Room-Temperature Pd-Catalyzed C-H Chlorination by Weak ...

Room-Temperature Pd-Catalyzed C-H Chlorination by

Weak Coordination: One-Pot Synthesis of 2-Chlorophenols

with Excellent Regioselectivity

Xiuyun Sun ‡, Yonghui Sun ‡, Chao Zhang, and Yu Rao*

Department of Pharmacology and Pharmaceutical Sciences, School of life

sciences and School of Medicine, Tsinghua University, Beijing 100084, China

[email protected]

SUPPORTING INFORMATION

Table of Contents Page

Materials and Methods S1

General procedure for synthesis of carbamates S1

General procedure for palladium-catalyzed the synthesis of

Ortho-halogenated carbamates

S1

Preliminary mechanism study S2

References S4

Data of products S4

Electronic Supplementary Material (ESI) for Chemical CommunicationsThis journal is © The Royal Society of Chemistry 2014

mailto:[email protected]

S2

Materials and Methods

All commercial materials (Alfa Aesar, Aladdin, J&K Chemical LTD.) were used

without further purification. All solvents were analytical grade. The 1H-NMR and

13C-

NMR spectra were recorded on a Bruker 400 MHz spectrometer in CDCl3 using TMS

or solvent peak as a standard. All 13

C-NMR spectra were recorded with complete

proton decoupling. Low-resolution mass spectral analyses were performed with a

Waters AQUITY UPLCTM

/MS. All reactions were carried out in oven-dried sealed

tube. Analytical TLC was performed on Yantai Chemical Industry Research Institute

silica gel 60 F254 plates and flash column chromatography was performed on

Qingdao Haiyang Chemical Co. Ltd silica gel 60 (200-300 mesh). The rotavapor was

BUCHI’s Rotavapor R-3. Benzoates were commercially available or easily

synthesized from benzoic acid.

General procedure

I Synthesis of carbamates[1]

A mixture of the phenol (1.0 equivl) and Me2NCOCl (1.2 equiv) and K2CO3 (1.5

equiv) in MeCN was refluxed for 2h. The reaction mixture was cooled to room

temperature and concentrated under a vacuum. The residue was dissolved in H2O and

extracted with dichloroethane. The organic fractions were combined and then washed

successively with 1 M KOH and water. Finally the organic layer was separated, dried

over anhydrous Na2SO4, and concentrated under a vacuum to yield the corresponding

carbamates.

II Synthesis of halogenated carbamates

Substituted carbamates (1.0 equiv), NCS or NBS (1.1 equiv), Pd(OAc)2 (0.05 – 0.10

equiv) and oxidant (1.2 equiv) were dissolved in commercial dichloroethane in a 15

mL sealed tube. Following that, TfOH (0.5~3.0 equiv) was added into the reaction

solution. Then the reaction mixture was stirred at room temperature for 3-24 h. The

reaction was monitored by TLC and LC-MS. After completion of the reaction, the

mixture was cooled to room temperature and then saturated NaHCO3 was added to

quench the reaction. The reaction mixture was diluted with dichloromethane and

washed once with saturated aqueous NaHCO3. Then organic layer was dried over

Na2SO4 and concentrated on rotavapor under reduced pressure. Finally the residue

was purified by silical gel column chromatography to give corresponding halogenated

products.

In some cases, NCS or NBS was 1.0 equiv and starting material was from 1.5 equiv to

2.0 equiv. For this reaction, the cooxidant could drive the reaction faster generally,

but in some cases, the yields were higher than the conditions without cooxidants.

III Intermolecular Competition Experiments


S3

To two separated sealed tubes, following the general procedure I, phenyl

dimethylcarbamate (33 mg, 0.20 mmol) or 3-fluorophenyl dimethylcarbamate (37 mg,

0.20 mmol), Pd(OAc)2 (2.3 mg, 0.010 mmol), NCS (30 mg, 0.22 mmol), Na2S2O8 (57

mg, 0.22 mmol), TfOH (1.8 equiv, 32 uL) and DCE was added. The mixture was

stirred at room temperature. After 10min, two reactions were quenched and added

4-nitrobenzaldyhyde as internal standard. Then, the mixture was washed once with

saturated aqueous NaHCO3 and extracted with dichloromethane and concentrated on

rotavapor under reduced pressure. The conversion ratio was determined by crude 1H-NMR. The ratio of (2a) to (5a) was 2.13.

IV Procedure for preliminary mechanistic study

1. Preparation of 2-deuterio phenyl dimethylcarbamate[2,3,4]

.

In an oven-dried 100-mL round-bottomed flask, a solution of 2-bromophenol (1g,

5.78 mmol) and Et2O (15 mL) were cooled to 0 °C. After 5 min, t-BuLi (1.6 M, 8 mL,

12.7 mmol) was added dropwise over 10 min. The mixture was stirred for 3.5 h at

0 °C. Then, D2O (500 mg, 24.9 mmol) was added via syringe. The mixture was then

warmed to room temperature slowly overnight. The cloudy, white mixture was diluted

with H2O (20 mL). The layers were separated. The organic layer was washed with

H2O (20 mL x 3), dried (Na2SO4), filtered and concentrated.

Following the general procedure I, the above compounds without further purification

(5.78 mmol, 1.0 equiv), K2CO3 (1.2 g, 8.68 mmol), dimethylcarbamoyl chloride (6.4

mL, 6.94 mmol) and MeCN (15 mL) was added. The reaction mixture was refluxed

for 4h. After completion of the reaction, the residue was purified by silical gel column

chromatography (Petrom ether: Ethyl acetate = 10:1). Finally, compound 5b (670 mg)

was isolated in 70% yield.

2. Intramolecular experiments

Following the general procedure I, to a 15 mL sealed tube, 2-deuterio phenyl

dimethylcarbamate (33 mg, 0.20 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol), NCS (30 mg,

0.22 mmol) and TfOH (1.5 equiv, 27 uL) were added and dissolved in 1.0 mL DCE.

The mixture was stirred at room temperature for 10min. Then the mixture was

quenched, washed once with saturated aqueous NaHCO3, extracted by

dichloromethane and concentrated on rotavapor under reduced pressure. The

conversion ratio was determined by crude 1H-NMR.

1H-NMR showed kH/kD = 3.00.


S4

V Gram Scale Reactions

1. 2-Chloro-5-methylphenyl dimethylcarbamate 10

To a 50 mL round bottom flask, following the general procedure II, m-tolyl

dimethylcarbamate (1.15 g, 6.42 mmol), NCS (0.90 g, 6.74 mmol), Pd(OAc)2 (15 mg,

1% mmol) and TfOH (1.0 equiv, 570 uL) were used. The reaction mixture was stirred

at room temperature for 8h. After completion of the reaction, the residue was purified

by silical gel column chromatography (Petroleum ether: Ethyl acetate = 6:1). Finally,

compound 10 (1.03 g) was isolated in 75% yield.

