Synthesis of [6,6,m]-Tricyclic Compounds via [4+2] Cycloaddition with Au or Cu Catalyst

Article abstract of DOI:10.1055/a-1479-6005

We synthesized [6,6,6]- and [6,6,7]-tricyclic compounds via intramolecular [4+2] cycloaddition by gold or copper catalysts. Substrates for cyclization were prepared by coupling reactions between eight types of diyne and four types of aromatic moieties. We have successfully synthesized eleven tricyclic compounds.

Full text of DOI:10.1055/a-1479-6005

SYNLETT
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 32, A–E
letter
A
en
J. Kang et al.
Letter
Synlett
Synthesis of [6,6,m]-Tricyclic Compounds via [4+2] Cycloaddition
with Au or Cu Catalyst
Juyeon Kang
R1
O
Cat:
Au or Cu
Seunghwan Ham
Chaehyeon Seong
R1
R2
R2
R3
Chang Ho Oh*
0
0
0
0
-
0
0
0
2
-
7
2
0
8
-
4
2
6
1
m
R3
O
R1 = H, Me
Department of Chemistry and Research Institute of Natural
Science, Hanyang University, Sungdong-Gu, Seoul 04763,
Korea
m = 6; 9 examples
m = 7; 2 examples
up to 91% yield
R
R
2 = OMe, i-Pr
3 = CO2Me, Me, OH, OTBS
changho@hanyang.ac.kr
CDeMheapanaiClgrotcHmhrroaeennsOgpthhooonf@dCihnaegnmAyiausntrhgyo.aarcn.kdrResearch Institute of Natural Science, Hanyang University, Sungdong-Gu, Seoul 04763, Korea
Received: 21.03.2021
Accepted after revision: 11.04.2021
Published online: 11.04.2021
al-catalyzed reaction can shorten the reaction pathway and
control the regioselectivity and stereoselectivity.
Synthesis of natural products using various transition-
metal catalysts such as palladium, gold, and copper has
been reported by several research groups. Shibasaki et al.
reported the synthesis of an intermediate for diterpene
synthesis through an asymmetric Heck reaction using a
palladium catalyst.9 Majetich et al. reported the conversion
of dienones into functionalized hydrophenanthrene natural
products using a BF3·Et2O catalyst.10 Dyker et al. reported
the synthesis of dihydrophenanthrene derivative using a
gold-catalyzed domino process. Hashmi et al. reported the
nucleophilic addition by gold catalyst for the synthesis of
C–C multiple bonds from various substrates.11 Yamamoto et
al. investigated the Lewis acid catalyzed intramolecular
[4+2] benzannulation reaction. The transition-metal-cata-
lyzed [4+2] approach was used for the regioselective syn-
thesis of polysubstituted benzene. Naphthyl ketone deriva-
tives were obtained through the benzannulation of o-
alkynyl(oxo)benzene and alkyne with gold and copper cat-
alysts.12 They also reported the synthesis of naphthyl ke-
tone products from alkynyl terminus substrates using cop-
per and gold catalysts through a bottom-up approach.13 In
this study, the benzopyrylium-type intermediate was pro-
duced by a metal-catalyzed cyclization. This structure is
important as the basis for the synthesis of [6,6,6]-tricyclic
compounds of abietane diterpenoids.
DOI: 10.1055/a-1479-6005; Art ID: st-2021-u0108-l
Abstract We synthesized [6,6,6]- and [6,6,7]-tricyclic compounds via
intramolecular [4+2] cycloaddition by gold or copper catalysts. Sub-
strates for cyclization were prepared by coupling reactions between
eight types of diyne and four types of aromatic moieties. We have suc-
cessfully synthesized eleven tricyclic compounds.
