Preparation of 2-(3-Methyleneindolin-2-yl)phenols via Sodium Hydride Promoted C-C/C-O Bond Cleavage

Article abstract of DOI:10.1055/s-0037-1611850

A variety of 2-(3-methyleneindolin-2-yl)phenols were prepared in good to excellent yields through a NaH-promoted C-C/C-O bond cleavage of fused indolines under mild and simple conditions. Mechanistic studies showed that NaH serves as a nucleophile, attacking the aldehyde group of indoline, which is followed by tandem C-C/C-O bond cleavage to afford the desired products. A representative 2-(3-methyleneindolin-2-yl)phenol was easily prepared on a gram scale.

Full text of DOI:10.1055/s-0037-1611850

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–H
paper
A
de
F.-P. Liu et al.
Paper
Synthesis
Preparation of 2-(3-Methyleneindolin-2-yl)phenols via Sodium
Hydride Promoted C–C/C–O Bond Cleavage
Feng-Ping Liu ◊a
Hong-Ping Zhao ◊a
Shuang Tana
CHO
R3
OH
R3
O
NaH
R1
R1
MeCN, rt
N
21 examples
51–95% yield
N
R2
H
Xiuqiang Lub
R2
H
Dong-Liang Mo*a
0
0
0
0-0
0
0
2-4
0
0
5-2
2
4
9
·Inexpensive and green NaH
·Tandem C–C/C–O bond cleavage
·Good functional group tolerance
·New application of NaH as a nucleophile
a State Key Laboratory for Chemistry and Molecular Engineering
of Medicinal Resources, Ministry of Science and Technology of
China, School of Chemistry and Pharmaceutical Sciences,
Guangxi Normal University, 15 Yu Cai Road, Guilin 541004,
P. R. of China
moeastlight@mailbox.gxnu.edu.cn
b Fuqing Branch of Fujian Normal University, Fuzhou, Fujian
350300, P. R. of China
◊ F.-P. Liu and H.-P. Zhao contributed equally to this work.
Received: 04.04.2019
Accepted after revision: 13.05.2019
Published online: 12.06.2019
applications of NaH in green organic transformations is de-
sirable, especially for the synthesis of indoline alkaloids be-
cause of their importance in pharmaceuticals.
DOI: 10.1055/s-0037-1611850; Art ID: ss-2019-h0103-op
A) Chiba's work, NaH-promoted C–C, C–N or C–Br bond cleavage
R2
R1
Abstract A variety of 2-(3-methyleneindolin-2-yl)phenols were pre-
pared in good to excellent yields through a NaH-promoted C–C/C–O
bond cleavage of fused indolines under mild and simple conditions.
Mechanistic studies showed that NaH serves as a nucleophile, attacking
the aldehyde group of indoline, which is followed by tandem C–C/C–O
bond cleavage to afford the desired products. A representative 2-(3-
methyleneindolin-2-yl)phenol was easily prepared on a gram scale.
R2
R1
Ar
C–C cleavage
C–N cleavage
H
H
Ar
CN
NaH (3.0 equiv)
NaI (2.0 equiv)
O
O
R
NMe2
Br
R
THF, 85 °C
H
Key words cascade reaction, C–C/C–O bond cleavage, indolines, phe-
nols, sodium hydride
R
R
C–Br cleavage
B) This work, NaH-promoted tandem C–C/C–O bond cleavage
CHO
Sodium hydride (NaH) is a structurally simple, inexpen-
sive, and environmentally benign reagent in organic syn-
thesis because hydrogen is usually produced as byproduct
in the reaction.1 It is usually used as a mixture of 60% NaH
(w/w) in mineral oil, available from many suppliers, which
is safer to handle and weigh than pure NaH.2 Typically, NaH
is one of the most widely used reagents as a base for the
deprotonation of alcohols, amides, or esters to promote
their substitution and related cascade reactions.3 However,
NaH is rarely used as a reductant or a nucleophile to pro-
mote an organic transformation.4 Chiba and co-workers de-
veloped a unique NaH–LiI or NaI composite system to pro-
mote C–C, C–N, or C–Br bond cleavage of nitriles, amides,
and aryl halides (Scheme 1-A).5 In this context, it is evident
that NaH possesses a highly important utility in organic re-
actions, greener and more environmentally friendly than
transition-metal catalysis in modern organic chemistry,
and thus a good complement to transition-metal catalysis
for purity requirements in biological and medicinal re-
search.6 Therefore, the development of novel and efficient
R3
R3
O
OH
R1
R1
NaH
MeCN, rt
N
N
H
R2
H
R2
Scheme 1 NaH-promoted C–C or carbon–heteroatom bond cleavage
Recently, we reported that fused indolines containing
C2/C3 quaternary carbons can be easily prepared in good
yields from oximes and diaryliodonium salts through a se-
lective N-arylation and cycloaddition cascade strategy.7
During the continuing research on these indoline scaffolds,
we found that the fused indolines containing C2/C3 quater-
nary carbons could be easily converted into 2-(3-methy-
leneindolin-2-yl)phenols via NaH-promoted C–C/C–O bond
cleavage under mild and simple conditions. However, the
role of NaH was unclear and the substrate scope to access
the 2-(3-methyleneindolin-2-yl)phenols remained unex-
plored. On the other hand, indoline scaffolds are important
cores, existing in a variety of indole alkaloids, such as kop-
sanone, scholarisine A, preakuammicine, and phalarine.8 To
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Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
F.-P. Liu et al.
Paper
Synthesis
date, many strategies to construct these scaffolds have been
developed and successfully used to synthesize complex nat-
ural products.9 To establish the role of NaH and the reaction
scope, herein we report a NaH-promoted C–C/C–O bond
cleavage of easily accessed fused indolines to prepare 2-(3-
methyleneindolin-2-yl)phenols under mild and simple con-
ditions (Scheme 1-B).
Table 1 Optimization of the Reaction Conditionsa
O
CHO
OH
conditions
N
N
H
H
Ph
Ph
2a
1a
Initially, we found that when fused indoline 1a was
treated with 3.0 equivalents of NaH in DMSO at room tem-
perature for 2 hours, the 2-(3-methyleneindolin-2-yl)phe-
nol product 2a was obtained in 89% yield (Table 1, entry 1).
