Copper-Catalyzed 6- endo - Dig O-Cyclization of 2-(But-3-en-1-yn-1-yl)benzamide

Article abstract of DOI:10.1055/s-0039-1690155

The copper-catalyzed synthesis of 3-vinylisocoumarin-1-imine is reported. The transformation proceeds smoothly with good yields in THF and the regioselectivity was determined by a O-nucleo?-philic 6- endo cyclization. Studies on the mechanism indicate tha

Full text of DOI:10.1055/s-0039-1690155

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–H
paper
A
en
R.-X. Wang et al.
Paper
Synthesis
Copper-Catalyzed 6-endo-dig O-Cyclization of
2-(But-3-en-1-yn-1-yl)benzamide
Rui-Xiang Wang*a
Zhuang Fanga
Guanyinsheng Qiu*b
Wenlin Xiec
NPh
OH
O
NR
Cu(TFA)2
(10 mol%)
0
0
0
0-0
0
0
2-
6
5
8
7-8
5
2
2
NHR
O
THF, reflux
Jin-Biao Liu*a
0
0
0
0-0
0
0
2-5
0
3
8-6
5
4
1
[Cu]
a Department of chemistry, Jiangxi University of Science
and Technology, 86 Hongqi Road, Ganzhou 341000,
P. R. of China
Selected examples:
liujinbiao@jxust.edu.cn
b College of Biological, Chemical Science and Engineering,
Jiaxing University, 118 Jiahang Road, Jiaxing 314001, P. R.
of China
N
O
N
N
N
O
O
qiuguanyinsheng@mail.zjxu.edu.cn
c School of Chemistry and Chemical Engineering, Hunan
University of Science and Technology, Hunan 411201,
P. R. of China
81%
74%
90%
Received: 21.06.2019
Accepted after revision: 23.07.2019
Published online: 14.08.2019
In 2009, Liu and co-workers developed a silver-
catalyzed cyclization of 2-alkynylbenzamide in which a dis-
tinctive O-nucleophilic 6-endo cyclization took place with
the formation of isocoumarin-1-imine derivatives (Scheme
1a).5 However, it was surprising that the reaction of sub-
strates with N-alkyl protecting groups provided isocouma-
rin-1-imine in good yields, and N-aryl protecting substrates
were not efficient reaction partners. For examples, the re-
action of N-phenyl-2-phenylethynylbenzamide provided
only N-phenylisocoumarin-1-imine 2a in a 23% yield. Sub-
sequently, many research groups also investigated O-nucleo-
philic 6-endo cyclization of 2-alkynylbenzamide.6 To our
surprise, silver salts have been used in most of the exam-
ples; other metal salt-catalyzed examples of O-nucleophilic
6-endo cyclization of 2-alkynylbenzamide remain rare.7 In-
spired by these reports, we wanted to explore O-nucleop-
hilic 6-endo cyclization of 2-alkynylbenzamide under other
metal catalysis with a view to expanding the scope of the
reaction by making it compatible with substrates bearing
various N-aryl protecting groups. Considering our ongoing
interest in copper catalysis8 and the high importance of the
isocoumarin-1-imine core,4,9 in this paper we would like to
report the development of a copper-catalyzed O-nucleo-
philic 6-endo-cyclization of 2-alkynylbenzamide 1.
DOI: 10.1055/s-0039-1690155; Art ID: ss-2019-f0342-op
Abstract The copper-catalyzed synthesis of 3-vinylisocoumarin-1-
imine is reported. The transformation proceeds smoothly with good
yields in THF and the regioselectivity was determined by a O-nucleo-
philic 6-endo cyclization. Studies on the mechanism indicate that copper
trifluoroacetate serves as a Lewis acid, and the use of vinyl-connected
2-alkynylbenzamide is important for this O-nucleophilic 6-endo cycliza-
tion.
Key words copper catalysis, O-nucleophilic 6-endo cyclization, Lewis
acid, vinyl-connected 2-alkynylbenzamide, isocoumarin
As a dual-functionalized synthon, 2-alkynylbenzamide
has attracted increasing attention from the scientific com-
munity because of its synthetic versatility in annulative re-
actions.1 Together with an improvement in reaction effi-
ciency, we wished to explore the selectivity of N- versus O-
nucleophilicity and 6-endo- versus 5-exo cyclization for 2-
alkynylbenzamide-based chemistry. The N/O-nucleophilic-
ity and 6-endo/5-exo-switch has been ascribed to the use of
various reaction systems. Generally, base-mediated reac-
tions of 2-alkynylbenzamide tend to undergo N-nucleophil-
ic 5-exo cyclization,2 and electrophilic cyclization of 2-
alkynylbenzamide resulted in the formation of a mixture of
O-nucleophilic 5-exo cyclization and O-nucleophilic 6-endo
cyclization products.3 Pleasingly, our recent work suggested
that either an O-nucleophilic 5-exo reaction4a or an O-nuc-
leophilic 6-endo reaction4b could be realized, respectively,
when radical cyclization of 2-alkynylbenzamide was con-
ducted.
A preliminary result from the copper chloride-catalyzed
reaction of 2-alkynylbenzamide 1 suggested the substitu-
ent R in substrate 1 had a significant impact on the out-
come of the reaction.10 Although the expected O-nucleop-
hilic 6-endo cyclization took place, the yields of isocouma-
rin-1-imine
2 varied depending on the use of the
substituent R in 2-alkynylbenzamide 1. As illustrated in
Scheme 1b, the reaction of 2-phenylethynylbenzamide pro-
vided the desired product 2a in 35% yield, whereas reaction
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Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
R.-X. Wang et al.
Paper
Synthesis
Table 1 Initial Studies for the Reaction of Regioselective 6-endo-dig
Cyclization of 2-Alkynylbenzamidea
(a) The previous works:
O
NR2
NPh
NHR2
[Ag]...
O
O
Ph
O
R1
N
R1
Ph
NH
O
R3
Ph
R
3 = aryl, alkyl
[Cu]
R3
23% yield
solvent, temp.
1c
2c
(b) This work:
O
NPh
OH
Ph
O
N
Entry
[Cu] (0.1 equiv)
Solvent
T (°C)
Yield of 2c (%)b
CuCl2 (10
mol%)
NHPh
1
2
CuCl2
THF
60
60
60
60
60
60
60
60
60
60
r.t.