Key words catalysis, [4+2] cycloaddition, abietane, Dendrobium,
[6,6,m]-cyclic compound, copper, gold
Ring formation is an important method to efficiently as-
semble compounds with complex molecular structures like
natural compounds.1 The rate enhancement of cycloaddi-
tion reaction is induced by thermal, photochemical, Lewis
acid, high pressure, and ultrasonic treatments.2 One of the
rate-enhancing factors, the metal-based Lewis acid addi-
tive, acts as an electron-pair acceptor in cyclization reac-
tions.3 The cooperation of Lewis acid with transition metals
increases the activity and selectivity as well as the reactivi-
ty of the substrate.4 Lewis acids can selectively promote the
activation of C–H bond through metal coordination.5 In ad-
dition, C–C and C–N bonds can be formed by introducing
Lewis acid additives into the transition-metal catalysts as a
bond-forming catalyst. Furthermore, the Au-catalyzed and
Pd-catalyzed alkyne functionalization reactions can be ac-
celerated by the addition of Lewis acids.6
One of the methods to synthesize natural products is to
form polycyclic compounds using transition-metal com-
pounds.7 Metal compounds are formed by binding of Lewis
base or ligand to a metal that acts as Lewis acid.8 The syn-
thesis of complex natural products with unique structural
motifs is difficult to obtain due to the long route, low yield,
and efficiency. However, total synthesis via transition-met-
Abietane is a naturally occurring diterpenoid isolated
from various terrestrial plants.14 Aromatic abietane is a
compound having an A–B–C ring skeleton of 20 carbons and
exhibits different oxidation degrees at B- and C-ring car-
bons. It is largely divided into three types according to the
number of double bonds of the C-ring and the type of car-
bon ring structure.15 And most of them have a variety of bi-
ological activities.16 Aromatic Dendrobium contains
phenanthrene, bibenzyl, flavone, aromatic acid and ester
© 2021. Thieme. All rights reserved. Synlett 2021, 32, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
J. Kang et al.
Letter
Synlett
series.17 Among them, the phenanthrene skeleton of Dend-
robium is a hydroxyl and/or methoxy-substituted 9,10-di-
hydro or hydro derivative.18 Dendrodevonin A, which is ex-
tracted from Dendrobium devonianum, is used as a Chinese
herbal medicine and exhibits cytotoxicity to human colon
cancer HT-29 cell (Figure 1).
sized. Diynal substrate 1a was synthesized by palladium-
catalyzed Sonogashira coupling reaction of the diyne ob-
tained from the alkylation of dimethyl malonate and 2-bro-
mobenzaldehyde.22 The [6,6,6]-tricyclic compound 1b was
synthesized by an intramolecular [4+2] cycloaddition reac-
tion using copper and gold catalysts. The product yield was
high, when the process was carried out with a gold catalyst
at 80 °C for 2 h or with a copper catalyst at 60 °C for 1 h
(entry 1).23 The 2a diyne substrate was obtained through
trimethylsilyl (TMS) protection at one end of the alkyne ob-
tained by alkylation of dimethyl malonate. Compound 2a
was synthesized via Sonogashira coupling between 2-bro-
mobenzaldehyde and diyne. As a result of the catalytic cy-
clization reaction, product 2b was obtained in reasonable
yield when using the AuBr3 catalyst (entry 2), but byprod-
uct was formed when using Cu(OTf)2 catalyst.
In the synthesis of substrate diynal 3a, the alkyne was
synthesized from ethyl isobutyrate through alkylation and
reduction. It was combined with 2-bromobenzaldehyde
through Sonogashira coupling reaction. After protecting the
aldehyde with an acetal protecting group, 3a was obtained
through Swern oxidation, ethynylation, and acetal depro-
tection. In synthesizing 3b, the reaction proceeded effi-
ciently at 55 °C for 2 h using the gold catalyst (entry 3). The
diyne for 4a was synthesized from ethyl isobutyrate in five
steps: alkylation, reduction, TMS protection, Swern oxida-
tion, and ethynylation. The substrate 4a was obtained
through Sonogashira coupling between the diyne and 2-
bromobenzaldehyde. It was confirmed that the gold-cata-
lyzed reaction proceeded efficiently at 60 °C for 1 h to ob-
tain 4b (entry 4). We synthesized acetophenone substrates
after diynal substrate studies.
