Palladium-Catalyzed Aryl-Furanylation of Alkenes: Synthesis of Benzofuran-Containing 3,3-Disubstituted Oxindoles

Hongbo Qi, Kaiming Han, and Shufeng Chen*

Article

Palladium-Catalyzed Aryl-Furanylation of Alkenes: Synthesis of

Benzofuran-Containing 3,3-Disubstituted Oxindoles

Cite This: J. Org. Chem. 2021, 86, 9384 −9395

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sı Supporting Information

ABSTRACT: A novel palladium-catalyzed aryl-furanylation of

alkenes is described. This protocol provided a straightforward

route to the synthesis of various benzofuran-containing 3,3-

disubstitutedoxindole derivatives bearing a quarternary carbon

center. In the cascade process, one C(sp )−O bond, two C(sp )−

C(sp ) bonds, an oxindole, and a furan ring are formed in a single

chemical operation.

INTRODUCTION

To our knowledge, the reported approaches that end in alkyl-

12 9b,13

■

Pd species include carbene, terminal alkynes,

unactivated

One of the approaches to discover or design modern drugs is

to combine molecules with diﬀerent biological activities.

Thus, the construction of diverse heterocycle compounds with

biological activities in a single step is of great signiﬁcance for

organic synthesis. 3,3-Disubstituted oxindole scaﬀolds as

important structural motifs broadly exist in many biologically

C(sp )−H bond, and sulfolene (Scheme 1a). Moreover,

the Lin group has recently reported a palladium-catalyzed

cascade Heck cyclization to construct bisindoles, where the in

situ-generated alkyl-Pd species was intercepted by the

cyclization of o-ethynylanilines. Inspired by these previous

works and as a continuation of our interest in the area of

active natural products and pharmaceutical molecules, such

9b,17

transition-metal-catalyzed cascade reactions,

herein we

as nelivaptan, amedalin, linopirdine, and isapheninum (Figure

describe a palladium-catalyzed domino aryl furanylation of

alkenes to construct diverse benzofuran-containing 3,3-

A−D, respectively). Over the past decades, various synthetic

methods to build 3,3-disubstituted oxindole scaﬀolds have

disubstituted oxindole compounds, where one C(sp )−O

been widely established. Moreover, benzofuran ring systems

are also valuable structures that have biological and

bond, two C(sp )−C(sp ) bonds, an oxindole, and a furan

ring are formed in a single chemical operation (Scheme 1b).

Signiﬁcantly, this method oﬀers facile access to a series of

bisheterocyclic compounds from readily available N-phenyl-

acrylamide and alkynylphenol derivatives without the assis-

tance of an additional ligand.

pharmacological activities in numerous compounds (Figure

E−H). Therefore, the preparation of benzofuran derivatives

has become a highly researched area in organic synthesis and

has attracted much attention in recent years. Consequently,

the integration of a benzofuran moiety into oxindole

derivatives may increase their biological activities or create

new medicinal properties. However, as far as our knowledge is

concerned, the method for the construction of these novel

benzofuran-containing oxindoles is still scarce. Therefore,

developing mild and rapid methods for the synthesis of

bisheterocyclic compounds in a single synthetic sequence is

highly desirable and urgent.

RESULTS AND DISCUSSION

■

We began our study by investigating the cascade reaction with

N-(2-iodophenyl)-N-methylmethacrylamide 1a and 2-

phenylethynyl)phenol 2a as the model substrates, and the

results are summarized in Table 1. To our delight, the desired

aryl-furanylation product 3aa was obtained in a 15% yield by

heating the mixture of 1a and 2a in MeCN with Pd(OAc) (10

(

On the other hand, the palladium-catalyzed domino reaction

has become a signiﬁcant strategy in the synthetic community

for the formation of carbon−carbon or carbon−heteroatom

bonds. Among the various reactions involving palladium

intermediates, the alkylpalladium species generated from the

carbopalladation of a double bond has attracted considerable

mol %), PPh (20 mol %), and K CO (2 equiv) at 80 °C

(

entry 1). Subsequently, diﬀerent palladium catalysts were

tested. Pd(PPh ) showed a great performance in comparison

Received: March 15, 2021

Published: July 2, 2021

−10

attention from synthetic chemists in recent years.

The

generation of alkyl-Pd species in situ has generally proved

more challenging due to their lower reactivity and stability

characteristics compared to those of the arylpalladium,

vinylpalladium, alkynylpalladium, and allylpalladium species.

2021 American Chemical Society

The Journal of Organic Chemistry

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Figure 1. Representative bioactive benzofuran and 3,3-disubstituted oxindoles.

Scheme 1. Strategies for the Palladium-Catalyzed Aryl

Functionalization of Alkenes

Table 1. Optimization of the Cascade Reaction Conditions

entry

catalyst

ligand

PPh₃

base

yield (%)

Pd(OAc)₂

Pd(PPh₃)₄

Pd(TFA)₂

K CO₃

PPh₃

Pd (dba)₃

PdCl (PPh )

PdCl (dppf)

Pd(PPh₃)₄

Na CO₃

KOCH₃

Cs CO₃

KOH

NaHCO₃

Li CO₃

t-BuOLi

83 , 87

Reaction conditions are as follows unless otherwise noted: 1a (0.1

mmol), 2a (0.15 mmol), catalyst (10 mol %), ligand (20 mol %),

MeCN (1.0 mL, 0.1 M), base (0.2 mmol), 80 °C, 10 h under an argon

atmosphere. Isolated yields. Pd(PPh ) (5 mol %). Pd(PPh ) (3

3 4

mol %). 70 °C. 90 °C.

with those of Pd(TFA) , Pd (dba) , PdCl (PPh ) , and

3 2

PdCl (dppf), aﬀording the corresponding product 3aa in an

0% yield (entries 2−6, respectively). Therefore, on using

Moreover, we also examined the eﬀect of leaving groups of

the acrylamide partner in this reaction (Scheme 2). It was

found that both aryl iodide 1a and aryl bromide 4 could

provide the desired product 3aa in excellent yields, while aryl

chloride 5 was conﬁrmed as an inactive substrate and the

corresponding product 3aa was not detected under the

identical conditions. The aryl triﬂate 6 only gave the product

3aa in a 25% yield. In addition, the reaction with N-methyl-N-

phenylmethacrylamide 7 under identical conditions resulted in

a complex mixture. These results indicated that neither aryl

iodide nor bromide was superior to other aryl coupling

partners in this cascade furanylation reaction.

Pd(PPh ) as the catalyst, the cascade reaction conditions

continued to be optimized. The speciﬁc identity of the base

proved critical, and the exploration of diﬀerent bases revealed

that t-BuOLi provided the best yield of 96% (entries 7−13). In

addition, decreasing the loading of the palladium catalyst to 5

mol % had almost no eﬀect on the outcome of the product

(

entry 14, 94%), whereas a moderate yield was obtained when

mol % Pd(PPh ) was used (entry 15, 64%). Therefore, for

economic reasons, the use of the 5 mol % catalyst is preferred.

Further screening of the reaction temperature suggested that

0 °C was the best choice (entry 16).

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Scheme 2. Reactions of Aryl Halides 1a, 4, 5, Aryl Triﬂate 6,

and N-Methyl-N-phenylmethacrylamide 7 with 2a

the 5-position showed a better performance than the 4-

position. For instance, the N-methylmethacrylamides with a 5-

methyl, 5-ﬂuoro, or 5-chloro substituent aﬀorded the desired

products 3ca, 3ea, and 3fa in 85%, 89%, and 94% yields,

respectively. However, the N-methylmethacrylamides with a 4-

methyl, 4-ﬂuoro, or 4-chloro substituent on the aromatic ring

provided the corresponding products 3ba, 3da, and 3ga in

80%, 86%, and 89% yields, respectively. Reactions of aryl

iodides bearing a strong electron-withdrawing group pro-

ceeded smoothly, providing the corresponding products 3ha−

ja in excellent yields. The chloro group at the 3-position also

furnished this reaction well, oﬀering the desired product 3ka in

a good yield. In addition, a benzyl-protected acrylamide also

eﬃciently underwent the cascade reaction and delivered the

desired product 3la in an 86% yield. Unfortunately, none of the

desired products 3ma and 3na were detected when p-

toluenesulfonyl- and t-butyloxycarbonyl-protected acrylamides

were used in this transformation. It should be noted that an

acrylamide with a free N−H bond also failed in this reaction.

Moreover, substrate 1p with an aryl group at the α-position of

the double bond proved to be a suitable reaction partner and

oﬀered 3pa with a high yield.

With the optimized reaction conditions in hand, we then

investigated the substrate scope of the aryl iodides to evaluate

the generality of this cascade reaction, and the results are

depicted in Scheme 3. The methyl substituent on the aryl

iodides at the para- or meta- osition could provide the products

3ba and 3ca in 80% and 85% yields, respectively. Fluoro and

chloro groups at the diﬀerent positions also performed well,

and the corresponding products 3da−3ga were isolated in 86−

4% yields. The exact structure of 3da was further

Subsequently, we continued to examine the reaction scope

with various ortho-alkynylphenols 2 using N-(2-iodophenyl)-

N-methylmethacrylamide 1a, and the results are shown in

unambiguously identiﬁed by single-crystal X-ray analysis.

