sonogashira cross-coupling reaction of 2 …different approach to 2-iodo-4-methoxyanisidine s2-3...

S1

Dramatic Enhancing Effect of InBr3 Towards the Oxidative Sonogashira Cross-Coupling Reaction of 2-Ethynylanilines

Akari Ikeda, Masaaki Omote, Miyuki Komori, Kana Kusumoto,

Atsushi Tarui, Kazuyuki Sato and Akira Ando*

Faculty of Pharmaceutical Sciences, Setsunan University

45-1, Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan

Supporting Information

Experimental Section S2-8

Synthesis of starting acetylenes S2-4

Iodonation of aniline derivatives S2

Sonogashira cross-coupling reaction and desilylation S2

Different approach to 2-iodo-4-methoxyanisidine S2-3

Spectroscopic data of iodoaniline derivatives and aryl acetylenes S3-8

References S81H and 13C NMR Charts S9-56

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2016

S2

Experimental Section

Synthesis of starting acetylenes

Iodination of aniline derivatives

Method A1; In a round bottom flask equipped with a magnetic stir bar aniline derivative (5.0

mmol) was added iodine (635 mg, 5.0 mmol) and Ag2SO4 (1.56 g, 5.0 mmol) and dissolved in

ethanol (15 mL). The mixture was stirred until the substrate was disappeared and then the solids

were removed by filtration with celite and the filtrate was concentrated under reduced pressure. The

crude was dissolved in CHCl3 (15 mL) and washed with Na2S2O3 (790 mg, 5.0 mmol) and water (5

mL). The organic layer was dried over anhydrous MgSO4 and filtered the solid off. After

evaporation of the solvent, the crude was purified by silica gel column chromatography to provide

the iodoaniline derivative 5.

Method B2; To aniline derivative (5.0 mmol) in 50 mL of H2O was added NaHCO3 (630 mg, 7.5

mmol) and iodine (635 mg, 5.0 mmol). The mixture was stirred until the substrate was disappeared

and then Na2S2O3 (790 mg, 5.0 mmol) was added. The reaction was extracted with CHCl3, the

combined organic layer was dried over anhydrous MgSO4 and filtered the solid off. The crude was

purified by silica gel column chromatography to provide the iodoaniline derivative 5.

Sonogashira cross-coupling reaction and desilylation3,4

To a mixture of aryl iodide (5.0 mmol), PdCl2 (PPh3)2 (175 mg, 5 mol%), CuI (48 mg, 5 mol%)

and Et3N (1.04 mL, 7.5 mmol) in dry THF (7.5 mL) was slowly added trimethylsilylacetylene (1.04

mL, 7.5 mmol). After the reaction mixture was stirred at room temperature for overnight, the

reaction was quenched by addition of water and the whole mixture was extracted with Et2O. The

organic layer was dried over anhydrous MgSO4 and filtered the solid off. After evaporation of the

solvent, the crude was purified by silica gel column chromatography to afford the silylated

arylacetylenes. The mixture of silylated arylacetylenes and K2CO3 (691 mg, 5.0 mmol) in MeOH

and H2O was stirred at room temperature until silylated acetylenes were disappeared. Then, the

mixture was extracted with CHCl3 and dried over anhydrous MgSO4. After filtration of the solid, the

organic layer was concentrated under reduced pressure. The residue was purified by silica gel

chromatography to provide the arylacetylenes 2.

Different approach to 2-iodo-4-methoxybenzenamine5,6,7

Under argon atmosphere, to the solution of p-anisidine (12.3 g, 100.0 mmol) in CH2Cl2 was

added Et3N (15.4 mL, 110.0 mmol) and Boc2O (25.3 mL, 110.0 mmol) slowly at 0 °C. After the

reaction mixture was stirred at same temperature for overnight, the reaction was quenched by

addition of water and the whole mixture was extracted with CH2Cl2. The organic layer was dried

over anhydrous MgSO4 and filtered the solid off. After evaporation of the solvent, the tert-butyl 4-

methoxyphenylcarbamate 6i was isolated as a white solid (21.9 g, 98%).

mp 95-96 °C; δH (CDCl3, 400 MHz) 1.51 (9H, s), 3.77 (3H, s), 6.37 (1H, br s), 6.8 (2H, d, J 8.3Hz),

S3

7.26 (2H, d, J 8.3Hz); δC (CDCl3, 400 MHz) 28.4, 55.5, 80.2, 114.1, 120.5, 131.3, 153.0, 155.6; m/z

(EI) 223.1201 (M+. C12H17NO3 requires 223.1208).

Under argon atmosphere, to a magnetically stirred solution of tert-butyl 4-

methoxyphenylcarbamate 6i (17.9 g, 80.0 mmol) in anhydrous Et2O (150 mL) was slowly added

tert-butyllithium (88.4 mL of a 1.9M solution in hexane, 168.0 mmol) at -20 °C. After stirring for 3

hours, the reaction mixture was cooled to -78 °C, and 1,2-diiodoethane (45.1 g, 160.0 mmol)

dissolved in anhydrous Et2O (300 mL) was added. Then the reaction mixture was gradually warmed

to room temperature and stirred for overnight. After addition of Na2S2O3 (150 mL of a saturated

aqueous solution), the whole mixture was extracted with Et2O and dried over anhydrous MgSO4.

The solid was filtered off, and the organic layer was concentrated under reduced pressure. The

residue was purified by silica gel chromatography (AcOEt : hexane = 10 : 90) to provide tert-butyl

2-iodo-4-methoxyphenlcarbamate 7i as a light yellow oil in 69% yield (19.3 g).

δH (CDCl3, 400 MHz) 1.52 (9H, s), 3.76 (3H, s), 6.54 (1H, br s), 6.90 (1H, dd, J 3.0Hz, 8.8Hz), 7.30

(1H, d, J 3.0Hz), 7.81 (1H, d, J 8.8Hz); δC (CDCl3, 400 MHz) 28.4, 55.7, 80.7, 90.4, 114.8, 122.0,

123.6, 132.3, 153.0, 155.9; m/z (EI) 349.0182 (M+. C12H16INO3 requires 349.0175).