Substrate 5a was easily synthesized by the Sonogashira
coupling of 2′-bromoacetophenone and diyne. For 5a, the
reaction proceeded at 60 °C for 1 h with gold catalyst (entry
5). The diyne of substrate 6a was synthesized from ethyl
formate by Grignard reaction with propargyl bromide. Sub-
strate 6a was synthesized by TBS protection with aromatic,
diyne moiety combined by Sonogashira reaction. Com-
pound 6b was synthesized at 60 °C and 1 h under gold cata-
lyst (entry 6). The aromatic part of substrate 7a was synthe-
sized from methyl 3,5-dihydroxybenzoate through four
steps: methylation, reduction, bromination, and oxidation.
We combined the aromatic part and 4-pentyn-1-ol through
the Sonogashira reaction, and then proceeded oxidation.
Dialdehyde in aromatic and aliphatic moiety was reacted
with ethynylmagnesium bromide solution, and only aliphat-
ic aldehyde was reacted. And 7a was synthesized through
TBS protection. Product 7b was mildly synthesized under
gold catalyst at room temperature within 1 h (entry 7).
Additionally, tricyclic compound 6c was synthesized
through TBS deprotection from 6b. And we got 7c with de-
methylation followed by TBS deprotection from 7b (Scheme
1). Product 7c plays an important role as an intermediate in
the synthesis of dendrodevonin A. Demethylation from 7b
16
7
8
6
17
B
C
5
910
12
HO
O
4
A
OH
O
1
O
O
2
abietane skeleton
arucadiol
1-oxomiltirone
R
8
R
9
10
R
R
R
MeO
7
C
B
R
R
1
OH
6
5
R
A
2
OH
4
R
3
O
R
Dendrobium phenanthrene
dendrodevonin A
skeleton
Figure 1 Abietane, Dendrobium phenanthrene skeleton, and structure
of arucadiol, 1-oxomiltirone, and dendrodevonin A
We have investigated the synthesis of polycyclic com-
pounds for the past 15 years by synthesizing natural prod-
ucts using transition-metal catalysts, such as platinum, pal-
ladium, and rhodium.19 When cyclization reaction was car-
ried out with o-alkynylbenzaldehyde using a gold catalyst,
[6,7,5]-tricyclic compound was obtained as major product
through Huisgen-type [3+2] cycloaddition. And [6,6,6]-tri-
cyclic compound was obtained by [4+2] cycloaddition reac-
tion.20 Our group is recently interested in the synthesis of
abietane diterpenoid skeleton [6,6,6]-tricyclic compound.
We have studied gold- and copper-catalyzed reactions
based on the research of Yamamoto group. We reported on
the synthesis of 1-oxomiltirone and arucadiol, which be-
long to the class of abietane diterpenoids, from diyne using
gold and copper catalysts.21
In this paper, we have described the synthesis of various
[6,6,6]-tricyclic compounds that can be used as building
blocks for natural product abietane diterpenoid skeleton
synthesis via transition-metal-catalyzed cyclization reac-
tion. In addition, we have discussed the pathway to synthe-
size [6,6,7]-tricyclic compounds by increasing the carbon
tether of the substrate. The tricyclic compounds were syn-
thesized by the reaction of either gold or copper catalyst.
We synthesized the substrates by coupling reactions be-
tween eight types of diyne and four types of aromatic parts.
The catalytic cyclization reaction was carried out using AuBr3
and Cu(OTf)2 as gold and copper catalysts, respectively.