60
77
THF, reflux
R
Cu(OAc)2
Cu(TFA)2
CuI
THF
35
[Cu]
Ph
R
N
1
2
3
THF
90
Ph
O
Ph
O
N
N
4
THF
62
O
5
CuBr
THF
68
S
Ph
2a, 35%
6
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
Cu(TFA)2
1,4-dioxane
DCE
85
2b, 54%
2c, 77%
7
73
Scheme 1 Copper-catalyzed ortho-group-assisted 6-endo-dig cycliza-
tion of 2-alkynylbenzamide
8
MeCN
toluene
DMF
61
9
67
10
11
12
complex
trace
39
of 2-(but-3-en-1-yn-1-yl)benzamide gave rise to the corre-
sponding product 2c in 77% yield without further reaction
optimization. We assumed that the substituent R probably
stabilized the resulting copper-involved species through a
coordination effect during the process. Given the synthetic
potential of the vinyl group for structural elaboration, we
optimized the reaction of 2-(but-3-en-1-yn-1-yl)benz-
amide for the formation of 3-vinylisocoumarin-1-imines.
The optimization of the reaction is summarized in Table
1. We initially explored a range of copper sources including
Cu(OAc)2, Cu(TFA)2, CuI and CuBr, and found that the use of
Cu(TFA)2 greatly improved the efficiency of the reaction to
deliver the desired product 2c in 90% yield (entry 3). Sol-
vent screening suggested that tetrahydrofuran (THF) was
optimal; other solvents including 1,4-dioxane, 1,2-dichlo-
roethane (DCE), MeCN, toluene, and DMF did not deliver
better yields (entries 6–10). Reducing either the reaction
temperature or the copper loading had a negative impact
on the outcome of the reaction (entries 11 and 12). As such,
we established the optimized conditions as Cu(TFA)2
(10 mol%), THF, and 60 °C.
THF
c
Cu(TFA)2
THF
a Standard conditions: 2-(but-3-en-1-yn-1-yl)benzamide (1c; 0.2 mmol),
copper catalysis (0.1 equiv), solvent (2 mL), overnight.
b Isolated yield based on 2-(but-3-en-1-yn-1-yl)benzamide (1c).
c Cu(TFA)2 (0.05 equiv) was added.
the expected isocoumarin-1-imine 2k in 78% yield. The
structure of 2j was confirmed by X-ray diffraction analysis
(CCDC 1941980).11
Subsequently, the substituent effect of N-protecting
groups was also examined. From the results, the N-protect-
ing group could be aryl, heteroaryl, alkyl, and complex mo-
lecular blocks. For example, N-pyridinyl-2-(but-3-en-1-yn-
1-yl)benzamide was recognized as an efficient reaction
partner, resulting in the formation of N-pyridinyl-3-vinyli-
socoumarin-1-imine (2o) in 74% yield. Other N-alkyl
group-linked substrates were also suitable for the reactions,
producing the corresponding products 2p–s in 72–92%
yield.
With the optimized conditions in hand, we then ex-
plored the scope and generality of the reaction. The results
are illustrated in Scheme 2. A range of vinyl group-connect-
ed substrates were compatible with the reaction condi-
tions. For instance, the reaction of cyclohexene-linked sub-
strate provided the desired product 2f in a 75% yield. The
screening of substituent R1 showed that this substituent
could be replaced with methyl, chloro, fluoro, or bromo
groups, and the corresponding products 2g–j were achieved
in moderated to good yields. Interestingly, the reaction of 3-
enynylnaphthalen-2-amide 1k also worked well, leading to
In particular, substrates with complex N-protecting
groups were also compatible with the reaction. For in-
stance, the reaction of the substrates with N-phenylalanine
and N-alanine worked uniquely well, leading to the desired
products 2u and 2v in 82% and 85% yields, respectively. The
rosin amine-connected substrate was also a good reaction
partner, producing the desired product 2w in 81% yield.
Additionally, the reaction of N-imine-2-alkynylbenz-
amide 1x was conducted under the standard conditions. As
expected, the desired N-imineisocoumarin-1-imine 2x was
achieved in moderated yield (Scheme 3).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

C
R.-X. Wang et al.
Paper
Synthesis
Subsequently, structural elaboration of 3-vinylisocou-
marin-1-imine 2 was investigated. The results are present-
ed in Scheme 4. Thus, 3-vinylisocoumarin 3 was readily ac-
cessible through hydrolysis of 3-vinylisocoumarin-1-imine
2c. Moreover, 3-vinylisocoumarin 3, generated in situ, was
readily converted into 1-amino-3-vinylisoquinoline 4 in
good yields.
R2
O
O
N
R2
Cu(TFA)2
(10 mol%)
N
H
R1
R2
R3
R4
THF, 60 °C
R3
R4
2
R5
1
R5
Ph
Ph
Ph
N
N
N
NPh
O
O
O
O
HCl (10%)
O
O
THF
88%
2e, 82%
Z/E = 3:1
2d, 83%
2c, 90%
Ph
3
Ph
O
N
NPh
NH2
N
2g, R = 3-Me, 88%
2h, R = 3-F, 83%
2i, R = 3-Cl, 71%
2j, R = 3-Br, 52%
R
R
1) HCl (10%)
R
O
O
N
2) NH4OAc (5 equiv)
4a, R = H, 62%
4b, R = F, 66%
2f, 75%
Ph
Ar
O
N
N
2l, Ar = 4-MeC6H4, 83%
2m, Ar = 4-FC6H4, 84%
2n, Ar = 4-ClC6H4, 80%
Scheme 4 Synthetic applications of isocoumarin-1-imine. Isolated
yields based on 3-vinylisocoumarin-1-imine 3 are given.
O
R
N
To gain insights into reaction mechanism, several con-
trol experiments were carried out. As presented in Scheme
5, the first trial was to confirm the role of the copper cata-
lyst. A control reaction with 2,2,6,6-tetramethylpiperidine-
1-oxyl (TEMPO) as an additive was conducted. The use of
TEMPO did not made significant impact on the reaction,
indicating the role of copper catalyst as a Lewis acid. We
then examined whether the vinyl group assisted in the re-
action. Under standard conditions we ran the reactions of
2k, 78%
O
N
Ph
N
N
O
O
2q, R = ethyl, 72%
2r, R = Cy, 78%
2s, R = allyl, 75%
2p, 72%
MeO
2o, 74%
O
BnO
O
N
Ph
N
N
O
O
O
O
H
standard
conditions
2t, 92%
NHPh
2u, 82%
2v, 85%
2w, 81%
(a)
O
TEMPO (2.0 equiv)
88%
2c
NPh
1c
N
O
H
O
standard
Ph
S
conditions
NHPh
Ph
(b)
(c)
O
49%
2a
Scheme 2 Generation of isocoumarins 2 through a regioselective 6-
endo-dig O-cyclization of 2-alkynylbenzamide. Isolated yields based on
2-alkynylbenzamide 1 are given.