2. 2-Chloro-6-methylphenyl dimethylcarbamate 2

To a 100 mL round bottom flask, following the general procedure II, o-tolyl

dimethylcarbamate (2.00 g, 11.17 mmol), NCS (1.57 g, 11.7 mmol), Pd(OAc)2 (25

mg, 1% mmol) and TfOH (1.05 equiv, 1.08 mL) were used. The reaction mixture was

stirred at room temperature for 8h. After completion of the reaction, the residue was

purified by silical gel column chromatography (Petroleum ether: Ethyl acetate = 6:1).

Finally, compound 2 (1.14 g) was isolated in 48% yield. Starting material remained

43%. The yield based on recovered materials was 84%.

VI Deprotection of products in one pot.

After the completion of the first step, DCE was removed by rotavapor under reduced

pressure directly. Then hydrazine hydride (1.0 mL) was added to the mixture as

solvent and stirred at room temperature or 60oC until the reaction finished. When the

deprotection was finished, the mixture was acidified by conc. HCl, washed by water

and extracted by dichloromethane. Then organic layer was dried over Na2SO4 and

concentrated on rotavapor under reduced pressure. Finally the residue was purified by

silical gel column chromatography to give corresponding deprotected products.

References

1. Alex, J.; Kenneth, M. N. J. Org. Chem. 2012, 77, 5600

2. John, J. T.; Irene, Q. E.; J. Org. Chem. 1984, 49(26), 5267

3. Cong, Y. W.; Isabel, P.; Frank, G. J. Am. Chem. Soc. 2009, 131, 4194

4. Danielle, M. S.; Srimoyee, D.; Mary, P. W. Org. Lett. 2011, 13(13), 3490

Date of products

2-Chloro-6-methylphenyl dimethylcarbamate 2

Following the general procedure II, o-tolyl dimethylcarbamate (36 mg, 0.20 mmol),

NCS (30 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol), Na2S2O8(57 mg, 0.24

mmol) and TfOH (1.5 equiv, 27 uL) were used. The reaction mixture was stirred at

room temperature for 11h. After completion of the reaction, the residue was purified

by silical gel column chromatography (Petrom ether: Ethyl acetate = 9:1). Finally,

compound 2 (32 mg) was isolated in 75% yield. 1H NMR (400 MHz, CDCl3) δ (ppm)


S5

7.25 (d, J = 8.76 Hz, 1H), 7.11 (d, J = 7.44 Hz, 1H), 7.04 (t, J = 7.72 Hz, 1H), 3.17 (s,

3H), 3.04 (s, 3H), 2.24 (s, 3H); 13

C NMR (100 MHz, CDCl3) δ (ppm) 153.6, 146.5,

133.5, 129.4, 127.8, 127.7, 126.3, 37.1, 36.7, 16.7; LRMS (ESI) calcd for

C10H13ClNO2 [M+H]+: 214.06, found 214.14

2-chlorophenyl dimethylcarbamate 3

Following the general procedure II, phenyl dimethylcarbamate (33 mg, 0.20 mmol),

NCS (30 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol) and TfOH (1.5 equiv, 27

uL) were used. The reaction mixture was stirred at room temperature for 11h. After

completion of the reaction, the residue was purified by silical gel column

chromatography (Petrom ether: Ethyl acetate = 8:1). Finally, compound 3 (30 mg)

was isolated in 75% yield. 1H NMR (400 MHz, CDCl3) δ (ppm) 7.39 (d, J = 7.96 Hz,

1H), 7.24-7.14 (m, 2H), 7.14 (t, J = 7.72 Hz, 1H), 3.13 (s, 3H), 3.01 (s, 3H); 13

C NMR

(100 MHz, CDCl3) δ (ppm) 154.0, 147.8, 130.2, 127.7, 127.2, 126.5, 124.3, 37.0, 36.7;

LRMS (ESI) calcd for C9H11ClNO2 [M+H]+: 200.05, found 200.14

2,6-Dichlorophenyl dimethylcarbamate 4

Following the general procedure II, 2-chlorophenyl dimethylcarbamate (40 mg, 0.20

mmol), NCS (30 mg, 0.22 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol) and TfOH (2.0

equiv, 36 uL) were used. The reaction mixture was stirred at room temperature for

10h. After completion of the reaction, the residue was purified by silical gel column



2H), 7.09 (t, J = 8.20 Hz, 1H), 3.18 (s, 3H), 3.05 (s, 3H); 13

C NMR (100 MHz, CDCl3)

δ (ppm) 152.7, 144.8, 129.7, 128.6, 126.8, 37.2, 36.8; LRMS (ESI) calcd for

C9H10ClNO2 [M+H]+: 234.01, found 234.05

2-Bromo-6-chlorophenyl dimethylcarbamate 5

Following the general procedure II, 2-bromophenyl dimethylcarbamate (49 mg, 0.20


equiv, 32 uL) were used. The reaction mixture was stirred at room temperature for

14h. After completion of the reaction, the residue was purified by silical gel column


was isolated in 72% yield.

Following the general procedure I, 2-chlorophenyl dimethylcarbamate (40 mg, 0.20


S6

mmol), NBS (35 mg, 0.20 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol) and TfOH (2.5

equiv, 45 uL) were used. The reaction mixture was stirred at room temperature for 6h.

After completion of the reaction, the residue was purified by silical gel column


was isolated in 75% yield. 1H NMR (400 MHz, CDCl3) δ (ppm) 7.49 (d, J = 8.08 Hz, 1H), 7.38 (d, J = 8.04 Hz,

1H), 7.03 (t, J = 8.00 Hz, 1H), 3.19 (s, 3H), 3.05 (s, 3H); 13


δ (ppm) 152.6, 145.8, 131.6, 129.5, 129.4, 127.3, 118.8, 37.2, 36.8; LRMS (ESI)

calcd for C9H10BrClNO2 [M+H]+: 277.96, found 278.05; HRMS (ESI) calcd for

C9H10BrClNO2 [M+H]+: 277.9578, found 277.9589

2-Chloro-5-methoxyphenyl dimethylcarbamate 6

Following the general procedure II, 3-methoxyphenyl dimethylcarbamate (39 mg,

0.20 mmol), NCS (30 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol) and TfOH (1.2





1H), 6.78 (d, J = 2.72 Hz, 1H), 6.71 (dd, J1 = 2.76 Hz, J2 = 8.84 Hz, 1H), 3.78 (s, 3H),

3.14 (s, 3H), 3.03 (s, 3H); 13

C NMR (100 MHz, CDCl3) δ (ppm) 159.0, 153.9, 130.1,

118.5, 112.8, 109.9, 55.8, 37.0, 36.7; LRMS (ESI) calcd for C10H13ClNO3 [M+H]+:

230.06, found 230.12; HRMS (ESI) calcd for C10H13ClNO3 [M+H]+: 230.0578, found

230.0590

2-Chloro-5-fluorophenyl dimethylcarbamate 7

Following the general procedure II, 3-fluorophenyl dimethylcarbamate (37 mg, 0.20

mmol), NCS (30 mg, 0.25 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol), Na2S2O8(57 mg,

0.24 mmol) and TfOH (2.5 equiv, 44 uL) were used. The reaction mixture was stirred

at room temperature for 12h. After completion of the reaction, the residue was

purified by silical gel column chromatography (Petrom ether: Ethyl acetate = 8:1).