To the solution of tert-butyl 2-iodo-4-methoxyphenylcarbamate 7i (17.5 g, 50.0 mmol) in

CH2Cl2 (250 mL) was added CF3COOH (44.6 mL, 600.0 mmol) at room temperature. After the

reaction mixture was stirred for overnight, 10% aqueous NaOH solution was added until pH of the

solution became 7. The mixture was extracted with CH2Cl2, and the organic layer was dried over

anhydrous MgSO4. The solid was filtered off, and the organic layer was concentrated under reduced

pressure. After purification by silica gel chromatography (AcOEt : hexane = 10 : 90), 2-iodo-4-

methoxybenzenamine 5i was isolated as a yellow oil in 98% (12.2 g).

Spectroscopic data of iodoaniline derivatives and aryl acetylenes

4-bromo-2-iodobenzenamine 5c

The title product 5c was obtained as a light yellow solid (715 mg, 48%) after

column chromatography (AcOEt : hexane = 10 : 90) using method A. mp 68-69 °C;

δH (CDCl3, 400 MHz) 4.10 (2H, br s), 6.62 (1H, d, J 8.8Hz), 7.23 (1H, dd, J 2.2Hz,

8.6Hz), 7.74 (1H, d, J 2.5Hz); δC (CDCl3, 400 MHz) 84.0, 109.8, 115.5, 132.0, 140.3, 145.8; m/z

(EI) 269.8659 (M+. C6H5BrIN requires 269.8650).

4-chloro-2-iodobenzenamine 5d

The title product 5d was obtained as a light yellow solid (811 mg, 64%) after

column chromatography (AcOEt : hexane = 10 : 90) using method A. mp 39-40 °C;

δH (CDCl3, 400 MHz) 4.08 (2H, br s), 6.66 (1H, d, J 8.3Hz), 7.11 (1H, dd, J 2.2Hz,

O

NH2

O

NH

OtBu

OO

NH

OtBu

OI O

NH2

IEt3N, Boc2O

6i 7i 5i

ICH2CH2I

tBuLi CF3COOH

Br I

NH2

Cl I

NH2

S4

8.6Hz), 7.61 (1H, d, J 2.0Hz); δC (CDCl3, 400 MHz) 83.4, 114.9, 123.1, 129.2, 137.7, 145.4; m/z

(EI) 252.9164 (M+. C6H5ClIN requires 252.9155).

1-(4-amino-3-iodophenyl)ethanone 5e

The title product 5e was obtained as a white solid (744 mg, 57%) after column

chromatography (AcOEt : hexane = 30 : 70) using method A. mp 45-46 °C; δH

(CDCl3, 400 MHz) 2.49 (3H, s), 4.60 (2H, br s), 6.71 (1H, d, J 8.7Hz), 7.77 (1H,

dd, J 1.4Hz, 8.2Hz), 8.28 (1H, d, J 1.4Hz); δC (CDCl3, 400 MHz) 26.0, 82.5, 113.1, 129.3, 130.3,

140.3, 150.9, 195.1; m/z (EI) 260.9653 (M+. C8H8INO requires 260.9651).

ethyl 4-amino-3-iodobenzoate 5f

The title product 5f was obtained as a white solid (1.22 g, 84%) after column


(CDCl3, 400 MHz) 1.36 (3H, t, J 7.3Hz), 4.32 (2H, q, J 7.2Hz), 4.51 (2H, br s),

6.70 (1H, d, J 8.3Hz), 7.83 (1H, dd, J 2.0Hz, 8.3Hz), 8.34 (1H, d, J 2.0Hz); δC (CDCl3, 400 MHz)

14.4, 60.7, 82.1, 113.0, 121.5, 131.0, 140.9, 150.5, 165.2; m/z (EI) 290.9762 (M+. C9H10INO2

requires 290.9756).

2-iodo-4-nitrobenzene 5g

The title product 5g was obtained as a yellow solid (1.10 g, 84%) after column

chromatography (CH2Cl2 : hexane = 80 : 20) using method A. mp 106-107 °C; δH

(CDCl3, 400 MHz) 4.85 (2H, br s), 6.71 (1H, d, J 8.8Hz), 8.06 (1H, dd, J 2.5Hz, 8.8Hz), 8.57 (1H, d,

J 2.5Hz); δC (CDCl3, 400 MHz) 80.5, 112.2, 125.7, 135.4, 139.2, 152.2; m/z (EI) 263.9403 (M+.

C6H5IN2O2 requires 263.9394).

2-iodo-4-methylbenzenamine 5h

The title product 5h was obtained as a light yellow solid (886 mg, 76%) after

column chromatography (AcOEt : hexane = 5 : 95) using method B. mp 36-37 °C; δH

(CDCl3, 400 MHz) 2.20 (3H, s), 3.93 (2H, br s), 6.66 (1H, d, J 8.2Hz), 6.94 (1H, dd,

J 1.8Hz, 8.2Hz), 7.47 (1H, d, J 1.8Hz); δC (CDCl3, 400 MHz) 19.8, 84.3, 114.6, 129.5, 130.0, 139.0,

144.3; m/z (EI) 232.9704 (M+. C7H8IN requires 232.9701).

2-iodo-4-methoxybenzenamine 5i

The title product 5i was obtained as a light yellow oil. δH (CDCl3, 400 MHz) 3.73

(3H, s), 3.79 (2H, br s), 6.70 (1H, d, J 8.3Hz), 6.77 (1H, dd, J 2.9Hz, 8.8Hz), 7.22

(1H, d, J 2.9Hz); δC (CDCl3, 400 MHz) 56.0, 84.3, 115.3, 116.1, 123.5, 140.7,

152.6; m/z (EI) 248.9655 (M+. C7H8INO requires 248.9651).