1a
NPh
H
O
standard
conditions
NHPh
O
74%
S
Ph
N
Ph
2b
NPh
O
1b
N
O
N
Ph
Cu(TFA)2 (10 mol%)
N
H
NR2
OH
NR2
Ph
THF, 60 °C
51%
NR2
H+
Ph
R1
O
Ph
R1
O
R1
1x
2x
[Cu]
Scheme 3 Generation of N-imineisocoumarin-1-imine 2 through regi-
oselective 6-endo-dig O-cyclization of N-imine-2-alkynylbenzamide. Iso-
lated yield based on N-imine-2-alkynylbenzamide 1x is given.
[Cu]
2
A
Scheme 5 Control experiments and proposed mechanism
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

D
R.-X. Wang et al.
Paper
Synthesis
N-phenyl-2-phenylethynylbenzamide, N-phenyl-2-(2-thio-
phene) ethynylbenzamide, and N-phenyl-2-(but-3-en-1-
yn-1-yl)benzamide. As expected, the yield of N-phenyl-2-
phenylethynylbenzamide was much lower than that of N-
phenyl-2-(but-3-en-1-yn-1-yl)benzamide, thus suggesting
a coordination effect of the vinyl group.
(Z)-N,3-Diphenyl-1H-isochromen-1-imine (2a)
Yield: 20.8 mg (35%); black solid.
1H NMR (400 MHz, CDCl3):  = 8.43 (d, J = 7.8 Hz, 1 H), 7.63–7.51 (m,
3 H), 7.47–7.43 (m, 3 H), 7.42–7.27 (m, 6 H), 7.20 (t, J = 7.3 Hz, 1 H),
6.70 (s, 1 H).
13C NMR (101 MHz, CDCl3):  = 151.6, 149.8, 146.8, 134.0, 132.5,
132.3, 129.5, 128.8, 128.2, 127.5, 125.7, 124.7, 123.7, 122.6, 100.9.
In light of these results, a plausible mechanism is pro-
posed in Scheme 5. In this process, the copper salt serves as
a Lewis acid to activate the triple bond. Nucleophilic addi-
tion then takes place through O-nucleophilic 6-endo and O-
nucleophilic 5-exo reactions. Through O-nucleophilic 6-
endo cyclization, intermediate A is formed, and subsequent
protonation provides the final isocoumarin-1-imine 2.
In conclusion, we have developed a copper-catalyzed O-
nucleophilic 6-endo-dig cyclization of 2-(but-3-en-1-yn-1-
yl)benzamide for the synthesis of 3-vinylisocoumarin-1-
imine derivatives. Compared to the use of 2-arylethynyl-
benzamide as substrates, substrates with a 2-enynyl group
were more efficient reaction partners. Studies on the mech-
anism indicated that the ortho-vinyl group serves as an as-
sisting group, and the reaction proceeds through Lewis acid
catalysis. The scope of the reaction showed that the N-pro-
tecting group in the substrates could be replaced by various
aryl groups, alkyl groups, and even many complex building
blocks. The copper-catalyzed O-nucleophilic 6-endo-dig cy-
clization of 2-(but-3-en-1-yn-1-yl)benzamide reported
herein represents an important complement for silver-cata-
lyzed O-nucleophilic 6-endo-dig cyclization of 2-(but-3-en-
1-yn-1-yl)benzamide. Copper-catalyzed N-nucleophilic cy-
clization studies are ongoing in our laboratory, and the re-
sults will be reported in due course.
HRMS (ESI): m/z [M + H]+ calcd for C21H16NO+: 298.1226; found:
298.1222.
(Z)-N-Phenyl-3-(thiophen-2-yl)-1H-isochromen-1-imine (2b)
Yield: 32.7 mg (54%); yellow solid.
1H NMR (400 MHz, CDCl3):  = 8.35 (d, J = 7.9 Hz, 1 H), 7.47–7.51 (m,
1 H), 7.34–7.41 (m, 3 H), 7.24–7.28 (m, 4 H), 7.19–7.20 (m, 1 H), 7.13
(t, J = 7.3 Hz, 1 H), 6.95–6.97 (m, 1 H), 6.51 (s, 1 H).
13C NMR (101 MHz, CDCl3):  = 149.2, 147.7, 146.4, 136.1, 133.8,
132.5, 128.7, 127.9, 127.6, 126.7, 125.4, 125.2, 123.8, 123.5, 122.7,
100.0.
HRMS (ESI): m/z [M + H]+ calcd for C19H14NOS+: 304.0791; found:
304.0795.
(Z)-N-Phenyl-3-vinyl-1H-isochromen-1-imine (2c)
Yield: 44.5 mg (90%); yellow solid.
1H NMR (400 MHz, CDCl3):  = 8.25 (d, J = 7.9 Hz, 1 H), 7.38 (t, J =
7.5 Hz, 1 H), 7.32–7.22 (m, 3 H), 7.12–7.15 (m, 3 H), 7.04–6.97 (m,
1 H), 6.05–6.09 (m, 1 H), 5.98 (s, 1 H), 5.48 (d, J = 17.1 Hz, 1 H), 5.10
(d, J = 11.0 Hz, 1 H).
13C NMR (101 MHz, CDCl3):  = 150.7, 149.6, 146.8, 133.9, 132.6,
129.0, 128.9, 128.5, 127.8, 125.8, 124.5, 123.9, 122.8, 117.5, 105.4.
HRMS (ESI): m/z [M + H]+ calcd for C17H14NO+: 248.1070; found:
248.1070.
(Z)-N-Phenyl-3-(prop-1-en-2-yl)-1H-isochromen-1-imine (2d)
Yield: 43.3 mg (83%); yellow solid.
The solvents were distilled from standard drying agents. Unless oth-
erwise stated, commercial reagents purchased from Aladdin and J&K®
chemical companies were used without further purifcation. Purifca-
tion of reaction products was carried out by flash chromatography
using Qing Dao Sea Chemical Reagent silica gel (200–300 mesh). 1H
NMR spectra were recorded on a Bruker Avance III 400 (400 MHz)
spectrometer and referenced internally to the residual proton reso-
nance in CDCl3 ( = 7.26 ppm), or with tetramethylsilane (TMS,  =
0.00 ppm) as the internal standard. Chemical shifts were reported as
parts per million (ppm) in the  scale downfeld from TMS. Multiplici-
ty is indicated as follows: s (singlet), d (doublet), t (triplet), q (quar-
tet), quint (quintet), m (multiplet), dd (doublet of doublet), bs (broad
singlet). Analytical TLC was performed using EM separations perco-
lated silica gel 0.2 mm layer UV 254 fluorescent sheets.