When studying position substituent eﬀects on the aniline part,

Scheme 3. Substrate Scope of the Aryl Iodides ^,

a b

Reaction conditions are as follows: 1 (0.1 mmol), 2a (0.15 mmol), Pd(PPh ) (5.0 mol %), t-BuOLi (0.2 mmol), MeCN (1.0 mL), under an

argon atmosphere for 10 h, sealed tube. Isolated yields.

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Scheme 4. Scope of ortho-Alkynylphenols^a^,^b

Reaction conditions are as follows: 1a (0.1 mmol), 2 (0.15 mmol), Pd(PPh ) (5.0 mol %), t-BuOLi (0.2 mmol), MeCN (1.0 mL), under an

argon atmosphere for 10 h, sealed tube. Isolated yields.

Scheme 4. With respect to the benzene rings of alkyne

moieties, both electron-withdrawing (3ab−3ae) and electron-

donating (3af−3ag) substituents at the para-positions were

also tolerated, giving the expected products in 85−92% yields.

Notably, the substrates bearing a thiophene and a tert-butyl

group were found to be a suitable reaction partners, aﬀording

the corresponding products 3ah and 3ai in 85% and 83%

yields, respectively. The n-butyl-, n-pentyl-, and n-hexyl-

substituted substrates were also adaptable and gave the

spirocyclic products 3aj−3al in good yields. In addition,

substitution at the meta- or ortho-position was also tested, and

the desired products 3am−3ap were formed in 75−85% yields.

To our delight, the desired product 3aq could also be isolated

in a 22% yield, although the terminal alkyne is a more

challenging substrate due to its inherent stability and the lack

of reactivity issues. However, compound 2r with a silyl group

failed to produce the desired product 3ar under the optimal

conditions, and a complex mixture was observed. Furthermore,

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the electronic eﬀects of R⁵were also investigated. The

substrates with a chloro, bromo, methyl, or tert-butyl group

at the 4-position could also proceed well, furnishing the target

products 3as−3av, respectively, with high yields. Unfortu-

nately, none of the desired product 3aw was obtained when the

phenol bearing an ester group at the 4-position was used. The

substrate possessing a triﬂuoromethyl group at the 4-position

could perform this reaction smoothly, and the desired product

Scheme 6. Control Experiments on Mechanistic Aspect

ax was isolated in a moderate yield.

Furthermore, to evaluate the productive practicability of this

cascade reaction, the gram-scale preparation of 3aa was

performed under the standard conditions, which also showed

a satisfactory result (Scheme 5, eq 1). In addition, we sought to

Scheme 5. Gram-Scale Experiment and Further

Transformation

demonstrate the transformation of functional groups of the

products. For example, the treatment of 3aa under conditions

with a DIBAL-H as the reducing reagent gave the indoline-

containing benzofuran derivative 8 in an 84% yield (Scheme 5,

eq 2).

Scheme 7. Proposed Mechanism

To gain some mechanistic insight into this reaction, several

control experiments were carried out. Although the furan 9

could be generated by the cyclization of o-alkynylphenol 2a in

the presence of a base (Scheme 6a), we could not obtain any

desired product 3aa when 1a and 9 were mixed under the

standard reaction conditions, and all starting materials were

recovered (Scheme 6b). Next, the reaction of 1a and 2a with

.0 equiv of Pd(PPh ) in the absence of a base could generate

3 4

product 3aa in an 83% isolated yield (Scheme 6c). These

results could eliminate the possibility in which the base-

promoted deprotonation of 2a and the cyclization occurr to

generate furan 9 as an intermediate. Furthermore, when a

radical inhibitor TEMPO or BHT was added, the reactions

were still furnished smoothly and aﬀorded the product 3aa in

high yields (Scheme 6d or e, respectively). These results

indicated that a radical pathway might not be involved in this

reaction.

On the basis of the above results, a mechanistic pathway for

the formation of 3aa is outlined in Scheme 7. The catalytic

cycle is initiated by the oxidative addition of the carbon−

halogen bond to Pd(0). Subsequently, the intermediate A

preferentially undergoes an intramolecular Heck cyclization,

produces the product 3aa and regenerates the active Pd(0)

species.

generating a primary alkylpalladium species B. Coordination

of the alkylpalladium intermediate B to the triple bond of 2a

enables the intramolecular nucleophilic attack of the oxygen

CONCLUSIONS

■

In conclusion, we have successfully developed a novel and

eﬃcient palladium-catalyzed cascade aryl-furanylation of

alkenes toward the synthesis of benzofuran-containing 3,3-

disubstituted oxindole derivatives. This transformation in-

atom and generates the intermediate C. Then, assisted by a

base, intermediate C could easily convert to the intermediate

D. Finally, the reductive elimination of intermediate D

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−

volves the processes of intramolecular Heck cyclization,

834, 807, 753, 691, 640 cm . HRMS (ESI) m/z: calcd for

C H NO [M + H] , 382.1801; found, 382.1790.

1,3,6-Trimethyl-3-((2-phenylbenzofuran-3-yl)methyl)indolin-2-

one (3ca). Puriﬁcation by column chromatography on silica gel

phenol-palladation, and furanylation in which one C(sp )−O

26 24

bond, two C(sp )−C(sp ) bonds, an oxindole, and a furan ring

are formed sequentially in a single step. The good functional

group tolerance, broad substrate scope, and moderate to high

yields make the present protocol attractive for both academia

and industry.

(

petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a brown solid (32 mg, 85% yield). mp: 201−204 °C.

H NMR (500 MHz, CDCl ): δ 7.52−7.47 (m, 3H), 7.43−7.38 (m,

H), 7.36 (ddd, J = 7.3, 3.5, 1.5 Hz, 1H), 7.25 (ddd, J = 9.4, 6.8, 2.7

Hz, 1H), 7.21−7.16 (m, 1H), 6.44 (d, J = 7.2 Hz, 2H), 6.40 (d, J =

.6 Hz, 1H), 3.56 (d, J = 14.3 Hz, 1H), 3.40 (d, J = 14.3 Hz, 1H),

.95 (s, 3H), 2.27 (s, 3H), 1.47 (s, 3H). C{ H} NMR (126 MHz,

EXPERIMENTAL SECTION

■

General Information. All commercially available reagents were

used directly without puriﬁcation unless otherwise stated. All solvents

were puriﬁed following standard procedures. For chromatography,

CDCl ): δ 180.7, 153.6, 153.2, 143.0, 137.6, 131.3, 130.0, 129.7,

28.3, 128.3, 127.8, 124.1, 123.5, 122.5, 122.2, 121.0, 111.5, 110.6,

08.5, 48.9, 32.7, 25.7, 23.0, 21.7. IR (KBr): 3025, 2968, 2922, 2869,

711, 1620, 1502, 1453, 1377, 1260, 1115, 1063, 810, 751, 722, 694,

00−300 mesh silica gel (Qingdao, China) was employed. H, C,

and F NMR spectra were recorded at 500, 126, and 470 or 475

MHz, respectively. Chemical shifts are reported in parts per million

−1

42, 617 cm . HRMS (ESI) m/z: calcd for C H NO Na [M +

Na] , 404.1621; found, 404.1613.

(

ppm) using tetramethylsilane as the internal standard in CDCl as

5-Fluoro-1,3-dimethyl-3-((2-phenylbenzofuran-3-yl)methyl)-

indolin-2-one (3da). Puriﬁcation by column chromatography on

silica gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a yellow solid (33 mg, 86% yield). mp: 141−143 °C. H

NMR (500 MHz, CDCl ): δ 7.58−7.53 (m, 1H), 7.49−7.47 (m, 2H),

the solvent. IR spectra were recorded on a FT-IR instrument. High-

resolution mass spectra were recorded with a ESI-Q-TOF mass

spectrometer. Melting points were determined with a melting point

10d

12a

apparatus and were uncorrected. The aryl halogens 1, 4, and 5;

aryl triﬂate 6; N-methyl-N-phenylmethacrylamide 7; and ortho-

.45−7.41 (m, 2H), 7.41−7.37 (m, 2H), 7.25−7.21 (m, 2H), 6.76−

.70 (m, 1H), 6.46 (dd, J = 8.4, 4.1 Hz, 1H), 6.21 (dd, J = 8.1, 2.6 Hz,

H), 3.60−3.54 (m, 1H), 3.49−3.44 (m, 1H), 2.90 (s, 3H), 1.46 (s,

20b

alkynylphenols 2

were prepared in the lab by the reported

procedures.

General Procedure for the Synthesis of Products 3. To a solution

of aryl halides 1 (0.1 mmol, 1.0 equiv), o-alkynylphenols 2 (0.15

mmol, 1.5 equiv), and t-BuOLi (16.0 mg, 0.2 mmol) in MeCN (1.0

H). C{ H} NMR (126 MHz, CDCl ): δ 180.0, 158.7 (d, J

C−F

40.4 Hz), 153.6, 153.5, 134.2 (d, J_C₋_F= 7.9 Hz), 113.7 (d, J_C₋_F

3.5 Hz), 128.6, 128.5, 127.8, 124.2, 122.3, 120.8, 113.8, 113.6, 112.0

= 8.2 Hz), 49.7, 32.6,

mL) was added Pd(PPh ) (5.78 mg, 5.0 mol %) under an argon

(d, J = 24.9 Hz), 110.9, 110.7, 107.7 (d, J

C−F

atmosphere in a sealed tube. The resulting mixture was stirred at 80

C in an oil bath for 10 h. The solvent was removed in a vacuum, and

the resulting residue was puriﬁed on a silica gel column to oﬀer the

products 3.