2-bromo-6-iodobenzenamine 5j

The title product 5j was obtained as a light yellow solid (655 mg, 44%) after column

chromatography (AcOEt : hexane = 10 : 90) using method A. mp 83-84 °C; δH (CDCl3,

400 MHz) 4.17 (2H, br s), 6.58 (1H, d, J 8.3Hz), 7.41 (1H, dd, J 2.0Hz, 8.8Hz), 7.74

I

NH2

O

I

NH2

O

O

I

NH2

O I

NH2

I

NH2Br

O2N I

NH2

S5

(1H, d, J 2.0Hz); δC (CDCl3, 400 MHz) 78.3, 110.0, 117.2, 136.9, 139.9, 143.8; m/z (EI) 269.8648

(M+. C6H5BrIN requires 297.8650).

1-(2-amino-3-iodophenyl)ethanone 5k

The title product 5k was obtained as a light yellow solid (1.25 g, 96%) after column


400 MHz) 2.55 (3H, s), 6.30 (2H, br s), 6.45 (1H, d, J 8.8Hz), 7.47 (1H, dd, J 1.9Hz,

8.8Hz), 7.97 (1H, d, J 2.0Hz); δC (CDCl3, 400 MHz) 27.7, 75.1, 119.4, 120.5, 140.5, 142.5, 149.7,

199.7; m/z (EI) 260.9651 (M+. C8H8INO requires 260.9651).

ethyl 2-amino-3-iodobenzoate 5l

The title product 5l was obtained as a white solid (1.19 g, 82%) after column


400 MHz) 1.38 (3H, t, J 7.1Hz), 4.33 (2H, q, J 7.1Hz), 5.77 (2H, br s), 6.45 (1H, d, J

8.8Hz), 7.47 (dd, J 2.0Hz, 8.8Hz), 8.14 (1H, d, J 2.5Hz); δC (CDCl3, 400 MHz) 14.4, 60.4, 75.9,

113.1, 118.7, 139.3, 142.0, 149.7, 166.8; m/z (EI) 290.9760 (M+. C9H10INO2 requires 290.9756).

2-iodo-6-nitrobenzenamine 5m

The title product 5m was obtained as a yellow solid (1.16 g, 88%) after column


(CDCl3, 400 MHz) 6.09 (2H, br s), 6.61 (1H, d, J 8.7Hz), 7.57 (1H, dd, J 2.0Hz, 8.8Hz),

8.43 (1H, d, J 2.3Hz); δC (CDCl3, 400 MHz) 75.9, 120.5, 133.1, 134.3, 143.6, 143.9; m/z (EI)

263.9399 (M+. C6H5IN2O2 requires 263.9396).

2-iodo-6-methylbenzenamine 5n

The title product 5n was obtained as a light yellow solid (746 mg, 64%) after column

chromatography (AcOEt : hexane = 10 : 90) using method B. mp 86-87 °C; δH (CDCl3,


8.2Hz), 7.34 (1H, d, J 1.8Hz); δC (CDCl3, 400 MHz) 17.0, 79.5, 116.8, 124.9, 135.5, 138.6, 144.3;

m/z (EI) 232.9701 (M+. C7H8IN requires 232.9701).

4-bromo-2-ethynylbenzenamine 2c

The title product 2c was obtained as a light yellow solid (892 mg, 91% for 2

steps) after column chromatography (AcOEt : hexane = 10 : 90). mp 65-66 °C;

δH (CDCl3, 400 MHz) 3.41 (1H, s), 4.26 (2H, br s), 6.58 (1H, d, J 8.8Hz), 7.22

(1H, dd, J 2.4Hz, 8.8Hz), 7.43 (1H, d, J 2.4Hz); δC (CDCl3, 400 MHz) 79.2, 83.5, 108.4, 108.7,

115.7, 132.9, 134.6, 147.4; m/z (EI) 196.9670 (M+. C8H6BrN requires 196.9684).

4-chloro-2-ethynylbenzenamine 2d

The title product 2d was obtained as a light yellow solid (531 mg, 70% for 2


δH (CDCl3, 400 MHz) 3.41 (1H, s), 4.24 (2H, br s), 6.62 (1H, d, J 8.8Hz), 7.09

I

NH2

O

I

NH2

OO

I

NH2

NH2

BrH

NH2

ClH

I

NH2NO2

S6


122.0, 130.1, 131.8, 147.0; m/z (EI) 151.0180 (M+. C8H6ClN requires 151.0189).

1-(4-amino-3-ethynylphenyl)ethanone 2e

The title product 2e was obtained as a white solid (661 mg, 83% for 2 steps)

after column chromatography (AcOEt : hexane = 20 : 80). mp 76-77 °C; δH

(CDCl3, 400 MHz) 2.50 (3H, s), 3.41 (1H, s), 4.74 (2H, br s), 6.69 (1H, d, J

8.6Hz), 7.80 (1H, dd, J 2.0Hz, 8.8Hz), 7.98 (1H, d, J 2.0Hz); δC (CDCl3, 400 MHz) 26.1, 79.5, 83.0,

105.6, 113.3, 127.4, 130.7, 134.2, 152.2, 195.5; m/z (EI) 159.0681 (M+. C10H9NO requires

159.0684).

ethyl 4-amino-3-ethynylbenzoate 2f

The title product 2f was obtained as a white solid (870 mg, 92% for 2

steps) after column chromatography (AcOEt : hexane = 20 : 80). mp 105-

106 °C; δH (CDCl3, 400 MHz) 1.36 (3H, t, J 7.3Hz), 3.40 (1H, s), 4.32 (2H,

q, J 7.3Hz), 4.67 (2H, br s), 6.67 (1H, d, J 8.7Hz), 7.83 (1H, dd, J 1.8Hz, 8.7Hz), 8.04 (1H, d, J

2.3Hz); δC (CDCl3, 400 MHz) 14.4, 60.5, 79.6, 82.9, 105.7, 113.2, 119.7, 131.8, 134.8, 152.0, 166.0;

m/z (EI) 189.0789 (M+. C11H11NO2 requires 189.0790).