1H NMR (400 MHz, CDCl3):  = 8.37 (d, J = 7.9 Hz, 1 H), 7.47–7.51 (m,
1 H), 7.44–7.33 (m, 3 H), 7.27 (d, J = 7.9 Hz, 1 H), 7.24–7.16 (m, 2 H),
7.11 (t, J = 7.3 Hz, 1 H), 6.25 (s, 1 H), 5.44 (s, 1 H), 5.05 (s, 1 H), 1.97 (s,
3 H).
13C NMR (101 MHz, CDCl3):  = 152.0, 149.7, 146.8, 134.5, 133.8,
132.4, 128.7, 128.2, 127.4, 125.8, 124.0, 123.5, 122.4, 115.9, 102.1,
18.7.
HRMS (ESI): m/z [M + H]+ calcd for C18H16NO+: 262.1226; found:
262.1200.
N-Phenyl-3-[(Z)-prop-1-en-1-yl]-1H-isochromen-1-imine (2e)
(Z/E = 3:1)
Yield: 42.8 mg (82%); brown liquid.
1H NMR (400 MHz, CDCl3):  = 8.36 (d, J = 7.9 Hz, 1 H), 7.53–7.44 (m,
1 H), 7.41 (d, J = 8.2 Hz, 1 H), 7.38 (d, J = 4.3 Hz, 1 H), 7.34 (d, J =
7.7 Hz, 1 H), 7.31–7.27 (m, 1 H), 7.22–7.11 (m, 2 H), 7.06–7.09 (m,
1 H), 6.17–6.03 (m, 1 H), 5.96 (s, 1 H), 5.88–5.96 (m, 1 H), 1.77–1.79
(m, 3 H).
13C NMR (101 MHz, CDCl3):  = 150.8, 149.7, 146.7, 134.2, 132.3,
131.9, 129.9, 128.7, 127.9, 127.5, 125.3, 123.6, 122.6, 121.9, 103.0,
18.4.
1H-Isochromen-1-imines 2; General Procedure
The 2-(but-3-en-1-yn-1-yl)benzamide 1 (0.2 mmol) and Cu(TFA)2 (10
mol%) were added to a test tube, and then solvent THF was added. The
mixture was stirred at 60 °C overnight. After the consumption of sub-
strate as indicated by TLC, the mixture was filtered , and the filtrate
was concentrated in vacuo. The resulting crude product was purified
by column chromatography by using an EtOAc/petroleum ether gradi-
ent mixture to afford the pure product 2.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

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R.-X. Wang et al.
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Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C18H16NO+: 262.1226; found:
HRMS (ESI): m/z [M + H]+ calcd for C17H13BrNO+: 326.0175; found:
262.1264.
326.0191.
(Z)-3-(Cyclohex-1-en-1-yl)-N-phenyl-1H-isochromen-1-imine (2f)
(Z)-N-Phenyl-3-vinyl-1H-benzo[g]isochromen-1-imine (2k)
Yield: 45.2 mg (75%); yellow solid.
Yield: 46.4 mg (78%); yellow solid.
1H NMR (400 MHz, CDCl3):  = 8.33 (d, J = 7.9 Hz, 1 H), 7.48 (t, J =
7.5 Hz, 1 H), 7.43–7.30 (m, 3 H), 7.20–7.26 (m, 3 H), 7.10 (t, J = 7.3 Hz,
1 H), 6.26 (s, 1 H), 6.12 (s, 1 H), 2.26–2.02 (m, 4 H), 1.64–1.71 (m, 4 H).
13C NMR (101 MHz, CDCl3):  = 152.5, 150.0, 146.9, 134.3, 132.2,
128.6, 128.6, 128.5, 127.6, 127.4, 125.5, 123.7, 123.4, 122.4, 99.4, 25.7,
24.0, 22.3, 21.8.
1H NMR (400 MHz, CDCl3):  = 8.41 (d, J = 8.7 Hz, 1 H), 8.28–8.10 (m,
1 H), 7.92–7.85 (m, 1 H), 7.82 (d, J = 8.7 Hz, 1 H), 7.68–7.54 (m, 2 H),
7.40 (t, J = 7.7 Hz, 2 H), 7.31 (d, J = 7.4 Hz, 2 H), 7.14 (t, J = 7.3 Hz, 1 H),
6.84 (s, 1 H), 6.31–6.38 (m, 1 H), 5.70 (d, J = 17.0 Hz, 1 H), 5.30 (d, J =
10.9 Hz, 1 H).
13C NMR (101 MHz, CDCl3):  = 151.6, 150.2, 146.6, 135.0, 131.6,
129.0, 128.8, 128.7, 128.5, 128.1, 127.9, 127.0, 123.7, 123.3, 122.6,
121.6, 117.8, 100.9.
HRMS (ESI): m/z [M + H]+ calcd for C21H20NO+: 302.1539; found:
302.1547.
HRMS (ESI): m/z [M + H]+ calcd for C21H16NO+: 298.1226; found:
298.1228.
(Z)-7-Methyl-N-phenyl-3-vinyl-1H-isochromen-1-imine (2g)
Yield: 46 mg (88%); yellow solid.
(Z)-N-(p-Tolyl)-3-vinyl-1H-isochromen-1-imine (2l)
1H NMR (400 MHz, CDCl3):  = 8.20 (s, 1 H), 7.45–7.29 (m, 3 H), 7.25
(d, J = 7.6 Hz, 2 H), 7.09–7.15 (m, 2 H), 6.14–6.21 (m, 1 H), 6.10 (s,
1 H), 5.56 (d, J = 17.1 Hz, 1 H), 5.20 (d, J = 11.0 Hz, 1 H), 2.45 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 148.8, 145.6, 137.6, 132.5, 130.2,
127.7, 126.5, 124.6, 123.0, 122.6, 121.5, 115.7, 104.2, 20.5.
Yield: 43.3 mg (83%); brown liquid.
1H NMR (400 MHz, CDCl3):  = 8.35 (t, J = 9.3 Hz, 1 H), 7.47–7.51 (m,
1 H), 7.38 (t, J = 7.4 Hz, 2 H), 7.24–7.15 (m, 4 H), 6.18–6.25 (m, 1 H),
6.10 (s, 1 H), 5.67 (d, J = 17.1 Hz, 1 H), 5.25 (d, J = 11.0 Hz, 1 H), 2.37 (s,
3 H).
13C NMR (101 MHz, CDCl3):  = 150.5, 149.2, 143.6, 133.6, 133.2,
132.2, 129.2, 128.8, 128.3, 127.5, 125.6, 124.4, 122.7, 117.3, 105.2,
21.1.