The structure of compound 2a was confirmed by X-ray dif-
fraction analysis,10 showing that the NaH-promoted C–C
bond and C–O bond cleavage had occurred in a one-pot
manner. It is noteworthy that the NaH we used was a mix-
ture of 60% NaH (w/w) in mineral oil. Next, solvent screen-
ing showed that low yields of product 2a were obtained in
DMF, DCE, or toluene, while the reaction in THF failed to af-
ford 2a (entries 2–5). However, a 38% yield of 2a was ob-
tained in THF when 3.0 equivalents of NaI were added (en-
try 6). Pleasingly, a 90% yield of 2a was obtained when
MeCN was used as solvent ( entry 7). We surmised that NaH
might play a role as a base. Consequently, the influence of
base was also investigated. Both KOH and NaOH promoted
the reaction and afforded product 2a in 46% yield (entries 8,
9). However, K2CO3 did not participate in the reaction and
no conversion was observed after 24 hours (entry 10). To
our surprise, when NaH was replaced by other hydrides,
such as NaBH4 and LiAlH4, desired product 2a was not ob-
served and only the aldehyde reduction product was ob-
tained in a quantitative yield (entries 11, 12). The use of 4.0
or 2.0 equivalents of NaH delivered 2a in 53% and 74% yield,
respectively (entries 13, 14). When the reaction tempera-
ture was increased to 60 °C, the yield of 2a dropped to 65%
(entry 15). No reaction occurred in the absence of NaH (en-
try 16). Hence, the optimal conditions for preparing prod-
uct 2a were 3.0 equivalents of NaH in MeCN at room tem-
perature.
With the optimal reaction conditions in hand, we next
explored the substrate scope with a variety of fused indo-
lines 1 to prepare 2-(3-methyleneindolin-2-yl)phenols 2
(Scheme 2). Various R2 styrenyl groups bearing an electron-
donating or electron-withdrawing group at the para-, meta-
, or ortho-position of the aryl ring were well tolerated, af-
fording the corresponding products 2a–2g in good to excel-
lent yields. It can be seen that the styrenyl groups with an
electron-donating group gave better yields than those with
an electron-withdrawing group (2a, 2b vs 2c, 2d). The R3
group on the aryl ring was compatible with various substit-
uents, including electron-donating and electron-withdraw-
ing groups at the para-, meta-, or ortho-positions, to result
in products 2h–2q in moderate to good yields. Some R3
electron-withdrawing groups resulted in lower yields be-
cause of the recovery of starting materials (2k and 2m).
Entry
Base
Solvent
Yield (%) of 2ab
1
2
NaH
NaH
NaH
NaH
NaH
NaH
NaH
KOH
NaOH
K2CO3
NaBH4
LiAlH4
NaH
NaH
NaH
–
DMSO
DMF
89
31
52
21
<5, 25c
38d
90
46
46
<5
3
DCE
4
toluene
THF
5
6
THF
7
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
8
9
10
11
12
13
14
15
16
–
–
53e
74f
65g
–
a Reaction conditions: 1a (0.2 mmol), base (0.6 mmol, 3.0 equiv), solvent
(2.0 mL), rt, 1–24 h.
b Isolated yield.
c Run for 48 h.
d NaI (3.0 equiv) added.
e NaH (4.0 equiv).
f NaH (2.0 equiv).
g Run at 60 °C.
Product 2r bearing a methoxy group as R1 was obtained in
better yield than 2s with a fluoro group. To our surprise,
when the reaction of substrate 1t with a methyl group as
the R2 group was conducted under the optimized condi-
tions, no desired product 2t was observed. However, lower-
ing the temperature to 0 °C afforded the desired 2t in 86%
yield.
Interestingly, when the R3 group was an ester at the
para-position of the aryl ring, namely 1u, the desired 2-(3-
methyleneindolin-2-yl)phenol was not observed. However,
decarbonylation product 3u was obtained in 36% yield
(Scheme 3-1). Similarly, 1v with R3 as a nitro group at the
meta-position of the aryl ring also afforded decarbonylation
product, in this case 3v in 32% yield (Scheme 3-2). The
yields of compound 3u and 3v were low because the reac-
tion did not run to completion even after a long reaction
time (48 h), and recovered starting material 1u/1v was iso-
lated. Moreover, compound 2u or 2v cannot be observed in
these two examples. In comparison, the reaction of 1k and
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

C
F.-P. Liu et al.
Paper
Synthesis
OH
CHO
O
R1
R1
NaH
R3
R3
MeCN, rt
N
N
R2
H
R2
H
2
1
OH
R = H,
R = 4-OMe, 2b, 95%
R = 4-F, 2c, 79%
R = 4-CF3, 2d, 75%a
R = 3-OMe, 2e, 87%a
R = 3-Br, 2f, 74%
R = 2-Br, 2g, 78%
2a, 90%
OH
Ph
R3 = OMe, 2h, 81%
R3 = Me, 2i, 79%
R3 = t-Bu, 2j, 90%
2k, 69%
2l, 78%a
R3 = CF3, 2m, 51%
R3
N
H
R3 = F,
R3 = Cl,
N
H
R
OH
Ph
Me
OH
Br
OH
N
H
N
Me
H
N
H
Me
Br
Ph
Ph
2n, 72%
2o, 72%
2p, 68%
OH
OH
OH
Me
Me
N
N
H
N
H
R1
H
Br
Me
Ph
Ph
2q, 78%a
2t, 86%b
R1 = OMe, 2r, 63%
R1 = F,
2s, 51%
Scheme 2 Reaction scope of C–C/C–O bond cleavage to prepare 2-(3-methyleneindolin-2-yl)phenols 2. Reagents and conditions: 1 (0.2 mmol), NaH
(0.6 mmol, 3.0 equiv, 60% NaH (w/w) in mineral oil), MeCN (2.0 mL), rt, 1–12 h; isolated yields. a Run for 4–6 h. b Run at 0 °C.
1m with F and CF3 at the para-position of the aryl ring
(Scheme 2) afforded 2k and 2m, and not 3k and 3m, under
the standard conditions. These results indicated that strong
electron-withdrawing groups at the aryl ring of the indo-
line moiety inhibit the sequential C–O bond cleavage. The
formation of compound 3 might require a strong electron-
withdrawing group, such as NO2 or CO2Me, to stabilize the
intermediate of C–C bond cleavage.
one equivalent of aldehyde through C–C bond cleavage by
NaH. Compound 1u was reacted with NaH; then, the reac-
tion was quenched with D2O. Expected product 3u was ob-
tained in 40% yield with a 5:1 dr, and 20% deuteration at the
indoline C3-position was observed (Scheme 4-2). This re-
sult indicates that the formation of compound 3 involved an
intermolecular protonation step. When 1a was subjected to
the standard conditions with the addition of TEMPO (1.0
equiv), product 2a was still obtained in 89% yield, which
suggests that the reaction might not involve a radical pro-
cess (Scheme 4-3). No reaction occurred with N-methyl-
protected substrate 1ab under the standard conditions,
with the recovery of starting material 1ab (Scheme 4-4).
