HRMS (ESI): m/z = 517.1183 calcd for C H N Se, found 7.12–7.23 (5H, m), 7.04 (1H, t, J = 7.1 Hz), 6.78 (1H, s), 6.66
3
2
25 2
+
5
17.1176 [M + H] .
(1H, t, J = 7.3 Hz), 6.18 (2H, d, J = 6.9 Hz), 6.10 (2H, t, J = 7.6
1
3
1
2-(1H-Indol-3-yl)-6-phenyl-7-(propylselanyl)-5,12-dihydro- Hz), 5.99 (1H, s), 3.99 (3H, s), 3.62 (3H, s); C-NMR (100 MHz,
benzo[4,5]cyclohepta[1,2-b]indole (3b). Yield: 52%; melting CDCl ) δ 149.6, 146.1, 141.1, 137.0, 136.4, 135.1, 133.8, 132.7,
3
point: 165–167 °C; IR (neat): 3423, 3057, 2961, 2870, 1721, 132.2, 131.9, 128.9, 128.4, 128.2, 127.3, 126.5, 126.4, 123.1,
1
7
598, 1490, 1456, 1443, 1354, 1313, 1217, 1151, 1137, 927, 743, 122.6, 122.0, 120.2, 119.8, 119.6, 118.7, 118.4, 116.9, 114.6,
03, 666 cm− ; H-NMR (400 MHz, CDCl ) δ 8.09 (1H, d, J = 7.8 111.6, 111.4, 111.0, 56.1, 55.7, 40.5; Se-NMR (75 MHz, CDCl3)
1
1
77
3
Hz), 7.83 (2H, t, J = 8.9 Hz), 7.72 (1H, d, J = 7.3 Hz), 7.51 (1H,
s), 7.43 (3H, s), 7.28 (1H, d, J = 7.3 Hz,), 7.15–7.23 (6H, m), 7.03
δ
445.8; HRMS (ESI): m/z
NaSe, found 599.1204 [M + Na] .
7-(Butylselanyl)-12-(1H-indol-3-yl)-9,10-dimethoxy-6-phenyl-
1H, s), 1.67–1.73 (1H, m), 1.38 (1H, d, J = 6.0 Hz), 0.74 (1H, t, J 5,12-dihydrobenzo[4,5]cyclohepta[1,2-b]indole (3f). Yield:
=
599.1214 calcd for
+
C
34 28 2 2
H N O
(1H, t, J = 7.3 Hz), 6.87 (1H, t, J = 7.6 Hz), 6.69 (1H, s), 6.03
(
=
1
3
7.1 Hz), 0.59 (1H, s), 0.23 (3H, t, J = 7.3 Hz); C-NMR 42%; melting point: 149–151 °C; IR (neat): 3374, 3055, 2956,
(
100 MHz, CDCl ) δ 144.0, 141.2, 136.8, 136.8, 136.7, 135.6, 2932, 1602, 1509, 1456, 1440, 1340, 1316, 1246, 1208, 1147,
3
34.4, 133.5, 132.6, 129.1, 128.8, 128.6, 127.5, 126.6, 125.9, 1116, 1101, 1043, 923, 857, 742, 703 cm− ; H-NMR (400 MHz,
23.0, 122.5, 121.7, 120.1, 119.9, 119.8, 119.3, 118.3, 115.0, CDCl ) δ 7.85 (1H, d, J = 8.7 Hz), 7.80 (1H, s), 7.70 (1H, s), 7.51
11.1, 111.0, 40.7, 31.1, 22.5, 14.1; Se-NMR (75 MHz, CDCl3) (1H, s), 7.42 (3H, s), 7.14–7.22 (6H, m), 7.03 (1H, t, J = 7.8 Hz),
1 1
1
1
1
3
7
7
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6
3
0
.87 (1H, t, J = 7.6 Hz), 6.65 (1H, s), 5.91 (1H, s), 4.06 (3H, s), melting point: 128–130 °C; IR (neat): 3417, 3330, 2928, 2854,
