Room Temperature Benzofused Lactam Synthesis Enabled by Cobalt(III)-Catalyzed C(sp2)?H Amidation

Title: Room Temperature Benzofused Lactam Synthesis Enabled by

Cobalt(III)-Catalyzed C(sp2)−H Amidation

Authors: Xun Tian, Xin Li, Shengzu Duan, Ya Du, Tongqi Liu,

Yongsheng Fang, Wen Chen, Hongbin Zhang, Minyan Li, and

Xiaodong Yang

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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202001254

Link to VoR: https://doi.org/10.1002/adsc.202001254

10.1002/adsc.202001254

Advanced Synthesis & Catalysis

FULL PAPER

DOI: 10.1002/adsc.2020#####

Room Temperature Benzofused Lactam Synthesis Enabled by

Cobalt(III)-Catalyzed C(sp²)−H Amidation

Xun Tian, Xin Li, Shengzu Duan, Ya Du, Tongqi Liu, Yongsheng Fang, Wen Chen,

Hongbin Zhang, Minyan Li* & Xiaodong Yang*

Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Provincial Center for

Research & Development of Natural Products; School of Chemical Science and Technology, Yunnan University,

Kunming, 650091, P. R. China. Fax: (+86)-871-65035538; e-mail: xdyang@ynu.edu.cn; kuiyuan666@gmail.com

Received: October ##, 2020; Revised: October ##, 2020; Published online: October ##, 2020

Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.2020#####.

Abstract. Benzofused lactams, especially indolin-2-one and dihydroquinolin-2-one are popular structural motives in durgs

and natural products. Herein, we developed a room temperature and robust synthesis of benzofused lactams through

cobalt(III)-catalyzed C(sp²)−H amidation. In this protocol, in-situ formation of Cp*Co(III)(ligand) catalyst from

Cp*Co(CO)I₂and ligand simplify the synthetic effort of cobalt complexes. Simple and readily synthesized 1,4,2-dioxazol-5-

ones underwent room temperature intramolecular C−H amidation and afforded a wide variety of functionalized benzofused

lactams in up to 86% yield. The scalability of the reaction is also be demonstrated.

Keywords: Cobalt catalysis; Benzofused lactams; Indolin-2-ones; Dihydroquinolin-2-ones; Intramolecular C−H amidation

Introduction

Benzofused lactams, especially five-membered

indolin-2-one and six-membered dihydroquinolin-2-

one are valuable hetero-cyclic skeletons widely

present in bioactive compounds and natural

products.^[1]They are important targets because of their

potent biological properties, including anticancer,

antiviral, antibacterial, analgestic, anti-inflammatory,

antihypertensive activities and NMDA antagonistic

effect.^[2](Figure 1). They also serve as synthetic blocks

for the construction of highly complex heterocycles.^[3]

Figure 1. Selected biological molecules bearing the

scaffolds of indolin-2-one and dihydroquinolin-2-one.

Consequently,

efficient

and

straightforward

approaches for the synthesis of indolin-2-one and

dihydroquinolin-2-one derivatives remain in demand.

For decades, organic chemists keep looking for new

and efficient routes to prepare these benzofused

lactams. Traditional synthetic routes for C(sp²)−N

bond construction generally employ the transition-

metal-mediated cross-coupling methodologies of

amines/amides with aryl halides,^[4]particularly Cu-

catalyzed Ullmann-type reactions^[5]and Pd-catalyzed

Buchwald-Hartwig aminations^[6](Scheme 1a). In 2020,

Radosevich developed an organocatalytic method to

by intramolecular C−H amination mediated by

transition−metal catalysts, such as Ir and Ru

complexes.^[8]Representative study by Chang reported

a series of elegant approaches to form benzofused

lactams via tailored Ir-catalyzed C−H amidation

reaction using dioxazolone as the nitrene precursor and

a number of well-designed Ir complexes as the

catalysts^[9](Scheme 1c). However, compared with Ir

and Ru catalysts, there are few reports on Co-catalyzed

C−H amidation and most of them employed organic

azides.^[10]An advantage of Earth abundant cobalt

catalysts over the precious metal iridium or rhodium

catalysts is their lower cost. So far, no reports

regarding Co-catalyzed synthesis of indolin-2-one and

dihydro-quinolin-2-one derivatives through an

intramolecular C−H amidation have been reported.

construct oxindoles, which used

organophosphorus-based catalyst (4·[O]) and a

hydrosilane reductant through tandem

a

small-ring

a

intermolecular C-N coupling of nitroarenes and

boronic acid, followed by intramolecular cyclization at

o

120 C^[7](Scheme 1b). Recently, significant progress

has been made in the construction of lactam

10.1002/adsc.202001254

Advanced Synthesis & Catalysis

Table 1. Optimization of Co-Catalyzed C−H Amidation. ^[a,b]

Yield of

2a (%)^a

Entry

[Co]

Ligand

[B]

[Ag]

T(^oC)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

Co1

Co2

Co3

Co1

-

L1

L2

L3

L4

L5

L6

L7

L1

NaBAr^F

KBPh₄

NaBPh₄

NaBF₄

/

60

rt

0

<5

28

20

45

74

52

60

38

73

76

83 (80)^c

40

80

<5

80

70

<5

4

AgSbF₆

Ag₂CO₃

AgPF₆

AgOTf

AgNTf₂

Ag₂CO₃

rt

<5

0

^[a]Reactions conducted on a 0.1 mmol scale and 0.1 M

reaction concentration, using 5 mol% Co as a cobalt source,

10 mol% L as ligand, 10 mol% borate and 20 mol% silver

salt. ^[b]NMR yield determined by ¹H NMR spectroscopy of

the crude reaction mixture using CH₂Br₂as an internal

standard. ^[c]Isolated yield after chromatographic purification.

Scheme 1. General strategies of indolin-2-one and

dihydroquinolin-2-one derivatives.

Herein, we report an efficient and straightforward

method for the synthesis of indolin-2-one and

dihydroquinolin-2-one

Cp*Co(CO)I₂catalyzed

derivatives

intramolecular

through

C−H

amidation for the first time. A readily available cobalt

catalyst and 1,4,2-dioxazol-5-ones led to wide

varieties indolin-2-ones and dihydroquinolin-2-ones in

good yields (27 examples, up to 86%) under mild

conditions. The scalability of the amidation was

demonstrated. This approach would deliver an

efficient and straightforward method for the synthesis

of valuable benzofused lactams of biologically active

compounds.