Large-Scale Preparation of 3aa. Compound 1a (4.0 mmol, 1,2 g),

compound 2a (6 mmol, 1.16 g), Pd(PPh ) (0.2 mmol, 231 mg), and

t-BuOLi (8 mmol, 640 mg) were added to a sealed tube. To the

mixture was added MeCN (40.0 mL) via syringe. Under an argon

atmosphere, the reaction mixture was stirred at 80 °C in an oil bath

until completion (monitored by TLC). After cooling at room

temperature, the mixture was concentrated under reduced pressure.

The residue was puriﬁed by silica gel chromatography (petroleum

ether/ethyl acetate = 10:1, v/v) to aﬀord the product 3aa (1.3 g,

6.1, 22.8. F NMR (470 MHz, CDCl ): δ −120.8. IR (KBr): 3036,

961, 2923, 2858, 1712, 1618, 1492, 1453, 1373, 1254, 1113, 1061,

37, 750, 720, 694, 643 cm . HRMS (ESI) m/z: calcd for

−1

C H FNO [M + H] , 386.1550; found, 386.1536.

-Fluoro-1,3-dimethyl-3-((2-phenylbenzofuran-3-yl)methyl)-

indolin-2-one (3ea). Puriﬁcation by column chromatography on

silica gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a yellow oil (34 mg, 89% yield). H NMR (500 MHz,

CDCl ): δ 7.54−7.48 (m, 3H), 7.44−7.41 (m, 2H), 7.41−7.37 (m,

2H), 7.27−7.23 (m, 1H), 7.22−7.17 (m, 1H), 6.43 (dd, J = 8.2, 5.4

Hz, 1H), 6.32 (dd, J = 8.9, 2.3 Hz, 1H), 6.22 (ddd, J = 10.4, 8.2, 2.3

Hz, 1H), 3.57 (d, J = 14.4 Hz, 1H), 3.43 (d, J = 14.3 Hz, 1H), 2.90 (s,

3H), 1.47 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ 180.7, 162.7

(d, J_C₋_F= 244.2 Hz), 153.6, 153.3, 144.4 (d, J_C₋_F= 11.4 Hz), 131.2,

129.8, 128.4 (d, J_C₋_F= 2.2 Hz), 127.8, 124.6 (d, J_C₋_F= 9.8 Hz),

8%).

,3-Dimethyl-3-((2-phenylbenzofuran-3-yl)methyl)indolin-2-one

3aa). Puriﬁcation by column chromatography on silica gel

petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a yellow solid (35 mg, 94% yield). mp: 104−105 °C.

(

24.3, 122.3, 120.8, 111.1, 110.7, 107.9, 107.7, 96.3, 96.1, 48.8, 32.7,

(

6.1, 23.0. F NMR (470 MHz, CDCl ): δ −113.3. IR (KBr): 3018,

972, 2927, 2869, 1711, 1615, 1512, 1455, 1385, 1258, 1138, 1025,

H NMR (500 MHz, CDCl ): δ 7.54−7.49 (m, 3H), 7.43−7.35 (m,

−1

836, 755, 718, 689, 641 cm . HRMS (ESI) m/z: calcd for

H), 7.27−7.23 (m, 1H), 7.20 (t, J = 7.0 Hz, 1H), 7.08−7.06 (m,

C H FNO [M + H] , 386.1550; found, 386.1562.

H), 6.63−6.56 (m, 3H), 3.60 (d, J = 14.4 Hz, 1H), 3.45 (d, J = 14.4

-Chloro-1,3-dimethyl-3-((2-phenylbenzofuran-3-yl)methyl)-

Hz, 1H), 2.97 (s, 3H), 1.51 (s, 3H). C{ H} NMR (126 MHz,

indolin-2-one (3fa). Puriﬁcation by column chromatography on silica

gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a yellow oil (38 mg, 94% yield). H NMR (500 MHz,

CDCl ): δ 180.4, 153.7, 153.3, 142.9, 132.7, 131.3, 123.0, 128.4,

28.3, 127.9, 127.6, 124.2, 123.7, 122.2, 122.1, 121.0, 111.4, 110.7,

07.5, 49.2, 32.7, 26.0, 23.0. IR (KBr): 3035, 3963, 2925, 2865, 1710,

612, 1492, 1450, 1256, 1117, 1064, 886, 816, 748, 693, 666, 640

CDCl ): δ 7.53 (d, J = 7.9 Hz, 1H), 7.48 (dd, J = 8.2, 1.4 Hz, 2H),

7.45−7.37 (m, 4H), 7.27−7.23 (m, 1H), 7.22−7.18 (m, 1H), 6.56 (d,

J = 1.8 Hz, 1H), 6.48 (d, J = 1.8 Hz, 1H), 6.40 (d, J = 7.9 Hz, 1H),

3.57 (d, J = 14.4 Hz, 1H), 3.44 (d, J = 14.3 Hz, 1H), 2.88 (s, 3H),

−

cm . HRMS (ESI) m/z: calcd for C H NO Na [M + Na] ,

90.1464; found, 390.1467.

,3,5-Trimethyl-3-((2-phenylbenzofuran-3-yl)methyl)indolin-2-

one (3ba). Puriﬁcation by column chromatography on silica gel

petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a yellow solid (31 mg, 80% yield). mp: 133−135 °C.

1.46 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ 180.3, 153.6,

53.3, 144.1, 133.3, 131.2, 130.8, 129.7, 128.5, 128.4, 127.8, 124.4,

24.3, 122.3, 121.6, 120.8, 110.9, 110.7, 108.1, 48.9, 32.7, 26.0, 22.7.

(

IR (KBr): 3006, 2962, 2921, 2862, 1717, 1608, 1492, 1453, 1373,

−

H NMR (500 MHz, CDCl ): δ 7.53 (dd, J = 8.8, 7.7 Hz, 3H), 7.43

1257, 1112, 1071, 836, 752, 717, 693, 670, 640 cm . HRMS (ESI)

m/z: calcd for C H ClNO [M + H] , 402.1255; found, 402.1279.

5-Chloro-1,3-dimethyl-3-((2-phenylbenzofuran-3-yl)methyl)-

indolin-2-one (3ga). Puriﬁcation by column chromatography on

silica gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

(

t, J = 7.4 Hz, 2H), 7.38 (dd, J = 7.4, 5.4 Hz, 2H), 7.26−7.22 (m,

H), 7.19 (dd, J = 11.0, 3.9 Hz, 1H), 6.84 (d, J = 7.7 Hz, 1H), 6.46

d, J = 7.8 Hz, 1H), 6.34 (s, 1H), 3.59 (d, J = 14.3 Hz, 1H), 3.44 (d, J

14.3 Hz, 1H), 2.92 (s, 3H), 1.95 (s, 3H), 1.46 (s, 3H). ¹³C{ H}

NMR (126 MHz, CDCl ): δ 180.4, 153.6, 153.2, 140.5, 132.6, 131.4,

compound as a yellow solid (36 mg, 89% yield). mp: 190−192 °C. H

31.4, 129.9, 128.4, 128.2, 127.8, 124.8, 124.8, 124.1, 122.1, 121.0,

11.4, 110.6, 107.1, 49.3, 32.7, 26.0, 22.9, 20.9. IR (KBr): 3062, 2971,

925, 2868, 1711, 1617, 1505, 1452, 1273, 1259, 1135, 1060, 895,

NMR (500 MHz, CDCl ): δ 7.56−7.53 (m, 1H), 7.49 (dd, J = 8.3,

1.4 Hz, 2H), 7.46 (t, J = 7.4 Hz, 2H), 7.42−7.37 (m, 2H), 7.25 (m,

1H), 7.21 (m, 1H), 7.01 (dd, J = 8.3, 2.0 Hz, 1H), 6.48−6.43 (m,

389

J. Org. Chem. 2021, 86, 9384−9395

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H), 3.57 (d, J = 14.4 Hz, 1H), 3.47 (d, J = 14.4 Hz, 1H), 2.89 (s,

1-Benzyl-3-methyl-3-((2-phenylbenzofuran-3-yl)methyl)indolin-

2-one (3la). Puriﬁcation by column chromatography on silica gel

(petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

H), 1.45 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ 179.9,

53.6, 141.5, 134.2, 131.0, 129.5, 128.7, 128.6, 127.9, 127.6, 127.4,

24.4, 124.2, 122.3, 120.8, 110.8, 110.7, 108.2, 49.6, 32.6, 26.1, 22.8.

compound as a yellow solid (38 mg, 86% yield). mp: 123−124 °C.