Finally, compound 7 (23 mg) was isolated in 52% yield. 1H NMR (400 MHz, CDCl3)

δ (ppm) 7.36 (dd, J1 = 5.72 Hz, J2 = 8.80 Hz, 1H), 7.02 (dd, J1 = 2.68 Hz, J2 = 8.88

Hz, 1H), 6.90 (t*d, J1 = 2.72 Hz, J2 = 8.12 Hz, 1H), 3.14 (s, 3H), 3.03 (s, 3H); 19

F-NMR (400 MHz, CDCl3) -112.99 (s, 1F); 13

C-NMR (100 MHz, CDCl3) δ (ppm)

161.3 (d, JC-F = 246 Hz, 1C), 153.4, 148.4 (d, JC-F = 11 Hz, 1C), 130.5 (d, JC-F = 9 Hz,


S7

1C), 122.5 (d, JC-F = 4 Hz, 1C), 113.6 (d, JC-F = 22 Hz, 1C), 112.3 (d, JC-F = 25 Hz,

1C), 37.0, 36.7; LRMS (ESI) calcd for C9H10ClFNO2 [M+H]+: 218.04, found 218.10

5-Bromo-2-chlorophenyl dimethylcarbamate 8


mmol), NCS (30 mg, 0.22 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol) and TfOH

(1.85equiv, 27 uL) were used. The reaction mixture was stirred at room temperature

for 13h. After completion of the reaction, the residue was purified by silical gel

column chromatography (Petrom ether: Ethyl acetate = 8:1). Finally, compound 8 (38

mg) was isolated in 69% yield. 1H NMR (400 MHz, CDCl3) δ (ppm) 7.40 (s, 1H),

7.27 (s, 2H), 3.13 (s, 3H), 3.02 (s, 3H); 13

C NMR (100 MHz, CDCl3) δ (ppm) 153.4,


C9H10BrClNO2 [M+H]+: 277.96, found 278.01

2-Chloro-5-iodophenyl dimethylcarbamate 9

Following the general procedure II, 3-iodophenyl dimethylcarbamate (58 mg, 0.20






δ (ppm) 7.56 (d, J = 1.36 Hz, 1H), 7.46 (d, J = 8.40 Hz, 1H), 7.12 (d, J = 8.44 Hz, 1H),

3.12 (s, 3H), 3.02 (s, 3H); 13


133.3, 131.4, 127.6, 90.7, 37.0, 36.7; LRMS (ESI) calcd for C9H10ClINO2 [M+H]+:

325.94, found 326.04


Following the general procedure II, m-tolyl dimethylcarbamate (36 mg, 0.20 mmol),

NCS (30 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol), Na2S2O8(57 mg, 0.24


room temperature for 6h. After completion of the reaction, the residue was purified by

silical gel column chromatography (Petrom ether: Ethyl acetate = 9:1). Finally,


S8


7.27 (d, J = 8.32 Hz, 1H), 7.02 (s, 1H), 6.95 (d, J = 8.08 Hz, 1H), 3.14 (s, 3H), 3.02 (s,

3H), 2.32 (s, 3H); 13

C NMR (100 MHz, CDCl3) δ (ppm) 154.1, 147.4, 138.0, 129.7,

124.8, 124.0, 36.9, 36.6, 21.0; LRMS (ESI) calcd for C10H13ClNO2 [M+H]+: 214.06,

found 214.16

2,5-Dichlorophenyl dimethylcarbamate 11

Following the general procedure II, 3-chlorophenyl dimethylcarbamate (40 mg, 0.20






1H), 7.19 (s, 1H), 7.06 (d, J = 8.56 Hz, 1H), 3.06 (s, 3H), 2.96 (s, 3H); 13

C NMR (100

MHz, CDCl3) δ (ppm) 153.4, 148.2, 132.9, 130.7, 126.7, 125.8, 124.8, 37.0, 36.7;

LRMS (ESI) calcd for C9H10Cl2NO2 [M+H]+: 234.01, found 234.08

Methyl 4-chloro-3-((dimethylcarbamoyl)oxy)benzoate 12

Following the general procedure II, methyl 3-((dimethylcarbamoyl)oxy)benzoate (45

mg, 0.20 mmol), NCS (30 mg, 0.22 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol) and TfOH

(2.5 equiv, 45 uL) were used. The reaction mixture was stirred at room temperature



was isolated in 56% yield. 1H NMR (400 MHz, CDCl3) δ (ppm) 7.88 (s, 1H), 7.83 (d,

J = 8.36 Hz, 1H), 7.48 (d, J = 8.32 Hz), 3.90 (s, 3H), 3.16 (s, 3H), 3.04 (s, 3H); 13

C

NMR (100 MHz, CDCl3) δ (ppm) 165.8, 153.6, 147.8, 132.6, 130.2, 130.0, 127.6,

125.5, 52.5, 37.1, 36.7; LRMS (ESI) calcd for C11H13ClNO4 [M+H]+: 258.05, found

258.14; HRMS (ESI) calcd for C11H13ClNO4 [M+H]+: 258.0528, found 258.0540

2-Chloro-5-(trifluoromethyl)phenyl dimethylcarbamate 13

Following the general procedure II, 3-(trifluoromethyl)phenyl dimethylcarbamate (47

mg, 0.20 mmol), NCS (30 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol) and TfOH


S9





1H), 7.52 (s, 1H), 7.41 (d, J = 7.80 Hz), 3.16 (s, 3H), 3.04 (s, 3H); 19

F-NMR (400

MHz, CDCl3) -62.60 (s, 3F); 13


130.9 (q, JC-F = 88 Hz, 1C), 130.0 (q, JC-F = 40 Hz, 1C), 130.8, 123.4 (q, JC-F = 271

Hz, 1C), 123.3 (q, JC-F = 4 Hz, 1C), 121.7 (q, JC-F = 4 Hz, 1C), 37.1, 36.7; LRMS (ESI)

calcd for C10H10ClF3NO2 [M+H]+: 268.03, found 268.11; HRMS (ESI) calcd for

C10H10ClF3NO2 [M+H]+: 268.0347, found 268.0360


Following the general procedure II, p-tolyl dimethylcarbamate (36 mg, 0.20 mmol),





was isolated in 73% yield. 1H NMR (400 MHz, CDCl3) δ (ppm) 7.22 (s, 1H), 7.08 (d,

J = 8.00 Hz, 1H), 7.04 (d, J = 8.28 Hz), 3.14 (s, 3H), 3.02 (s, 3H), 2.31 (s, 3H); 13

C

NMR (100 MHz, CDCl3) δ (ppm) 154.2, 145.5, 136.6, 130.5, 128.3, 126.6, 123.8,

37.0, 36.6, 20.8; LRMS (ESI) calcd for C10H13ClNO2 [M+H]+: 214.06, found 214.14

2-Chloro-4-fluorophenyl dimethylcarbamate 15

Following the general procedure II, 4-fluorophenyl dimethylcarbamate (37 mg, 0.20

mmol), NCS (30 mg, 0.25 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol), N-Fluoropyridium

trifluorormethylsulfonate (66 mg, 0.24 mmol) and TfOH (2.0 equiv, 36 uL) were used.