First, 1,6-diynes 1a–7a were cyclized under gold cata-
lyst (Table 1 entries 1–7). And some of the compounds (1a,
3a–5a) were also reacted under copper catalyst. In the syn-
thesis of 1a, the aromatic part was 2-bromobenzaldehyde,
and the diyne part was, respectively, coupled and synthe-
© 2021. Thieme. All rights reserved. Synlett 2021, 32, A–E

C
J. Kang et al.
Letter
Synlett
Table 1 Synthesis of 1b–11b with Au- or Cu-Catalyzed Cyclizationa
O
R1
R1
R2
R2
Cat
DCE
R3
R3
m
O
1a–11a
1b–9b
m = 6
10b–11b m = 7
O
R
O
R
OH
HO
CO2Me
CO2Me
CO2Me
CO2Me
O
O
1b R = H
2b R = TMS
1a R = H
2a R = TMS
3a
3b
O
O
TMS
TMS
CO2Me
CO2Me
O
CO2Me
CO2Me
O
OH
OH
4b
5a
5b
4a
O
O
MeO
MeO
OTBS
TBSO
OMe
O
OTBS
O
OTBS
OMe
O
7b
7a
6a
6b
O
CO2Me
CO2Me
MeO
MeO
MeO
MeO
CO2Me
CO2Me
OMe
CO2Me
CO2Me
OMe
OMe
9a
OMe
O
O
8a
8b
9b
O
O
O
O
MeO
MeO
O
O
OMe
O
O
OMe
11a
10b
10a
11b
Entry
Reactant
Catalyst
Temp (°C)
Time (h)
Product
Yield (%)
1
2
1a
2a
AuBr3
AuBr3
AuBr3
AuBr3
AuBr3
AuBr3
AuBr3
Cu(OTf)2
Cu(OTf)2
AuBr3
AuBr3
80
50
55
60
60
60
rt
2
1b
2b
82
88
91
73
85
72
67
79
76
91
76
1.5
2
3
3a
3b
4
4a
1
4b
5
5a
1
5b
6
6a
1
6b
7
7a
1
7b
8b
9b
10
11
8a
120
120
60
60
0.5
1
8b
9a
9b
10a
11a
1
10b
11b
2
a Reaction conditions: AuBr3 (2–20 mol%), 1,2-dichloroethane (DCE) under argon atmosphere.
b Reaction conditions: Cu(OTf)2 (5–10 mol%), 1,2-dichloroethane (DCE) under argon atmosphere.
© 2021. Thieme. All rights reserved. Synlett 2021, 32, A–E

D
J. Kang et al.
Letter
Synlett
O
O
M+
1 M HCl
MeOH
Metal = Cu, Au
M(+)
CO2Me
CO2Me
CO2Me
MeO2C
O
OTBS
O
OH
6b
6c, 83%
1a
A
MeO
HO
OTBS
OH
BBr3
OMe
O
OMe
O
DCM
7b
7c, 61%
Scheme 1 Synthesis of 6c and 7c with deprotection
M(+)
– M+
CO2Me
CO2Me
O
CO2Me
CO2Me
to 7c was deprotected only at one position due to the influ-
ence of ketone and OMe groups closely attached to the A-
and C-rings. By controlling the protecting group of the aro-
matic moiety, we plan to synthesize the dendrodevonin se-
ries through further study.Second, 1,6-diynes 8a and 9a
were cyclized with copper catalyst (Table 1 entries 8 and 9).
The aromatic parts of substrate 8a and 9a were obtained
from 1,2-dimethoxybenzene in four steps.21 Diynal sub-
strate 8a can be synthesized through Sonogashira coupling
between the aromatic and diyne parts. Product 8b was syn-
thesized in good yield by cyclization using a copper catalyst
at 120 °C for 0.5 h (entry 8). The reaction did not proceed
with gold catalyst. The diyne of 9a was synthesized from
ethyl isobutyrate in six steps. First, an aldehyde was ob-
tained through alkylation, reduction, and oxidation. And al-
dehyde was converted into an alkyne via Corey–Fuchs reac-
tion and elimination. After the introduction of the CO2Me
group, diyne was synthesized with a functional group at-
tached only at one side after TMS deprotection. Substrate
9a was synthesized through a Sonogashira coupling reac-
tion between the aromatic and diyne moiety. Finally, 9b
was synthesized using the copper catalyst at 120 °C for 1 h
(entry 9). The reaction did not proceed with the gold catalyst.