method^[9c]and replaced Ir complexes with the Co

catalyst, using 5 mol% Cp*Co(CO)I₂(Co1) as a cobalt

source, 10 mol% 8-hydroxyquinoline (L1) as a ligand,

and

10

mol%

sodium

tetrakis(3,5-

bis(trifluoromethyl)phenyl) borate (NaBAr^F) in

4

hexafluoro-2-propanol (HFIP) at 60 °C. However,

only trace amount of the product dihydroquinolin-2-

one 2a was detected (Table 1, entry 1). Then, reducing

the reaction temperature to room temperature and 0 ^oC

led to 28% and 20% NMR yield (Determined after

reaction workup by ¹H NMR integration), respectively

(entries 2 and 3). To our delight, with 20% Ag₂CO₃

additive, the cyclization product 2a was obtained in

74% at room temperature (entry 4). Switching to other

silver salts, such as AgSbF₆, AgPF₆, AgOTf and

AgNTf₂, however, resulted in lower NMR yield (38-

Results and Discussion

We selected 3-phenethyl-1,4,2-dioxazol-5-one 1a as

the model substrate, which was easily derived from 2-

phenylacetic acids (95% yield, see Supporting

Information). We began to study the cyclization

reaction of 1,4,2-dioxazol-5-one 1a followed Chang’s

10.1002/adsc.202001254

Advanced Synthesis & Catalysis

60%, entries 5–8). Replacing borate NaBAr^Fwith

4

KBPh₄, NaBPh₄and NaBF₄furnished increased NMR

yield with 73%, 76% and 83% (80% isolated yield),

respectively (entries 9-11). We next studied the effect

of Co catalysts and ligands. Switching the Cp* ring of

Cp*Co(CO)I₂, a methyl group was missing (Co2) or a

methyl group was replaced with a propyl group (Co3),

caused the NMR yield to drop to 40% and 80%,

respectively (entries 12 and 13). When replacing

ligand 8-hydroxyquinoline (L1) with quinolone (L2),

substituted

8-hydroxyquinoline

(L3-L6),

8-

aminoquinoline (L7), no improvement of yield was

observed (entries 14-19). Removing the Co catalyst

from the system led to no reaction (entry 20). Thus, the

optimal conditions for the intramolecular C−H

amidation that will be used for the remainder of the

study are listed in entry 11 of Table 1.

With the optimal conditions in hand (Table 1, entry

11), we subsequently studied the substrate scope of the

intramolecular C−H amidation using a variety of 3-

phenethyl-1,4,2-dioxazol-5-ones and 3-benzyl-1,4,2-

dioxazol-5-ones. As noted, 1,4,2-dioxazol-5-one

derivatives were readily synthesized from

commercially available carboxylic acids (56–95%

yields).^[8a]

For

synthesis

of

six-membered

dihydroquinolin-2-one derivatives, 3-phenethyl-1,4,2-

dioxazol-5-one 1a via intramolecular C−H amidation

delivered product 2a in 80% yield. Moreover, 2a was

characterized by X-ray crystallography, confirming its

structure (CCDC 2033458, see Supporting

Information for details). Phenylacetyl substrates

bearing ortho-substituted groups were smoothly

cyclized to obtain the corresponding dihydroquinolin-

2-one. Ortho-alkyl (Me, 1b) and electro-donating

(OMe, 1c) substituents furnished products 2b and 2c

in 65% and 60%. Electro-withdrawing (Cl, 1d; Br, 1e;

I, 1f) substituents, led to products 2d, 2e and 2f in 38%,

42% and 45%, respectively. Electron-deficient (CF₃,

1g and CO₂Me, 1h) substituents provided products 2g

and 2h in 40% and 46%. Meta-substituted substrates

afforded a mixture of isomeric desired products 2i/2i’

and 2j/2j’ in a total of 81% and 83% yields with 1.6:1

and 4:1 regioselectivities, probably owing to the

steric hindrance of meta-position. Substrates bearing

multiple substituent 3,4-dimethoxy (1k), polycyclic

substrates benzo[1,3]dioxol (1l) and naphthalen-1-yl

(1m), were also suitable reactants in C−H amidation,

giving products 2k, 2l and 2m in 86%, 58% and 61%,

respectively. α-Substituted phenylacetyl substrates

(1n-1p) underwent cyclization to obtain a series of

^[a]Reactions conducted on a 0.2 mmol scale and 0.1 M

reaction concentration, using 5 mol% Cp*Co(CO)I₂as

cobalt source, 10 mol% 8-Hydroxyquinoline as ligand, 10

mol% NaBF₄and 20 mol% Ag₂CO₃. ^[b]Yield of isolated

product after chromatographic purification.

functionalized

lactam

products

(2n),

(2o)

4-methyl-

4,4-dimethyl-

4-phenyl-

dihydroquinolin-2-one

and

dihydroquinolin-2-one (2p) in 58%, 74% and 52%,

respectively.

We next explored the method to synthesis of five-

membered indolin-2-one derivatives. Various

substituted 3-benzyl-1,4,2-dioxazol-5-ones provided

cyclization products in good yields. Benzyl substrate

bearing ortho-substituted electro-donating (OMe, 1q)

and electron-deficient (CF₃, 1r) groups furnished

products 2q in 85% and 42 yields. Meta-substituted

substrate (Cl, 1s) gave a C4-selective cyclization

Table 2. Scope of C−H Amidation.^[a,b]

10.1002/adsc.202001254

Advanced Synthesis & Catalysis

product (2s), suggesting that the steric hindrance may

lead to this regioselectivity. Substrates bearing

multiple substituents, such as 3,4-dimethoxy (1t), 3,5-

dimethoxy (1u), 3,5-dimethyl (1v) and 2-bromo-4-

methoxy (1w) groups, afforded products 2t, 2u, 2v and

2w in 83%, 64%, 58 and 61%, respectively. Polycyclic

substrates

benzo[1,3]dioxol

(1x),

2,3-

dihydrobenzofuran (1y) and naphthalen-1-yl (1z) led

to products 2x, 2y and 2z in 53%, 67% and 62%,

respectively. Naphthalen-2-yl

substrate (1z’)

generated a mixture of isomeric desired products

2z’/2z’’ in a total of 72% yield with 3.8:1

regioselectivity, and the regioselectivity presumably

due to the electronic effects^[10a]. The structures of

isomers were confirmed from literature report^[11]

.

Subsequently, we evaluated the scalability of our

method. We conducted 1,4,2-dioxazol-5-ones 1a and

1u on a 1.2 g scale under the standard conditions of the

intramolecular C−H amidation (Scheme 2). The

desired dihydroquinolin-2-one 2a and 5,6-

dimethoxyindolin-2-one 2t were isolated in 0.69 g (75%

yield) and 0.75 g (78% yield). This means that the

method has application value.

Scheme 3. Proposed reaction mechanism.

Conclusion

In summary, we have successfully synthesized a series

of

indolin-2-one

and

dihydroquinolin-2-one

derivatives employing an Earth abundant cobalt

catalyst and 1,4,2-dioxazol-5-ones for the first time. In

this protocol, readily synthesized 1,4,2-dioxazol-5-

ones underwent intramolecular C−H amidation to

provide a wide variety of functionalized benzofused

lactams under mild conditions. Gram-scale reactions

were demonstrate the scalability of the amidation and

the competition and deuterium-labeling experiments

were also probed. It is noteworthy that this method

does not require

a

tailored transition-metal

complexes,^[9-10]which enables the synthesis of a

diverse array of benzofused lactams in a convenient

and straightforward means. Furthermore, because

1,4,2-dioxazol-5-ones are easily synthesized from

abundant carboxylic acids, we anticipated that the

approach would deliver an efficient method for the

synthesis of valuable benzofused lactams of

biologically active compounds.