The reaction mixture was stirred at room temperature for 5h. After completion of the

reaction, the residue was purified by silical gel column chromatography (Petrom ether:

Ethyl acetate = 8:1). Finally, compound 15 (31 mg) was isolated in 77% yield. 1H

NMR (400 MHz, CDCl3) δ (ppm) 7.19-7.14 (m, 2H), 6.99-6.95 (m, 1H), 3.14 (s, 3H),

3.02 (s, 3H); 19

F-NMR (400 MHz, CDCl3) -115.34 (s, 1F); 13

C-NMR (100 MHz,

CDCl3) δ (ppm) 159.7 (d, JC-F = 246 Hz, 1C), 153.9, 144.1 (d, JC-F = 3 Hz, 1C), 128.0

(d, JC-F = 11 Hz, 1C), 125.0 (d, JC-F = 9 Hz, 1C), 117.3 (d, JC-F = 26 Hz, 1C), 114.6 (d,

JC-F = 22 Hz, 1C), 37.0, 36.6; LRMS (ESI) calcd for C9H10ClFNO2 [M+H]+: 218.04,

found 218.10; HRMS (ESI) calcd for C9H10ClFNO2 [M+H]+: 218.0379, found

218.0391;


S10

Methyl 3-chloro-4-((dimethylcarbamoyl)oxy)benzoate 16


mg, 0.20 mmol), NCS (30 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol),

Na2S2O8(57 mg, 0.24 mmol) and TfOH (2.0 equiv, 35 uL) were used. The reaction

mixture was stirred at room temperature for 6h. After completion of the reaction, the

residue was purified by silical gel column chromatography (Petrom ether: Ethyl

acetate = 9:1). Finally, compound 16 (33 mg) was isolated in 63% yield. 1H NMR

(400 MHz, CDCl3) δ (ppm) 8.10 (d, J = 1.96 Hz, 1H), 7.93 (dd, J1 = 2.04 Hz, J2 =

8.48 Hz, 1H), 7.31 (d, J = 8.48 Hz, 1H), 3.90 (s, 3H), 3.15 (s, 3H), 3.02 (s, 3H); 13

C

NMR (100 MHz, CDCl3) δ (ppm) 165.6, 153.2, 151.5, 131.6, 129.2, 128.5, 127.4,

124.1, 52.5, 37.0, 36.7; LRMS (ESI) calcd for C11H13ClNO4 [M+H]+: 258.05, found

258.14

4-(Tert-butyl)-2-chlorophenyl dimethylcarbamate 17

Following the general procedure II, 4-(tert-butyl)phenyl dimethylcarbamate (45 mg,

0.20 mmol), NCS (30 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol), Na2S2O8(57

mg, 0.24 mmol) and TfOH (1.0 equiv, 18 uL) were used. The reaction mixture was




δ (ppm) 7.40 (d, J = 2.20 Hz, 1H), 7.25 (dd, J1 = 2.24 Hz, J2 = 8.48 Hz, 1H), 7.12 (d,

J = 8.52 Hz, 1H), 3.14 (s, 3H), 3.02 (s, 3H), 1.30 (s, 9H); 13


δ (ppm) 154.2, 149.9, 145.3, 127.2, 126.4, 124.8, 123.5, 36.9, 36.6, 31.4; LRMS (ESI)

calcd for C13H19ClNO2 [M+H]+: 256.11, found 256.20

3-Chloro-[1,1'-biphenyl]-4-yl dimethylcarbamate 18

Following the general procedure II, [1,1'-biphenyl]-4-yl dimethylcarbamate (73 mg,

0.30 mmol), NCS (27 mg, 0.20 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol) and TfOH (1.8





1H), 7.53 (d, J = 8.76 Hz, 2H), 7.47-7.41 (m, 3H), 7.35 (t, J = 7.02 Hz, 1H), 7.28 (d, J


S11

= 8.40 Hz, 1H), 3.17 (s, 3H), 3.05 (s, 3H); 13

C NMR (100 MHz, CDCl3) δ (ppm)

154.0, 147.1, 140.3, 139.5, 129.0, 128.8, 127.9, 127.2, 126.4, 124.4, 37.0, 36.7;

LRMS (ESI) calcd for C15H15ClNO2 [M+H]+: 276.08, found 276.16

2-Chloro-4,5-dimethylphenyl dimethylcarbamate 19

Following the general procedure II, 3,4-dimethylphenyl dimethylcarbamate (39 mg,

0.20 mmol), NCS (30 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol), Na2S2O8(57





δ (ppm) 7.16 (s, 1H), 6.97 (s, 1H), 3.13 (s, 3H), 3.02 (s, 3H), 2.21 (s, 6H); 13

C NMR

(100 MHz, CDCl3) δ (ppm) 154.3, 145.3, 136.4, 135.2, 130.7, 125.0, 123.6, 37.0, 36.6,

19.5, 19.2; LRMS (ESI) calcd for C11H15ClNO2 [M+H]+: 228.08, found 228.14

3-Chloronaphthalen-2-yl dimethylcarbamate 20

Following the general procedure II, naphthalen-2-yl dimethylcarbamate (43 mg, 0.20



at room temperature for 4.5h. After completion of the reaction, the residue was


Finally, compound 20 12 mg) was isolated in 51% yield. 1H NMR (400 MHz, CDCl3)

δ (ppm) 7.87-7.84 (m, 3H), 7.80 (s, 1H), 7.53-7.45 (m, 2H), 2.78 (s, 3H), 2.67 (s, 3H); 13

C NMR (100 MHz, CDCl3) δ (ppm) 154.3, 147.4, 133.5, 131.0, 130.8, 130.5, 127.8,

127.5, 126.4, 125.6, 119.2, 36.6, 36.1; LRMS (ESI) calcd for C13H13ClNO2 [M+H]+:

250.06, found 250.12

8-Chloronaphthalen-1-yl dimethylcarbamate 21






S12



1H), 7.95 (d, J = 8.12 Hz, 1H), 7.64-7.54 (m, 3H), 7.22 (d, J = 8.12 Hz, 1H), 3.27 (s,

3H), 3.08 (s, 3H); 13


128.6, 127.5, 127.1, 125.8, 125.0, 121.9, 118.4, 37.1, 36.8; LRMS (ESI) calcd for

C13H13ClNO2 [M+H]+: 250.06, found 250.15

6-Chlorobenzo[d][1,3]dioxol-5-yl dimethylcarbamate 22

Following the general procedure II, benzo[d][1,3]dioxol-5-yl dimethylcarbamate (42

mg, 0.20 mmol), NCS (30 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol),