HRMS (ESI): m/z [M + H]+ calcd for C18H16NO+: 262.1226; found:
262.1248.
(Z)-7-Fluoro-N-phenyl-3-vinyl-1H-isochromen-1-imine (2h)
HRMS (ESI): m/z [M + H]+ calcd for C18H16NO+: 262.1226; found:
262.1268.
Yield: 44 mg (83%); yellow solid.
1H NMR (400 MHz, CDCl3):  = 8.02 (d, J = 9.2 Hz, 1 H), 7.43–7.32 (m,
2 H), 7.28–7.21 (m, 2 H), 7.18–7.25 (m, 2 H), 7.09–7.13 (m, 1 H), 6.13–
6.20 (m, 1 H), 6.05 (s, 1 H), 5.58 (d, J = 17.1 Hz, 1 H), 5.21 (d, J =
11.0 Hz, 1 H).
(Z)-N-(4-Fluorophenyl)-3-vinyl-1H-isochromen-1-imine (2m)
Yield: 44.5 mg (84%); yellow solid.
1H NMR (400 MHz, CDCl3):  = 8.33 (d, J = 7.9 Hz, 1 H), 7.47–7.51 (m,
1 H), 7.36–7.40 (m, 1 H), 7.32–7.14 (m, 3 H), 7.13–6.98 (m, 2 H), 6.17–
6.24 (m, 1 H), 6.09 (s, 1 H), 5.60 (d, J = 17.1 Hz, 1 H), 5.24 (d,
J = 11.0 Hz, 1 H).
13C NMR (101 MHz, CDCl3):  = 162.2 (d, J = 248.4 Hz), 149.9 (d, J =
2.9 Hz), 148.5 (s), 146.0 (s), 130.1 (d, J = 2.7 Hz), 128.7 (s), 128.6 (s),
127.6 (d, J = 7.9 Hz), 126.2 (d, J = 8.6 Hz), 124.0 (s), 122.6 (s), 120.3 (d,
J = 23.1 Hz), 117.3 (s), 113.7 (d, J = 24.2 Hz), 104.3 (d, J = 1.5 Hz).
13C NMR (101 MHz, CDCl3):  = 159.4 (d, J = 241.8 Hz), 150.4 (s), 149.6
(s), 142.5 (d, J = 2.9 Hz), 133.6 (s), 132.4 (s), 128.8 (s), 128.3 (s), 127.5
(s), 125.7 (s), 124.1 (t, J = 8.6 Hz), 117.2 (s), 115.4 (s), 115.2 (s), 105.7
(s).
HRMS (ESI): m/z [M + H]+ calcd for C17H13FNO+: 266.0976; found:
266.0980.
HRMS (ESI): m/z [M + H]+ calcd for C17H13FNO+: 266.0976; found:
266.0978.
(Z)-7-Chloro-N-phenyl-3-vinyl-1H-isochromen-1-imine (2i)
Yield: 38.5 mg (71%); yellow solid.
1H NMR (400 MHz, CDCl3):  = 8.31 (d, J = 1.8 Hz, 1 H), 7.47–7.29 (m,
3 H), 7.23 (d, J = 7.4 Hz, 2 H), 7.09–7.13 (m, 2 H), 6.12–6.19 (m, 1 H),
6.02 (s, 1 H), 5.59 (d, J = 17.1 Hz, 1 H), 5.22 (d, J = 11.0 Hz, 1 H).
13C NMR (101 MHz, CDCl3):  = 150.7, 148.1, 145.9, 134.0, 132.5,
132.1, 128.6, 127.3, 126.9, 125.6, 124.0, 122.6, 117.8, 104.3.
(Z)-N-(4-Chlorophenyl)-3-vinyl-1H-isochromen-1-imine (2n)
Yield: 44.96 mg (80%); yellow solid.
1H NMR (400 MHz, CDCl3):  = 8.31 (d, J = 7.9 Hz, 1 H), 7.48–7.52 (m,
1 H), 7.42–7.34 (m, 1 H), 7.35–7.26 (m, 2 H), 7.26–7.12 (m, 3 H), 6.16–
6.23 (m, 1 H), 6.10 (s, 1 H), 5.58 (d, J = 17.1 Hz, 1 H), 5.23 (d,
J = 11.0 Hz, 1 H).
HRMS (ESI): m/z [M + H]+ calcd for C17H13ClNO+: 282.0680; found:
282.0662.
13C NMR (101 MHz, CDCl3):  = 150.4, 149.9, 145.1, 133.7, 132.5,
128.7, 128.4, 127.6, 125.7, 124.0, 117.3, 105.4.
HRMS (ESI): m/z [M + H]+ calcd for C17H13ClNO+: 282.0680; found:
282.0668.
(Z)-7-Bromo-N-phenyl-3-vinyl-1H-isochromen-1-imine (2j)11
Yield: 33.8 mg (52%); yellow solid.
1H NMR (400 MHz, CDCl3):  = 8.48 (d, J = 1.4 Hz, 1 H), 7.56–7.58 (m,
1 H), 7.36 (t, J = 7.8 Hz, 2 H), 7.23 (d, J = 7.5 Hz, 2 H), 7.17–7.00 (m,
2 H), 6.13–6.20 (m, 1 H), 6.03 (s, 1 H), 5.60 (d, J = 17.1 Hz, 1 H), 5.24
(d, J = 10.9 Hz, 1 H).
13C NMR (101 MHz, CDCl3):  = 150.8, 147.9, 145.9, 135.4, 132.5,
130.2, 128.6, 127.0, 125.8, 124.0, 122.5, 121.9, 117.9, 104.4.
(Z)-N-(Pyridin-2-yl)-3-vinyl-1H-isochromen-1-imine (2o)
Yield: 36.7 mg (74%); brown liquid.
1H NMR (400 MHz, CDCl3):  = 8.54 (s, 1 H), 8.34 (d, J = 6.2 Hz, 2 H),
7.52–7.57 (m, 2 H), 7.41 (t, J = 7.6 Hz, 1 H), 7.25–7.30 (m, 2 H), 6.32–
6.07 (m, 2 H), 5.55 (d, J = 17.2 Hz, 1 H), 5.24 (d, J = 11.0 Hz, 1 H).
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

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R.-X. Wang et al.
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13C NMR (101 MHz, CDCl3):  = 150.9, 150.3, 144.6, 142.9, 133.8,
132.8, 129.8, 128.5, 127.7, 125.7, 123.7, 123.4, 117.5, 105.5.