IR (KBr): 3044, 2969, 2920, 2869, 1712, 1609, 1516, 1453, 1274,

m/z: calcd for C H ClNO Na [M + Na] , 424.1074; found,

H NMR (500 MHz, CDCl ): δ 7.54−7.46 (m, 4H), 7.39−7.35 (m,

−

221, 1140, 1071, 883, 806, 754, 719, 688, 635 cm . HRMS (ESI)

3H), 7.30−7.27 (m, 1H), 7.25−7.16 (m, 4H), 6.99−6.94 (m, 1H),

6.84 (d, J = 7.0 Hz, 2H), 6.68 (d, J = 7.2 Hz, 1H), 6.61 (t, J = 7.5 Hz,

1H), 6.46 (d, J = 7.8 Hz, 1H), 4.95 (d, J = 15.8 Hz, 1H), 4.54 (d, J =

15.8 Hz, 1H), 3.67 (d, J = 14.4 Hz, 1H), 3.57 (d, J = 14.3 Hz, 1H),

24.1078.

,3-Dimethyl-5-nitro-3-((2-phenylbenzofuran-3-yl)methyl)-

indolin-2-one (3ha). Puriﬁcation by column chromatography on

silica gel (petroleum ether/ethyl acetate = 5:1, v/v) aﬀorded the title

compound as a yellow solid (38 mg, 93% yield). mp: 190−191 °C. H

NMR (500 MHz, CDCl ): δ 7.95 (dd, J = 8.6, 2.2 Hz, 1H), 7.60 (dd,

J = 7.0, 1.7 Hz, 1H), 7.38 (dd, J = 7.6, 4.9 Hz, 2H), 7.35 (d, J = 4.4

Hz, 4H), 7.32−7.30 (m, 1H), 7.27−7.20 (m, 2H), 6.54 (d, J = 8.6 Hz,

1.62 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ 180.3, 153.8,

153.5, 142.2, 135.7, 132.7, 131.3, 130.0, 128.6, 128.4, 128.3, 127.9,

127.6, 127.2, 126.8, 124.3, 123.7, 122.4, 122.2, 121.1, 111.4, 110.7,

108.8, 49.3, 43.6, 32.5, 24.0. IR (KBr): 3059, 2959, 2923, 2854, 1708,

−

1609, 1490, 1443, 1260, 1115, 1065, 803, 751, 696 cm . HRMS

(ESI) m/z: calcd for C31H25NO Na[M + Na] , 466.1777; found,

H), 3.72−3.62 (m, 1H), 3.54 (d, J = 14.3 Hz, 1H), 2.82 (s, 3H),

466.1778.

.54 (s, 3H). ¹³C{ H} NMR (126 MHz, CDCl ): δ 180.3, 153.5,

-Methyl-3-phenyl-3-((2-phenylbenzofuran-3-yl)methyl)indolin-

-one (3pa). Puriﬁcation by column chromatography on silica gel

petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

53.3, 148.7, 142.7, 133.0, 130.7, 129.3, 128.9, 128.6, 127.4, 125.0,

24.5, 122.4, 120.5, 119.5, 110.8, 110.0, 106.7, 49.2, 33.0, 26.2, 22.0.

(

compound as a yellow solid (37 mg, 86% yield). mp: 133−134 °C.

IR (KBr): 3066, 2966, 2920, 2867, 1730, 1616, 1512, 1454, 1275,

m/z: calcd for C H N O Na [M + Na] , 435.1315; found,

−

H NMR (500 MHz, CDCl ): δ 7.57 (d, J = 7.9 Hz, 2H), 7.43−7.35

258, 1071, 1053, 871, 832, 754, 721, 691, 641 cm . HRMS (ESI)

(m, 10H), 7.25−7.21 (m, 1H), 7.15 (t, J = 7.5 Hz, 1H), 7.13−7.09

(

m, 1H), 6.64 (t, J = 7.5 Hz, 1H), 6.58 (dd, J = 7.3, 5.0 Hz, 2H), 4.10

35.1306.

,3-Dimethyl-3-((2-phenylbenzofuran-3-yl)methyl)-5-

triﬂuoromethyl)indolin-2-one (3ia). Puriﬁcation by column chro-

d, J = 14.2 Hz, 1H), 4.05 (d, J = 14.1 Hz, 1H), 2.87 (s, 3H). C{ H}

NMR (126 MHz, CDCl ): δ 178.3, 153.9, 153.6, 143.6, 140.1, 131.2,

(

30.2, 129.3, 128.6, 128.5, 128.4, 128.3, 128.0, 127.5, 127.4, 126.0,

24.1, 122.2, 122.1, 121.2, 111.0, 110.6, 107.7, 56.9, 33.4, 26.2. IR

matography on silica gel (petroleum ether/ethyl acetate = 10:1, v/v)

aﬀorded the title compound as a yellow solid (37 mg, 95% yield). mp:

(KBr): 3050, 2985, 2915, 2844, 1709, 1606, 1487, 1438, 1257, 1115,

C H NO Na[M + Na] , 452.1621; found, 452.1649.

36−138 °C. H NMR (500 MHz, CDCl ): δ 7.52 (dd, J = 8.2, 1.4

−

064, 800, 746, 691, cm . HRMS (ESI) m/z: calcd for

Hz, 2H), 7.47 (dd, J = 7.8, 0.6 Hz, 1H), 7.44−7.38 (m, 3H), 7.38 (d, J

2.7 Hz, 1H), 7.34 (dd, J = 8.1, 0.9 Hz, 1H), 7.26−7.22 (m, 1H),

30 23

-((2-(4-Bromophenyl)benzofuran-3-yl)methyl)-1,3-dimethylin-

.20−7.16 (m, 1H), 6.82 (d, J = 0.8 Hz, 1H), 6.64 (d, J = 8.1 Hz,

dolin-2-one (3ab). Puriﬁcation by column chromatography on silica

gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

H), 3.64 (d, J = 14.5 Hz, 1H), 3.51 (d, J = 14.4 Hz, 1H), 2.96 (s,

H), 1.49 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ 180.4, 153.5

compound as a brown solid (41 mg, 92% yield). mp: 158−160 °C. H

(d, J_C₋_F= 24.0 Hz), 145.9, 133.1, 130.8, 129.6, 128.7, 127.6, 125.7 (d,

NMR (500 MHz, CDCl3): δ 7.51 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 7.8

Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.36 (d, J = 8.5 Hz, 2H), 7.27−

J_C₋_F= 3.8 Hz), 125.2, 124.3, 123.0, 122.3, 120.6, 110.8, 110.6, 107.3,

9.3, 32.7, 26.2, 22.8. F NMR (470 MHz, CDCl ): δ −61.3. IR

.23 (m, 1H), 7.18 (t, J = 7.6 Hz, 1H), 7.11−7.08 (m, 1H), 6.67−

(KBr): 3035, 2970, 2921, 2872, 1723, 1616, 1497, 1372, 1260,1116,

.60 (m, 3H), 3.52 (d, J = 14.4 Hz, 1H), 3.39 (d, J = 14.4 Hz, 1H),

−

1056, 819, 753, 718, 692, 626 cm . HRMS (ESI) m/z: calcd for

.96 (s, 3H), 1.51 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ

C H F NO Na [M + Na] , 458.1338; found, 458.1352.

80.2, 153.6, 152.0, 143.0, 132.6, 131.6, 130.2, 129.8, 129.2, 127.8,

24.5, 123.7, 122.4, 122.4, 122.1, 121.0, 111.95, 110.71, 107.6, 49.1,

2.8, 26.0, 22.9. IR (KBr): 3056, 2971, 2920, 2869, 1709, 1610, 1462,

273, 1265, 1139, 1070, 881, 825, 755, 717, 685, 636 cm . HRMS

(ESI) m/z: calcd for C25

,3-Dimethyl-2-oxo-3-((2-phenylbenzofuran-3-yl)methyl)-

indoline-5-carbonitrile (3ja). Puriﬁcation by column chromatogra-

phy on silica gel (petroleum ether/ethyl acetate = 5:1, v/v) aﬀorded

the title compound as a yellow solid (36 mg, 92% yield). mp: 201−

−

H21BrNO [M + H] , 446.0750; found,

03 °C. H NMR (500 MHz, CDCl ): δ 7.59−7.55 (m, 1H), 7.49−

46.0744.

.47 (m, 3H), 7.44−7.40 (m, 2H), 7.38 (dd, J = 7.3, 1.2 Hz, 1H), 7.33

-((2-(4-Chlorophenyl)benzofuran-3-yl)methyl)-1,3-dimethylin-

(

dd, J = 8.1, 1.6 Hz, 1H), 7.25−7.21 (m, 2H), 6.66 (d, J = 1.5 Hz,

dolin-2-one (3ac). Puriﬁcation by column chromatography on silica

gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

H), 6.55 (d, J = 8.1 Hz, 1H), 3.62 (d, J = 14.4 Hz, 1H), 3.51 (d, J =

4.4 Hz, 1H), 2.85 (s, 3H), 1.48 (s, 3H). C{ H} NMR (126 MHz,

compound as a white solid (34 mg, 86% yield). mp: 190−192 °C. H

CDCl ): δ 180.1, 153.6, 153.5, 146.8, 133.3, 133.0, 130.8, 129.2,

NMR (500 MHz, CDCl ): δ 7.48−7.45 (m, 1H), 7.44−7.38 (m, 3H),

28.9, 127.7, 126.9, 124.5, 122.4, 120.6, 119.0, 110.8, 110.3, 107.6,

05.0, 49.1, 32.6, 26.1, 22.5. IR (KBr): 3046, 2972, 2927, 2867, 2219,

721, 1616, 1496, 1454, 1258, 1142, 1058, 826, 753, 718, 689,637

.38−7.34 (m, 2H), 7.28−7.23 (m, 1H), 7.20−7.16 (m, 1H), 7.11−

.08 (m, 1H),, 6.67−6.60 (m, 3H), 3.52 (d, J = 14.4 Hz, 1H), 3.39 (d,

J = 14.4 Hz, 1H), 2.96 (s, 3H), 1.51 (s, 3H). C{ H} NMR (126

−

cm . HRMS (ESI) m/z: calcd for C H N O Na [M + Na] ,

MHz, CDCl ) 180.2, 153.6, 152.0, 143.0, 134.2, 132.6, 129.8, 129.7,

415.1416; found, 415.1408.