.89 (3H, s), 1.77 (1H, d, J = 11.0 Hz), 1.38 (1H, t, J = 5.7 Hz), 2457, 2213, 2130, 1925, 1838, 1749, 1621, 1524, 1456, 1439,
1
3
−1
1
.65–0.71 (4H, m), 0.49 (3H, t, J = 7.1 Hz); C-NMR (100 MHz, 1090, 1071, 995, 920, 817, 740, 662, 589 cm
) δ 149.7, 146.6, 141.4, 137.1, 136.7, 135.1, 133.9, 132.6, (400 MHz, CDCl ) δ 7.89–7.94 (2H, m), 7.80 (1H, d, J = 7.8 Hz),
29.3, 128.4, 127.3, 126.5, 122.9, 122.4, 121.6, 120.0, 119.8, 7.68 (1H, d, J = 2.3 Hz), 7.47–7.56 (5H, m), 7.36 (1H, d, J = 8.2
19.7, 119.3, 118.2, 116.2, 115.6, 111.3, 111.1, 111.0, 56.3, 56.1, Hz), 7.16–7.23 (4H, m), 7.08 (1H, t, J = 7.1 Hz), 6.95 (1H, dd, J =
;
H-NMR
CDCl
3
3
1
1
4
7
7
3
0.3, 31.2, 28.9, 22.6, 13.4; Se-NMR (75 MHz, CDCl ) δ 320.2; 8.7, 2.3 Hz), 6.82 (1H, s), 6.67 (1H, d, J = 7.3 Hz), 6.10–6.18
1
3
HRMS (ESI): m/z = 641.1683 calcd for C H N O NaSe, found (4H, m), 6.04 (1H, s); C-NMR (100 MHz, CDCl ) δ 144.2,
6
3
7
34
2
2
3
+
41.1693 [M + Na] .
140.6, 137.0, 135.1, 134.6, 134.6, 134.4, 132.6, 132.3, 131.4,
1
2-(1H-Indol-3-yl)-9,10-dimethoxy-6-phenyl-7-(phenylselanyl)- 129.0, 128.4, 128.4, 127.3, 126.5, 126.3, 125.6, 123.5, 122.8,
5
,12-dihydrobenzo[4,5]cyclohepta[1,2-b]indole (3g). Yield: 66%; 122.2, 120.1, 120.0, 119.9, 118.5, 118.3, 113.5, 111.4, 111.0,
7
7
3
melting point: 144–146 °C; IR (neat): 3413, 3367, 3055, 3006, 40.6; Se-NMR (75 MHz, CDCl ) δ 446.1; HRMS (ESI): m/z =
+
2
1
6
2
935, 2842, 1605, 1575, 1509, 1462, 1439, 1343, 1317, 1247, 635.0769 calcd for C37H25ClN NaSe, found 635.0758 [M + Na] .
209, 1117, 1101, 1021, 1008, 809, 783, 740, 703, 691,
12-(1H-Indol-3-yl)-7-(methylselanyl)-6-(p-tolyl)-5,12-dihydro-
) δ 7.90 (1H, s), 7.80 (1H, benzo[4,5]cyclohepta[1,2-b]indole (3k). Yield: 64%; melting
67 cm− ; H-NMR (400 MHz, CDCl
1
1
3
d, J = 7.8 Hz), 7.52 (6H, dd, J = 13.5, 5.3 Hz), 7.33 (1H, d, J = 7.8 point: 139–141 °C; IR (neat): 3416, 3056, 3005, 2873, 2776,
Hz), 7.12–7.23 (5H, m), 7.04 (1H, t, J = 7.1 Hz), 6.78 (1H, s), 2663, 2439, 1456, 1432, 1352, 1314, 1218, 1136, 1011, 910, 814,
.66 (1H, t, J = 7.3 Hz), 6.18 (2H, d, J = 6.9 Hz), 6.10 (2H, t, J = 742 cm− ; H-NMR (400 MHz, CDCl
1
1
) δ 8.03 (1H, d, J = 6.9 Hz),
.6 Hz), 5.99 (1H, s), 3.99 (3H, s), 3.62 (3H, s); C-NMR 7.86–7.88 (1H, m), 7.79 (1H, s), 7.69 (1H, d, J = 7.3 Hz), 7.58