Scheme 2. Gram-scale synthesis.

Based on the relevant literatures on C-H amidation

using Ir catalysts^{[8a, 9c]}and above study, we proposed

the plausible mechanism for this intramolecular C−H

amidation as shown in Scheme 3. First, a cationic

Co(III) catalyst from Cp*Co(CO)I₂undergoes the

N,O-coordination of 8-hydroxyquinoline, forming a

cobaltacycle intermediate I. Next, it further

coordinates with dioxazolone of 1 to form intermediate

II with releasing a molecule of CO₂. The electrons on

the electron-rich aromatic ring transfer to the electron-

deficient N atom to form intermediate III. Finally, it

undergoes an elimination to obtain product 2a and

regenerates the active cobalt complex I to continue the

catalytic cycle. The reaction proceeds by an

electrophilic aromatic substitution (SEAr), which

provides support for Chang’s proposed mechanistic

Experimental Section

General Methods

Unless otherwise stated, all reagents were commercially

available and used as received without further purification.

Chemicals were obtained from Sigma-Aldrich, Acros, TCI

and Alfa-Aesar. TLC was performed with Merck TLC Silica

gel60 F₂₅₄plates with detection under UV light at 254 nm.

Silica gel (200-300 mesh, Qingdao) was used for flash

chromatography. ¹H and ¹³C{¹H} NMR spectra were

obtained using a Brüker DRX 600/400 spectrometer at

600/400 MHz and 150/100 MHz, respectively. Chemical

shifts were reported in units of parts per million (ppm)

downfield from tetramethylsilane (TMS), and all coupling

constants were reported in hertz. The infrared (IR) spectra

were measured on a Nicolet iS10 FTIR spectrometer with 4

cm⁻¹resolution and 32 scans between wavenumber of 4000

cm⁻¹and 400 cm⁻¹. High Resolution Mass spectra were

pathways^[9c]

.

10.1002/adsc.202001254

Advanced Synthesis & Catalysis

2940, 2840, 1682, 1618, 1497, 1449, 1301, 1260, 1092, 792,

taken on AB QSTAR Pulsar mass spectrometer. Melting

points were obtained on a XT-4 melting-point apparatus and

were uncorrected.

733, 713, 535 cm^-1; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd

+

for C₁₀H₁₂NO₂178.0863; Found 178.0870.

5-Chloro-3,4-dihydroquinolin-2(1H)-one (2d)

General Procedure for the Preparation and

Characterization

of

Indolin-2-ones

and

Dihydroquinolin-2-ones (2a–2z’’).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.31); White

solid (14.0 mg, 38%); m.p. 109 – 111 ℃. ¹H NMR (400 MHz,

Chloroform-d) δ 7.88 (s, 1H), 7.22 (dd, J = 8.0, 1.2 Hz, 1H),

7.09 – 7.04 (m, 1H), 6.91 (t, J = 8.0 Hz, 1H), 3.00 – 2.95 (m,

2H), 2.66 – 2.60 (m, 2H) ppm. ¹³C NMR (100 MHz,

Chloroform-d) δ 170.5 , 134.1 , 127.8 , 126.5 , 125.5 , 123.3 ,

119.7 , 30.6 , 25.8 ppm. IR (thin film): 3379, 3041, 2945,

1764, 1695, 1530, 1358, 1320, 1178, 1136, 813, 755, 681

cm^-1; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for

C₉H₉ClNO⁺182.0367; Found 182.0367.

To an oven-dried reaction flask were added Cp*Co(CO)I₂

(5 mg, 5.0 mol%), 8-Hydroxyquinoline (3 mg, 10 mol%),

Ag₂CO₃(11 mg, 20 mol%), NaBF₄(2 mg, 10 mol%), and

hexafluoro-2-propanol (2 mL) under argon atmosphere and

stirred for 1 min. To the reaction flask was added 1,4,2-

dioxazol-5-one (1, 0.2 mmol) and then sealed. The reaction

mixture was vigorously stirred for 3 hours at room

temperature. Filtered through a pad of celite with DCM (10

mL × 2) and concentrated under reduced pressure. Desired

product 2 was obtained by silica chromatography (eluent:

Petroleum ether/EtOAc, 3:1 ~ 1:1).

5-Bromo-3,4-dihydroquinolin-2(1H)-one (2e).

3,4-Dihydroquinolin-2(1H)-one (2a).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.32); White

solid (18.9 mg, 42%); m.p. 102 – 104 ℃. ¹H NMR (400 MHz,

Chloroform-d) δ 7.81 (s, 1H), 7.39 (dd, J = 8.0, 1.2 Hz, 1H),

7.11 (d, J = 7.6 Hz, 1H), 6.86 (t, J = 7.6 Hz, 1H), 2.99 (t, J

= 7.6 Hz, 2H), 2.64 (dd, J = 8.4, 6.4 Hz, 2H) ppm. ¹³C NMR

(100 MHz, Chloroform-d) δ 170.7, 135.3, 131.0, 127.3,

125.7, 123.9, 109.7, 30.8, 26.1 ppm. IR (thin film): 3382,

3241, 2948, 1784, 1698, 1481, 1362, 1322, 1190, 1139, 803,

764, 597, 522 cm^-1; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd

for C₉H₉BrNO⁺225.9862; Found 225.9869.

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.30); White

solid (24.1 mg, 82%); m.p. 159 – 161 ℃. ¹H NMR (400 MHz,

Chloroform-d) δ 9.84 (s, 1H), 7.19 – 7.12 (m, 2H), 6.97 (td,

J = 7.6, 1.2 Hz, 1H), 6.89 (d, J = 7.6 Hz, 1H), 2.95 (t, J =

8.0 Hz, 2H), 2.64 (t, J = 8.0 Hz, 2H) ppm. ¹³C NMR (100

MHz, Chloroform-d) δ 172.7, 137.4, 127.9, 127.5, 123.6,

123.1, 115.8, 30.7, 25.3 ppm. IR (thin film): 3050, 1683,

1591, 1489, 1383, 1280, 1245, 940, 813, 745, 681 cm^-1;

HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for C₉H₁₀NO⁺

148.0757; Found 148.0761.