HRMS (ESI): m/z [M + H]+ calcd for C16H13N2O+: 249.1022; found:
249.1042.
1H NMR (400 MHz, CDCl3):  = 8.16 (d, J = 7.9 Hz, 1 H), 7.40–7.44 (m,
1 H), 7.34–7.27 (m, 1 H), 7.17 (d, J = 7.6 Hz, 1 H), 6.25–6.32 (m, 1 H),
6.04 (s, 1 H), 5.90 (d, J = 17.1 Hz, 1 H), 5.52 (s, 1 H), 5.37 (d, J = 11.0 Hz,
1 H), 3.62–3.66 (m, 2 H), 2.34 (t, J = 7.7 Hz, 2 H), 1.99–2.05 (m, 4 H),
1.70–1.48 (m, 4 H).
13C NMR (101 MHz, CDCl3):  = 150.4, 149.7, 136.5, 132.8, 131.5,
129.5, 128.0, 126.7, 125.4, 124.7, 121.9, 116.4, 105.0, 45.6, 38.9, 28.7,
25.3, 23.1, 22.5.
HRMS (ESI): m/z [M + H]+ calcd for C19H22NO+: 280.1696; found:
280.1686.
(Z)-N-Benzyl-3-vinyl-1H-isochromen-1-imine (2p)
Yield: 37.6 mg (72%); brown liquid.
1H NMR (400 MHz, CDCl3):  = 8.30 (d, J = 7.8 Hz, 1 H), 7.51 (d, J =
7.8 Hz, 2 H), 7.45 (t, J = 7.5 Hz, 1 H), 7.33–7.38 (m, 3 H), 7.26 (t,
J = 7.1 Hz, 1 H), 7.20 (d, J = 7.7 Hz, 1 H), 6.28–6.34 (m, 1 H), 6.09 (s,
1 H), 5.92 (d, J = 17.1 Hz, 1 H), 5.39 (d, J = 10.9 Hz, 1 H), 4.81 (s, 2 H).
13C NMR (101 MHz, CDCl3):  = 150.4, 150.3, 140.9, 132.9, 131.7,
129.4, 128.3, 128.1, 127.7, 127.0, 126.5, 125.5, 124.6, 116.6, 105.2,
49.8.
Methyl (Z)-3-Phenyl-2-[(3-vinyl-1H-isochromen-1-ylidene)ami-
no]propanoate (2u)
Yield: 54.6 mg (82%); brown liquid.
1H NMR (400 MHz, CDCl3):  = 8.30 (d, J = 7.7 Hz, 1 H), 7.43–7.47 (m,
1 H), 7.32–7.35 (m, 3 H), 7.30–7.23 (m, 2 H), 7.23–7.13 (m, 2 H), 6.17–
6.24 (m, 1 H), 6.03 (s, 1 H), 5.81 (d, J = 17.1 Hz, 1 H), 5.33 (d,
J = 11.0 Hz, 1 H), 4.77–4.80 (m, 1 H), 3.67 (s, 3 H), 3.19–3.31 (m, 2 H).
13C NMR (101 MHz, CDCl3):  = 173.4, 151.7, 150.2, 138.4, 132.9,
132.1, 129.5, 129.0, 128.2, 127.4, 126.4, 125.4, 124.0, 116.8, 105.3,
60.8, 51.9, 40.4.
HRMS (ESI): m/z [M + H]+ calcd for C18H16NO+: 262.1226; found:
262.1232.
(Z)-N-Ethyl-3-vinyl-1H-isochromen-1-imine (2q)
Yield: 28.7 mg (72%); yellow liquid.
1H NMR (400 MHz, CDCl3):  = 8.06 (d, J = 7.6 Hz, 1 H), 7.30 (t, J =
7.3 Hz, 1 H), 7.19 (t, J = 7.3 Hz, 1 H), 7.05 (d, J = 7.3 Hz, 1 H), 6.30–6.07
(m, 1 H), 5.91 (s, 1 H), 5.78 (d, J = 17.1 Hz, 1 H), 5.25 (d, J = 10.8 Hz,
1 H), 3.48–3.53 (m, 2 H), 1.23 (t, J = 7.0 Hz, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C21H20NO3+: 334.1438; found:
334.1448.
13C NMR (101 MHz, CDCl3):  = 150.3, 149.5, 132.7, 131.3, 129.4,
127.9, 126.5, 125.3, 124.6, 116.2, 104.8, 40.6, 15.5.
HRMS (ESI): m/z [M + H]+ calcd for C13H14NO+: 200.1070; found:
200.1098.
Benzyl (Z)-2-[(3-Vinyl-1H-isochromen-1-ylidene)amino]propa-
noate (2v)
Yield: 56.6 g (85%); brown liquid.
1H NMR (400 MHz, CDCl3):  = 8.29 (d, J = 7.9 Hz, 1 H), 7.51–7.42 (m,
1 H), 7.41–7.29 (m, 5 H), 7.29–7.12 (m, 2 H), 6.19–6.26 (m, 1 H), 6.07
(s, 1 H), 5.78 (d, J = 17.2 Hz, 1 H), 5.21–5.30 (m, 2 H), 5.15 (d, J =
12.4 Hz, 1 H), 4.73 (q, J = 7.0 Hz, 1 H), 1.60 (d, J = 7.0 Hz, 3 H).
(Z)-N-Cyclohexyl-3-vinyl-1H-isochromen-1-imine (2r)
Yield: 25.3 mg (78%); brown liquid.
1H NMR (400 MHz, CDCl3):  = 8.09 (d, J = 7.8 Hz, 1 H), 7.30–7.34 (m,
1 H), 7.24–7.18 (m, 1 H), 7.07 (d, J = 7.6 Hz, 1 H), 6.17–6.24 (m, 1 H),
5.94 (s, 1 H), 5.82–5.70 (m, 1 H), 5.27 (d, J = 11.2 Hz, 1 H), 3.86–3.71
(m, 1 H), 1.86–1.70 (m, 4 H), 1.44–1.19 (m, 6 H).
13C NMR (101 MHz, CDCl3):  = 150.4, 132.9, 131.3, 129.6, 127.9,
126.8, 125.3, 124.9, 116.1, 104.8, 54.6, 33.5, 26.0, 25.2.
13C NMR (101 MHz, CDCl3):  = 173.9, 151.4, 150.3, 136.0, 132.9,
132.1, 129.0, 128.5, 128.1, 127.3, 125.5, 124.0, 116.8, 105.4, 66.4, 54.4,
19.1.
HRMS (ESI): m/z [M + H]+ calcd for C21H20NO3+: 334.1438; found:
334.1430.