6
7
3
1
3
(
100 MHz, CDCl ) δ 149.6, 146.1, 141.1, 137.0, 136.4, 135.1, (1H, s), 7.41 (1H, dd, J = 7.6, 6.2 Hz), 7.28 (2H, t, J = 8.2 Hz),
3
1
1
1
33.9, 132.7, 132.2, 131.9, 128.9, 128.4, 128.2, 127.3, 126.5, 7.16–7.22 (5H, m), 7.10 (1H, d, J = 8.2 Hz), 7.01 (1H, t, J = 7.8
26.4, 123.1, 122.6, 122.0, 120.2, 119.8, 119.6, 118.7, 118.4, Hz), 6.84 (1H, t, J = 7.1 Hz), 6.67 (1H, s), 6.01 (1H, s), 2.41 (3H,
77
13
16.9, 114.6, 111.6, 111.4, 111.0, 56.1, 55.7, 40.5; Se-NMR s), 0.98 (3H, d, J = 6.4 Hz); C-NMR (100 MHz, CDCl ) δ 144.6,
3
(
3
75 MHz, CDCl ) δ 445.8; HRMS (ESI): m/z = 661.1370 calcd for 138.6, 137.9, 136.6, 136.6, 136.1, 135.3, 133.3, 132.6, 129.9,
+
C
39
H
1
30
N
2
O
2
NaSe, found 661.1388 [M + Na] .
0-Chloro-12-(1H-indol-3-yl)-7-(methylselanyl)-6-phenyl-5,12- 119.8, 119.2, 118.3, 115.3, 111.1, 111.0, 40.5, 21.5, 8.8; Se-
dihydrobenzo[4,5]cyclohepta[1,2-b]indole (3h). Yield: 59%; NMR (75 MHz, CDCl ) δ 245.1; HRMS (ESI): m/z = 531.1339
melting point: 164–166 °C; IR (neat): 3458, 3381, 3020, 2400, calcd for C33 Se, found 531.1324 [M + H] .
128.9, 128.5, 127.3, 126.6, 125.9, 122.9, 122.5, 121.5, 120.1,
7
7
3
+
27 2
H N
2
8
082, 1710, 1453, 1352, 1306, 1215, 1148, 1125, 1038, 927, 908,
12-(1H-Indol-3-yl)-7-(propylselanyl)-6-(p-tolyl)-5,12-dihydro-
−
1 1
92, 755, 668, 502, 490 cm ; H-NMR (400 MHz, CDCl
3
) δ 7.97 benzo[4,5]cyclohepta[1,2-b]indole (3l). Yield: 58%; melting
(
1H, d, J = 8.7 Hz), 7.84–7.88 (2H, m), 7.69 (1H, d, J = 2.3 Hz), point: 132–135 °C; IR (neat): 3422, 3020, 2962, 1506, 1455,
−
1
7
1
0
1
1
.55 (1H, s), 7.43 (3H, s), 7.19–7.23 (5H, m), 7.06 (2H, dd, J = 1353, 1338, 1312, 1217, 1151, 1089, 1011, 923, 815, 742 cm ;
1
7.4, 7.8 Hz), 6.89 (1H, t, J = 7.6 Hz), 6.68 (1H, s), 5.97 (1H, s),
H-NMR (400 MHz, CDCl
3
) δ 8.07–8.09 (1H, m), 7.82–7.84 (1H,
1
3
.99 (3H, s); C-NMR (100 MHz, CDCl
3
) δ 140.5, 136.5, 134.7, m), 7.77 (1H, s), 7.71 (1H, d, J = 7.8 Hz), 7.53 (1H, s), 7.42 (1H,
34.6, 134.4, 132.4, 128.8, 128.0, 126.4, 126.0, 123.2, 122.7, td, J = 7.6, 1.4 Hz), 7.26–7.28 (2H, m), 7.12–7.23 (6H, m), 7.02
21.8, 120.1, 120.0, 119.4, 118.3, 114.5, 111.2, 111.1, 40.3, 8.8; (1H, t, J = 7.1 Hz), 6.86–6.90 (1H, m), 6.68 (1H, t, J = 1.8 Hz),