Based on the experimental results, a plausible mecha-
nism for the formation of compounds 2 and 3 is proposed.
As shown in Scheme 5, deprotonation of compound 1 forms
intermediate A and releases hydrogen. Then, NaH might
serve as a nucleophile to attack the aldehyde group of A,
which then undergoes C–C bond cleavage to provide car-
banion intermediate B with release of HCHO. C–O bond
cleavage of B provides intermediate C. Intermediate C is
quenched with water affording compound 2. Alternatively,
R3 as a strong electron-withdrawing group stabilizes the
carbanion of B. Finally, intermediate B undergoes protona-
tion to afford compound 3. It is noteworthy that the substit-
uent effect of the aryl ring of indoline controls the selectivi-
ty for formation of compounds 2 and 3.
O
CHO
O
CO2Me
H
CO2Me
NaH
MeCN, rt
36%
1)
N
N
H
H
Ph
Ph
1u
CHO
3u
O
H
O
NaH
2)
NO2
NO2
N
MeCN, rt
32%
N
H
H
Ph
Ph
1v
3v
Scheme 3 Substituent effect on the formation of fused indolines 3
To better understand the mechanism for the formation
of compounds 2 and 3, control experiments were per-
formed (Scheme 4). When compound 1aa was subjected to
the optimized conditions, desired 2a was obtained in 55%
yield accompanied by a 21% yield of benzaldehyde (Scheme
4-1). This result revealed that the reaction should release
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

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F.-P. Liu et al.
Paper
Synthesis
gram-scale preparation of 2-(3-methyleneindolin-2-
yl)phenols by this simple procedure allows further poten-
tial applications of these compounds in pharmaceuticals.
O
OH
Ph
O
NaH
MeCN, rt
PhCHO
21%
+
1)
N
N
H
H
CHO
OH
O
NaH
Ph
2a, 55%
Ph
O
MeCN, rt
1aa
N
N
H
H
20% D
H(D)
O
CHO
CO2Me
CO2Me
Ph
Ph
1a (4.0 mmol, 1.4 g)
D2O
NaH
2)
2a (1.14 g, 88% yield)
MeCN, rt
N
N
H
H
Scheme 6 Gram-scale preparation of 2-(3-methyleneindolin-2-yl)phe-
nol 2a
Ph
Ph
O
1u
3u, 40%, dr = 5:1
OH
CHO
In summary, we have developed a novel NaH-promoted
tandem C–C/C–O bond cleavage of fused indolines to pre-
pare a variety of 2-(3-methyleneindolin-2-yl)phenols. Pre-
liminary results show that NaH serves as a nucleophile in
the reaction. The present method features mild and simple
conditions, gram-scale preparation, tandem C–C/C–O bond
cleavage, and a new application of NaH in organic transfor-
mations.
NaH
3)
MeCN, rt
N
H
N
H
TEMPO (1.0 equiv)
Ph
Ph
O
2a, 89%
1a
CHO
OH
NaH
4)
N
MeCN, rt
N
Me
Me
Ph
Ph
All reactions were performed under a N2 atmosphere except noted.
Commercially available reagents were used without further purifica-
tion. NMR spectra were recorded in CDCl3 or DMSO-d6 on a 400 or
500 MHz Bruker Avance instrument with TMS as the internal stan-
dard. NMR data are represented as follows: chemical shift (ppm),
multiplicity (standard abbreviations), coupling constant(s) in hertz
(Hz), and integration. IR spectra were recorded on a PerkinElmer/
Spectrum Two FT-IR spectrophotometer, and only major peaks are re-
ported (in cm–1). HRMS were measured on a Thermo Fisher Scientif-
ic/Exactive spectrometer in ESI mode with a TOF mass analyzer. Flash
column chromatography was performed on silica gel (300–400
mesh). The fused indolines 1a–1q, 1s–1v, 1aa, and 1ab7 were pre-
pared according to literature methods and their spectroscopic data
matched literature values.
2ab, 0%
1ab
Scheme 4 Mechanistic studies
CHO
O
CHO
O
R1
R1
NaH
R3
R3
N
N
R2
H
R2
H2
Na
1
A
NaH
HCHO
O
O
R1
R3
R1
C–O
cleavage
R3
N
R2
Fused Indolines 1; General Procedure7
Na
N
R2
Na
C
A Teflon-sealed reaction flask was charged with an alkynyl-tethered
oxime (0.2 mmol), a diaryliodonium salt (0.4 mmol, 2.0 equiv), and
KOH (0.24 mmol, 1.2 equiv) under an air atmosphere, and CCl4 (2.0
mL) was added. The reaction vessel was sealed with a Teflon cap and
stirred vigorously at 25 °C for 3–12 h until the starting material disap-
peared (monitored by TLC). Then, the reaction mixture was stirred
vigorously at 80 °C for 3–6 h (monitored by TLC). After this time, the
solvent was removed under reduced pressure and the crude product
was purified by flash chromatography (the crude residue was dry-
loaded with silica gel; EtOAc/petroleum ether, 1:50 to 1:10) to pro-
vide the fused indoline 1.
B
H2O
H2O
R2 = EWG
OH
R2
O
H
R1
R1
R3
R3
N
N
H
R2
H
3
2
Scheme 5 Proposed mechanism
(E)-2-Methoxy-11a-styryl-6,6a,11,11a-tetrahydrochromeno[4,3-
b]indole-6a-carbaldehyde (1r)
To show the efficiency of this protocol for preparing 2-
(3-methyleneindolin-2-yl)phenols, a gram-scale prepara-
tion of 2a was performed (Scheme 6). When compound 1a
(1.4 g) was subjected to the optimal NaH conditions for 4
hours, phenol 2a was obtained in 88% yield (1.14 g). The
Yield: 0.054 g (70%); yellow solid; mp 119–120 °C.
IR (thin film): 3454, 2834, 1605, 1496, 1210, 1055, 813, 749 cm–1
.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

E
F.-P. Liu et al.
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Synthesis
1H NMR (400 MHz, CDCl3):  = 9.57 (s, 1 H), 7.37–7.36 (m, 2 H), 7.32–
7.24 (m, 3 H), 7.15–7.11 (m, 2 H), 7.00 (d, J = 16.0 Hz, 1 H), 6.84–6.77
(m, 2 H), 6.73–6.68 (m, 3 H), 6.46 (d, J = 15.6 Hz, 1 H), 4.70 (d, J = 12.4
Hz, 1 H), 4.38 (s, 1 H), 4.34 (d, J = 12.0 Hz, 1 H), 3.70 (s, 3 H).