5-Iodo-3,4-dihydroquinolin-2(1H)-one (2f)

5-Methyl-3,4-dihydroquinolin-2(1H)-one (2b).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.33); White

solid (24.6 mg, 45%); m.p. 115 – 117 ℃.¹H NMR (400 MHz,

Chloroform-d) δ 7.69 (s, 1H), 7.60 (dd, J = 8.0, 1.2 Hz, 1H),

7.12 (d, J = 7.2 Hz, 1H), 6.71 (t, J = 7.6 Hz, 1H), 2.94 (dd,

J = 8.4, 6.4 Hz, 2H), 2.64 – 2.57 (m, 2H) ppm. ¹³C NMR

(100 MHz, Chloroform-d) δ 170.9 , 137.8 , 137.4 , 128.3 ,

125.3 , 124.5 , 84.9 , 30.9 , 26.3 ppm. IR (thin film): 3388,

3265, 2966, 1795, 1496, 1377, 1335, 1212, 1151, 786, 588

cm^-1; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for C₉H₉INO⁺

273.9723; Found 273.9719.

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.28); White

solid (20.8 mg, 65%); m.p. 160 – 162 ℃. ¹H NMR (400 MHz,

Chloroform-d) δ 9.69 (s, 1H), 7.06 (t, J = 7.6 Hz, 1H), 6.86

(d, J = 7.6 Hz, 1H), 6.75 (d, J = 8.0 Hz, 1H), 2.91 (t, J = 7.6

Hz, 2H), 2.64 (t, J = 7.6 Hz, 2H), 2.28 (s, 3H) ppm. ¹³C

NMR (100 MHz, 172.4, 137.4, 136.0, 127.1, 125.0, 122.0,

113.8, 30.4, 22.0, 19.4 ppm. IR (thin film): 3204, 3076,

2948, 1676, 1591, 1478, 1391, 1217, 1198, 813, 769, 540,

452 cm^-1; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for

C₁₀H₁₂NO⁺162.0913; Found 162.0914.

5-(Trifluoromethyl)-3,4-dihydroquinolin-2(1H)-one

(2g)

5-Methoxy-3,4-dihydroquinolin-2(1H)-one (2c).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.30); White

solid (17.2 mg, 40%); m.p. 132 – 134 ℃.¹H NMR (400 MHz,

Chloroform-d) δ 7.68 (d, J = 7.6 Hz, 1H), 7.54 (t, J = 7.6 Hz,

1H), 7.40 (t, J = 7.6 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 3.22

(t, J = 8.0 Hz, 2H), 2.99 – 2.92 (t, J = 8.0 Hz, 2H) ppm.¹³C

NMR (100 MHz, Chloroform-d) δ 165.6, 154.0, 136.8,

132.5, 131.1, 128.8 (q, ²J_C-F= 29.8 Hz),.127.6, 126.7 (q, ³J_C-

_F= 5.6 Hz), 124.5 (q, ¹J_C-F= 272.1 Hz), 27.8, 26.8 ppm. IR

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 2:1, R_f= 0.25); White

solid (21.2 mg, 60%); m.p. 169 – 171 ℃. ¹H NMR (400 MHz,

Chloroform-d) δ 7.86 (s, 1H), 6.91 (t, J = 8.0 Hz, 1H), 6.74

(d, J = 8.0 Hz, 2H), 3.83 (s, 3H), 2.93 (t, J = 7.6 Hz, 2H),

2.59(t, J = 7.2 Hz, 2H) ppm. ¹³C{¹H} NMR (100 MHz,

Chloroform-d) δ: 170.4, 145.8, 126.5, 124.0, 122.7, 120.0,

109.0, 55.8, 30.7, 25.4 ppm. IR (thin film): 3416, 3239,

10.1002/adsc.202001254

Advanced Synthesis & Catalysis

(thin film): 3088, 2953, 17108, 1585, 1432, 1255, 1210, 985, Isolated from flash chromatography on silica gel (eluted

802, 734, 551 cm^-1; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd

for C₁₀H₉F₃NO⁺216.0631; Found 216.0630.

with petroleum ether : ethyl acetate = 2:1, R_f= 0.23); White

solid (6 mg, 17%); m.p. 165 – 167 ℃. ¹H NMR (400 MHz,

Chloroform-d) δ 7.86 (s, 1H), 6.94 (t, J = 8.0 Hz, 1H), 6.76

(d, J = 7.6 Hz, 2H), 3.86 (d, J = 2.0 Hz, 3H), 2.96 (t, J = 7.6

Hz, 2H), 2.65 – 2.60 (m, 2H) ppm. ¹³C NMR (100 MHz,

Chloroform-d) δ 172.3, 155.5, 131.0, 124.9, 116.5, 113.7,

112.3, 55.5, 30.5, 25.6 ppm. IR (thin film): 3058, 2972,

1775, 1680, 1489, 1447, 1382, 1274, 1239, 1148, 1036, 879,

764, 554 cm^-1; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for

Methyl 2-oxo-1,2,3,4-tetrahydroquinoline-5-

carboxylate (2h)

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.28); White

solid (18.9 mg, 46%); m.p. 145 – 157 ℃.¹H NMR (400 MHz,

Chloroform-d) δ 9.57 (s, 1H), 7.58 (dd, J = 8.0, 1.2 Hz, 1H),

7.22 (t, J = 8.0 Hz, 1H), 7.03 (dd, J = 8.0, 1.2 Hz, 1H), 3.90

(s, 3H), 3.39 (t, J = 8.0 Hz, 2H), 2.61 (t, J = 8.0 Hz, 2H)

ppm. ¹³C NMR (100 MHz, Chloroform-d) δ 172.5 , 167.6 ,

138.7 , 129.7 , 127.3 , 125.7 , 125.4 , 119.6 , 52.3 , 30.2 ,

22.9 ppm. IR (thin film): 3088, 2953, 17108, 1585, 1432,

+

C₁₀H₁₂NO₂178.0863; Found 178.0869.

6,7-Dimethoxy-3,4-dihydroquinolin-2(1H)-one (2k).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 1:1, R_f= 0.22); White

1255, 1210, 985, 802, 734, 551 cm^-1; HRMS (ESI-TOF) m/z: solid (35.6 mg, 86%); m.p. 180 – 182 ℃. ¹H NMR (400 MHz,

+

[M+H]⁺Calcd for C₁₁H₁₁NO₃206.0812; Found 206.0815.

Chloroform-d) δ 9.26 (s, 1H), 6.67 (s, 1H), 6.41 (s, 1H), 3.85

(s, 3H), 3.84 (s, 3H), 2.89 (t, J = 7.2 Hz, 2H), 2.66 – 2.56

(m, 2H) ppm. ¹³C NMR (100 MHz, Chloroform-d) δ 172.3,

148.5, 144.8, 130.8, 114.9, 111.7, 100.5, 56.5, 56.3, 31.1,

25.2 ppm. IR (thin film): 3218, 2938, 2844, 1675, 1522,

1395, 1233, 1201, 1132, 1029, 933, 857, 772, 585 cm^-1;

6-Methyl-3,4-dihydroquinolin-2(1H)-one/8-Methyl-3,4-

dihydroquinolin-2(1H)-one (2i)/(2i’)

+

HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for C₁₁H₁₄NO₃

208.0968; Found 208.0971.