Na2S2O8(57 mg, 0.24 mmol) and TfOH (0.8 equiv, 14 uL) were used. The reaction

mixture was stirred at room temperature for 20h. After completion of the reaction, the



(400 MHz, CDCl3) δ (ppm) 6.85 (s, 1H), 6.71 (s, 1H), 5.98 (s, 2H), 3.12 (s, 3H), 3.01

(s, 3H); 13

C NMR (100 MHz, CDCl3) δ (ppm) 154.1, 146.8, 145.6, 141.9, 118.8,

109.3, 105.5, 102.3, 37.0, 36.6; LRMS (ESI) calcd for C10H11ClNO4 [M+H]+: 244.04,

found 244.12; HRMS (ESI) calcd for C10H11ClNO4 [M+H]+: 244.0371, found

244.0385

(8R,9S,13S,14S)-2-chloro-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclope

nta[a]phenanthren-3-yl dimethylcarbamate 23

Following the general procedure II, estrone dimethylcarbamate (68 mg, 0.20 mmol),




chromatography (Toluene: Ethyl acetate = 6:1). Finally, compound 23 (35 mg) was

isolated in 47% yield. 1H NMR (400 MHz, CDCl3) δ (ppm) 7.30 (s, 1H), 6.92 (s, 1H),

3.13 (s, 3H), 3.02 (s, 3H), 2.88-2.85 (m, 1H), 2.54-2.47 (m, 1H), 2.36-2.32 (m, 1H),

2.28-1.94 (m, 6H), 1.65-1.39 (m, 7H), 0.90-0.87 (m, 4H); 13

C-NMR (100 MHz,

CDCl3) δ (ppm) 154.3, 145.4, 138.6, 136.5, 127.1, 124.1, 124.0, 50.5, 48.0, 44.1, 37.8,

37.0, 36.6, 36.0, 31.6, 29.0, 26.3, 25.8, 21.7, 13.9; LRMS (ESI) calcd for

C21H27ClNO3 [M+H]+: 376.17, found 376.29; HRMS (ESI) calcd for C21H27ClNO3

[M+H]+: 376.1674, found 376.1694


S13

2-Bromo-4-methylphenyl dimethylcarbamate 24

Following the general procedure II, p-tolyl dimethylcarbamate (36 mg, 0.20 mmol),

NBS (40 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol) and TfOH (1.5 equiv, 27




was isolated in 71% yield. Without cooxidant 65%. 1H NMR (400 MHz, CDCl3) δ

(ppm) 7.39 (s, 1H), 7.08 (s, 2H), 3.15 (s, 3H), 3.02 (s, 3H), 2.31 (s, 3H); 13

C NMR

(100 MHz, CDCl3) δ (ppm) 154.1, 146.6, 136.9, 133.5, 129.1, 123.8, 116.0, 37.0, 36.7,

20.7; LRMS (ESI) calcd for C10H13BrNO2 [M+H]+: 258.01, found 258.08


Following the general procedure II, o-tolyl dimethylcarbamate (36 mg, 0.20 mmol),

NBS (39 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol), Na2S2O8 (57 mg, 0.24


room temperature for 20h. After completion of the reaction, the residue was purified

by silical gel column chromatography (Petrom ether: Ethyl acetate = 9:1). Finally,


7.40 (d, J = 7.92 Hz, 1H), 7.15 (d, J = 7.52 Hz, 1H), 6.98 (t, J = 7.76 Hz, 1H), 3.18 (s,

3H), 3.04 (s, 3H), 2.25 (s, 3H); 13



C10H13BrNO2 [M+H]+: 258.01, found 258.13; HRMS (ESI) calcd for C10H13BrNO2

[M+H]+: 258.0124, found 258.0139


Following the general procedure II, m-tolyl dimethylcarbamate (36 mg, 0.20 mmol),

NBS (39 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol), Na2S2O8(57 mg, 0.24


room temperature for 4h. After completion of the reaction, the residue was purified by

silical gel column chromatography (Petrom ether: Ethyl acetate = 9:1). Finally,



S14

7.43 (d, J = 8.16 Hz, 1H), 7.03 (s, 1H), 6.89 (d, J = 8.12 Hz, 1H), 3.15 (s, 3H), 3.03 (s,

3H), 2.31 (s, 3H); 13


127.7, 124.9, 113.0, 37.0, 36.7, 21.1; LRMS (ESI) calcd for C10H13BrNO2 [M+H]+:

258.01, found 258.12

2-Bromo-4-(tert-butyl)phenyl dimethylcarbamate 27

Following the general procedure II, 4-(tert-butyl)phenyl dimethylcarbamate (45 mg,

0.20 mmol), NBS (40 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol), Na2S2O8(57





δ (ppm) 7.56 (s, 1H), 7.31 (d, J = 8.48 Hz, 1H), 7.12 (d, J = 8.48 Hz, 1H), 3.15 (s, 3H),

3.03 (s, 3H), 1.30 (s, 9H); 13



C13H19BrNO2 [M+H]+: 300.06, found 300.18

1-Bromonaphthalen-2-yl dimethylcarbamate 28


mmol), NBS (40 mg, 0.22 mmol), Pd(OAc)2 (2.3 mg, 0.01 mmol), Na2S2O8 (57 mg,





δ (ppm) 8.24 (d, J = 8.48 Hz, 1H), 7.81 (t, J = 7.20 Hz, 2H), 7.56 (t, J = 7.32 Hz, 1H),

7.48 (t, J = 7.48 Hz, 1H), 7.35 (d, J = 8.80 Hz, 1H), 3.22 (s, 3H), 3.05 (s, 3H); 13

C

NMR (100 MHz, CDCl3) δ (ppm) 154.1, 147.1, 132.8, 132.4, 128.6, 128.3, 127.7,


294.01, found 294.05; HRMS (ESI) calcd for C13H13BrNO2 [M+H]+: 294.0124, found

294.0138

2,6-Dibromophenyl dimethylcarbamate 29





S15




2H), 6.94 (d, J = 8.04 Hz, 1H), 3.17 (s, 3H), 3.03 (s, 3H); 13

C-NMR (100 MHz,

CDCl3) δ (ppm) 152.5, 146.8, 132.4, 127.8, 118.6, 37.2, 36.8; LRMS (ESI) calcd for

C9H10Br2NO2 [M+H]+: 321.91, found 322.01

Methyl 4-bromo-3-((dimethylcarbamoyl)oxy)benzoate 30


mg, 0.20 mmol), NBS (35 mg, 0.20 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol) and TfOH




was isolated in 72% yield. 1H NMR (400 MHz, CDCl3) δ (ppm) 7.86 (s, 1H), 7.74 (dd,

J1 = 8.32 Hz, J2 = 1.00 Hz, 1H), 7.64 (d, J = 8.32 Hz, 1H), 3.88 (s, 3H), 3.16 (s, 3H),

3.03 (s, 3H); 13

C-NMR (100 MHz, CDCl3) δ (ppm) 165.8, 153.5, 149.0, 133.3, 130.7,


302.00, found 302.09; HRMS (ESI) calcd for C11H13BrNO4 [M+H]+: 302.0022, found

302.0037

2,6-Dichlorophenol 31

Following the general procedure VI, 2-chlorophenyl dimethylcarbamate (40 mg, 0.20



Then DCE was removed. NH2NH2.H2O (1.0 mL) was added to the reaction mixture

and the mixture was stirred at 60oC for 2h. After completion of the reaction, the



(400 MHz, CDCl3) δ (ppm) 7.26 (d, J = 8.12 Hz, 2H), 6.82 (t, J = 8.04 Hz, 1H), 5.87

(bs, 1H); 13

C-NMR (100 MHz, CDCl3) δ (ppm) 148.0, 128.4, 121.3

2-Bromo-6-chlorophenol 32

Following the general procedure VI, 2-bromophenyl dimethylcarbamate (49 mg, 0.20



S16



and the mixture was stirred at room temperature for 12h. After completion of the

reaction, the residue was purified by silical gel column chromatography (Petrom ether:

Ethyl acetate = 30:1). Finally, compound 32 (23 mg) was isolated in 56% yield.