1H NMR (400 MHz, DMSO-d6):  = 9.94 (s, 1 H), 7.45–7.42 (m, 3 H),
7.31 (d, J = 7.6 Hz, 1 H), 7.14–7.11 (m, 2 H), 7.09–7.05 (m, 1 H), 6.83
(d, J = 8.0 Hz, 1 H), 6.78–6.73 (m, 2 H), 6.69–6.57 (m, 3 H), 6.38 (d, J =
16.0 Hz, 1 H), 5.71 (s, 1 H), 4.85 (s, 1 H).
13C NMR (100 MHz, CDCl3):  = 197.0, 154.6, 149.9, 148.3, 135.7,
132.6, 130.1, 129.0, 128.6, 128.2, 127.6, 126.8, 124.7, 122.8, 120.3,
118.5, 115.0, 111.9, 110.8, 70.1, 63.3, 61.7, 55.7.
HRMS (ESI): m/z calcd for C25H22NO3 [M + H]+: 384.1594; found:
384.1617.
13C NMR (125 MHz, CDCl3):  = 163.6 (d, J = 246.9 Hz), 156.8, 148.0,
147.0, 132.1 (d, J = 2.8 Hz), 130.2, 130.1, 129.6, 129.0, 128.8, 128.4,
128.3, 126.3, 122.0, 121.4, 119.2, 118.0, 115.6 (d, J = 21.0 Hz), 113.7,
106.8, 74.5.
19F NMR (376 MHz, CDCl3):  = –113.5.
HRMS (ESI): m/z calcd for C23H19FNO [M + H]+: 344.1445; found:
344.1440.
2-(3-Methyleneindolin-2-yl)phenols 2 and Fused Indolines 3;
General Procedure
A Teflon-sealed flask was charged with a fused indoline 1 (0.2 mmol)
and NaH (0.6 mmol, 3.0 equiv, 60% NaH (w/w) in mineral oil) under
N2 atmosphere. Then, MeCN (2.0 mL) was added. The reaction vessel
was sealed with a Teflon cap and stirred vigorously at rt (about 30 °C)
for 1–12 h until the substrate 1 disappeared (monitored by TLC). After
this time, the reaction was quenched with H2O (5 mL) and the mix-
ture was extracted with EtOAc (3 × 10 mL). The combined organic lay-
ers were dried over Na2SO4 and filtered. The solvent was removed un-
der reduced pressure and the crude product was purified by flash col-
umn chromatography (the crude residue was dry-loaded with silica
gel; EtOAc/petroleum ether, 1:50 to 1:10) to provide compounds 2
and 3.
(E)-2-(3-Methylene-2-(4-(trifluoromethyl)styryl)indolin-2-
yl)phenol (2d)
Yield: 0.059 g (75%); white solid; mp 181–182 °C.
IR (thin film): 2963, 1616, 1461, 1327, 1106, 804 cm–1
.
1H NMR (400 MHz, DMSO-d6):  = 9.93 (s, 1 H), 7.62 (s, 3 H), 7.43 (d,
J = 7.6 Hz, 1 H), 7.33 (d, J = 7.6 Hz, 1 H), 7.15–7.11 (m, 1 H), 7.09–7.05
(m, 1 H), 6.85–6.70 (m, 5 H), 6.66–6.62 (m, 1 H), 6.49 (d, J = 15.6 Hz, 1
H), 5.74 (s, 1 H), 4.91 (s, 1 H).
13C NMR (100 MHz, DMSO-d6):  = 156.3, 151.5, 150.7, 141.5, 137.8,
130.7, 129.3, 129.0, 128.9, 128.5, 128.4, 128.1 (q, J = 31.3 Hz), 127.5,
126.3 (q, J = 3.8 Hz), 123.6 (q, J = 245.8 Hz), 121.7, 119.1, 118.3, 117.1,
110.7, 105.1, 72.9.
(E)-2-(3-Methylene-2-styrylindolin-2-yl)phenol (2a)
19F NMR (376 MHz, CDCl3):  = –62.6.
Yield: 0.059 g (90%); white solid; mp 178–179 °C.
IR (thin film): 3324, 2926, 1502, 1459, 1251, 1124, 875, 751 cm–1
HRMS (ESI): m/z calcd for C24H19F3NO [M + H]+: 394.1413; found:
394.1408.
.
1H NMR (400 MHz, CDCl3):  = 9.98 (s, 1 H), 7.50 (d, J = 7.6 Hz, 1 H),
7.37 (d, J = 7.2 Hz, 2 H), 7.31–7.27 (m, 2 H), 7.24–7.17 (m, 4 H), 6.97 (t,
J = 7.6 Hz, 1 H), 6.90–6.85 (m, 3 H), 6.60 (d, J = 15.6 Hz, 1 H), 6.47 (d,
J = 15.6 Hz, 1 H), 5.71 (s, 1 H), 4.71 (s, 1 H), 4.44 (br s, 1 H).
13C NMR (100 MHz, CDCl3):  = 156.8, 148.2, 147.1, 136.0, 131.3,
130.4, 130.2, 129.5, 129.1, 128.8, 128.6, 128.1, 126.8, 126.4, 122.0,
121.4, 119.2, 117.9, 113.6, 106.7, 74.5.
(E)-2-(2-(3-Methoxystyryl)-3-methyleneindolin-2-yl)phenol (2e)
Yield: 0.061 g (87%); white solid; mp 158–159 °C.
IR (thin film): 3321, 2932, 1577, 1459, 1250, 1156, 883, 762 cm–1
.
1H NMR (400 MHz, DMSO-d6):  = 9.96 (s, 1 H), 7.44 (d, J = 7.2 Hz, 1
H), 7.33 (d, J = 7.2 Hz, 1 H), 7.23–7.19 (m, 1 H), 7.15–7.06 (m, 2 H),
6.98–6.95 (m, 2 H), 6.85–6.81 (m, 1 H), 6.79–6.77 (m, 2 H), 6.75–6.72
(m, 1 H), 6.69–6.66 (m, 2 H), 6.39 (d, J = 16.0 Hz, 1 H), 5.73 (s, 1 H),
4.88 (s, 1 H), 3.73 (s, 3 H).
HRMS (ESI): m/z calcd for C23H20NO [M + H]+: 326.1539; found:
326.1534.
13C NMR (100 MHz, DMSO-d6):  = 160.1, 156.4, 151.3, 150.8, 138.7,
134.7, 130.6, 130.2, 129.1, 129.0, 128.6, 127.6, 126.2, 121.7, 119.4,
119.0, 118.3, 117.1, 113.9, 111.8, 110.8, 105.0, 73.0, 55.6.