7
7
Se-NMR (75 MHz, CDCl
3
) δ 247.7; HRMS (ESI): m/z = 6.02 (1H, s), 2.43 (3H, s), 1.66–1.69 (1H, m), 1.30–1.36 (1H, m),
+
5
73.0613 calcd for C H ClN NaSe, found 573.0602 [M + Na] . 0.72 (1H, dd, J = 16.0, 6.9 Hz), 0.62 (1H, d, J = 7.3 Hz), 0.22
3
2
23
2
1
3
7
3
-(Butylselanyl)-10-chloro-12-(1H-indol-3-yl)-6-phenyl-5,12- (3H, t, J = 7.3 Hz); C-NMR (100 MHz,CDCl ) δ 144.0, 138.5,
dihydrobenzo[4,5]cyclohepta[1,2-b]indole (3i). Yield: 53%; 138.2, 136.8, 136.6, 135.3, 134.3, 133.5, 132.7, 129.0, 128.7,
melting point: 189–191 °C; IR (neat): 3412, 3363, 2454, 1932, 127.5, 126.6, 125.7, 122.8, 122.5, 121.6, 120.0, 119.8, 119.6,
1
1
875, 1737, 1456, 1440, 1417, 1355, 1308, 1262, 1218, 1152, 119.3, 118.3, 114.9, 111.0, 110.9, 40.7, 31.0, 22.5, 21.5, 14.1;
087, 1014, 881, 820, 747, 699, 619, 582, 498 cm−1; H-NMR
1
77
3
Se-NMR (75 MHz, CDCl ) δ 323.0; HRMS (ESI): m/z =
+
(400 MHz, CDCl ) δ 8.03 (1H, d, J = 8.5 Hz), 7.84 (2H, d, J = 8.5 559.1652 calcd for C H N Se, found 559.1672 [M + H] .
3 35 31 2
Hz), 7.71 (1H, d, J = 2.2 Hz), 7.53 (1H, s), 7.44 (2H, s),
.16–7.25 (7H, m), 7.05 (1H, t, J = 7.6 Hz), 6.91 (1H, t, J = 7.4 benzo[4,5]cyclohepta[1,2-b]indole (3m). Yield: 49%; melting
Hz), 6.70 (1H, s), 5.97 (1H, s), 1.73 (1H, dd, J = 11.0, 8.8 Hz), point: 125–127 °C; IR (neat): 3424, 3055, 2873, 1576, 1507,
12-(1H-Indol-3-yl)-7-(phenylselanyl)-6-(p-tolyl)-5,12-dihydro-
7
1
.26–1.31 (1H, m), 0.67–0.79 (4H, m), 0.48 (3H, t, J = 7.0 Hz); 1430, 1438, 1432, 1313, 1176, 1151, 1090, 970, 815, 739,
C-NMR (100 MHz, CDCl ) δ 145.1, 140.8, 136.7, 135.5, 134.8, 690 cm ; H-NMR (400 MHz, CDCl ) δ 7.94 (1H, d, J = 6.7 Hz),
3 3
1
3
−1 1
1
1
1
3
34.5, 134.5, 132.5, 128.7, 128.1, 127.2, 126.4, 125.8, 123.2, 7.87 (1H, s), 7.79 (1H, d, J = 7.6 Hz), 7.67 (1H, d, J = 6.7 Hz),
22.6, 121.8, 120.0, 119.9, 119.5, 119.3, 118.3, 114.3, 111.1, 7.52–7.56 (2H, m), 7.28–7.33 (4H, m), 7.10–7.20 (4H, m), 7.03
7
7
3
11.0, 40.4, 31.0, 28.8, 22.6, 13.4; Se-NMR (75 MHz, CDCl ) δ (1H, t, J = 7.0 Hz), 6.96 (1H, t, J = 7.2 Hz), 6.81 (1H, s), 6.62
25.1; HRMS (ESI): m/z = 615.1082 calcd for C H ClN NaSe, (1H, t, J = 7.4 Hz), 6.16 (2H, d, J = 7.2 Hz), 6.04–6.09 (3H, m),
3
5
29
2
+
13
found 615.1060 [M + Na] .