Following the general procedure VI, 2-chlorophenyl dimethylcarbamate (40 mg, 0.20






acetate = 30:1). Finally, compound 35 (21 mg) was isolated in 51% yield. 1

H NMR (400 MHz, CDCl3) δ (ppm) 7.40 (d, J = 8.08 Hz, 1H), 7.29 (d, J = 8.04 Hz,

1H), 6.76 (t, J = 8.04 Hz, 1H), 5.88 (bs, 1H); 13

C-NMR (100 MHz, CDCl3) δ (ppm)

148.83, 131.5, 129.1, 122.0, 121.0, 110.4; LRMS (ESI) calcd for C6H3BrClO [M-H]-:

204.91, found 204.88

2,6-Dibromophenol 33

Following the general procedure VI, 2-bromophenyl dimethylcarbamate (49 mg, 0.20







(400 MHz, CDCl3) δ (ppm) 7.44 (d, J = 8.00 Hz, 2H), 6.70 (t, J = 8.00 Hz, 1H); 13

C-NMR (100 MHz, CDCl3) δ (ppm) 149.6, 132.2, 122.6, 110.1; LRMS (ESI) calcd

for C6H3Br2O [M-H]-: 248.86, found 248.86

2-Deuterio-phenyl dimethylcarbamate 1H NMR (400 MHz, CDCl3) δ (ppm) 7.37-7.34 (m, 2H), 7.19 (t, J = 7.40 Hz, 1H),

7.11 (d, J = 8.40 Hz, 1H), 3.10 (s, 3H), 3.01 (s, 3H); 13

C NMR (100 MHz, CDCl3) δ

(ppm) 155.0, 151.6, 129.3, 129.2, 125.2, 121.8, 121.6 (JC-D = 24.5 Hz), 36.8, 36.5;

LRMS (ESI) calcd for C9H11DNO2 [M+H]+: 167.09, found 167.12


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

2.2382

3.0423

3.1742

7.0253

7.0445

7.0638

7.1013

7.1199

7.2371

7.2590

3.00

3.01

2.97

1.01

0.98

1.50

7.07.17.27.37.4 ppm7.0253

7.0445

7.0638

7.1013

7.1199

7.2371

7.2590

1.01

0.98

1.50

2


160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

16.68

36.71

37.06

76.84

77.16

77.48

126.26

127.67

127.76

129.36

133.48

146.45

153.56

2


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

3.0312

3.1544

7.1252

7.1299

7.1431

7.1450

7.1477

7.1496

7.1629

7.1676

7.2003

7.2049

7.2205

7.2251

7.2420

7.2459

7.2594

7.2637

7.2660

7.2801

7.2840

7.4006

7.4044

7.4204

7.4243

3.04

3.02

1.03

2.37

1.00

3


170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.66

36.97

76.84

77.16

77.48

124.30

126.52

127.22

127.69

130.20

147.82

153.96

3


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

1.5710

3.0531

3.1850

7.0807

7.1016

7.1214

7.2596

7.3270

7.3474

2.91

2.91

1.00

1.91

4


160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

36.79

37.18

76.84

77.16

77.48

126.79

128.66

129.70

144.81

152.71

4


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

3.0569

3.1896

7.0185

7.0387

7.0590

7.2599

7.3672

7.3708

7.3874

7.3911

7.4834

7.4870

7.5036

7.5072

3.03

3.02

1.01

0.99

1.00

5


190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.81

37.17

76.85

77.17

77.48

118.80

127.34

129.40

129.53

131.64

145.82

152.61

5


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

3.0288

3.1439

3.7753

6.6977

6.7046

6.7198

6.7267

6.7816

6.7884

7.2699

7.2921

3.02

3.04

3.04

1.07

1.00

1.22

6.66.76.86.97.07.17.27.37.4 ppm

6.698

6.705

6.720

6.727

6.782

6.788

7.270

7.292

1.070

1.000

1.224

6


200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.67

36.97

55.78

76.85

77.16

77.48

109.91

112.76

118.53

130.12

148.28

153.86

159.05

6


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

3.0295

3.1432

6.8659

6.8732

6.8854

6.8881

6.8927

6.8954

6.9076

6.9148

7.0077

7.0149

7.0300

7.0373

7.2591

7.3414

7.3556

7.3636

7.3779

3.08

3.07

1.02

1.00

1.00

7


170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

36.69

37.03

76.84

77.16

77.48

112.14

112.39

113.53

113.75

122.47

122.51

130.46

130.55

148.36

148.47

153.38

160.04

162.50

7


−200−190−180−170−160−150−140−130−120−110−100−90−80−70−60−50−40−30−20−1010 0 ppm

−112.99

7


9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

3.0245

3.1323

7.2593

7.2755

7.4027

3.22

3.23

1.99

1.00

8


170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

36.68

37.03

76.85

77.16

77.48

120.24

126.49

127.60

129.62

131.05

148.29

153.41

8


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

3.02

3.12

7.11

7.13

7.26

7.44

7.45

7.46

7.47

7.56

7.57

3.03

3.04

1.04

1.04

1.00

O N

OCl

I

9


190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.67

37.03

76.85

77.16

77.48

90.72

127.55

131.41

133.29

135.55

148.22

153.41

9


9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

2.31

73

3.02

413.

1397

6.93

966.

9598

7.02

527.