(E)-2-(2-(4-Methoxystyryl)-3-methyleneindolin-2-yl)phenol (2b)
Yield: 0.067 g (95%); white solid; mp 153–154 °C.
IR (thin film): 2927, 1604, 1460, 1257, 1100, 807 cm–1
.
HRMS (ESI): m/z calcd for C24H22NO2 [M + H]+: 356.1645; found:
1H NMR (400 MHz, DMSO-d6):  = 9.98 (s, 1 H), 7.44 (d, J = 7.2 Hz, 1
H), 7.33–7.29 (m, 3 H), 7.14–7.06 (m, 2 H), 6.87–6.85 (m, 2 H), 6.82 (d,
J = 8.8 Hz, 1 H), 6.78 (d, J = 7.6 Hz, 1 H), 6.74 (d, J = 9.6 Hz, 1 H), 6.68–
6.64 (m, 1 H), 6.50 (d, J = 16.0 Hz, 1 H), 6.33 (d, J = 16.0 Hz, 1 H), 5.70
(s, 1 H), 4.81 (s, 1 H), 3.72 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 159.6, 156.8, 148.2, 147.1, 130.7,
130.1, 129.4, 129.1, 128.9, 128.6, 128.3, 128.0, 126.6, 121.9, 121.4,
119.1, 117.9, 114.0, 113.7, 106.7, 74.7, 55.3.
356.1640.
(E)-2-(2-(3-Bromostyryl)-3-methyleneindolin-2-yl)phenol (2f)
Yield: 0.060 g (74%); white solid; mp 185–186 °C.
IR (thin film): 3325, 2962, 1602, 1457, 1248, 1101, 805, 760 cm–1
.
1H NMR (400 MHz, DMSO-d6):  = 9.91 (s, 1 H), 7.62 (s, 1 H), 7.42–
7.38 (m, 3 H), 7.31 (d, J = 7.6 Hz, 1 H), 7.27–7.23 (m, 1 H), 7.14–7.05
(m, 2 H), 6.82 (d, J = 8.4 Hz, 1 H), 6.78–6.70 (m, 2 H), 6.66–6.62 (m, 2
H), 6.39 (d, J = 16.0 Hz, 1 H), 5.72 (s, 1 H), 4.89 (s, 1 H).
13C NMR (100 MHz, DMSO-d6):  = 158.3, 151.4, 150.7, 136.4, 134.0,
131.4, 130.7, 130.5, 129.2, 129.0, 128.6, 126.1, 126.0, 122.8, 121.7,
119.1, 118.3, 117.1, 110.8, 105.1, 72.8.
HRMS (ESI): m/z calcd for C24H22NO2 [M + H]+: 356.1645; found:
356.1640.
(E)-2-(2-(4-Fluorostyryl)-3-methyleneindolin-2-yl)phenol (2c)
Yield: 0.054 g (79%); white solid; mp 156–157 °C.
IR (thin film): 3316, 2926, 1600, 1459, 1251, 1232, 816, 756 cm–1
HRMS (ESI): m/z calcd for C23H19BrNO [M + H]+: 404.0645; found:
404.0638.
.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

F
F.-P. Liu et al.
Paper
Synthesis
(E)-2-(2-(2-Bromostyryl)-3-methyleneindolin-2-yl)phenol (2g)
1H NMR (400 MHz, DMSO-d6):  = 9.96 (s, 1 H), 7.40–7.38 (m, 2 H),
7.32–7.28 (m, 4 H), 7.22–7.19 (m, 1 H), 7.15–7.11 (m, 1 H), 6.94–6.89
(m, 1 H), 6.83–6.77 (m, 1 H), 6.74–6.71 (m, 1 H), 6.65–6.62 (m, 2 H),
6.41 (d, J = 15.6 Hz, 1 H), 5.78 (s, 1 H), 4.91 (s, 1 H).
13C NMR (100 MHz, DMSO-d6):  = 157.7 (d, J = 231.1 Hz), 156.4, 150.5
(d, J = 2.9 Hz), 147.8, 137.2, 134.2, 129.3, 129.2, 128.9, 128.6, 128.0 (d,
J = 23.3 Hz), 127.7, 127.6, 127.0, 119.1, 117.1, 116.9, 111.5 (d, J = 8.0
Hz), 108.5 (d, J = 23.3 Hz), 106.6, 73.7.
Yield: 0.063 g (78%); white solid; mp 149–150 °C.
IR (thin film): 3431, 1606, 1461, 1246, 747 cm–1
.
1H NMR (400 MHz, CDCl3):  = 9.93 (s, 1 H), 7.52–7.47 (m, 3 H), 7.27–
7.19 (m, 4 H), 7.11–7.07 (m, 1 H), 6.99–6.96 (m, 2 H), 6.91–6.87 (m, 3
H), 6.37 (d, J = 15.6 Hz, 1 H), 5.74 (s, 1 H), 4.75 (s, 1 H), 4.48 (br s, 1 H).
13C NMR (125 MHz, CDCl3):  = 156.7, 148.1, 146.9, 136.2, 133.1,
132.9, 130.6, 130.2, 129.6, 129.2, 129.0, 128.7, 127.5, 127.2, 126.0,
124.1, 122.0, 121.5, 119.2, 118.0, 113.5, 106.8, 74.5.
19F NMR (376 MHz, CDCl3):  = –121.7.
HRMS (ESI): m/z calcd for C23H19FNO [M + H]+: 344.1445; found:
HRMS (ESI): m/z calcd for C23H19BrNO [M + H]+: 404.0645; found:
404.0638.
344.1441.
(E)-2-(5-Chloro-3-methylene-2-styrylindolin-2-yl)phenol (2l)
(E)-2-(5-Methoxy-3-methylene-2-styrylindolin-2-yl)phenol (2h)
Yield: 0.056 g (78%); white solid; mp 165–166 °C.
Yield: 0.058 g (81%); white solid; mp 165–166 °C.
IR (thin film): 3337, 1462, 1261, 1105, 822, 755 cm–1
.
IR (thin film): 3433, 2924, 1640, 1459, 1116, 761 cm–1
.
1H NMR (400 MHz, DMSO-d6):  = 9.79 (s, 1 H), 7.47 (s, 1 H), 7.40–
7.38 (m, 2 H), 7.31–7.28 (m, 3 H), 7.22–7.19 (m, 1 H), 7.15–7.11 (m, 1
H), 7.07 (d, J = 8.4 Hz, 1 H), 6.84 (d, J = 7.6 Hz, 1 H), 6.80–6.76 (m, 1 H),
6.71 (d, J = 8.0 Hz, 1 H), 6.66 (d, J = 16.0 Hz, 1 H), 6.40 (d, J = 15.6 Hz, 1
H), 5.79 (s, 1 H), 4.93 (s, 1 H).