2-ethynyl-4-nitrobenzenamine 2g

The title product 2g was obtained as a yellow solid (609 mg, 75% for 2 steps)

after column chromatography (AcOEt : hexane = 30 : 70). mp 128-129 °C; δH

(CDCl3, 400 MHz) 3.47 (1H, s), 5.00 (2H, br s), 6.69 (1H, d, J 8.7Hz), 8.05


126.3, 129.2, 138.3, 153.4; m/z (EI) 162.0423 (M+. C8H6N2O2 requires 162.0429).

2-ethynyl-4-methylbenzenamine 2h

The title product 2h was obtained as a light yellow solid (584 mg, 89% for 2

steps) after column chromatography (AcOEt : hexane = 5 : 95). mp 34-35 °C; δH

(CDCl3, 400 MHz) 2.20 (3H, s), 3.35 (1H, s), 4.10 (2H, br s), 6.61 (1H, d, J 8.2Hz),

6.96 (1H, dd, J 1.8Hz, 8.2Hz), 7.13 (1H, d, J 1.6z); δC (CDCl3, 400 MHz) 20.2, 80.8, 82.1, 106.6,

114.5, 127.1, 131.0, 132.6, 146.2; m/z (EI) 131.0730 (M+. C9H9N requires 131.0735).

2-ethynyl-4-methoxybenzenamine 2i

The title product 2i was obtained as a light yellow oil (623 mg, 94% for 2

steps) after column chromatography (AcOEt : hexane = 10 : 90). δH (CDCl3, 400

MHz) 3.38 (1H, s), 3.73 (3H, s), 3.98 (2H, br s), 6.65 (1H, d, J 8.8Hz), 6.79 (1H,

dd, J 2.9Hz, 8.8Hz), 6.88 (1H, d, J 2.9Hz); δC (CDCl3, 400 MHz) 55.7, 80.6, 82.4, 107.1, 115.8,

116.2, 117.8, 142.7, 151.6; m/z (EI) 147.0687 (M+. C9H9NO requires 141.684).

NH2

HO

NH2

HO

O

NH2

H

NH2

OH

O2N

NH2

H

S7

2-bromo-6-ethynylbenzenamine 2j

The title product 2j was obtained as a light yellow solid (882 mg, 90% for 2 steps)

after column chromatography (AcOEt : hexane = 20 : 80). mp 46-47 °C; δH (CDCl3,


8.3Hz), 7.57 (1H, d, J 1.9Hz); δC (CDCl3, 400 MHz) 75.8, 82.8, 108.1, 112.5, 114.9,

132.3, 136.2, 144.7; m/z (EI) 196.9666 (M+. C8H6BrN requires 196.9684).

1-(2-amino-3-ethynylphenyl)ethanone 2k

The title product 2k was obtained as a light yellow solid (788 mg, 99% for 2 steps)

after column chromatography (AcOEt : hexane = 20 : 80). mp 50-51 °C; δH (CDCl3,

400 MHz) 2.57 (3H,s), 2.97 (1H, s), 6.47 (2H, br s), 6.58 (1H, d, J 8.8Hz), 7.36 (1H,

dd, J 1.9Hz, 8.3Hz), 7.89 (1H, d, J 1.9Hz); δC (CDCl3, 400 MHz) 27.6, 74.9, 83.6,

109.0, 117.3, 117.9, 136.6, 137.6, 150.5, 200.2; m/z (EI) 159.0688 (M+. C10H9NO requires

159.0684).

ethyl 2-amino-3-ethynylbenzoate 2l

The title product 2l was obtained as a white solid (539 mg, 57% for 2 steps) after

column chromatography (AcOEt : hexane = 5 : 95). mp 65-66 °C; δH (CDCl3, 400

MHz) 1.39 (3H, t, J 7.3Hz), 2.95 (1H, s), 4.33 (2H, q, J 7.3Hz), 5.93 (2H, br s), 6.59

(1H, d, J 8.7Hz), 7.36 (1H, dd, J 1.8Hz, 8.7Hz), 8.05 (1H, d, J 1.8Hz); δC (CDCl3,

400 MHz) 14.3, 60.6, 74.8, 83.7, 109.3, 110.7, 116.6, 135.7, 137.2, 150.6, 167.4; m/z (EI) 189.0782

(M+. C11H11NO2 requires 189.0790).

2-ethynyl-6-methylbenzenamine 2m

The title product 2m was obtained as a yellow solid (800 mg, 99% for 2 steps) after

column chromatography (AcOEt : hexane = 20 : 80). mp 119-120 °C; δH (CDCl3,


8.8Hz), 8.29 (1H, d, J 2.0Hz) ; δC (CDCl3, 400 MHz) 76.5, 81.8, 110.9, 118.9, 130.4,

131.9, 138.6, 144.6; m/z (EI) 162.0427(M+. C8H6N2O2 requires 162.0429).

2-ethynyl-6-methylbenzenamine 2n

The title product 2n was obtained as a yellow oil (151 mg, 23% for 2 steps) after

column chromatography (AcOEt : hexane = 5 : 95). δH (CDCl3, 400 MHz) 2.13 (3H,

s), 2.94 (1H, s), 3.76 (2H, br s), 6.58 (1H, d, J 8.2Hz), 7.18 (1H, dd, J 1.8Hz, 8.2Hz),

7.21 (1H, d, J 1.8Hz); δC (CDCl3, 400 MHz) 17.1, 74.6, 84.6, 111.3, 114.4, 121.9,

131.2, 134.3, 145.3; m/z (EI) 131.0728 (M+. C9H9N requires 131.0735).