29.0, 128.6, 127.8, 124.5, 123.7, 122.3, 122.0, 121.0, 111.9, 110.7,

07.6, 49.1, 32.8, 26.0, 22.9. IR (KBr): 3062, 2960, 2921, 2851, 1712,

611, 1490, 1452, 1375, 1255, 1120, 1094, 833, 750, 715, 687, 638

-Chloro-1,3-dimethyl-3-((2-phenylbenzofuran-3-yl)methyl)-

indolin-2-one (3ka). Puriﬁcation by column chromatography on

silica gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a yellow solid (36 mg, 88% yield). mp: 112−113 °C. H

NMR (500 MHz, CDCl ): δ 7.53−7.51 (m, 1H), 7.49−7.46 (m, 2H),

−1

cm . HRMS (ESI) m/z: calcd for C H ClNO [M + H] ,

02.1255; found, 402.1264.

3-((2-(4-Fluorophenyl)benzofuran-3-yl)methyl)-1,3-dimethylin-

.44−7.38 (m, 3H), 7.34 (d, J = 7.9 Hz, 1H), 7.23−7.18 (m, 1H),

dolin-2-one (3ad). Puriﬁcation by column chromatography on silica

gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a yellow solid (33 mg, 85% yield). mp: 142−144 °C. H

NMR (500 MHz, CDCl ): δ 7.46 (ddd, J = 8.0, 5.5, 2.6 Hz, 3H), 7.39

.17−7.14 (m, 1H), 6.98 (t, J = 8.0 Hz, 1H), 6.60 (dd, J = 8.2, 0.7 Hz,

H), 6.39 (dd, J = 7.7, 0.5 Hz, 1H), 3.86 (d, J = 14.2 Hz, 1H), 3.53

d, J = 14.2 Hz, 1H), 2.71 (s, 3H), 1.70 (d, J = 7.1 Hz, 3H). ¹³C{ H}

(

NMR (126 MHz, CDCl ): δ 179.3, 153.8, 153.6, 145.0, 131.2, 130.9,

(d, J = 8.1 Hz, 1H), 7.27−7.22 (m, 1H), 7.18 (dd, J = 11.1, 3.9 Hz,

1H), 7.12−7.06 (m, 3H), 6.65 (dd, J = 11.3, 4.0 Hz, 1H), 6.62−6.59

(m, 2H), 3.51 (d, J = 14.4 Hz, 1H), 3.39 (d, J = 14.4 Hz, 1H), 2.96 (s,

29.4, 129.0, 129.0, 128.5, 128.4, 128.3, 124.0, 123.4, 122.0, 120.9,

10.6, 110.5, 105.8, 50.6, 31.2, 26.0, 20.3. IR (KBr): 3036, 2956,

918, 2869, 1715, 1599, 1522, 1454, 1273, 1218, 1144, 1073, 885,

3H), 1.50 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ 180.3, 162.6

−

12, 754, 719, 686, 637 cm . HRMS (ESI) m/z: calcd for

(d, J_C₋_F= 248.8 Hz), 153.6, 152.3, 143.0, 132.7, 129.8, 129.7 (d, J_C₋_F

= 8.2 Hz), 127.7, 127.5 (d, J_C₋_F= 3.3 Hz), 124.2, 123.6, 122.3, 122.0,

C H ClNO Na [M + Na] , 424.1074; found, 424.1080.

390

J. Org. Chem. 2021, 86, 9384−9395

The Journal of Organic Chemistry

Article

20.9, 115.5 (d, J

= 21.7 Hz), 111.2, 110.6, 107.5, 49.1, 32.8, 26.0,

J = 14.7 Hz, 1H), 3.26 (d, J = 14.7 Hz, 1H), 3.17 (s, 3H), 1.58 (s,

C−F

2.9. ¹⁹F NMR (470 MHz, CDCl ): δ −112.5. IR (KBr): 3041, 2961,

3H), 1.22 (s, 9H). C{ H} NMR (126 MHz, CDCl ): δ 180.8,

921, 2851, 1712, 1612, 1501, 1454, 1375, 1276, 1257, 1061, 838,

161.8, 153.0, 143.1, 133.6, 130.7, 128.0, 124.6, 123.2, 122.1, 121.5,

120.6, 110.2, 108.4, 107.8, 48.9, 35.1, 32.0, 29.8, 26.2, 23.5. IR (KBr):

3046, 2970, 2925, 2883, 1714, 1613, 1511, 1491, 1456, 1377, 1260,

−

52, 719, 690, 629 cm . HRMS (ESI) m/z: calcd for C H FNO

[

M + H] , 386.1550; found, 386.1558.

−

,3-Dimethyl-3-((2-(4-nitrophenyl)benzofuran-3-yl)methyl)-

1126, 1058, 896, 754, 722, 690, 640 cm . HRMS (ESI) m/z: calcd

indolin-2-one (3ae). Puriﬁcation by column chromatography on

silica gel (petroleum ether/ethyl acetate = 5:1, v/v) aﬀorded the title

compound as a yellow solid (36 mg, 88% yield). mp: 193−195 °C. H

NMR (500 MHz, CDCl ): δ 8.21 (d, J = 9.0 Hz, 2H), 7.68 (d, J = 9.0

for C H NO [M + H] , 348.1958; found, 348.1976.

3-((2-Butylbenzofuran-3-yl)methyl)-1,3-dimethylindolin-2-one

(3aj). Puriﬁcation by column chromatography on silica gel (petroleum

ether/ethyl acetate = 10:1, v/v) aﬀorded the title compound as a

Hz, 2H), 7.52−7.42 (m, 2H), 7.32 (ddd, J = 8.3, 7.2, 1.2 Hz, 1H),

yellow solid (28 mg, 81% yield). mp: 96−97 °C. H NMR (500 MHz,

.21 (dd, J = 11.1, 4.0 Hz, 1H), 7.10 (td, J = 7.7, 1.2 Hz, 1H), 6.69−

CDCl ): δ 7.31 (dd, J = 10.9, 4.1 Hz, 2H), 7.21−7.18 (m, 1H), 7.16−

.57 (m, 3H), 3.56 (d, J = 14.4 Hz, 1H), 3.44 (d, J = 14.4 Hz, 1H),

.97 (s, 3H), 1.54 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ

7.11 (m, 1H), 7.11−7.08 (m, 2H), 7.00−6.96 (m, 1H), 6.67 (d, J =

7.7 Hz, 1H), 3.16−3.08 (m, 2H), 3.03 (s, 3H), 2.54−2.48 (m, 1H),

2.42−2.36 (m, 1H), 1.62−1.56 (m, 1H), 1.55 (s, 3H), 1.51−1.41 (m,

1H), 1.32 (dd, J = 14.9, 7.4 Hz, 2H), 0.92 (t, J = 7.3 Hz, 3H).

79.9, 154.0, 150.3, 146.9, 143.0, 137.4, 132.3, 129.7, 128.1, 127.8,

25.6, 123.6, 122.8, 122.1, 121.4, 114.7, 111.0, 107.8, 49.0, 33.0, 26.1,

2.7. IR (KBr): 3051, 2963, 2918, 2887, 1711, 1607, 1515, 1469,

C{ H} NMR (126 MHz, CDCl ): δ 180.5, 157.1, 153.6, 143.3,

−

453, 1377, 1342, 1257, 1106, 1058, 854,754, 631 cm . HRMS

133.3, 129.5, 127.9, 123.6, 122.8, 122.0, 121.8, 120.1, 110.2, 109.4,

107.8, 49.1, 33.0, 29.9, 26.4, 26.0, 22.6, 22.5, 13.9. IR (KBr): 3044,

2972, 2923, 2873, 1724, 1615, 1521, 1495, 1456, 1379, 1260, 1126,

(ESI) m/z: calcd for C H N O [M + H] , 413.1495; found,

25 21 2 4

13.1492.

,3-Dimethyl-3-((2-(p-tolyl)benzofuran-3-yl)methyl)indolin-2-

one (3af). Puriﬁcation by column chromatography on silica gel

petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

−

1058, 896, 754, 724, 680, 638 cm . HRMS (ESI) m/z: calcd for

C H NO [M + H] , 348.1958; found, 348.1965.