13C NMR (125 MHz, CDCl3):  = 156.6, 147.1, 145.6, 135.7, 131.5,
130.4, 130.0, 129.9, 129.7, 129.0, 128.7, 128.3, 127.2, 126.8, 126.0,
121.5, 119.3, 118.0, 114.6, 108.2, 75.2.
1H NMR (400 MHz, CDCl3):  = 10.45 (s, 1 H), 7.38–7.37 (m, 2 H),
7.32–7.28 (m, 2 H), 7.25–7.20 (m, 3 H), 7.04 (s, 1 H), 6.90–6.80 (m, 4
H), 6.60 (d, J = 15.6 Hz, 1 H), 6.49 (d, J = 15.6 Hz, 1 H), 5.69 (s, 1 H),
4.72 (s, 1 H), 4.28 (br s, 1 H), 3.81 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 157.0, 155.6, 148.5, 140.6, 136.0,
131.3, 130.5, 130.1, 129.5, 129.0, 128.6, 128.1, 126.8, 126.3, 119.0,
117.9, 117.1, 114.7, 106.9, 105.9, 75.2, 55.8.
HRMS (ESI): m/z calcd for C24H22NO2 [M + H]+: 356.1645; found:
356.1638.
HRMS (ESI): m/z calcd for C23H19ClNO [M + H]+: 360.1150; found:
360.1145.
(E)-2-(5-Methyl-3-methylene-2-styrylindolin-2-yl)phenol (2i)
(E)-2-(3-Methylene-2-styryl-5-(trifluoromethyl)indolin-2-yl)phe-
nol (2m)
Yield: 0.054 g (79%); white solid; mp 153–154 °C.
IR (thin film): 3432, 1638, 1384, 749 cm–1
.
Yield: 0.040 g (51%); white solid; mp 168–169 °C.
1H NMR (500 MHz, CDCl3):  = 10.25 (s, 1 H), 7.38–7.37 (m, 2 H),
7.32–7.29 (m, 2 H), 7.24–7.21 (m, 4 H), 7.03 (d, J = 8.0 Hz, 1 H), 6.90
(d, J = 8.0 Hz, 1 H), 6.87 (d, J = 8.0 Hz, 1 H), 6.81 (d, J = 8.0 Hz, 1 H), 6.61
(d, J = 15.5 Hz, 1 H), 6.48 (d, J = 15.5 Hz, 1 H), 5.69 (s, 1 H), 4.69 (s, 1 H),
4.36 (br s, 1 H), 2.33 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 156.9, 148.2, 144.7, 136.0, 131.6,
131.3, 131.0, 130.5, 129.5, 129.1, 129.0, 128.6, 128.5, 128.1, 126.8,
126.7, 126.4, 121.8, 119.0, 117.9, 113.6, 106.4, 74.9, 20.6.
IR (thin film): 3331, 2962, 2925, 1513, 1451, 1262, 1102, 803, 748
cm–1
.
1H NMR (400 MHz, DMSO-d6):  = 9.67 (s, 1 H), 7.69 (s, 1 H), 7.43–
7.41 (m, 2 H), 7.38 (s, 1 H), 7.35–7.29 (m, 4 H), 7.23–7.20 (m, 1 H),
7.15–7.11 (m, 1 H), 6.82 (d, J = 8.0 Hz, 1 H), 6.78–6.74 (m, 1 H), 6.69
(d, J = 16.0 Hz, 1 H), 6.42 (d, J = 16.0 Hz, 1 H), 5.84 (s, 1 H), 4.99 (s, 1 H).
13C NMR (125 MHz, CDCl3):  = 156.2, 150.1, 146.8, 135.7, 131.4,
129.9, 129.8, 129.0, 128.7, 128.5, 128.4, 127.5 (q, J = 3.6 Hz), 126.8,
126.1, 119.6, 118.8 (q, J = 3.6 Hz), 118.1, 112.9, 108.6, 74.9.
HRMS (ESI): m/z calcd for C24H22NO [M + H]+: 340.1696; found:
340.1691.
19F NMR (470 MHz, CDCl3):  = –61.4.
HRMS (ESI): m/z calcd for C24H19F3NO [M + H]+: 394.1413; found:
394.1408.
(E)-2-(5-tert-Butyl-3-methylene-2-styrylindolin-2-yl)phenol (2j)
Yield: 0.069 g (90%); white solid; mp 150–151 °C.
IR (thin film): 3318, 2961, 1609, 1490, 1257, 1108, 815, 748 cm–1
.
(E)-2-(4,6-Dimethyl-3-methylene-2-styrylindolin-2-yl)phenol
1H NMR (400 MHz, CDCl3):  = 10.26 (s, 1 H), 7.51 (s, 1 H), 7.39–7.37
(m, 2 H), 7.32–7.28 (m, 3 H), 7.24–7.20 (m, 3 H), 6.89–6.81 (m, 3 H),
6.62 (d, J = 16.0 Hz, 1 H), 6.48 (d, J = 16.0 Hz, 1 H), 5.72 (s, 1 H), 4.69 (s,
1 H), 4.35 (br s, 1 H), 1.32 (s, 9 H).
13C NMR (125 MHz, CDCl3):  = 156.9, 148.7, 145.2, 144.7, 136.1,
131.3, 130.5, 129.4, 129.0, 128.6, 128.5, 128.1, 127.6, 126.8, 126.6,
119.0, 118.0, 117.9, 113.3, 106.1, 74.9, 34.5, 31.6.
(2n)
Yield: 0.051 g (72%); white solid; mp 180–181 °C.
IR (thin film): 3433, 2963, 1533, 1383, 1261, 1097, 803 cm–1
.
1H NMR (400 MHz, CDCl3):  = 9.98 (s, 1 H), 7.38–7.36 (m, 2 H), 7.32–
7.28 (m, 2 H), 7.26–7.21 (m, 3 H), 6.91 (d, J = 7.6 Hz, 1 H), 6.83–6.82
(m, 1 H), 6.58–6.53 (m, 3 H), 6.47 (d, J = 16.0 Hz, 1 H), 5.62 (s, 1 H),
4.71 (s, 1 H), 4.39 (br s, 1 H), 2.48 (s, 3 H), 2.27 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 156.9, 148.7, 148.0, 140.0, 136.1,
135.0, 131.0, 130.9, 129.5, 129.3, 128.6, 128.0, 126.8, 126.7, 125.3,
123.9, 119.0, 118.0, 111.7, 109.2, 74.9, 21.5, 20.7.