2-ethynylpyridine 2o

The title product 2o was obtained as a light yellow oil (382 mg, 74% for 2 steps)

after column chromatography (AcOEt : hexane = 30 : 70). δH (CDCl3, 400 MHz)

3.16 (1H, s), 7.25-7.29 (1H, m), 7.49 (1H, d, J 7.8Hz), 7.64-7.69 (1H, m), 8.60 (1H,

NH2

H

Br

NH2

H

O

NH2

H

OO

NH2

H

N

H

NH2

H

NO2

S8

d, J 4.9Hz); δC (CDCl3, 400 MHz) 77.1, 82.7, 123.3, 127.3, 136.0, 142.2, 149.9; m/z (EI) 103.0420

(M+. C7H5N requires 103.0422).

5-ethynyl-1H-indole 2p

The title product 2p was obtained as a light yellow solid (536 mg, 76% for 2


δH (CDCl3, 400 MHz) 3.00 (1H, s), 6.53-6.55 (1H, m), 7.21-7.23 (1H, m), 7.32

(2H, s), 7.84 (1H, s), 8.20 (1H, br s); δC (CDCl3, 400 MHz) 74.6, 85.3, 102.9, 111.0, 113.1, 125.1,

125.3, 125.9, 127.6, 135.6; m/z (EI) 141.0579 (M+. C10H7N requires 141.0578).

References:

1. C. Koradin, W. Dohle, A. L. Rodriguez, B. Schmid, P. Knochel, Tetrahedron, 2003, 59, 1571; A.

J. B. Lapierre, S. J. Geib, D. P. Curran, J. Am. Chem. Soc., 2007, 129, 494; N. Charrier, E.

Demont, R. Dunsdon, G. Maile, A. Naylor, A. O’Brien, S. Redshaw, P. Theobald, D. Vesey, D.

Walter, Synthesis, 2006, 20, 3467.

2. M. Layek, U. Lakshmi, D. Kalita, D. K. Barange, A. Islam, K. Mukkanti, M. Pal, Beilstein J.

Org. Chem., 2009, 5, No. 46; D. Rambabu, G. Raja, B. Yogi Sreenivas, G. P. K. Seerapu, K.

Lalith Kumar, G. S. Deora, D. Haldar, M. V. B. Devyani, M. Pal, Bioorg. Med. Chem. Lett.,

2013, 23, 1351.

3. B. Zhou, H. Chen and C. Wang, J. Am. Chem. Soc., 2013, 135, 1264; S. Thorand and N. Krause,

J. Org. Chem., 1998, 63, 8551; S. Loeb and R. Ziessel, Org. Lett., 2007, 9, 737.

4. A. Molad, I. Goldberg, A. Vigalok, J. Am. Chem. Soc., 2012, 134, 7290; A. J. Lennox and G. C.

Lloyd-Jones, J. Am. Chem. Soc., 2012, 134, 7431; A. Pearson and J. B. Kim, Tetrahedron Lett.,

2003, 44, 8525.

5. Y. Kobayashi, J. Igarashi, C. Feng, T. Tojo, Tetrahedron Lett., 2012, 53, 3742.

6. Y. Kondo, S. Kojima, T. Sakamoto, J. Org. Chem., 1997, 62, 6507; C. R. Edwankar, R. V.

Edwankar, O. A. Namjoshi, X. Liao, J. M. Cook, J. Org. Chem., 2013, 78, 6471; T. Ozawa, M.

Kanematsu, H. Yokoe, M. Yoshida, K. Shishido, Heterocycles, 2012, 85, 2927.

7. D. E. Lizos, J. A. Murphy, Org. Biomol. Chem., 2003, 1, 117; P. P. Sharp, M. G. Banwell, J.

Renner, K. Lohmann, A. C. Willis, Org. Lett., 2013, 15, 2616.

NH

H

S9

1H and 13C NMR Charts:

4-bromo-2-iodobenzenamine 5c

1H NMR spectrum

13C NMR spectrum

Br I

NH2

S10

4-chloro-2-iodobenzenamine 5d

1H NMR spectrum

13C NMR spectrum

Cl I

NH2

S11

1-(4-amino-3-iodophenyl)ethanone 5e

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

X : parts per Million : Proton

12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

8.

277

8.

275

8.

273

7.

778

7.

776

7.

774

7.

767

7.

764

7.

757

7.

755

7.

754

6.

724

6.

713

6.

702

4.

602

2.

494

1.37

1.37

8.23

8.23

1.37

8.69

3.38

2.00

1.10

1.08

0.93

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.0

X : parts per Million : Carbon13

220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

195

.117

150

.854

140

.323

130

.251

129

.264

113

.098

82.

539

26.

010

I

NH2

O

S12

ethyl 4-amino-3-iodobenzoate 5f

1H NMR spectrum

13C NMR spectrum

I

NH2

O

O

S13

2-iodo-4-nitrobenzene 5g

1H NMR spectrum

13C NMR spectrum

O2N I

NH2

S14

2-iodo-4-methylbenzenamine 5h

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

7.

470

7.

465

6.

954

6.

948

6.

933

6.

929

6.

666

6.

645

3.

932

2.

201

3.69

2.00

1.23

1.16

1.15

13C NMR spectrum

I

NH2

(Tho

usan

ds)

010

.020

.030

.040

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

144

.290

139

.000

130

.021

129

.504

114

.631

84.

283

19.

820

S15

tert-butyl 4-methoxyphenylcarbamate 6i

1H NMR spectrum

13C NMR spectrum

NH

O

OtBu

O

S16

tert-butyl 2-iodo-4-methoxyphenlcarbamate 7i

1H NMR spectrum

13C NMR spectrum

NH

O

OtBu

OI

S17

2-iodo-4-methoxybenzenamine 5i

1H NMR spectrum

13C NMR spectrum

O I

NH2

S18

2-bromo-6-iodobenzenamine 5j

1H NMR spectrum

13C NMR spectrum

I

NH2Br

S19

1-(2-amino-3-iodophenyl)ethanone 5k

1H NMR spectrum

13C NMR spectrum

I

NH2

O

S20

ethyl 2-amino-3-iodobenzoate 5l

1H NMR spectrum

13C NMR spectrum

I

NH2

OO

S21

2-iodo-6-nitrobenzenamine 5m

1H NMR spectrum

13C NMR spectrum

I

NH2NO2

S22

2-iodo-6-methylbenzenamine 5n

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0

6.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

7.