HRMS (ESI): m/z [M + H]+ calcd for C17H20NO+: 254.1539; found:
254.1537.
(Z)-N-[(7-Isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydro-
phenanthren-1-yl)methyl]-3-vinyl-1H-isochromen-1-imine (2w)
Yield: 71.2 mg (81%); brown liquid.
(Z)-N-Allyl-3-vinyl-1H-isochromen-1-imine (2s)
1H NMR (400 MHz, CDCl3):  = 8.19 (d, J = 7.6 Hz, 1 H), 7.42 (t,
J = 7.0 Hz, 1 H), 7.35–7.21 (m, 2 H), 7.17 (d, J = 7.5 Hz, 1 H), 7.06 (d,
J = 7.5 Hz, 1 H), 6.93 (s, 1 H), 6.43–6.24 (m, 1 H), 6.04 (s, 1 H), 5.94 (d,
J = 17.1 Hz, 1 H), 5.41 (d, J = 10.8 Hz, 1 H), 3.61 (d, J = 14.6 Hz, 1 H),
3.24 (d, J = 14.6 Hz, 1 H), 2.87 (d, J = 7.0 Hz, 3 H), 2.34 (d, J = 12.1 Hz,
1 H), 2.06–1.85 (m, 2 H), 1.85–1.65 (m, 3 H), 1.52 (d, J = 9.1 Hz, 2 H),
1.41–1.14 (m, 9 H), 1.09–1.04 (m, 4 H).
13C NMR (101 MHz, CDCl3):  = 150.5, 148.5, 147.9, 145.2, 135.3,
132.7, 131.3, 129.8, 128.0, 127.0, 125.2, 124.5, 123.8, 116.3, 104.9,
57.0, 45.2, 38.6, 37.7, 36.5, 33.5, 30.8, 25.7, 24.1, 24.1, 19.8, 19.1.
Yield: 33.8 mg (80%); yellow liquid.
1H NMR (400 MHz, CDCl3):  = 8.22 (d, J = 7.9 Hz, 1 H), 7.43 (t,
J = 7.5 Hz, 1 H), 7.31 (t, J = 7.6 Hz, 1 H), 7.17 (d, J = 7.7 Hz, 1 H), 6.35–
6.21 (m, 1 H), 6.20–6.07 (m, 1 H), 6.05 (s, 1 H), 5.95–5.80 (m, 1 H),
5.34–5.39 (m, 2 H), 5.13–5.17 (m, 1 H), 4.21 (d, J = 5.6 Hz, 2 H).
13C NMR (101 MHz, CDCl3):  = 150.3, 136.4, 132.8, 131.7, 129.4,
128.0, 126.8, 125.4, 124.5, 116.5, 115.0, 105.1, 48.9.
HRMS (ESI): m/z [M + H]+ calcd for C14H14NO+: 212.1070; found:
212.1076.
HRMS (ESI): m/z [M + H]+ calcd for C31H38NO+: 440.2948; found:
440.2942.
(Z)-N-[2-(Cyclohex-1-en-1-yl)ethyl]-3-vinyl-1H-isochromen-1-
imine (2t)
(Z)-1-(Diphenylmethylene)-2-(3-phenyl-1H-isochromen-1-
ylidene)hydrazine (2x)
Yield: 51.37 mg (92%); brown liquid.
Yield: 40.8 mg (51%); brown solid.
© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

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R.-X. Wang et al.
Paper
Synthesis
1H NMR (400 MHz, CDCl3):  = 7.96 (d, J = 7.8 Hz, 1 H), 7.92 (d, J =
7.9 Hz, 2 H), 7.87–7.89 (m, 2 H), 7.53–7.37 (m, 12 H), 7.27 (d,
J = 9.5 Hz, 2 H), 6.70 (s, 1 H).
13C NMR (101 MHz, CDCl3):  = 162.1, 151.7, 150.1, 138.8, 135.8,
132.9, 132.5, 131.7, 129.7, 129.6, 129.5, 128.8, 128.7, 128.6, 128.2,
128.0, 127.8, 126.2, 125.5, 124.9, 122.8, 101.0.
References
(1) For selected reviews on dual-functionalized synthons, see:
(a) Boyarskiy, V. P.; Ryabukhin, D. S.; Bokach, N. A.; Vasilyev, A.
V. Chem. Rev. 2016, 116, 5894. (b) Zheng, Z.; Wang, Z.; Wang, Y.;
Zhang, L. Chem. Soc. Rev. 2016, 45, 4448. (c) Pirnot, M.; Wang, Y.-
M.; Buchwald, S. Angew. Chem. Int. Ed. 2016, 55, 48.
(d) Fuerstner, A. Angew. Chem. Int. Ed. 2013, 52, 2794. For exam-
ples, see: (e) Wu, C.; Wang, Z.; Hu, Z.; Zeng, F.; Zhang, X.-Y.; Cao,
Z.; Tang, Z.; He, W.-M.; Xu, X.-H. Org. Biomol. Chem. 2018, 16,
3177. (f) Xie, L.-Y.; Peng, S.; Liu, F.; Yi, J.-Y.; Wang, M.; Tang, Z.;
Xu, X.; He, W.-M. Adv. Synth. Catal. 2018, 360, 4259. (g) Wu, C.;
Lu, L.-H.; Peng, A.-Z.; Jia, G.-K.; Peng, C.; Cao, Z.; Tang, Z.; He, W.-
M.; Xu, X. Green Chem. 2018, 20, 3683. (h) Zheng, Y.; Liu, M.;
Qiu, G.; Xie, W.; Wu, J. Tetrahedron 2019, 75, 1663. (i) Zong, Y.;
Lang, Y.; Yang, M.; Li, X.; Fan, X.; Wu, J. Org. Lett. 2019, 21, 1935.
(j) Gong, X.; Chen, J.; Li, X.; Xie, W.; Wu, J. Chem. Asian J. 2018,
13, 2543. (k) Zhao, Y.; Luo, Y.; Zhu, Y.; Wang, H.; Zhou, H.; Tan,
H.; Zhou, Z. Synlett 2018, 29, 773. (l) Zhao, Y.-H.; Li, Y.; Luo, M.;
Tang, Z.; Deng, K. Synlett 2016, 27, 2597. (m) Zhao, Y.; Li, Y.;
Guo, T.; Tang, Z.; Xie, W.; Zhao, G. Tetrahedron Lett. 2016, 57,
2257. (n) Guo, T.; Liu, Y.; Zhao, Y.-H.; Zhang, P.-K.; Han, S.-L.; Liu,
H.-M. Tetrahedron Lett. 2016, 57, 4629. (o) Guo, T.; Liu, Y.; Zhao,
Y.-H.; Zhang, P.-K.; Han, S.-L.; Liu, H.-M. Tetrahedron Lett. 2016,
57, 3920. (p) Zhen, L.; Fang, C.; Zheng, Y.; Qiu, G.; Li, X.; Zhou, H.