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.29); White

solid (26.1 mg, 81 %); Obtained as mixture of two isomers

(1.6 : 1). Major isomer: 6-Methyl-3,4-dihydroquinolin-

7,8-Dihydro-[1,3]dioxolo[4,5-g]quinolin-6(5H)-one (2l).

1

2(1H)-one H NMR (600 MHz, Chloroform-d) δ 9.02 (s,

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 2:1, R_f= 0.25); White

solid (22.2 mg, 58%); m.p. 189 – 191 ℃. ¹H NMR (400 MHz,

DMSO-d₆) δ 9.86 (s, 1H), 6.77 (s, 1H), 6.46 (s, 1H), 5.92 (s,

2H), 2.75 (t, J = 7.6 Hz, 2H), 2.37 (t, J = 7.6 Hz, 2H) ppm.

¹³C NMR (100 MHz, DMSO-d₆) δ 170.4, 146.4, 142.5,

132.8, 116.3, 108.5, 101.2, 97.6, 30.9, 25.1 ppm. IR (thin

film): 3148, 2781, 1705, 1635, 1503, 1358, 1290, 1192,

1034, 940, 850, 683 cm^-1; HRMS (ESI-TOF) m/z: [M+Na]⁺

1H), 6.98 – 6.97 (m, 2H), 6.75 (d, J = 7.8 Hz, 1H), 2.93 (t,

J = 6.0 Hz, 2H), 2.64(t, J = 6.0 Hz, 2H), 2.29 (s, 3H) ppm.

¹³C NMR (150 MHz, Chloroform-d) δ 172.4, 134.9, 132.7,

128.6, 128.0, 116.4, 115.6, 30.9, 25.4, 20.8 ppm. Minor

isomer: 8-Methyl-3,4-dihydroquinolin-2(1H)-one ¹H

NMR (600 MHz, Chloroform-d) δ 9.05 (s, 1H), 7.03 (d, J =

7.8 Hz, 1H), 6.80 (d, J = 4.2 Hz, 1H), 6.67 (s, 1H), 2.93 (t,

J = 6.0 Hz, 2H), 2.64 (t, J = 6.0 Hz, 2H), 2.30 (s, 3H) ppm.

¹³C NMR (150 MHz, Chloroform-d) δ 172.7, 137.6, 137.3,

127.8, 123.9, 123.6, 120.7, 31.0, 25.0, 21.1 ppm. HRMS

(ESI-TOF) m/z: [M+H]⁺Calcd for C₁₀H₁₂NO⁺162.0913;

Found 162.0912.

+

Calcd for C₁₀H₉NaNO₃214.0475; Found 214.0480.

1,4-Dihydrobenzo[f]quinolin-3(2H)-one (2m).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.33); White

solid (24.0 mg, 61%); m.p. 192 – 194 ℃. ¹H NMR (400 MHz,

DMSO-d₆) δ 10.22 (s, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.83 (d,

1H), 7.75 (d, J = 8.8 Hz, 1H), 7.52 (ddd, J = 8.4, 6.8, 1.6 Hz,

1H), 7.37 (ddd, J = 8.0, 6.8, 1.2 Hz, 1H), 7.14 (d, J = 8.8 Hz,

1H), 3.25 (t, J = 7.6 Hz, 2H), 2.59 (t, J = 7.6 Hz, 2H) ppm.

¹³C NMR (100 MHz, DMSO-d₆) δ 170.1, 135.7, 131.2,

129.9, 128.4, 127.5, 126.7, 123.7, 122.7, 116.8, 115.5, 30.0,

20.5 ppm. IR (thin film): 2905, 2783, 1863, 1835, 1637,

1505, 1492, 1448, 1344, 1302, 1149, 773, 632 cm^-1; HRMS

(ESI-TOF) m/z: [M+Na]⁺Calcd for C₁₃H₁₁NaNO⁺220.0733;

Found 220.0728.

6-Methoxy-3,4-dihydroquinolin-2(1H)-one (2j).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 2:1, R_f= 0.22); White

solid (23.5 mg, 66%); m.p. 169 – 171 ℃. ¹H NMR (400 MHz,

Chloroform-d) δ 10.01 (s, 1H), 6.85 – 6.76 (m, 1H), 6.66 (d,

J = 7.6 Hz, 2H), 3.72 (s, 3H), 2.88 (t, J = 7.6 Hz, 2H), 2.63

– 2.54 (m, 2H) ppm. ¹³C NMR (100 MHz, Chloroform-d) δ

172.3, 155.5, 131.0, 124.9, 116.5, 113.7, 112.3, 55.5, 30.5,

25.6 ppm. IR (thin film): 3064, 2970, 2935, 1976, 1770,

1661, 1497, 1463, 1418, 1294, 1240, 1120, 792, 764, 600

cm^-1; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for

+

C₁₀H₁₂NO₂178.0863; Found 178.0865.

4-Methyl-3,4-dihydroquinolin-2(1H)-one (2n).

8-Methoxy-3,4-dihydroquinolin-2(1H)-one (2j’).

10.1002/adsc.202001254

Advanced Synthesis & Catalysis

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.28); White

solid (16.9 mg, 42%); m.p. 172 – 174 ℃. ¹H NMR (400 MHz,

DMSO-d₆) δ 10.72 (s, 1H), 7.38 (t, J = 8.0 Hz, 1H), 7.21 (d,

solid (18.7 mg, 58%); m.p. 166 – 168 ℃. ¹H NMR (400 MHz, J = 8.0 Hz, 1H), 7.07 (d, J = 8.0 Hz, 1H), 3.62 (s, 2H) ppm.

Chloroform-d) δ 9.33 (s, 1H), 7.18 (ddd, J = 9.2, 7.6, 1.6 Hz,

2H), 7.02 (td, J = 7.6, 1.2 Hz, 1H), 6.90 – 6.83 (m, 1H), 3.13

(m, 1H), 2.74 (dd, J = 16.0, 6.0 Hz, 1H), 2.44 (dd, J = 16.0,

7.2 Hz, 1H), 1.31 (d, J = 7.2 Hz, 3H) ppm. ¹³C NMR (100

MHz, Chloroform-d) δ 171.9, 136.6, 128.8, 127.6, 126.6,

123.4, 115.9, 38.5, 30.8, 19.9 ppm. IR (thin film): 3204,

3076, 2948, 1676, 1591, 1478, 1391, 1217, 1198, 813, 769,

540 cm^-1; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for

C₁₀H₁₂NO⁺162.0913; Found 162.0916.

¹³C NMR (100 MHz, DMSO-d₆) δ 175.4 , 145.0 , 128.6 ,

125.0 (q, ²J_C-F= 32.0 Hz), 124.0 (q, ¹J_C-F= 271.2 Hz), 123.6

3

(q, J_C-F= 3.0 Hz), 117.3 (q, J_C-F= 4.4 Hz), 112.8 , 35.1

ppm.IR (thin film): 3083, 2958, 1702, 1622, 1484, 1425,

1365, 1257, 1218, 1089, 721, 653 cm^-1; HRMS (ESI-TOF)

m/z: [M+H]⁺Calcd for C₉H₇F₃NO⁺202.0474; Found

202.0478.