344

7.

342

7.

340

7.

326

7.

303

7.

301

7.

298

7.

293

7.

288

7.

283

7.

281

7.

278

6.

456

6.

446

6.

436

3.

606

2.

111

1.83

1.83

7.78

8.23

2.29

8.23

3.00

1.49

0.92

0.76

0.67

13C NMR spectrum

I

NH2

S23

(Tho

usan

ds)

010

.020

.030

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

144

.309

138

.627

135

.531

124

.904

116

.845

79.

492

17.

003

4-bromo-2-ethynylbenzenamine 2c

1H NMR spectrum

13C NMR spectrum

NH2

BrH

S24

4-chloro-2-ethynylbenzenamine 2d

1H NMR spectrum

13C NMR spectrum

NH2

ClH

S25

1-(4-amino-3-ethynylphenyl)ethanone 2e

1H NMR spectrum

13C NMR spectrum

NH2

HO

S26

ethyl 4-amino-3-ethynylbenzoate 2f

1H NMR spectrum

NH2

HO

O

S27

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

8.

047

8.

044

8.

041

7.

843

7.

841

7.

838

7.

832

7.

821

7.

819

7.

817

6.

685

6.

674

6.

663

4.

660

4.

344

4.

336

4.

327

4.

318

4.

309

4.

300

4.

290

3.

399

1.

381

1.

372

1.

363

1.

354

1.

345

2.29

1.83

8.69

8.69

1.83

8.69

6.86

7.32

7.32

7.32

6.86

3.09

2.03

2.00

1.12

1.04

1.01

0.87

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

165

.966

152

.023

134

.841

131

.832

119

.682

113

.232

105

.739

82.

903

79.

559

60.

518

14.

377

2-ethynyl-4-nitrobenzenamine 2g

1H NMR spectrum

O2N

NH2

H

S28

13C NMR spectrum

2-ethynyl-4-methylbenzenamine 2h

NH2

H

S29

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0

6.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

7.

136

7.

134

7.

132

6.

969

6.

967

6.

964

6.

959

6.

954

6.

948

6.

946

6.

944

6.

624

6.

614

6.

604

4.

099

3.

352

2.

204

1.60

1.83

8.23

8.23

1.83

8.23

3.35

2.15

1.12

1.04

1.00

0.97

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.040

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

146

.178

132

.628

130

.960

127

.051

114

.497

106

.620

82.

098

80.

776

20.

194

2-ethynyl-4-methoxybenzenamine 2i

NH2

OH

S30

1H NMR spectrum

13C NMR spectrum

2-bromo-6-ethynylbenzenamine 2j

NH2

H

Br

S31

1H NMR spectrum

13C NMR spectrum

1-(2-amino-3-ethynylphenyl)ethanone 2k

NH2

H

O

S32

1H NMR spectrum

13C NMR spectrum

ethyl 2-amino-3-ethynylbenzoate 2l

NH2

H

OO

S33

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

8.

056

8.

053

8.

051

7.

370

7.

350

7.

344

6.

600

6.

590

6.

579

5.

933

4.

355

4.

346

4.

337

4.

328

4.

319

4.

310

4.

301

2.

950

1.

404

1.

395

1.

387

1.

378

1.

368

1.83

1.83

8.23

8.69

2.29

8.69

6.86

7.32

7.32

6.86

7.32

3.78

2.59

1.93

1.28

1.19

1.15

1.00

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.040

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

167

.423

150

.557

137

.160

135

.685

116

.586

110

.693

109

.303

83.

650

74.

844

60.

594

14.

291

2-ethynyl-6-methylbenzenamine 2m

NH2

H

NO2

S34

1H NMR spectrum

13C NMR spectrum

2-ethynyl-6-methylbenzenamine 2n

NH2

H

S35

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

7.

205

7.

195

7.

192

7.

191

7.

185

7.

180

7.

175

7.

172

7.

170

6.

591

6.

581

6.

571

3.

757

2.

940

1.83

8.23

8.23

1.83

8.23

2.16

1.94

1.03

1.00

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

145

.334

134

.295

131

.162

121

.876

114

.392

111

.258

84.

561

74.

614

17.

079

2-ethynylpyridine 2o

N

H

S36

1H NMR spectrum

13C NMR spectrum

5-ethynyl-1H-indole 2p

NH

H

S37

1H NMR spectrum

13C NMR spectrum

(E)-4-bromo-2-(5,5,5-trifluoropent-3-en-1-ynel)benzenamine 3c

NH2

BrCF3

S38

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

7.

399

7.

396

7.

393

7.

255

7.

249

7.

233

7.

230

7.

227

6.

597

6.

575

6.

163

6.

147

6.

130

6.

124

6.

107

4.

238

2.29

2.29

8.69

8.69

2.29

8.69

2.29

2.29

2.29

16.0

116

.01

16.0

116

.01

2.29

2.29

2.29

6.86

16.0

16.

4015

.55

6.86

6.40

16.0

16.

8616

.01

6.86

2.00

1.24

0.98

0.95

0.92

0.73

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

147

.232

134

.496

133

.663

127

.357

127

.022

123

.783

121

.100

118

.541

118

.464

115

.992

108

.978

108

.067

91.

652

90.

282

34.6

833

.72

33.7

226

9.73

269.

737.

718.

677.

71

(E)-4-chloro-2-(5,5,5-trifluoropent-3-en-1-ynel)benzenamine 3d

NH2

ClCF3

S39

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

7.

259

7.

256

7.

253

7.

129

7.

123

7.

107

7.

104

7.

102

6.

647

6.

626

6.

185

6.

169

6.

152

6.

129

6.

112

4.