2612

7.28

20

3.16

3.01

3.04

1.03

1.00

1.16

Scale: 0.3803 ppm/cm, 152.2 Hz/cm

6.97.07.17.27.37.4 ppm

6.940

6.960

7.025

7.261

7.282

1.032

1.000

1.164

10


200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

21.37

24.92

76.84

77.16

77.48

119.73

122.34

125.55

128.60

134.25

137.95

168.35

10


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

3.03

3.14

7.12

7.13

7.15

7.15

7.26

7.26

7.27

7.33

7.35

2.97

3.19

0.99

1.57

1.00

O N

OCl

Cl

11


180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

36.68

37.04

76.84

77.16

77.48

124.77

125.80

126.70

130.69

132.90

148.19

153.41

11


10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

3.0389

3.1599

3.9006

7.2588

7.4746

7.4955

7.8208

7.8258

7.8417

7.8466

7.8869

7.8917

3.07

3.00

3.15

1.05

1.06

1.00

12


180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

36.70

37.06

52.51

76.84

77.16

77.48

125.48

127.57

130.01

130.24

132.55

147.79

153.60

165.77

12


Administrator

图章

10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

3.0429

3.1606

7.2595

7.4008

7.4021

7.4058

7.4073

7.4217

7.4230

7.4268

7.4282

7.5173

7.5222

7.5289

7.5301

7.5500

7.5511

3.07

3.04

1.00

1.99

13


180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.67

37.04

76.83

77.14

77.46

119.30

121.61

121.64

121.68

121.72

122.01

123.19

123.23

123.27

123.30

124.72

127.43

129.75

130.08

130.42

130.76

131.32

148.07

153.27

118119120121122123124125126127128129130131132133134 ppm

119.304

121.607

121.643

121.681

121.719

122.012

123.191

123.228

123.266

123.303

124.719

127.425

129.750

130.084

130.416

130.762

131.323

F3C

Cl

OCONMe2

13


−200−180−160−140−120−100−80−60−40−200 ppm

−62.61

13


9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

1.6024

2.3140

3.0200

3.1394

7.0311

7.0526

7.0663

7.0869

7.2193

7.2599

3.06

3.00

2.97

2.09

1.00

14


170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

20.80

36.63

36.96

76.84

77.16

77.48

123.82

126.63

128.33

130.52

136.59

145.45

154.19

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

20.80

36.63

36.96

76.84

77.16

77.48

123.82

126.63

128.33

130.52

136.59

145.45

154.19

14


9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

3.02

123.

1383

6.94

816.

9554

6.97

026.

9750

6.97

706.

9898

6.99

707.

1449

7.15

287.

1659

7.17

257.

1742

7.18

887.

2599

2.99

3.02

1.00

1.94


6.66.76.86.97.07.17.27.37.4 ppm

6.948

6.955

6.970

6.975

6.977

6.990

6.997

7.145

7.153

7.166

7.173

7.174

7.189

7.260

1.000

1.943

15


190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.63

37.01

76.84

77.16

77.48

114.48

114.70

117.17

117.43

124.96

125.05

127.91

128.02

144.14

144.17

153.86

158.47

160.93

15


−200−190−180−170−160−150−140−130−120−110−100−90−80−70−60−50−40−30−20−1010 0 ppm

−115.34

15


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

3.04

3.16

3.92

7.31

7.33

7.93

7.94

7.95

7.96

8.11

8.11

3.06

2.91

3.06

1.09

1.07

1.00

O N

OClMeOOC

16


190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.71

37.00

52.51

76.85

77.16

77.48

124.06

127.38

128.46

129.15

131.63

151.47

153.22

165.55

16


9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

1.29

67

3.02

173.

1386

7.10

857.

1298

7.24

467.

2503

7.25

787.

2659

7.27

157.

3971

7.40

26

9.28

3.02

3.03

1.00

1.15

1.00


7.057.107.157.207.257.307.357.407.45 ppm

7.109

7.130

7.245

7.250

7.258

7.266

7.271

7.397

7.403

0.995

1.153

1.000

17


190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

31.38

34.71

36.64

36.95

76.84

77.16

77.48

123.52

124.77

126.43

127.25

145.31

149.88

154.16

17


9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

3.04

633.

1713

7.25

327.

2676

7.28

867.

3538

7.37

217.

4120

7.43

137.

4487

7.45

287.

4690

7.47

427.

5241

7.54

297.

6251

7.63

03

3.04

3.05

1.06

1.07

3.26

2.10

1.00


7.157.207.257.307.357.407.457.507.557.607.657.707.75 ppm7.253

7.268

7.289

7.354

7.372

7.412

7.431

7.449

7.453

7.469

7.474

7.524

7.543

7.625

7.630

1.059

1.074

3.257

2.103

1.000

18


190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.72

37.04

76.85

77.17

77.48

124.42

126.44

127.23

127.88

128.81

129.02

139.52

140.03

147.08

154.01

18


9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

2.20

61

3.01

903.

1330

6.97

07

7.16

167.