5-Chloroindolin-2-one (2s).

4,4-Dimethyl-3,4-dihydroquinolin-2(1H)-one (2o).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.30); White

solid (20.0 mg, 60%); m.p. 158 – 160 ℃. ¹H NMR (400 MHz,

DMSO-d₆) δ 10.47 (s, 1H), 7.25 (s, 1H), 7.20 (d, J = 8.4 Hz,

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.27); White

solid (25.9 mg, 74%); m.p. 170 – 172 ℃. ¹H NMR (400 MHz, 1H), 6.79 (d, J = 8.4 Hz, 1H), 3.49 (s, 2H) ppm. ¹³C NMR

DMSO-d₆) δ 10.12 (s, 1H), 7.28 (dd, J = 7.6, 1.6 Hz, 1H),

7.13 (td, J = 7.6, 1.6 Hz, 1H), 6.96 (td, J = 7.6, 1.2 Hz, 1H),

6.86 (dd, J = 8.0, 1.2 Hz, 1H), 2.34 (s, 2H), 1.21 (s, 6H) ppm.

¹³C NMR (100 MHz, DMSO-d₆) δ 169.3, 136.9, 132.1,

127.1, 124.2, 122.4, 115.4, 44.9, 33.5, 27.3 ppm. IR (thin

film): 3204, 3076, 2948, 1676, 1591, 1478, 1391, 1217,

1198, 813, 769, 540 cm^-1; HRMS (ESI-TOF) m/z: [M+Na]⁺

Calcd for C₁₁H₁₃NaNO⁺198.0889; Found 198.0892.

(100 MHz, DMSO-d₆) δ 176.0, 142.6, 128.0, 127.2, 125.1,

124.5, 110.3, 35.8 ppm. IR (thin film): 3159, 2961, 2582,

1704, 1618, 1476, 1316, 1244, 1024, 869, 798, 656, 561 cm^-

¹; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for C₈H₇ClNO⁺

168.0211; Found 168.0217.

5,6-Dimethoxyindolin-2-one (2t).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 1:1, R_f= 0.20); White

solid (32.0 mg, 83%); m.p. 184 – 186 ℃. ¹H NMR (400 MHz,

Chloroform-d) δ 9.17 (s, 1H), 6.83 (s, 1H), 6.55 (s, 1H), 3.86

(s, 3H), 3.84 (s, 3H), 3.49 (s, 2H) ppm. ¹³C NMR (100 MHz,

4-Phenyl-3,4-dihydroquinolin-2(1H)-one (2p).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.28); White

solid (21.2 mg, 60%); m.p. 188 – 190 ℃. ¹H NMR (400 MHz, Chloroform-d) δ 179.4, 149.4, 145.1, 136.3, 116.0, 109.7,

DMSO-d₆) δ 10.28 (s, 1H), 7.32 (t, J = 7.5 Hz, 2H), 7.28 –

7.14 (m, 4H), 6.94 (m, 3H), 4.32 (t, J = 6.4 Hz, 1H), 2.84 (d,

J = 6.4 Hz, 1H), 2.81 – 2.72 (m, 1H) ppm. ¹³C NMR (100

MHz, DMSO-d₆) δ 169.2, 142.5, 138.1, 128.6, 128.1, 127.7,

127.5, 126.8, 126.3, 122.2, 115.5, 40.9, 37.9 ppm. IR (thin

film): 3060, 2890, 1675, 1612, 1488, 1387, 1265, 1188,

1030, 944, 759, 715, 508 cm^-1; HRMS (ESI-TOF) m/z:

[M+H]⁺Calcd for C₁₅H₁₄NO⁺224.1070; Found 224.1065.

95.9, 56.9, 56.4, 37.1 ppm. IR (thin film): 3218, 2937, 1675,

1521, 1394, 1284, 1260, 1234, 1131, 1012, 933, 859, 585

cm^-1; HRMS (ESI-TOF) m/z: [M+Na]⁺Calcd for

+

C₁₀H₁₁NaNO₃216.0631; Found 216.0632.

5,7-Dimethoxyindolin-2-one (2u).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 1:1, R_f= 0.21); White

solid (24.7 mg, 53%); m.p. 183 – 185 ℃. ¹H NMR (600 MHz,

DMSO-d₆) δ 10.16 (s, 1H), 6.49 (s, 1H), 6.49 (s, 1H), 3.79

(s, 3H), 3.71 (s, 3H), 3.43 (s, 2H) ppm. ¹³C NMR (150 MHz,

DMSO-d₆) δ 176.4, 156.0, 144.3, 127.3, 126.0, 102.9, 98.9,

4-Methoxyindolin-2-one (2q).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 2:1, R_f= 0.22); White

solid (31.0 mg, 85%); m.p. 175 – 177 ℃. ¹H NMR (400 MHz, 56.2, 56.1, 37.2 ppm. IR (thin film): 3065, 2948, 1695, 1642,

Chloroform-d) δ 9.30 (s, 1H), 6.95 (t, J = 8.0 Hz, 1H), 6.81

1480, 1340, 1257, 1223, 1075, 763, 653, 568 cm^-1; HRMS

+

(m, 2H), 3.86 (s, 3H), 3.54 (s, 2H) ppm. ¹³C NMR (100 MHz, (ESI-TOF) m/z: [M+Na]⁺Calcd for C₁₀H₁₁NaNO₃

Chloroform-d) δ 177.6, 143.9, 131.6, 126.2, 122.7, 116.9,

110.2, 55.7, 36.9 ppm. IR (thin film): 3160, 3073, 2938,

1698, 1628, 1495, 1465, 1328, 1259, 1211, 1078, 761, 721,

653, 569 cm^-1; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for

216.0631; Found 216.0636.

5,7-Dimethylindolin-2-one (2v).

+

C₉H₁₀NO₂164.0706; Found 164.0709.

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.31); White

solid (18.8 mg, 58%); m.p. 168 – 170 ℃. ¹H NMR (400 MHz,

DMSO-d₆) δ 10.30 (s, 1H), 6.81 (s, 1H), 6.77 (s, 1H), 3.40

(s, 2H), 2.19 (s, 3H), 2.14 (s, 3H) ppm. ¹³C NMR (100 MHz,

DMSO-d₆) δ 176.7, 139.8, 129.8, 129.0, 125.4, 122.3, 118.1,

4-Methoxyindolin-2-one (2r)

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.28); White

10.1002/adsc.202001254

Advanced Synthesis & Catalysis

36.1, 20.6, 16.4 ppm. IR (thin film): 3028, 2924, 2869, 1824, 1,3-Dihydro-2H-benzo[g]indol-2-one (2z’).