225

2.74

2.29

8.69

8.69

2.29

8.69

2.29

2.29

2.29

16.0

116

.01

16.0

116

.01

2.29

2.29

2.29

6.40

16.0

16.

8616

.01

6.86

6.40

16.0

16.

8615

.55

6.40

2.00

1.18

1.10

1.07

0.95

0.80

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.040

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

146

.820

131

.641

130

.912

127

.721

127

.386

127

.041

123

.792

122

.345

118

.484

118

.397

115

.666

107

.531

91.

796

90.

157

33.7

234

.68

33.7

226

9.73

269.

737.

718.

677.

71

(E)-1-(4-amino-3-(5,5,5-trifluoropent-3-en-1-ynyl)phenyl)ethanone 3e

NH2

CF3O

S40

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0

6.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

7.

949

7.

947

7.

945

7.

831

7.

829

7.

827

7.

810

7.

807

7.

805

6.

718

6.

697

6.

525

6.

520

6.

194

6.

178

6.

154

6.

138

4.

709

2.

511

1.83

1.83

8.69

8.69

1.83

8.69

2.29

2.29

1.83

16.0

116

.01

15.5

516

.01

2.29

1.83

2.29

6.86

16.0

16.

4016

.01

6.86

6.86

6.40

16.0

16.

86

3.00

1.89

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

195

.596

151

.879

134

.247

131

.430

127

.587

127

.434

127

.099

123

.792

121

.109

118

.541

118

.464

118

.388

113

.644

105

.336

91.

930

89.

774

26.

029

34.6

833

.72

34.6

826

9.73

269.

737.

717.

717.

71

(E)-ethyl 4-amino-3-(5,5,5-trifluoropent-3-en-1-ynyl)benzoate 3f

NH2

CF3O

O

S41

1H NMR spectrum

(Mill

ions

)0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.8

1.9

2.0

2.1

2.2


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

8.

020

8.

018

8.

016

7.

865

7.

862

7.

859

7.

854

7.

843

7.

841

7.

838

6.

701

6.

679

6.

521

6.

516

6.

185

6.

168

6.

145

6.

128

4.

629

4.

352

4.

344

4.

335

4.

326

4.

317

4.

308

4.

300

1.

388

1.

379

1.

370

1.

360

1.

351

1.83

2.29

8.69

8.23

1.83

8.69

2.29

2.29

2.29

16.0

116

.01

16.0

116

.01

2.29

2.29

2.29

6.40

15.5

56.

8616

.01

6.86

6.86

16.0

120

.13

6.86

15.5

56.

40

6.86

7.32

6.86

7.32

7.32

2.26

2.00

0.93

0.86

0.83

0.55

0.39

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

165

.813

151

.611

134

.861

132

.455

127

.635

127

.300

126

.955

126

.619

123

.821

120

.026

118

.541

118

.464

113

.539

105

.489

92.

064

89.

697

60.

623

14.

367

33.7

234

.68

33.7

226

9.73

269.

737.

717.

717.

71

(E)-4-methyl-2-(5,5,5-trifluoropent-3-en-1-ynyl)benzenamine 3h

NH2

CF3

S42

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

7.

106

7.

001

6.

980

6.

637

6.

616

6.

558

6.

552

6.

518

6.

512

6.

150

6.

134

6.

116

6.

114

6.

094

6.

076

6.

059

4.

086

2.

214

8.23

2.29

16.0

116

.01

2.29

6.40

6.86

16.0

116

.01

6.86

6.86

3.00

1.72

0.95

0.91

0.90

0.84

0.83

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

145

.996

132

.503

131

.880

127

.348

126

.437

126

.092

123

.975

121

.301

119

.020

118

.944

114

.718

106

.304

93.

731

89.

266

20.

174

33.7

234

.68

33.7

226

9.73

268.

7626

9.73

7.71

7.71

7.71

(E)-4-methoxy-2-(5,5,5-trifluoropent-3-en-1-ynyl)benzenamine 3i

NH2

OCF3

S43

1H NMR spectrum

13C NMR spectrum

(E)-2-bromo-6-(5,5,5-trifluoropent-3-en-1-ynel)benzenamine 3j

NH2

CF3

Br

S44

1H NMR spectrum

13C NMR spectrum

(E)-1-(2-amino-3-(5,5,5-trifluoropent-3-en-1-ynyl)phenyl)ethanone 3k

NH2

CF3

O

S45

1H NMR spectrum

13C NMR spectrum

(E)-ethyl 2-amino-3-(5,5,5-trifluoropent-3-en-1-ynyl)benzoate 3l

NH2

CF3

OO

S46

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

8.

034

8.

031

8.

028

7.

344

7.

340

7.

323

6.

622

6.

602

6.

452

6.

100

6.

083

6.

060

6.

043

6.

026

4.

367

4.

358

4.

349

4.

341

4.

332

4.

322

4.

313

1.

415

1.

407

1.

398

1.

389

1.

380

2.29

1.83

8.23

8.69

2.29

8.23

2.74

2.29

2.29

16.0

115

.55

15.5

515

.55

2.29

2.29

2.29

6.40

6.86

6.86

6.86

6.86

6.86

7.32

6.86

7.32

6.86

7.32

3.00

2.71

2.02

0.88

0.88

0.86

0.76

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

167

.308

150

.998

136

.911

135

.780

125

.939

125

.604

124

.118

119

.212

119

.126

116

.749

110

.837

109

.016

96.

980

82.

577

60.

709

14.

310

33.7

233

.72

269.

7333

.72

269.

7326

8.76

7.71

8.67

7.71

(E)-2-methyl-2-(5,5,5-trifluoropent-3-en-1-ynyl)benzenamine 3n

NH2

CF3

S47

1H NMR spectrum

(Mill

ions

)0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.8

1.9

2.0

2.1

2.2

2.3

2.4

2.5

2.6

2.7

2.8

2.9


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

7.

184

7.

152

6.

614

6.

594

6.