2587

6.22

3.02

2.99

1.00

1.07


6.86.97.07.17.27.37.4 ppm

6.971

7.162

7.259

1.000

1.066

19


190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

19.22

19.52

36.64

36.97

76.85

77.16

77.48

123.61

125.05

130.67

135.25

136.41

145.34

154.34

19


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

2.6733

2.7798

7.2592

7.4548

7.4713

7.4916

7.5121

7.5270

7.7967

7.8442

7.8695

3.00

3.04

2.07

1.03

3.00

7.17.27.37.47.57.67.77.87.9 ppm

7.2592

7.4548

7.4713

7.4916

7.5121

7.5270

7.7967

7.8442

7.8695

2.07

1.03

3.00

20


180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

36.05

36.57

76.70

77.02

77.33

119.16

125.58

126.40

127.50

127.80

130.48

130.77

131.00

133.53

147.44

154.29

20


−1.0−0.510.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

3.0794

3.2745

7.2135

7.2338

7.2598

7.5395

7.5516

7.5600

7.5686

7.5888

7.6002

7.6186

7.6359

7.9425

7.9628

8.2515

8.2723

3.04

3.02

1.02

2.98

1.00

1.00

7.17.27.37.47.57.67.77.87.98.08.18.28.38.4 ppm

7.213

7.234

7.260

7.540

7.552

7.560

7.569

7.589

7.600

7.619

7.636

7.942

7.963

8.252

8.272

1.016

2.979

0.997

0.999

21


190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.77

37.09

76.84

77.16

77.48

118.41

121.92

124.96

125.78

127.13

127.52

128.79

131.69

146.45

21


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm3.0138

3.1222

5.9761

6.7118

6.8460

7.2630

3.03

3.13

2.14

0.98

1.00

22


180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.60

36.99

76.84

77.16

77.47

102.26

105.46

109.34

118.81

141.94

145.59

146.83

154.12

22


−1.0−0.58.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

0.8739

0.9012

1.2487

1.3897

1.4132

1.4386

1.4661

1.4806

1.4944

1.5099

1.5233

1.5566

1.5861

1.6163

1.6532

1.9443

1.9742

1.9940

2.0106

2.0317

2.0448

2.0612

2.0749

2.0926

2.1147

2.1391

2.1622

2.1856

2.2402

2.2515

2.2765

2.3184

2.3435

2.3583

2.4669

2.4881

2.5136

2.5358

2.8533

2.8654

2.8753

3.0165

3.1288

6.9223

7.2593

7.3005

3.58

2.24

7.09

5.84

1.08

1.05

2.06

3.01

2.93

1.03

1.00

3.0 2.5 2.0 1.5 1.0 0.5 ppm

0.874

0.901

1.249

1.390

1.413

1.439

1.466

1.481

1.494

1.510

1.523

1.557

1.586

1.616

1.653

1.944

1.974

1.994

2.011

2.032

2.045

2.061

2.075

2.093

2.115

2.139

2.162

2.186

2.240

2.252

2.277

2.318

2.344

2.358

2.467

2.488

2.514

2.536

2.853

2.865

2.875

3.017

3.129

3.582

2.235

7.088

5.842

1.084

1.047

2.065

3.014

2.932

23

X


Administrator

文本框

X

−10210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

13.92

21.68

25.84

26.32

28.97

29.82

31.56

35.95

36.63

36.96

37.84

44.09

48.00

50.47

76.84

77.16

77.48

124.05

124.13

127.06

136.47

138.57

145.37

154.26

23

X


Administrator

文本框

X

10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

2.3146

3.0224

3.1486

7.0835

7.2588

7.3878

3.21

3.01

3.05

2.09

1.00

24


180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

20.69

36.66

36.96

76.83

77.15

77.46

116.05

123.79

129.06

133.46

136.87

146.65

154.11

24


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

2.2487

3.0448

3.1799

6.9640

6.9835

7.0029

7.1407

7.1595

7.2596

7.3974

7.4172

3.10

3.08

3.08

1.01

1.03

1.00

25


170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

16.9427

36.7161

37.0357

76.8331

77.1512

77.4685

117.3126

126.7369

130.1014

130.6863

133.5850

147.5503

153.3950

25


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

2.31

3.03

3.15

6.88

6.88

6.90

6.90

7.03

7.26

7.42

7.44

3.07

3.00

3.06

1.02

0.99

1.00

O N

OBr

26


170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

21.07

36.70

36.98

76.85

77.16

77.48

113.00

124.92

127.76

132.70

138.83

148.63

154.03

26


−0.59.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

1.2972

3.0250

3.1491

7.1133

7.1345

7.2984

7.3196

7.5601

9.15

3.11

3.17

1.04

1.05

1.00

7.17.27.37.47.57.6 ppm

7.113

7.135

7.298

7.320

7.560

1.038

1.045

1.000

27


170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

31.39

34.66

36.66

36.95

76.84

77.16

77.47

115.94

123.50

125.53

130.17

146.48

150.15

154.07

27


10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

3.0715

3.2386

7.2602

7.3535

7.3755

7.4835

7.5024

7.5206

7.5775

7.5976

7.6152

7.8068

7.8280

7.8471

8.2465

8.2676

3.03

2.93

0.99

1.01

1.03

2.09

1.00

28


200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.80

37.03

76.84

77.16

77.48

115.23

122.72

126.20

127.05

127.73

128.27

128.65

132.37

132.81

147.13

154.07

28


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

3.06

3.19

6.95

6.97

6.99

7.26

7.53

7.55

3.01

3.02

1.00

1.98

O N

OBr

Br

29


190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

36.81

37.17

76.83

77.15

77.47

118.64

127.83

132.40

146.83

152.48

29


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm3.0426

3.1704

3.8990

7.2594

7.6471

7.6678

7.7441

7.7647

7.8745

3.00

3.00

3.15

1.04

1.07

1.00

30


−10210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

36.69

37.02

52.49

76.84

77.16

77.48

122.28

125.29

127.69

130.72

133.27

148.99

153.53

165.82

30


−1.5−1.0−0.59.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

5.8654

6.8019

6.8223

6.8424

7.2482

7.2621

7.2685

0.98

1.00

2.25

5.86.06.26.46.66.87.07.27.47.6 ppm

5.8654

6.8019

6.8223

6.8424

7.2482

7.2621

7.2685

0.98

1.00

2.25

31


200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

76.84

77.16

77.48

121.31

128.44

148.05

31


9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

1.5860

5.8788

6.7435

6.7637

6.7838

7.2579

7.2845

7.3046

7.3950

7.4152

1.01

1.01

0.97

1.00

32


190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

76.82

77.14

77.46

110.43

120.96

121.96

129.09

131.49

148.83

32


9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

5.8806

6.6847

6.7048

6.7249

7.2611

7.4364

7.4565

0.95

1.00

2.00

33


−10210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

76.84

77.16

77.48

110.15

122.62

132.22

149.59

33


10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

3.0105

3.0991

7.1012

7.1222

7.1685

7.1869

7.2054

7.2596

7.3379

7.3540

7.3702

3.02

3.09

1.05

1.00

1.98

7.057.107.157.207.257.307.357.407.45 ppm

7.1012

7.1222

7.1685

7.1869

7.2054

7.2596

7.3379

7.3540

7.3702

1.05

1.00

1.98


170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

36.54

36.78

76.84

77.16

77.48

121.35

121.59

121.85

125.25

129.21

129.31

151.59

155.05

120122124126128 ppm

121.35

121.59

121.85

125.25

129.21

129.31


13 12 11 10 9 8 7 6 5 4 3 2 1 0 ppm

2.8500

2.9799

2.9988

3.0759

3.1263

7.0666

7.0877

7.1145

7.1323

7.1500

7.1685

7.2209

7.2598

7.3005

7.3047

7.3175

7.3338

7.3625

7.3824

8.0275

8.0485

8.3406

8.3616

10.1148

2.90

2.14

0.75

1.69

0.05

0.24

1.39

0.24

2.03

2.01

1.00

6.97.07.17.27.37.4 ppm

7.0666

7.0877

7.1145

7.1323

7.1500

7.1685

7.2209

7.2598

7.3005

7.3047

7.3175

7.3338

7.3625

7.3824

1.69

0.05

0.24

1.39

0.24


11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

2.8441

2.9795

2.9984

3.0752

3.1255

3.6987

7.0674

7.0881

7.1131

7.1301

7.1480

7.1669

7.1892

7.2134

7.2316

7.2956

7.3152

7.3344

7.3598

7.3796

8.0245

8.0455

8.3369

8.3580

10.1114

2.99

1.91

1.04

1.30

1.59

1.29

0.34

2.04

1.99

1.00

6.97.07.17.27.37.47.5 ppm

7.0674

7.0881

7.1131

7.1301

7.1480

7.1669

7.1892

7.2134

7.2316

7.2956

7.3152

7.3344

7.3598

7.3796

1.30

1.59

1.29

0.34


11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

2.8176

2.9226

2.9419

3.0079

3.0603

3.6450

6.7835

6.8057

6.8196

6.8383

6.9154

6.9223

6.9377

6.9446

7.1806

7.2009

7.2183

7.2377

7.2504

7.2647

7.2725

7.2868

7.9767

7.9978

8.2869

8.3081

10.0645

1.00

3.03

2.51

0.54

2.52

0.16

0.90

0.16

2.04

2.00

1.00

6.66.76.86.97.07.17.27.37.4 ppm

6.7835

6.8057

6.8196

6.8383

6.9154

6.9223

6.9377

6.9446

7.1806

7.2009

7.2183

7.2377

7.2504

7.2647

7.2725

7.2868

2.52

0.16

0.90

0.16


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Room-Temperature Pd-Catalyzed C-H Chlorination by Weak ...

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