1634, 1492, 1352, 1262, 1148, 956, 764, 632 cm^-1; HRMS

(ESI-TOF) m/z: [M+H]⁺Calcd for C₁₀H₁₂NO⁺162.0913;

Isolated from flash chromatography on silica gel (eluted

Found 162.0912.

with petroleum ether : ethyl acetate = 3:1, R_f= 0.32); White

solid (20.9 mg, 57%); m.p. 176 – 178 ℃. ¹H NMR (400 MHz,

4-Bromo-6-methoxyindolin-2-one (2w).

DMSO-d₆) δ 11.13 (s, 1H), 8.04 (d, J = 7.9 Hz, 1H), 7.87 (d,

J = 6.4 Hz, 1H), 7.51 (d, J = 8.2 Hz, 1H), 7.49 – 7.35 (m,

3H), 3.65 (s, 2H) ppm. ¹³C NMR (100 MHz, DMSO-d₆) δ

177.6, 139.4, 132.7, 128.3, 125.5, 125.5, 122.6, 121.9, 120.8,

120.3, 119.1, 36.9 ppm. IR (thin film): 3148, 2929, 1675,

1558, 1462, 1318, 1254, 1198, 805, 661, 564, 532 cm^-1;

HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for C₁₂H₁₀NO⁺

184.0757; Found 184.0759.

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 2:1, R_f= 0.27); White

solid (29.3 mg, 61%); m.p. 178 – 180 ℃. ¹H NMR (400 MHz,

Chloroform-d) δ 7.94 (s, 1H), 6.88 (s, 1H), 6.79 (s, 1H), 3.77

(s, 3H), 3.61 (s, 2H) ppm. ¹³C NMR (100 MHz, Chloroform-

d) δ 175.5, 156.3, 135.5, 127.4, 115.2, 111.7, 102.3, 56.2,

37.8 ppm. IR (thin film): 3147, 2926, 2852, 1683, 1579,

1457, 1387, 1286, 1172, 1120, 877, 700, 638, 560 cm^-1;

1,3-Dihydro-2H-benzo[f]indol-2-one (2z’’).

HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for C₉H₉BrNO₂

+

241.9811; Found 241.9813.

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.31); White

solid (5.5 mg, 15%); m.p. 173 – 175 ℃. ¹H NMR (400 MHz,

Chloroform-d) δ 10.44 (s, 1H), 7.88 (dd, J = 8.0, 2.0 Hz,

2H), 7.56 (t, J = 7.6 Hz, 2H), 7.49 (t, J = 7.6 Hz, 1H), 7.40

(d, J = 8.4 Hz, 1H), 3.80 (s, 2H) ppm. ¹³C NMR (100 MHz,

Chloroform-d) δ 179.7, 138.7, 133.4, 128.8, 126.4, 126.1,

122.4, 122.3, 121.4, 120.1, 119.8, 37.8 ppm. IR (thin film):

3120, 2928, 1676, 1557, 1438, 1325, 1268, 1098, 798, 656,

558 cm^-1; HRMS (ESI-TOF) m/z: [M+H]⁺Calcd for

C₁₂H₁₀NO⁺184.0757; Found 184.0759.

5,7-Dihydro-6H-[1,3]dioxolo[4,5-f]indol-6-one (2x).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 2:1, R_f= 0.24); White

solid (18.8 mg, 53%); m.p. 175 – 177 ℃. ¹H NMR (400 MHz,

Chloroform-d) δ 8.36 (s, 1H), 6.74 (s, 1H), 6.48 (s, 1H), 5.92

(s, 2H), 3.46 (s, 2H) ppm. ¹³C NMR (100 MHz, Chloroform-

d) δ 178.0, 147.2, 143.3, 136.3, 116.8, 106.2, 101.1, 93.5,

36.6 ppm. IR (thin film): 3148, 2781, 1704, 1635, 1476,

1358, 1319, 1192, 1152, 1035, 938, 848, 652 cm^-1; HRMS

(ESI-TOF) m/z: [M+H]⁺Calcd for C₉H₈NO₃178.0499;

Gram scale synthesis

+

Found 178.0499.

To an oven-dried 100 mL reaction flask were added

Cp*Co(CO)I₂(0.157 g, 5.0 mol%), 8-hydroxyquinoline

(0.095 g, 10 mol %), Ag₂CO₃(0.347 g, 20 mol%), NaBF4

(0.07 g, 10 mol %), and hexafluoro-2-propanol (50 mL)

under argon atmosphere and stirred for 1 min. To the

reaction flask was added 1a or 1t and then sealed. The

reaction mixture was vigorously stirred for 3 hours at room

temperature. Filtered through a pad of celite with DCM (50

mL × 2) and concentrated under reduced pressure. Desired

product 2a was obtained by silica chromatography (eluent:

Petroleum ether/EtOAc, 3:1) with 0.69 g, 75% yield.

Desired product 2t was obtained by silica chromatography

(eluent: Petroleum ether/EtOAc, 1:1) with 0.75 g, 78% yield.

2,3,5,7-Tetrahydro-6H-furo[3,2-f]indol-6-one (2y).

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 2:1, R_f= 0.28); White

solid (23.5 mg, 67%); m.p. 172 – 174 ℃. ¹H NMR (400 MHz,

DMSO-d₆) δ 10.13 (s, 1H), 6.69 (s, 1H), 6.66 (s, 1H), 4.45

(t, J = 8.8 Hz, 2H), 3.37 (s, 2H), 3.12 (t, J = 8.8 Hz, 2H)

ppm. ¹³C NMR (100 MHz, DMSO-d₆) δ 176.3, 154.6, 136.7,

125.4, 124.8, 106.2, 70.6, 36.3, 29.6 ppm. IR (thin film):

3133, 2919, 2580, 1697, 1668, 1479, 1399, 1297, 1259,

1182, 1014, 590, 854, 665, 539 cm^-1; HRMS (ESI-TOF) m/z:

+

[M+H]⁺Calcd for C₁₀H₁₀NO₂176.0706; Found 176.0710.

Acknowledgements

1,3-Dihydro-2H-benzo[e]indol-2-one (2z).

This work was supported by grants from the National

Key R&D Program of China (2019YFE0109200),

NSFC (21662043 and U1702286), Program for

Changjiang Scholars and Innovative Research Teams

in Universities (IRT17R94) and IRTSTYN, Ling-Jun

Isolated from flash chromatography on silica gel (eluted

with petroleum ether : ethyl acetate = 3:1, R_f= 0.32); White

solid (22.7 mg, 62%); m.p. 175 – 177 ℃. ¹H NMR (400 MHz,

DMSO-d₆) δ 11.17 (s, 1H), 8.07 (d, J = 8.0 Hz, 1H), 7.93 –

7.86 (m, 1H), 7.56 – 7.40 (m, 4H), 3.69 (s, 2H) ppm. ¹³C

NMR (100 MHz, DMSO-d₆) δ 177.6, 139.4, 132.7, 128.3,

125.6, 125.5, 122.6, 121.9, 120.8, 120.3, 119.1, 36.9 ppm.