After synthesizing various [6,6,6]-tricyclic compounds,
we experimented to expand [6,6,7] ring compounds. Ring
expansion can proceed by introducing additional carbons
or heteroatoms into the ring.24 However, we increased the
number of carbon chains by changing the substrate from
1,6-diyne to 1,7-diyne. According to the mechanistic study
of Scheme 2, the number of rings can be adjusted by in-
creasing the carbon chain of the diyne unit.
O
1b
B
Scheme 2 Proposed mechanism of the metal-catalyzed reaction of 1a
synthesis of allenic and propargylic alcohols by treating al-
dehyde and propargyl halide with zinc in THF/aq. NH4Cl
solution.25 Based on this, the aldehyde was treated with al-
lenyl bromide and zinc dust in solvent mixture to obtain
propargylic alcohol by Barbier reaction. Then, 10a was syn-
thesized through oxidation and acetal deprotection. Sub-
strate 11a was synthesized from the aromatic part obtained
from 1,2-dimethoxybenzene, and the synthetic method
was the same as for substrate 10a.21 As a result of the gold-
catalyzed reaction of two substrates, the desired [6,6,7]-tri-
cyclic compounds 10b and 11b were obtained at 60 °C
within 1–2 h (entries 10 and 11). However, in the case of
the copper catalyst, the desired product could not be ob-
tained due to the byproduct.
We attached various functional groups while synthesiz-
ing diynal substrates and observed the tolerance of the cat-
alytic cyclization reaction for those functional groups. The
catalytic reaction of diynal obtained from 1,6-diyne pro-
ceeded differently depending on the aromatic type. Sub-
strates 1a–4a from 2-bromobenzaldehyde proceeded better
under gold catalyst. Substrates 5a and 6a from 2′-bromoac-
etophenone performed better under gold catalyst. Sub-
strate 7a has attached a substituent at the meta position of
the aromatic part from methyl 3,5-dihydroxybenzoate, and
the gold-catalyzed reaction proceeded as a major. However,
when OMe groups were attached as substituent (8a, 9a) at
the ortho position of the aromatic part, the reaction pro-
ceeded only with copper catalyst. In the case of diynal (10a,
11a) obtained with 1,7-diyne, the reaction proceeded bet-
ter under gold catalyst. The methoxy group at the ortho po-
sition of the aromatic moiety creates a ring closure of inter-
mediate A. So, it forms another intermediate to proceed to
the [6,6,5]-tricyclic compound.21 This is because the Lewis
acidity of AuBr3 is stronger than that of Cu(OTf)2. Therefore,
in this case (8a, 9a) it was confirmed that the copper cata-
lyst reacted better than the gold catalyst.
Third, 1,7-diynes 10a and 11a were cyclized with gold
catalyst (Table 1, entries 10 and 11). Two types of substrates
10a and 11a were synthesized according to the functional
group attached to the aromatic part. Substrate 10a (R1, R2,
R3 = H) was synthesized through the reactions mentioned
below. After combining 2-bromobenzaldehyde and 4-pen-
tyn-1-ol through Sonogashira coupling, aliphatic aldehyde
was introduced through acetal protection and Swern oxida-
tion. The synthesis of aldehyde to propargylic alcohol has
been reported in the literature. They reported a selective
© 2021. Thieme. All rights reserved. Synlett 2021, 32, A–E

E
J. Kang et al.
Letter
Synlett
The proposed mechanism shows a metal-catalyzed re-
action from diynal to a [6,6,6]-tricyclic compound. Here,
the metal catalyst can be gold, copper, or platinum. When
the metal catalyst is mediated with substrate 1a, it under-
goes a benzannulation process. Through this process, it is
activated by M+ and forms the benzopyrylium intermediate
A.26 Then, the bridged intermediate B is formed by the in-
tramolecular [4+2] cycloaddition reaction. Finally, M+ is
continuously removed to synthesize a cyclic compound 1b
(Scheme 2).