Tetrahedron Lett. 2018, 59, 3934. (q) Zhang, L.; Ma, L.; Zhou, H.;
Yao, J.; Li, X.; Qiu, G. Org. Lett. 2018, 20, 2407.
HRMS (ESI): m/z [M + H]+ calcd for C28H21N2O+: 401.1648; found:
401.1648.
3-Vinyl-1H-isochromen-1-one (3)
Yield: 30.3 mg (88%); yellow solid.
1H NMR (400 MHz, CDCl3):  = 8.24–8.27 (m, 1 H), 7.65–7.69 (m, 1 H),
7.54–7.42 (m, 1 H), 7.39 (d, J = 7.8 Hz, 1 H), 6.42–6.24 (m, 2 H), 6.09
(d, J = 17.2 Hz, 1 H), 5.46 (d, J = 11.0 Hz, 1 H).
13C NMR (101 MHz, CDCl3):  = 162.0, 152.1, 137.2, 134.8, 129.7,
128.5, 128.3, 125.9, 121.1, 118.7, 105.6.
HRMS (ESI): m/z [M + H]+ calcd for C11H9O2+: 173.0597; found:
173.0577.
3-Vinylisoquinolin-1-amine (4a)
Yield: 21.1 mg (62%); brown solid.
1H NMR (400 MHz, CDCl3):  = 7.79 (d, J = 8.3 Hz, 1 H), 7.67 (d, J =
8.2 Hz, 1 H), 7.59 (t, J = 7.5 Hz, 1 H), 7.44 (t, J = 7.6 Hz, 1 H), 6.97 (s,
1 H), 6.71–6.78 (m, 1 H), 6.28 (d, J = 17.1 Hz, 1 H), 5.40 (d, J = 10.7 Hz,
3 H).
13C NMR (101 MHz, CDCl3):  = 155.81, 145.6–145.4 (m), 137.8, 135.5,
130.9, 127.4, 126.3, 123.1, 117.7, 117.1, 110.9.
(2) For 5-exo-dig N-attacked cyclization of o-alkynylbenzamide,
see: (a) Li, D. Y.; Shi, K. J.; Mao, X. F.; Zhao, Z. L.; Wu, X. Y.; Liu, P.
N. Tetrahedron 2014, 70, 7022. (b) Hu, J.; Wang, X.; Hu, Y.; Yang,
S.; Liang, Y. Green Sustainable Chem. 2011, 1, 165. (c) Kanazawa,
C.; Terada, M. Asian J. Chem. 2009, 4, 1668. (d) Brahmchari, D.;
Akhilesh, A. K.; Mehta, S. J. Org. Chem. 2018, 83, 3339. (e) Tan, J.;
Tong, Y.; Chen, Z. ChemistrySelect 2018, 3, 3886. (f) Wu, C.;
Wang, J.; Zhang, X.-Y.; Jia, G.-K.; Cao, Z.; Tang, Z.; Yu, X.; Xu, X.;
He, W.-M. Org. Biomol. Chem. 2018, 16, 5050.
HRMS (ESI): m/z [M + H]+ calcd for C11H11N2+: 171.0917; found:
171.0929.
7-Fluoro-3-vinylisoquinolin-1-amine (4b)
Yield: 24.8 mg (66%); brown solid.
1H NMR (400 MHz, CDCl3):  = 7.74–7.62 (m, 1 H), 7.34–7.41 (m, 2 H),
6.97 (s, 1 H), 6.70–6.77 (m, 1 H), 6.27 (d, J = 17.2 Hz, 1 H), 5.39 (d,
J = 10.5 Hz, 1 H), 5.20 (s, 2 H).
13C NMR (101 MHz, CDCl3):  = 160.4 (d, J = 247.8 Hz), 155.2 (s), 135.9
(s), 134.8 (s), 129.8 (d, J = 8.3 Hz), 120.5 (d, J = 24.4 Hz), 118.1 (d,
J = 7.7 Hz), 118.2–114.9 (m), 110.9 (s), 107.4 (d, J = 21.7 Hz), 105.0 (s).
(3) For selected examples of electrophilic cyclization, see: (a) Neto,
J. S. S.; Back, D. F.; Zeni, G. Eur. J. Org. Chem. 2015, 1583.
(b) Mehta, S.; Yao, T.; Larock, R. C. J. Org. Chem. 2012, 77, 10938.
(c) Schlemmer, C.; Andernach, L.; Schollmeyer, D.; Straub, B. F.;
Opatz, T. J. Org. Chem. 2012, 77, 10118. (d) Mehta, S.; Waldo, J.
P.; Larock, R. C. J. Org. Chem. 2009, 74, 1141. (e) Chinta, B. S.;
Sanapa, H.; Vasikarla, K. P.; Baire, B. Org. Biomol. Chem. 2018, 16,
3947. (f) Oliver, M. A.; Gandour, R. D. J. Org. Chem. 1984, 49, 558.
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Org. Chem. Front. 2019, 6, 2471.
HRMS (ESI): m/z [M + H]+ calcd for C11H10FN2+: 189.0823; found:
189.08.
Funding Information
Financial support from the National Natural Science Foundation of
China (51564021, 21762018 and 21772067), the Program of Qingji-
ang Excellent Young Talents, Jiangxi University of Science and Tech-
nology, and the Science and Technology Innovation Outstanding
Young Talents Program of Jiangxi Province (20192BCBL23009) is
(5) Liu, G.; Ye, D.; Zhang, D.; Ding, X.; Jiang, H.; Liu, H. Adv. Synth.
Catal. 2009, 351, 2605.
(6) For 6-endo-dig O-attacked cyclization of 2-alkynylbenzamide,
see: (a) Madich, Y.; Alvarez, R.; Aurrecoechea, J. M. Eur. J. Org.
Chem. 2015, 6298. (b) Bian, M.; Yao, W.; Ding, H.; Ma, C. J. Org.
Chem. 2010, 75, 269. (c) Bianchi, G.; Chiarini, M.; Marinelli, F.;
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2012, 77, 8206. (h) Doherty, S.; Knight, J. G.; Perry, D. O.; Ward,
gratefully acknowledged.
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690156.
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© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H

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© 2019. Thieme. All rights reserved. — Synthesis 2019, 51, A–H