HRMS (ESI): m/z calcd for C27H28NO [M + H]+: 382.2165; found:
382.2156.
(E)-2-(5-Fluoro-3-methylene-2-styrylindolin-2-yl)phenol (2k)
HRMS (ESI): m/z calcd for C25H24NO [M + H]+: 354.1852; found:
354.1848.
Yield: 0.047 g (69%); white solid; mp 162–163 °C.
IR (thin film): 3327, 2924, 1580, 1484, 1254, 1114, 805, 750 cm–1
.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

G
F.-P. Liu et al.
Paper
Synthesis
(E)-2-(5,7-Dibromo-3-methylene-2-styrylindolin-2-yl)phenol (2o)
IR (thin film): 3434, 2963, 1605, 1480, 1261, 1097, 800, 749 cm–1
.
1H NMR (400 MHz, CDCl3):  = 9.74 (s, 1 H), 7.52 (d, J = 7.6 Hz, 1 H),
7.38–7.36 (m, 2 H), 7.32–7.27 (m, 3 H), 7.23–7.19 (m, 1 H), 7.00–6.95
(m, 2 H), 6.94–6.88 (m, 2 H), 6.83–6.80 (m, 1 H), 6.62 (d, J = 15.6 Hz, 1
H), 6.43 (d, J = 15.6 Hz, 1 H), 5.74 (s, 1 H), 4.75 (s, 1 H), 4.46 (br s, 1 H).
13C NMR (100 MHz, CDCl3):  = 157.1 (d, J = 235.5 Hz), 152.7 (d, J = 2.2
Hz), 147.8, 147.0, 135.7, 131.9, 130.3, 129.5, 128.7, 128.6, 128.3,
126.8, 122.1, 121.4, 118.6, 118.5, 115.9 (d, J = 22.6 Hz), 115.5 (d, J =
24.1 Hz), 113.7, 106.9, 74.3.
Yield: 0.069 g (72%); white solid; mp 101–102 °C.
IR (thin film): 3406, 2926, 1580, 1444, 1241, 1108, 752, 692 cm–1
.
1H NMR (400 MHz, DMSO-d6):  = 9.96 (s, 1 H), 7.66 (s, 1 H), 7.44–
7.40 (m, 3 H), 7.32–7.28 (m, 3 H), 7.23–7.20 (m, 1 H), 7.17–7.13 (m, 1
H), 6.85–6.82 (m, 1 H), 6.80–6.76 (m, 1 H), 6.67 (d, J = 15.6 Hz, 1 H),
6.34 (d, J = 16.0 Hz, 1 H), 5.91 (s, 1 H), 5.04 (s, 1 H).
13C NMR (100 MHz, DMSO-d6):  = 156.0, 149.4, 149.1, 137.0, 133.8,
133.6, 129.5, 129.4, 129.2, 128.5, 128.4, 128.2, 128.1, 127.0, 123.8,
119.2, 117.1, 108.8, 103.0, 73.1.
19F NMR (376 MHz, CDCl3):  = –124.7.
HRMS (ESI): m/z calcd for C23H19FNO [M + H]+: 344.1445; found:
HRMS (ESI): m/z calcd for C23H18Br2NO [M + H]+: 481.9750; found:
481.9746.
344.1439.
4,5-Dimethyl-2-(2-methyl-3-methyleneindolin-2-yl)phenol (2t)
Yield: 0.046 g (86%); white solid; mp 138–139 °C.
(E)-2-(7-Methyl-3-methylene-2-styrylindolin-2-yl)phenol (2p)
Yield: 0.046 g (68%); white solid; mp 140–141 °C.
IR (thin film): 3431, 2963, 1614, 1383, 1262, 1096, 803 cm–1
.
IR (thin film): 3432, 3328, 2925, 2857, 1615, 1463, 1261, 1103, 801,
749 cm–1
.
1H NMR (500 MHz, CDCl3):  = 10.08 (s, 1 H), 7.39–7.36 (m, 3 H),
7.32–7.29 (m, 2 H), 7.26–7.21 (m, 3 H), 7.05 (d, J = 7.0 Hz, 1 H), 6.92–
6.84 (m, 3 H), 6.61 (d, J = 15.5 Hz, 1 H), 6.50 (d, J = 16.0 Hz, 1 H), 5.71
(s, 1 H), 4.72 (s, 1 H), 4.29 (br s, 1 H), 2.21 (s, 3 H).
13C NMR (125 MHz, CDCl3):  = 156.8, 148.6, 145.7, 136.0, 131.3,
131.0, 130.6, 129.5, 129.0, 128.6, 128.4, 128.2, 126.8, 126.5, 122.9,
122.2, 119.2, 118.9, 117.9, 106.7, 74.5, 16.5.
1H NMR (400 MHz, CDCl3):  = 9.45 (s, 1 H), 7.45 (d, J = 7.2 Hz, 1 H),
7.25–7.20 (m, 1 H), 7.08 (s, 1 H), 6.97–6.89 (m, 2 H), 6.67 (s, 1 H), 5.39
(s, 1 H), 4.65 (s, 1 H), 4.16 (br s, 1 H), 2.24 (s, 3 H), 2.20 (s, 3 H), 1.74 (s,
3 H).
13C NMR (125 MHz, CDCl3):  = 154.1, 152.8, 147.6, 137.6, 130.0,
128.1, 127.9, 126.8, 125.0, 121.7, 121.6, 118.9, 113.5, 102.8, 69.4, 29.1,
19.4, 19.1.
HRMS (ESI): m/z calcd for C24H22NO [M + H]+: 340.1696; found:
340.1726.
HRMS (ESI): m/z calcd for C18H20NO [M + H]+: 266.1539; found:
266.1535.
(E)-2-(7-Bromo-3-methylene-2-styrylindolin-2-yl)phenol (2q)
Methyl (E)-11a-Styryl-6,6a,11,11a-tetrahydrochromeno[4,3-b]in-
dole-8-carboxylate (3u)
Yield: 0.064 g (78%); white solid; mp 143–144 °C.
IR (thin film): 3330, 2925, 1639, 1441, 1244, 1102, 813, 750 cm–1
.
Yield: 0.028 g (36%); white solid; mp 109–110 °C.
1H NMR (400 MHz, DMSO-d6):  = 10.02 (s, 1 H), 7.47 (d, J = 7.6 Hz, 1
H), 7.41–7.39 (m, 2 H), 7.36 (d, J = 7.6 Hz, 1 H), 7.31–7.27 (m, 3 H),
7.23–7.19 (m, 1 H), 7.17–7.13 (m, 1 H), 6.88 (d, J = 7.6 Hz, 1 H), 6.83–
6.80 (m, 1 H), 6.67–6.58 (m, 2 H), 6.31 (d, J = 16.0 Hz, 1 H), 5.86 (s, 1
H), 5.03 (s, 1 H).