IR (thin film): 3039, 2850, 1679, 1576, 1528, 1375, 1318,

1254, 1198, 928, 805, 774, 661, 565 cm^-1; HRMS (ESI-TOF)

m/z: [M+H]⁺Calcd for C₁₂H₁₀NO⁺184.0757; Found

184.0759.

Scholars

(202005AB160003)

and

NSF

(2019FY003010) of Yunnan Province, the DongLu

Scholar and the YunLing Scholar Programs.

References

10.1002/adsc.202001254

Advanced Synthesis & Catalysis

[1] F.-X. Felpin, J. Coste, C. Zakri, E. Fouquet, Chem. Eur.

J., 2009, 15, 7238-7245.

[6] a) C.-H. Cheng, P. Gandeepan, P. Rajamalli, Synthesis,

2016, 48, 1872-1879; b) B. Gao, G. Zhang, X. Zhou, H.

Huang, Chem. Sci., 2018, 9, 380-386; c) Z. Xu, K. Li, R.

Zhai, T. Liang, X. Gui, R. Zhang, RSC Adv., 2017, 7,

51972-51977; d) L. Zhang, L. Sonaglia, J. Stacey, M.

Lautens, Org. Lett., 2013, 15, 2128–2131.

[7] T. V. Nykaza, G. Li, J. Yang, M. R. Luzung, A. T.

Radosevich, Angew. Chem. Int. Ed., 2020, 59, 4505-

4510.

[8] a) J. Liu, W. Ye, S. Wang, J. Zheng, W. Tang, X. Li, J.

Org. Chem., 2020, 85, 4430-4440; b) Y. Park, S. Chang,

Nat. Catal., 2019, 2, 219-227; c) H. Wang, Y. Park, Z.

Bai, S. Chang, G. He, G. Chen, J. Am. Chem. Soc., 2019,

141, 7194-7201; d) Q. Xing, C. M. Chan, Y. W. Yeung,

W. Y. Yu, J. Am. Chem. Soc., 2019, 141, 3849-3853; e)

Z. Zhou, S. Chen, Y. Hong, E. Winterling, Y. Tan, M.

Hemming, K. Harms, K. N. Houk, E. Meggers, J. Am.

Chem. Soc., 2019, 141, 19048-19057.

[9] a) S. Y. Hong, Y. Park, Y. Hwang, Y. B. Kim, M.-H.

Baik, S. Chang, Science, 2018, 359, 1016–1021; b) Y.

Hwang, H. Jung, E. Lee, D. Kim, S. Chang, J. Am. Chem.

Soc., 2020, 142, 8880-8889; c) Y. Hwang, Y. Park, Y.

B. Kim, D. Kim, S. Chang, Angew. Chem. Int. Ed., 2018,

57, 13565-13569.

[2] a) R. Bergmann, R. Gericke, J. Med. Chem., 1990, 33,

492-504; b) J. J.-W. Duan, L. Chen, Z. R. Wasserman,

Z. Lu, R.-Q. Liu, M. B. Covington, M. Qian, K. D.

Hardman, R. L. Magolda, R. C. Newton, D. D. Christ,

R. R. Wexler, C. P. Decicco, J. Med. Chem., 2002, 45,

4954-4957; c) R. H. Feling, G. O. Buchanan, T. J.

Mincer, C. A. Kauffman, P. R. Jensen, W. Fenical,

Angew. Chem. Int. Ed., 2003, 42(3), 355-357; d) A.

Millemaggi, R. J. K. Taylor, Eur. J. Org. Chem., 2010,

4527-4547; e) V. V. Vintonyak, K. Warburg, H. Kruse,

S. Grimme, K. Hübel, D. Rauh, H. Waldmann, Angew.

Chem. Int. Ed., 2010, 49, 5902-5905.

[3] P. Gandeepan, P. Rajamalli, C.-H. Cheng, Synthesis,

2016, 48, 1872-1879.

[4] a) B. Egle, J. Muñoz, N. Alonso, W. De Borggraeve, A.

de la Hoz, A. Díaz-Ortiz, J. Alcázar, J. Flow Chem.,

2015, 4, 22-25; b) Y. Motoyama, K. Kamo, H.

Nagashima, Org. Lett., 2009, 11, 1345-1348; c) L. Yang,

L. Shi, Q. Xing, K. W. Huang, C. Xia, F. Li, ACS Catal.,

2018, 8, 10340-10348; d) T. Yoshino, S. Matsunaga,

Adv. Synth. Catal., 2017, 359, 1245-1262; e) W. H. Li,

C. Li, L. Dong, Asian J. Org. Chem., 2018, 7, 2448-2451;

f) C. Rajitha, P. K. Dubey, V. Sunku, V. R. Veeramaneni, [10] a) J. Lee, J. Lee, H. Jung, D. Kim, J. Park, S. Chang, J.

M. Pal, J. Heterocyclic Chem., 2013, 50, 630-637. g) S.-

B. Wang, Q. Gu, S.-L. You, Organometallics, 2017, 36,

4359-4362.

Am. Chem. Soc., 2020, 142, 12324-12332; b) V.

Lyaskovskyy, A. I. Suarez, H. Lu, H. Jiang, X. P. Zhang,

B. de Bruin, J. Am. Chem. Soc., 2011, 133, 12264-12273;

c) O. Villanueva, N. M. Weldy, S. B. Blakey, C. E.

MacBeth, Chem. Sci., 2015, 6, 6672-6675. d) S.-B.

Wang, Q. Gu, S.-L. You, J. Catal., 2018, 361, 393-397.

[11] A. Ganguly, J.-F Zhu, T. L. Kelly, J. Phys. Chem. C,

2017, 121, 9110−9119.

[5] a) B. Lu, D. Ma, Org. Lett., 2006, 8, 6115-6118; b) F.

Monnier, M. Taillefer, Angew. Chem. Int. Ed., 2009, 48,

6954-6971; c) C. Sambiagio, S. P. Marsden, A. J.

Blacker, P. C. McGowan, Chem. Soc. Rev, 2014, 43,

3525-3550.

10.1002/adsc.202001254

Advanced Synthesis & Catalysis

FULL PAPER

Room Temperature Benzofused Lactam

Synthesis Enabled by Cobalt(III)-Catalyzed

C(sp²)−H Amidation

Adv. Synth. Catal. 2020, 362, Page – Page

Xun Tian, Xin Li, Shengzu Duan, Ya Du, Tongqi

Liu, Yongsheng Fang, Wen Chen, Hongbin Zhang,

Minyan Li* and Xiaodong Yang*

Article Doi

Room Temperature Benzofused Lactam Synthesis Enabled by Cobalt(III)-Catalyzed C(sp2)?H Amidation

DOI: 10.1002/adsc.202001254

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Article abstract of DOI:10.1002/adsc.202001254

Full text of DOI:10.1002/adsc.202001254

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