In conclusion, transition-metal-catalyzed cyclization re-
actions were carried out with substrates obtained from the
Sonogashira coupling with seven types of 1,6-diynes and
four types of aromatic moieties. When the aromatic parts
were 2-bromobenzaldehyde and 2′-bromoacetophenone,
gold- or copper-catalyzed reactions were carried out with
six substrates resulting in the formation of [6,6,6]-tricyclic
compounds. The reaction using the gold catalyst proceeded
well compared to that with the copper catalyst. When me-
thoxy groups are attached to the aromatic parts, the reac-
tivity varies depending on where they are attached. When
the methoxy groups were in the meta position, the reaction
proceeded well with the gold catalyst. However, when the
methoxy groups were in the ortho position, the reaction
proceeded well with the copper catalyst. This was because
of the stronger Lewis acidity of the gold catalyst than that
of the copper catalyst. In addition, we obtained [6,6,7]-tri-
cyclic compounds in high yields through a gold-catalyzed
cyclization reaction with diynal obtained from 1,7-diyne.
(6) Becica, J.; Dobereiner, G. E. Org. Biomol. Chem. 2019, 17, 2055.
(7) (a) Chen, D. Y.-K.; Ma, D. Beilstein J. Org. Chem. 2013, 9, 1192.
(b) Yuan, C.; Liu, B. Org. Chem. Front. 2018, 5, 106.
(8) Elsby, M. R.; Baker, R. T. Chem. Soc. Rev. 2020, 49, 8933.
(9) Kondo, K.; Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1995, 60,
4322.
(10) Majetich, G.; Liu, S.; Fang, J.; Siesel, D.; Zhang, Y. J. Org. Chem.
1997, 62, 6928.
(11) (a) Dyker, G.; Hildebrandt, D. J. Org. Chem. 2005, 70, 6093.
(b) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180.
(12) (a) Saito, S.; Yamamoto, Y. Chem. Rev. 2000, 100, 2901. (b) Asao,
N.; Nogami, T.; Lee, S.; Yamamoto, Y. J. Am. Chem. Soc. 2003, 125,
10921.
(13) Asao, N.; Sato, K.; Menggenbateer; Yamamoto, Y. J. Org. Chem.
2005, 70, 3682.
(14) Sadowska, B.; Kuźma, Ł.; Micota, B.; Budzyńska, A.; Wysokińska,
H.; Kłys, A.; Więckowska-Szakiel, M.; Różalska, B. Microb.
Pathog. 2016, 98, 132.
(15) González, M. A. Nat. Prod. Rep. 2015, 32, 684.
(16) González, M. A. Eur. J. Med. Chem. 2014, 87, 834.
(17) Wu, L.; Lu, Y.; Ding, Y.; Zhao, J.; Xu, H.; Chou, G. Nat. Prod. Res.
2019, 33, 2160.
(18) Xu, J.; Han, Q.-B.; Li, S.-L.; Chen, X.-J.; Wang, X.-N.; Zhao, Z.-Z.;
Chen, H.-B. Phytochem. Rev. 2013, 12, 341.
(19) (a) Oh, C. H.; Piao, L.; Jung, J.; Kim, J. Asian J. Org. Chem. 2016, 5,
1237. (b) Park, M. S.; Kim, G.; Won, H.; Han, J. W.; Oh, C. H. Bull.
Korean Chem. Soc. 2020, 41, 88. (c) Le, T. Q.; Karmakar, S.; Lee,
S.; Chai, U.; Le, M. H.; Oh, C. H. ChemistrySelect 2019, 4, 11926.
(d) Shin, S.; Gupta, A. K.; Rhim, C. Y.; Oh, C. H. Chem. Commun.