0-Chloro-12-(1H-indol-3-yl)-6-phenyl-7-(phenylselanyl)-5,12- 137.0, 136.9, 135.8, 135.4, 134.6, 133.8, 132.8, 132.3, 131.8,
dihydrobenzo[4,5]cyclohepta[1,2-b]indole (3j). Yield: 68%; 129.1, 128.9, 128.2, 127.5, 126.6, 126.1, 125.5, 123.1, 122.7,
3
2.46 (3H, s); C-NMR (100 MHz, CDCl ) δ 143.2, 138.9, 137.9,
1
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1
4
21.9, 120.2, 119.8, 119.6, 118.8, 118.5, 114.2, 111.3, 110.9,
H.-Y. Cheong, K. N. Houk and N. K. Garg, J. Am. Chem.
Soc., 2010, 132, 17933–17944; (e) X. Yu and J. Wu, J. Comb.
Chem., 2010, 12, 238–244; (f) R.-Y. Tang and J.-H. Li, Chem.
– Eur. J., 2010, 16, 4733–4738.
7
7
0.8, 21.6; Se-NMR (75 MHz, CDCl ) δ 448.0; HRMS (ESI):
3
+
m/z = 593.1496 calcd for C38
29 2
H N Se, found 593.1484 [M + H] .
6
-(4-Fluorophenyl)-12-(1H-indol-3-yl)-7-(methylselanyl)-5,12-
dihydrobenzo[4,5]cyclohepta[1,2-b]indole (3n). Yield: 45%;
melting point: 126–128 °C; IR (neat): 3420, 3057, 3008, 2928,
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E. Buyukbingol, Farmaco., 1998, 53, 525–527.
1
1
8
7
601, 1505, 1456, 1432, 1354, 1312, 1219, 1155, 1137, 1093,
−
1 1
012, 847, 831, 744, 667 cm ; H-NMR (400 MHz, CDCl ) δ
3
.00 (1H, d, J = 6.9 Hz), 7.87 (1H, d, J = 8.2 Hz), 7.77 (1H, s),
.67 (1H, d, J = 6.9 Hz), 7.48 (1H, s) 7.42 (1H, t, J = 6.9 Hz), 7.29
(1H, t, J = 7.1 Hz), 7.17–7.21 (4H, m), 7.09 (2H, s), 7.02 (2H, t, J
=
8.5 Hz), 6.83 (1H, t, J = 7.1 Hz), 6.60 (1H, s), 6.00 (1H, s), 1.03
1
3
(3H, t, J = 6.2 Hz); C-NMR (100 MHz, CDCl
3
) δ 144.6, 136.7,
36.6, 135.9, 135.9, 133.2, 133.1, 132.3, 129.2, 128.6, 127.2,
26.6, 126.0, 123.1, 122.4, 121.6, 120.4, 120.2, 120.0, 119.3,
1
1
1
7
7
3
18.3, 115.4, 111.2, 111.1, 40.5, 8.9; Se-NMR (75 MHz, CDCl )
δ 245.3; HRMS (ESI): m/z = 535.1089 calcd for C H N SeF,
3
2
24 2
+
found 535.1091 [M + H] .
-(4-Fluorophenyl)-12-(1H-indol-3-yl)-7-(phenylselanyl)-5,12-
6
dihydrobenzo[4,5]cyclohepta[1,2-b]indole (3o). Yield: 47%;
melting point: 114–116 °C; IR (neat): 3426, 3057, 3009, 2875,
1
1
7
7
7
601, 1576, 1505, 1476, 1456, 1439, 1354, 1311, 1219, 1156,
4 J. L. Stanton and M. H. Ackerman, J. Med. Chem., 1983, 26,
986–989.