(

,3-Dimethyl-3-((2-pentylbenzofuran-3-yl)methyl)indolin-2-one

compound as a brown oil (34 mg, 89% yield). H NMR (500

MHz, CDCl ): δ 7.45 (d, J = 7.7 Hz, 1H), 7.40 (d, J = 8.1 Hz, 3H),

(3ak). Puriﬁcation by column chromatography on silica gel

(petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

.23−7.21 (m, 3H), 7.16 (dd, J = 11.0, 3.9 Hz, 1H), 7.10−7.07 (m,

compound as a yellow solid (25 mg, 70% yield). mp: 103−104 °C.

1H), 6.65−6.57 (m, 3H), 3.57 (d, J = 14.4 Hz, 1H), 3.39 (d, J = 14.4

H NMR (500 MHz, CDCl ): δ 7.33−7.29 (m, 2H), 7.21−7.18 (m,

Hz, 1H), 2.99 (s, 3H), 2.43 (s, 3H), 1.49 (s, 3H). C{ H} NMR

1H), 7.16−7.12 (m, 1H), 7.11−7.07 (m, 2H), 7.00−6.96 m, 1H),

6.67 (d, J = 7.7 Hz, 1H), 3.15−3.08 (m, 2H), 3.03 (s, 3H), 2.53−2.47

(m, 1H), 2.41−2.35 (m, 1H), 1.55 (s, 3H), 1.52−1.46 (m, 1H),

(

126 MHz, CDCl ): δ 180.5, 153.6, 153.6, 142.9, 138.3, 132.8, 130.0,

29.1, 128.4, 127.8, 127.6, 123.9, 123.8, 122.1, 122.0, 120.8, 110.9,

10.6, 107.4, 49.2, 32.7, 26.0, 23.0, 21.4. IR (KBr): 3063, 2964, 2925,

871, 1711, 1611, 1493, 1453, 1376, 1274, 1256, 1122, 1060, 819,

1.35−1.25 (m, 5H), 0.91 (t, J = 7.1 Hz, 3H). C{ H} NMR (126

MHz, CDCl ): δ 180.5, 157.1, 153.6, 143.3, 133.3, 129.5, 127.9,

−

52, 717, 690, 636 cm . HRMS (ESI) m/z: calcd for C H NO [M

123.6, 122.8, 122.0, 121.8, 120.1, 110.2, 109.4, 107.8, 49.1, 33.0, 31.6,

27.5, 26.6, 26.1, 22.6, 22.5, 14.0. IR (KBr): 3035, 2967, 2927, 2885,

1720, 1615, 1513, 1500, 1458, 1379, 1260, 1126, 1058, 896, 756, 723,

H] , 382.1801; found, 382.1786.

-((2-(4-Methoxyphenyl)benzofuran-3-yl)methyl)-1,3-dimethy-

lindolin-2-one (3ag). Puriﬁcation by column chromatography on

silica gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a brown oil (37 mg, 92% yield). H NMR (500 MHz,

−1

92, 638 cm . HRMS (ESI) m/z: calcd for C H NO [M + H] ,

24 28 2

62.2114; found, 362.2117.

,3-Dimethyl-3-((2-hexylbenzofuran-3-yl)methyl)indolin-2-one

CDCl ): δ 7.46−7.42 (m, 3H), 7.38 (d, J = 8.0 Hz, 1H), 7.24−7.19

(3al). Puriﬁcation by column chromatography on silica gel (petroleum

ether/ethyl acetate = 10:1, v/v) aﬀorded the title compound as a

(

m, 1H), 7.16 (t, J = 7.5 Hz, 1H), 7.10−7.08 (m, 1H), 6.95−6.91 (m,

H), 6.66 (t, J = 7.4 Hz, 1H), 6.63−6.59 (m, 2H), 3.89 (s, 3H), 3.54

yellow solid (28 mg, 74% yield). mp: 101−102 °C. H NMR (500

(d, J = 14.4 Hz, 1H), 3.38 (d, J = 14.4 Hz, 1H), 2.99 (s, 3H), 1.49 (s,

MHz, CDCl ): δ 7.33−7.29 (m, 2H), 7.21−7.18 (m, 1H), 7.16−7.12

H). ¹³C{ H} NMR (126 MHz, CDCl ): δ 180.5, 159.7, 153.5, 153.4,

(m, 1H), 7.11−7.08 (m, 2H), 7.00−6.96 (m, 1H), 6.67 (d, J = 7.7 Hz,

1H), 3.16−3.08 (m, 2H), 3.03 (s, 3H), 2.53−2.47 (m, 1H), 2.42−

2.35 (m, 1H), 1.55 (s, 3H), 1.53−1.44 (m, 1H), 1.34−1.25 (m, 7H),

42.9, 132.8, 130.1, 129.3, 127.6, 123.8, 123.8, 123.8, 122.1, 122.0,

20.7, 113.9, 110.5, 110.3, 107.5, 55.4, 49.2, 32.7, 26.0, 23.0. IR

(KBr): 3047, 2965, 2925, 2868, 1710, 1612, 1505, 1453, 1375, 1255,

0.91 (t, J = 6.9 Hz, 3H). C{ H} NMR (126 MHz, CDCl ): δ 180.5,

−

121, 1062, 833, 752, 718, 692, 632 cm . HRMS (ESI) m/z: calcd

157.2, 153.6, 143.3, 133.3, 129.5, 127.9, 123.6, 122.8, 122.0, 121.8,

120.1, 110.2, 109.3, 107.8, 49.1, 33.0, 31.6, 29.1, 27.8, 26.7, 26.0, 22.6,

for C H NO [M + H] , 398.1750; found, 398.1736.

,3-Dimethyl-3-((2-(thiophen-2-yl)benzofuran-3-yl)methyl)-

14.1. IR (KBr): 3054, 2972, 2925, 2883, 1720, 1618, 1511, 1491,

indolin-2-one (3ah). Puriﬁcation by column chromatography on

silica gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a brown oil (32 mg, 85% yield). H NMR (500 MHz,

−1

(

457, 1378, 1263, 1126, 1060, 896, 754, 725, 686, 652 cm . HRMS

ESI) m/z: calcd for C H NO [M + H] , 376.2271; found,

25 30 2

76.2268.

CDCl ): δ 7.43 (dd, J = 12.9, 7.9 Hz, 2H), 7.33 (dd, J = 5.0, 1.0 Hz,

3-((2-(2-Bromophenyl)benzofuran-3-yl)methyl)-1,3-dimethylin-

H), 7.28−7.23 (m, 2H), 7.21−7.16 (m, 1H), 7.14−7.11 (m, 1H),

dolin-2-one (3am). Puriﬁcation by column chromatography on silica

gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a yellow solid (37 mg, 84% yield). mp: 100−102 °C. H

NMR (500 MHz, CDCl ): δ 7.68 (dd, J = 7.9, 0.8 Hz, 1H), 7.52 (d, J

.05 (dd, J = 5.0, 3.7 Hz, 1H), 6.82 (d, J = 6.8 Hz, 1H), 6.76−6.66

(m, 2H), 3.57 (d, J = 14.5 Hz, 1H), 3.34 (d, J = 14.5 Hz, 1H), 3.10 (s,

H), 1.58 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ 180.4,

53.6, 148.7, 143.0, 132.8, 132.8, 130.0, 127.9, 127.3, 126.1, 126.0,

24.4, 123.9, 122.5, 122.1, 120.8, 111.2, 110.7, 107.7, 49.1, 33.0, 26.2,

2.8. IR (KBr): 3003, 2970, 2926, 2867, 1709, 1610, 1492, 1452,

= 7.8 Hz, 1H), 7.41−7.34 (m, 2H), 7.33−7.30 (m, 1H), 7.27−7.23

(m, 1H), 7.22−7.15 (m, 2H), 7.15−7.10 (m, 1H), 6.73 (t, J = 7.5 Hz,

1H), 6.60 (dd, J = 18.0, 7.5 Hz, 2H), 3.33 (q, J = 14.3 Hz, 2H), 2.98

−

257, 1115, 1061, 885, 854, 751, 716, 695, 639 cm . HRMS (ESI)

(s, 3H), 1.41 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ 180.2,

m/z: calcd for C H NO SNa [M + Na] , 396.1028; found,

154.0, 152.3, 143.1, 133.2, 132.9, 132.7, 132.0, 130.6, 128.9, 127.7,

127.1, 124.3, 124.2, 123.3, 122.3, 122.3, 121.3, 113.4, 110.8, 107.7,

96.1053.

-((2-(Tert-butyl)benzofuran-3-yl)methyl)-1,3-dimethylindolin-2-

one (3ai). Puriﬁcation by column chromatography on silica gel

petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a brown solid (29 mg, 83% yield). mp: 119−120 °C.

48.8, 32.9, 26.1, 23.5. IR (KBr): 3059, 2958, 2863, 2806, 1712, 1601,

−1

(

485, 1453, 1253, 1117, 1066, 962, 923, 801, 742, 694 cm . HRMS

(

ESI) m/z: calcd for C H BrNO Na [M + Na] , 470.0552; found,

25 20 2

70.0577.