2005, 4429.
(20) Kim, N.; Kim, Y.; Park, W.; Sung, D.; Gupta, A. K.; Oh, C. H. Org.
Lett. 2005, 7, 5289.
(21) Seong, C.; Kang, J.; Chai, U.; Mac, D. H.; Oh, C. H. Synlett 2020, 31,
1953.
(22) Kanwal, I.; Mujahid, A.; Rasool, N.; Rizwan, K.; Malik, A.; Ahmad,
G.; Shah, S. A. A.; Rashid, U.; Nasir, N. M. Catalysts 2020, 10, 443.
(23) Procedure for the AuBr3-Catalyzed Cyclization
In a sealed tube was added 1a (1.0 equiv, 30.9 mg, 0.10 mmol),
AuBr3 (1.3 mg, 3 mol%), and dry 1,2-dichloroethane (0.4 mL)
under argon atmosphere. The mixture was then stirred at 80 °C
for 2 h. The solvent was removed under reduced pressure to give
crude products, which were purified by flash silica gel chroma-
tography using a mixture of ethyl acetate/hexane (1:30) to
furnish 1b (24.9 mg, 82% yield, yellow liquid).
Conflict of Interest
The authors declare no conflict of interest.
Funding Information
This work was supported by a grant from the National Research Foun-
dation of Korea (NRF), funded by the Korean Government, through
the Center for New Directions in Organic Synthesis (NRF-
Procedure for the Cu(OTf)2-Catalyzed Cyclization
In a sealed tube was added 1a (1.0 equiv, 34.1 mg, 0.11 mmol),
Cu(OTf)2 (2.4 mg, 6 mol%), and dry 1,2-dichloroethane (0.4 mL)
under argon atmosphere. The mixture was then stirred at 60 °C
for 1 h. The solvent was removed under reduced pressure to give
crude products, which were purified by flash silica gel chroma-
tography using a mixture of ethyl acetate/hexane (1:30) to
furnish 1b (26.8 mg, 78% yield, yellow liquid). 1H NMR (400
MHz, CDCl3):  = 9.44 (dt, J = 8.8, 0.9 Hz, 1 H), 7.96 (dd, J = 8.3,
2.4 Hz, 1 H), 7.81 (dd, J = 8.1, 1.6 Hz, 1 H), 7.64 (ddt, J = 8.7, 6.9,
1.7 Hz, 1 H), 7.51 (ddt, J = 8.0, 6.8, 1.2 Hz, 1 H), 7.34 (dd, J = 8.5,
2.4 Hz, 1 H), 3.72–3.65 (m, 8 H), 3.27 (t, J = 1.3 Hz, 2 H). 13C NMR
(101 MHz, CDCl3):  = 195.35, 170.30, 142.05, 135.47, 133.24,
131.17, 129.42, 128.47, 126.81, 126.43, 126.08, 55.00, 53.32,
45.26, 36.78.
2021R1A5A6002803).National
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esearch
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/a-1479-6005.
S
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p
p
ortingInformaitonS
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p
p
ortingInformaito
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References and Notes
(1) Bertz, S. H. J. Am. Chem. Soc. 1981, 103, 3599.
(2) Lautens, M.; Klute, W.; Tam, W. Chem. Rev. 1996, 96, 49.
(3) Denmark, S. E.; Beutner, G. L. Angew. Chem. Int. Ed. 2008, 47,
1560.
(4) Wang, C.; Xi, Z. Chem. Soc. Rev. 2007, 36, 1395.
(5) Sasmal, S.; Dutta, U.; Lahiri, G. K.; Maiti, D. Chem. Lett. 2020, 49,
1406.
(24) Saito, H.; Yorimitsu, H. Chem. Lett. 2019, 48, 1019.
(25) Jõgi, A.; Mäeorg, U. Molecules 2001, 6, 964.
(26) Sato, K.; Asao, N.; Yamamoto, Y. J. Org. Chem. 2005, 70, 8977.
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