5 B. Joseph, D. Alagille, J.-Y. Merour and S. Leonce, Chem.
Pharm. Bull., 2000, 48, 1872–1876.
6 M. Macchia, C. Manera, S. Nencetti, A. Rossello, G. Broccali
and D. Limonta, Farmaco., 1996, 51, 75–78.
7 J. Ackrell, F. Franco, R. G. A. Guzman and J. M. Muchowski,
J. Heterocycl. Chem., 1980, 17, 1081.
8 (a) A. Suarez, S. Suarez-Pantiga, O. Nieto-Faza and R. Sanz,
Org. Lett., 2017, 19, 5074–5077; (b) A. Chandra,
R. Viswanathan and J. N. Johnston, Org. Lett., 2007, 9,
5027–5029; (c) K. Higuchi and T. Kawasaki, Nat. Prod. Rep.,
−
1 1
092, 999, 831, 740, 690 cm ; H-NMR (400 MHz, CDCl ) δ
3
.92 (1H, d, J = 7.8 Hz), 7.89 (1H, s), 7.82 (1H, d, J = 7.8 Hz),
.67 (1H, d, J = 7.8 Hz), 7.49 (1H, s), 7.44 (1H, d, J = 8.2 Hz),
.27–7.35 (2H, m), 7.15–7.22 (6H, m), 7.01 (2H, td, J = 7.0, 3.8
Hz), 6.74 (1H, s), 6.67 (1H, t, J = 7.1 Hz), 6.12–6.20 (4H, m),
1
3
6
1
1
1
.08 (1H, s); C-NMR (100 MHz, CDCl
33.5, 132.5, 132.4, 131.6, 129.3, 128.9, 128.2, 127.4, 126.3,
25.6, 123.3, 122.6, 122.0, 120.2, 120.0, 119.7, 119.2, 118.5,
3
) δ 143.2, 136.9, 135.9,
7
7
3
14.5, 111.3, 111.0, 40.8; Se-NMR (75 MHz, CDCl ) δ 447.9;
HRMS (ESI): m/z = 597.1245 calcd for C H N SeF, found
3
7
26 2
+
5
97.1246 [M + H] .
2
8
007, 24, 843–868; (d) S. E. Lewis, Tetrahedron, 2006, 62,
655–8681; (e) R. G. Vaswani, J. J. Day and J. L. Wood, Org.
Conflicts of interest
Lett., 2009, 11, 4532–4535; (f) T. Yanagisawa, K. Kosakai,
T. Tomiyama, M. Yasunami and K. Takase, Chem. Pharm.
Bull., 1990, 38, 3355–3358.
There are no conflicts to declare.
9
(a) K. Sun, X. Wang, C. Li, H. Wang and L. Li, Org. Chem.
Front., 2020, 7, 3100; (b) K. Sun, S. Wang, R. Feng,
Y. Zhang, X. Wang, Z. Zhang and B. Zhang, Org. Lett., 2019,
Acknowledgements
2
1, 2052.
This study was supported by JSPS KAKENHI Grant Number
7550099 (to MK). KMNW and ADS are thankful to MEXT:
Monbukagakusho for the scholarship and thankful to
Masayuki Ninomiya and Horiyama Eito for the help in elemen-
tal analysis.
1
0 (a) L. Savegnago, A. I. Vieira, N. Seus, B. S. Goldani,
M. R. Castro, E. J. Lenardão and D. Alves, Tetrahedron Lett.,
2
J. A. Roehrs, D. Alves, C. Luchese and E. A. Wilhelm,
J. Psychiatr. Res., 2017, 84, 191–199; (c) M. Pinz, A. S. Reis,
V. Duarte, M. J. Rocha, B. S. Goldani, D. Alves,
L. Savegnago, C. Luchese and E. A. Wilhelm,
Eur. J. Pharmacol., 2016, 780, 122–128; (d) A. D. Sonawane,
R. A. Sonawane, M. Ninomiya and M. Koketsu, Adv. Synth.
Catal., 2020, 362, 3485–3515.
1
013, 54, 40–44; (b) A. S. Reis, M. Pinz, L. F. B. Duarte,
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