H NMR (500 MHz, CDCl ): δ 7.37−7.32 (m, 2H), 7.24 (td, J = 7.7,

3-((2-(3-Bromophenyl)benzofuran-3-yl)methyl)-1,3-dimethylin-

.2 Hz, 1H), 7.21−7.17 (m, 1H), 7.14−7.07 (m, 1H), 6.96−6.93 (m,

H), 6.84 (dd, J = 7.4, 0.8 Hz, 1H), 6.77 (d, J = 7.7 Hz, 1H), 3.35 (d,

dolin-2-one (3an). Puriﬁcation by column chromatography on silica

gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

391

J. Org. Chem. 2021, 86, 9384−9395

The Journal of Organic Chemistry

Article

compound as a white solid (34 mg, 75% yield). mp: 118−120 °C. H

3-((5-Bromo-2-phenylbenzofuran-3-yl)methyl)-1,3-dimethylin-

dolin-2-one (3at). Puriﬁcation by column chromatography on silica

gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

NMR (500 MHz, CDCl ): δ 7.55 (d, J = 7.7 Hz, 1H), 7.48−7.42 (m,

H), 7.41 (d, J = 8.1 Hz, 1H), 7.28−7.25 (m, 1H), 7.25−7.19 (m,

H), 7.13−7.10 (m, 1H), 6.66−6.62 (m, 2H), 6.59 (dd, J = 7.6, 1.2

compound as a yellow solid (40 mg, 90% yield). mp: 110−112 °C. H

NMR (500 MHz, CDCl ): δ 7.57−7.53 (m, 2H), 7.46−7.38 (m, 4H),

Hz, 1H), 3.51 (d, J = 14.4 Hz, 1H), 3.38 (d, J = 14.4 Hz, 1H), 2.96 (s,

.30 (dd, J = 8.6, 2.0 Hz, 1H), 7.24 (d, J = 8.6 Hz, 1H), 7.12−7.11

m, 1H), 6.71−6.68 (m, 1H), 6.65−6.60 (m, 2H), 3.50 (d, J = 14.5

Hz, 1H), 3.39 (d, J = 14.4 Hz, 1H), 2.99 (s, 3H), 1.48 (s, 3H).

H), 1.53 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ 180.2,

(

53.7, 151.4, 143.0, 133.1, 132.3, 131.1, 130.5, 129.8, 129.7, 127.8,

26.1, 124.7, 123.6, 122.5, 122.5, 122.0, 121.1, 112.4, 110.8, 107.7,

9.0, 32.7, 26.0, 22.8. IR (KBr): 3062, 2961, 2866, 2803, 1712, 1607,

C{ H} NMR (126 MHz, CDCl ): δ 180.2, 154.6, 152.3, 143.0,

−

482, 1447, 1250, 1111, 1066, 962, 920, 804, 745, 691 cm . HRMS

132.6, 131.7, 130.6, 128.8, 128.5, 128.0, 127.9, 127.0, 123.6, 123.6,

122.1, 115.30, 112.1, 111.0, 107.6, 49.0, 32.9, 26.1, 23.0. IR (KBr):

(ESI) m/z: calcd for C H BrNO Na [M + Na] , 470.0552; found,

25 20 2

056, 2955, 2922, 2854, 1706, 1613, 1491, 1453, 1256, 1116, 1066,

70.0562.

−

01, 748, 691 cm . HRMS (ESI) m/z: calcd for C H BrNO Na

-((2-(2-Chlorophenyl)benzofuran-3-yl)methyl)-1,3-dimethylin-

25 20

dolin-2-one (3ao). Puriﬁcation by column chromatography on silica

gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a white solid (33 mg, 83% yield). mp: 124−125 °C. H

NMR (500 MHz, CDCl ): δ 7.56 (dd, J = 11.4, 7.8 Hz, 1H), 7.49

[M + Na] , 470.0552; found, 470.0572.

1,3-Dimethyl-3-((5-methyl-2-phenylbenzofuran-3-yl)methyl)-

indolin-2-one (3au). Puriﬁcation by column chromatography on

silica gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a yellow solid (35 mg, 92% yield). mp: 112−114 °C. H

(

dd, J = 8.0, 1.1 Hz, 1H), 7.43−7.37 (m, 2H), 7.32 (m, 1H), 7.28−

.23 (m, 1H), 7.21−7.17 (m, 2H), 7.11−7.10 (m, 1H), 6.71−6.68

m, 1H), 6.60 (d, J = 7.7 Hz, 1H), 6.55 (d, J = 7.1 Hz, 1H), 3.38 (d, J

NMR (500 MHz, CDCl3): δ 7.52 (dd, J = 8.3, 1.3 Hz, 2H), 7.42−

.37 (m, 2H), 7.37−7.34 (m, 1H), 7.28 (d, J = 5.8 Hz, 1H), 7.17 (s,

H), 7.09 (m, 1H), 7.05 (dd, J = 8.3, 1.3 Hz, 1H), 6.67−6.60 (m,

14.3 Hz, 1H), 3.32 (d, J = 14.3 Hz, 1H), 2.95 (s, 3H), 1.41 (s, 3H).

3H), 3.54 (d, J = 14.4 Hz, 1H), 3.38 (d, J = 14.4 Hz, 1H), 3.00 (s,

C{ H} NMR (126 MHz, CDCl ): δ 180.2, 154.1, 151.1, 143.0,

H), 2.42 (s, 3H), 1.50 (s, 3H). C{ H} NMR (126 MHz, CDCl ):

34.3, 132.7, 132.6, 131.5, 130.3, 130.0, 128.9, 127.7, 126.5, 124.3,

23.1, 122.3, 122.2, 121.2, 113.6, 110.8, 107.6, 48.8, 32.9, 26.0, 23.5.

δ 180.5, 153.4, 152.1, 143.0, 132.9, 131.5, 131.4, 130.1, 128.4, 128.2,

27.7, 127.7, 125.4, 123.9, 122.0, 120.8, 111.2, 110.1, 107.5, 49.1,

32.8, 26.0, 22.9, 21.4. IR (KBr): 3053, 2957, 2916, 2848, 1716, 1606,

IR (KBr): 3053, 2967, 2922, 2854, 1712, 1610, 1491, 1451, 1250,

calcd for C H ClNO Na [M + Na] , 424.1074; found, 424.1096.

−

118, 1099, 929, 821, 747, 714, 700, 654 cm . HRMS (ESI) m/z:

−

1493, 1462, 1257, 1118, 1065, 799, 752, 692 cm . HRMS (ESI) m/z:

calcd for C H NO Na [M + Na] , 404.1621; found, 404.1621.

-((2-(3-Chlorophenyl)benzofuran-3-yl)methyl)-1,3-dimethylin-

-((5-(tert-Butyl)-2-phenylbenzofuran-3-yl)methyl)-1,3-dimethy-

dolin-2-one (3ap). Puriﬁcation by column chromatography on silica

gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

lindolin-2-one (3av). Puriﬁcation by column chromatography on

silica gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a yellow solid (39 mg, 92% yield). mp: 109−111 °C. H

NMR (500 MHz, CDCl ): δ 7.52 (d, J = 6.9 Hz, 3H), 7.41 (t, J = 7.4

compound as a yellow solid (31 mg, 77% yield). mp: 115−117 °C. H

NMR (500 MHz, CDCl ): δ 7.54 (dd, J = 7.8, 0.5 Hz, 1H), 7.44−

.38 (m, 2H), 7.35 (d, J = 1.0 Hz, 1H), 7.33−7.29 (m, 2H), 7.30−

.25 (m, 1H), 7.23−7.19 (m, 1H), 7.11−7.10 (m, 1H), 6.66−6.58

Hz, 2H), 7.38−7.31 (m, 3H), 7.09−7.06 (m, 1H), 6.64−6.57 (m,

H), 6.54 (d, J = 7.3 Hz, 1H), 3.64 (d, J = 14.4 Hz, 1H), 3.42 (d, J =

4.4 Hz, 1H), 2.99 (s, 3H), 1.49 (s, 3H), 1.41 (s, 9H). C{ H} NMR

(m, 3H), 3.52 (d, J = 14.4 Hz, 1H), 3.40 (d, J = 14.4 Hz, 1H), 2.96 (s,

H), 1.53 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ 180.2,

(126 MHz, CDCl ): δ 180.5, 153.5, 151.9, 145.2, 142.9, 132.7, 131.5,

53.7, 151.6, 143.0, 134.4, 132.9, 132.4, 129.7, 129.6, 128.2, 127.8,

27.7, 125.7, 124.7, 123.61, 122.4, 122.0, 121.1, 112.4, 110.8, 107.6,

9.0, 32.8, 26.0, 22.8. IR (KBr): 3049, 2959, 2922, 2849, 1712, 1612,

29.6, 128.4, 128.2, 127.8, 127.6, 123.9, 122.1, 122.0, 117.3, 111.5,

09.9, 107.4, 49.2, 34.8, 32.6, 31.9, 26.0, 22.8. IR (KBr): 3027, 2958,

920, 2854, 1706, 1610, 1494, 1447, 1259, 1117, 1069, 798, 751, 691

−1

491, 1450, 1251, 1120, 1095, 927, 717, 701, 654 cm . HRMS (ESI)

−1

cm . HRMS (ESI) m/z: calcd for C H NO Na [M + Na] ,

29 29

m/z: calcd for C H ClNO Na [M + Na] , 424.1074; found,

446.2090; found, 446.2090.

24.1095.