13C NMR (100 MHz, DMSO-d6):  = 155.9, 150.1, 149.5, 137.0, 133.8,
132.5, 129.4, 129.1, 128.3, 128.2, 128.1, 128.0, 127.7, 126.9, 121.0,
119.7, 119.2, 117.1, 107.7, 102.9, 73.1.
IR (thin film): 3482, 1712, 1602, 1436, 1263, 804, 752 cm–1
.
1H NMR (500 MHz, CDCl3):  = 8.04–8.02 (m, 2 H), 7.82 (d, J = 16.0 Hz,
1 H), 7.51–7.50 (m, 3 H), 7.42 (d, J = 7.0 Hz, 1 H), 7.36–7.34 (m, 5 H),
7.19–7.13 (m, 2 H), 6.66 (d, J = 16.0 Hz, 1 H), 4.72 (s, 2 H), 3.40 (s, 3 H),
2.45 (s, 1 H).
13C NMR (125 MHz, CDCl3):  = 166.9, 163.0, 159.2, 155.7, 141.1,
135.9, 131.7, 131.4, 130.8, 129.5, 128.7, 127.8, 123.8, 123.5, 121.7,
116.9, 114.4, 114.3, 113.1, 78.3, 75.7, 56.0, 51.9.
HRMS (ESI): m/z calcd for C23H19BrNO [M + H]+: 404.0645; found:
404.0638.
HRMS (ESI): m/z calcd for C25H22NO3 [M + H]+: 384.1594; found:
384.1591.
(E)-4-Methoxy-2-(3-methylene-2-styrylindolin-2-yl)phenol (2r)
(E)-9-Nitro-11a-styryl-6,6a,11,11a-tetrahydrochromeno[4,3-b]in-
dole (3v)
Yield: 0.045 g (63%); yellow solid; mp 160–161 °C.
IR (thin film): 3453, 2926, 1640, 1488, 1248, 1041, 879, 750 cm–1
.
Yield: 0.024 g (32%); white solid; mp 107–108 °C.
1H NMR (400 MHz, CDCl3):  = 9.42 (s, 1 H), 7.48 (d, J = 7.6 Hz, 1 H),
7.34–7.15 (m, 6 H), 6.94–6.91 (m, 1 H), 6.87–6.76 (m, 4 H), 6.59 (d, J =
15.6 Hz, 1 H), 6.43 (d, J = 15.6 Hz, 1 H), 5.71 (s, 1 H), 4.76 (s, 1 H), 4.47
(s, 1 H), 3.72 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 152.3, 150.4, 148.0, 147.3, 135.9,
131.3, 130.2, 130.1, 128.6, 128.5, 128.0, 127.4, 126.8, 121.7, 121.3,
118.1, 115.6, 113.6, 113.4, 106.6, 74.4, 55.7.
IR (thin film): 3386, 1616, 1525, 802 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.56 (d, J = 8.0 Hz, 1 H), 7.30–7.27 (m, 5
H), 7.24–7.21 (m, 3 H), 7.01–7.00 (m, 3 H), 6.54 (d, J =16.0 Hz, 1 H),
6.25 (d, J = 16.0 Hz, 1 H), 4.82 (s, 1 H), 4.64 (dd, J = 10.5, 5.0 Hz, 1 H),
4.25 (dd, J = 10.5, 4.5 Hz, 1 H), 3.84 (t, J = 11.0 Hz, 1 H).
13C NMR (125 MHz, CDCl3):  = 154.5, 151.9, 146.7, 135.8, 133.3,
129.8, 129.2, 129.1, 128.6, 128.5, 127.9, 126.6, 124.2, 122.3, 121.9,
117.9, 114.4, 114.1, 65.3, 64.7, 48.2.
HRMS (ESI): m/z calcd for C24H22NO2 [M + H]+: 356.1645; found:
356.1664.
HRMS (ESI): m/z calcd for C23H19N2O3 [M + H]+: 371.1390; found:
371.1385.
(E)-4-Fluoro-2-(3-methylene-2-styrylindolin-2-yl)phenol (2s)
Yield: 0.035 g (51%); white solid; mp 158–159 °C.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

H
F.-P. Liu et al.
Paper
Synthesis
Funding Information
(c) Huang, Y.; Chan, G. H.; Chiba, S. Angew. Chem. Int. Ed. 2017,
56, 6544. (d) Kaga, A.; Hayashi, H.; Hakamata, H.; Oi, M.;
Uchiyama, M.; Takita, R.; Chiba, S. Angew. Chem. Int. Ed. 2017,
56, 11807. (e) Hong, Z.; Ong, D. Y.; Muduli, S. K.; Too, P. C.; Chan,
G. H.; Tnay, Y. L.; Chiba, S.; Nishiyama, Y.; Hirao, H.; Soo, H. S.
Chem. Eur. J. 2016, 22, 7108.
Financial support from the National Natural Science Foundation of
China (21562005, 51503037), the Natural Science Foundation of
Guangxi Province (2016GXNSFFA380005), the Overseas 100 Talents
Program of Guangxi Higher Education, and the One Thousand Young
and Middle-Aged College and University Backbone Teachers Cultiva-
(6) (a) Rosso, V. W.; Lust, D. A.; Bernot, P. J.; Grosso, J. A.; Modi, S. P.;
Rusowicz, A.; Sedergran, T. C.; Simpson, J. H.; Srivastava, S. K.;
Humora, M. J.; Anderson, N. G. Org. Process Res. Dev. 1997, 1,
311. (b) Garrett, C. E.; Prasad, K. Adv. Synth. Catal. 2004, 346,
889.
tion Program of Guangxi is greatly appreciated.
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Supporting Information
(7) Ma, X.-P.; Li, K.; Wu, S.-Y.; Liang, C.; Su, G.-F.; Mo, D.-L. Green
Chem. 2017, 19, 5761.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611850.
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(8) (a) Leng, L.; Zhou, X.; Liao, Q.; Wang, F.; Song, H.; Zhang, D.; Liu,
X.-Y.; Qin, Y. Angew. Chem. Int. Ed. 2017, 56, 3703. (b) Smith, M.
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I.; Qureshi, A. A. J. Am. Chem. Soc. 1969, 91, 5874. (d) Cockrum, P.
A.; Colegate, S. M.; Edgar, J. A.; Flower, K.; Gardner, D.; Willing,
R. I. Phytochemistry 1999, 51, 153.
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© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H