,3-Dimethyl-3-((2-phenyl-5-(triﬂuoromethyl)benzofuran-3-yl)-

-(Benzofuran-3-ylmethyl)-1,3-dimethylindolin-2-one (3aq). Pu-

methyl)indolin-2-one (3ax). Puriﬁcation by column chromatography

on silica gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the

title compound as a yellow solid (34 mg, 77% yield). mp: 121−122

riﬁcation by column chromatography on silica gel (petroleum ether/

ethyl acetate = 10:1, v/v) aﬀorded the title compound as a white solid

(

7 mg, 22% yield). mp: 157−159 °C. H NMR (500 MHz, CDCl ): δ

°C. H NMR (500 MHz, CDCl ): δ 7.60 (dd, J = 8.2, 1.3 Hz, 3H),

.40 (d, J = 7.8 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.23−7.18 (m,

H), 7.17−7.12 (m, 1H), 7.07−7.02 (m, 1H), 7.00 (s, 1H), 6.68 (d, J

7.5 Hz, 1H), 3.27 (d, J = 14.4 Hz, 1H), 3.14 (d, J = 14.4 Hz, 1H),

.48−7.43 (m, 5H), 7.12−7.09 (m, 1H), 6.70−6.67 (m, 1H), 6.65−

.62 (m, 1H), 6.59 (d, J = 7.8 Hz, 1H), 3.57 (d, J = 14.5 Hz, 1H),

.48 (d, J = 14.4 Hz, 1H), 2.93 (s, 3H), 1.49 (s, 3H). C{ H} NMR

.01 (s, 3H), 1.55 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ

(126 MHz, CDCl ): δ 180.1, 155.2, 154.9, 143.0, 132.5, 130.5, 129.8,

80.1, 154.7, 143.4, 142.93, 133.4, 128.0, 128.0, 123.9, 123.0, 122.3,

22.2, 120.1, 115.2, 111.0, 108.0, 49.0, 32.4, 26.0, 23.0. IR (KBr):

045, 2971, 2927, 2867, 1708, 1611, 1511, 1453, 1373, 1273, 1256,

129.0, 128.6, 128.1, 127.9, 124.9 (d, J_C₋_F= 32.0 Hz), 123.5, 122.2,

121.1 (d, J_C₋_F= 3.5 Hz), 118.8 (d, J

107.6, 49.0, 32.8, 25.9, 23.1. F NMR (75 MHz, CDCl ): δ −58.6. IR

(KBr): 3033, 2975, 2922, 2871, 1725, 1617, 1497, 1375, 1266, 1120,

1056, 819, 753, 721, 694, 632 cm . HRMS (ESI) m/z: calcd for

C H F NO Na [M + Na] , 458.1338; found, 458.1340.

= 4.0 Hz), 111.7, 111.0,

C−F

−

135, 1069, 833, 753, 718, 686, 635 cm . HRMS (ESI) m/z: calcd

−1

for C H NO [M + H] , 292.1332; found, 292.1359.

-((5-Chloro-2-phenylbenzofuran-3-yl)methyl)-1,3-dimethylin-

dolin-2-one (3as). Puriﬁcation by column chromatography on silica

gel (petroleum ether/ethyl acetate = 10:1, v/v) aﬀorded the title

compound as a yellow solid (35 mg, 88% yield). mp: 107−109 °C. H

NMR (500 MHz, CDCl ): δ 7.56−7.53 (m, 2H), 7.45−7.37 (m, 3H),

Synthesis of Compound 8. DIBAL-H (1.0 M in hexane, 4.8 mL,

4.8 mmol) was added dropwise to a solution of product 3aa (220.2

mg, 0.6 mmol) in toluene (6.0 mL) at −78 °C. After stirring at −78

°C for 3 h, the mixture was quenched with 2.0 N NaOH (aq) and

extracted with ethyl acetate. The combined organic extracts were

dried over Na SO and evaporated under reduced pressure. The

residue was puriﬁed by ﬂash chromatography on silica gel (petroleum

ether/ethyl acetate = 10:1, v/v) to aﬀord the corresponding product 8

as a white solid in an 84% yield (178.2 mg). mp: 120−121 °C. H

NMR (500 MHz, CDCl ): δ 7.80 (dd, J = 5.2, 3.3 Hz, 2H), 7.54 (d, J

= 9.0 Hz, 2H), 7.47−7.41 (m, 2H), 7.39−7.35 (m, 1H), 7.35−7.31

(m, 1H), 7.26 (dd, J = 8.4, 7.4 Hz, 1H), 7.15−7.12 (m, 1H), 6.94 (dd,

J = 7.2, 0.8 Hz, 1H), 6.66−6.63 (m, 1H), 6.55 (d, J = 7.8 Hz, 1H),

.31 (d, J = 2.1 Hz, 1H), 7.29 (d, J = 3.0 Hz, 1H), 7.17 (dd, J = 8.6,

.1 Hz, 1H), 7.12−7.11 (m, 1H), 6.69−6.66 (m, 1H), 6.64−6.60 (m,

H), 3.51 (d, J = 14.5 Hz, 1H), 3.40 (d, J = 14.4 Hz, 1H), 2.98 (s,

H), 1.49 (s, 3H). C{ H} NMR (126 MHz, CDCl ): δ 180.2,

54.8, 152.0, 143.0, 132.6, 131.2, 130.7, 128.7, 128.5, 128.0, 127.9,

27.8, 124.3, 123.6, 122.1, 120.6, 111.6, 111.2, 107.6, 49.0, 32.9, 26.0,

3.1. IR (KBr): 3059, 2955, 2925, 2851, 1715, 1611, 1492, 1448,

−

260, 1121, 1079, 800, 751, 698 cm . HRMS (ESI) m/z: calcd for

C H ClNO Na [M + Na] , 424.1074; found, 424.1072.

392

J. Org. Chem. 2021, 86, 9384−9395

The Journal of Organic Chemistry

Zhao, Y.-X.; Yang, D.-L.; Zeng, Y.-B.; Jiang, B.; Dai, H.-F. Two New

Article

.34 (d, J = 8.8 Hz, 1H), 3.28 (d, J = 2.7 Hz, 2H), 2.76 (d, J = 8.8 Hz,

10, 5165−5181. (b) Ma, S.-S.; Mei, W.-L.; Guo, Z.-K.; Liu, S.-B.;

Types of Bisindole Alkaloid from Trigonostemon lutescens. Org. Lett.

2013, 15, 1492−1495. (c) Pillaiyar, T.; Köse, M.; Sylvester, K.;

H), 2.70 (s, 3H), 1.34 (s, 3H). C{ H} NMR (126 MHz, CDCl ):

δ 153.8, 152.5, 152.3, 137.6, 131.8, 131.7, 128.5, 128.1, 127.9, 127.3,

24.2, 122.5, 122.3, 120.6, 117.8, 113.3, 110.9, 107.3, 68.0, 46.2, 35.5,

3.4, 24.2. IR (KBr): 3053, 2957, 2928, 2862, 1675, 1603, 1489, 1453,

255, 1109, 1059, 969, 919, 807, 745, 692 cm . HRMS (ESI) m/z:

Weighardt, H.; Thimm, D.; Borges, G.; Förster, I.; von Ku

Muller, C. E. Diindolylmethane Derivatives: Potent Agonists of the

gelgen, I.;

−

calcd for C H NONa [M + Na] , 376.1671; found, 376.1669.

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CCDC 2013828 contains the supplementary crystallographic

data for this paper. These data can be obtained free of charge

via www.ccdc.cam.ac.uk/data_request/cif, or by emailing

data_request@ccdc.cam.ac.uk, or by contacting The Cam-

bridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Author

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Fused 9,10-Dihydrophenanthrenes. Org. Lett. 2017 , 19 , 842 −845.

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Shufeng Chen − Inner Mongolia Key Laboratory of Fine

Organic Synthesis, Department of Chemistry and Chemical

Engineering, Inner Mongolia University, Hohhot 010021,

China; orcid.org/0000-0002-7021-2581;

Email: shufengchen@imu.edu.cn

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Authors

Hongbo Qi − Inner Mongolia Key Laboratory of Fine Organic

Synthesis, Department of Chemistry and Chemical

Engineering, Inner Mongolia University, Hohhot 010021,

China

Kaiming Han − Inner Mongolia Key Laboratory of Fine

Organic Synthesis, Department of Chemistry and Chemical

Engineering, Inner Mongolia University, Hohhot 010021,

China

2003, 5, 4943−4945. (e) Krautwald, S.; Sarlah, D.; Schafroth, M. A.;

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Notes

the permeability transition inhibitory characteristics of paramagnetic

The authors declare no competing ﬁnancial interest.

and diamagnetic amiodarone derivatives. Bioorg. Med. Chem. 2005, 13,

629−2636. (b) Yoneda, F.; Moto, T.; Sakae, M.; Ohde, H.; Knoll,

ACKNOWLEDGMENTS

B.; Miklya, I.; Knoll, J. Structure-activity studies leading to (−)1-

■

Benzofuran-2-yl)-2-propylaminopentane, ((−)BPAP), a highly po-

Generous ﬁnancial support from the National Natural Science

Foundation of China (22061031) and the Natural Science

Foundation of Inner Mongolia of China (2020MS02013) is

gratefully acknowledged. We thank Prof. Shuo Guo for helpful

discussions.

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