081

6.

064

6.

047

6.

029

6.

025

6.

008

3.

849

2.

141

8.23

2.29

2.29

2.29

16.0

116

.01

16.0

116

.01

2.29

2.29

2.29

6.86

15.5

56.

8615

.55

6.86

6.86

15.5

56.

8615

.55

6.86

3.00

1.95

1.78

0.97

0.95

0.94

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

146

.034

134

.209

131

.219

125

.422

125

.086

124

.205

121

.943

119

.461

119

.384

114

.449

110

.894

98.

053

82.

548

17.

079

33.7

226

9.73

33.7

233

.72

268.

7626

9.73

7.71

7.71

7.71

(E)-2-(5,5,5-trifluoropent-3-en-1-ynyl)pyridine 3o

N

CF3

S48

1H NMR spectrum

13C NMR spectrum

(E)-5-(5,5,5-trifluoropent-3-en-1-ynyl)-1H-indole 3p

CF3

NH

S49

1H NMR spectrum

13C NMR spectrum

(E)-2-(3,3,3-trifluoroprop-1-enyl)-1H-indole 4b

NH

CF3

S50

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

8.

123

7.

602

7.

348

7.

130

6.

744

6.

017

6.

000

5.

984

5.

976

5.

968

5.

960

5.

944

5.

927

8.23

0.91

8.23

8.23

0.91

1.37

8.23

8.23

0.91

1.37

8.23

8.23

0.91

1.83

2.29

1.83

16.4

716

.01

0.91

8.23

1.83

8.23

0.91

6.86

6.86

0.91

6.86

16.4

76.

4016

.01

6.40

6.40

16.0

16.

4016

.47

6.86

2.20

1.81

1.26

1.26

1.23

1.00

0.93

13C NMR spectrum

(E)-5-bromo-2-(3,3,3-trifluoroprop-1-enyl)-1H-indole 4c

NH

CF3

Br

S51

1H NMR spectrum

(Mill

ions

)0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

8.

178

7.

739

7.

330

7.

326

7.

243

6.

681

6.

058

6.

042

6.

026

6.

018

6.

010

6.

002

5.

986

5.

969

1.83

1.83

8.69

8.69

1.83

8.69

1.83

2.29

1.83

16.0

116

.47

16.0

12.

291.

83

6.40

16.0

16.

4016

.01

6.40

6.40

6.40

16.4

76.

86

1.76

1.18

1.16

1.14

1.13

1.03

1.00

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.040

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

135

.924

132

.963

129

.935

127

.721

127

.654

127

.621

127

.587

127

.549

127

.511

127

.290

124

.645

123

.888

121

.972

119

.298

114

.948

114

.603

114

.430

114

.258

113

.884

112

.494

106

.917

6.74

6.74

7.71

268.

7626

8.76

34.6

834

.68

(E)-5-chloro-2-(3,3,3-trifluoroprop-1-enyl)-1H-indole 4d

NH

CF3

Cl

S52

1H NMR spectrum

(Mill

ions

)0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

8.

226

7.

577

7.

288

7.

118

6.

682

6.

059

6.

051

6.

043

6.

035

6.

027

6.

023

6.

019

6.

011

6.

007

6.

003

5.

995

5.

991

5.

987

5.

979

5.

971

6.40

6.40

16.0

16.

4016

.01

6.40

16.0

16.

40

3.65

1.04

1.00

0.97

0.96

13C NMR spectrum

(Tho

usan

ds)

01.

02.

03.

04.

05.

06.

07.

08.

09.

010

.011

.012

.013

.014

.015

.016

.017

.018

.019

.020

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

135

.665

133

.145

129

.264

127

.779

127

.741

127

.702

127

.635

127

.568

127

.348

126

.370

124

.751

124

.674

122

.001

120

.745

119

.327

114

.861

114

.516

114

.171

113

.826

112

.092

107

.042

7.71

6.74

6.74

268.

7626

8.76

268.

76

34.6

834

.68

34.6

8

(E)-1-(2-(3,3,3-trifluoroprop-1-enyl)-1H-indol-5-yl)ethanone 4e

NH

CF3

O

S53

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

8.

456

8.

288

8.

287

8.

286

7.

954

7.

932

7.

410

7.

389

7.

169

6.

862

6.

110

6.

094

6.

078

6.

070

6.

062

6.

054

6.

038

6.

021

2.

669

0.91

1.37

8.69

8.69

1.37

8.69

1.83

2.29

1.83

16.0

116

.47

16.0

116

.01

2.29

1.83

1.83

6.40

16.0

16.

4016

.01

6.40

6.40

16.0

16.

4016

.01

6.40

3.00

1.10

1.02

1.02

0.97

0.91

0.73

0.72

13C NMR spectrum

(Tho

usan

ds)

01.

02.

03.

04.

05.

06.

07.

08.

09.

010

.011

.012

.013

.014

.015

.016

.017

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

197

.771

140

.371

134

.132

129

.695

127

.836

127

.803

127

.769

127

.731

127

.693

127

.626

127

.309

124

.914

123

.419

123

.227

122

.240

119

.566

114

.919

114

.583

114

.239

114

.076

113

.913

111

.057

108

.134

26.

192

6.74

7.71

6.74

268.

7626

8.76

33.7

234

.68

32.7

5

(E)-ethyl 2-(3,3,3-trifluoroprop-1-enyl)-1H-indol-5-carboxylate 4f

NH

CF3

O

O

S54

1H NMR spectrum

(Mill

ions

)0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.8

1.9


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

8.

440

8.

401

8.

002

7.

980

7.

401

7.

379

7.

177

6.

854

6.

093

6.

077

6.

060

6.

052

6.

036

4.

442

4.

434

4.

425

4.

416

4.

407

4.

398

4.

389

1.

453

1.

444

1.

435

1.

426

1.

417

1.37

8.69

8.69

1.37

8.69

1.83

16.4

716

.47

1.83

6.40

16.4

76.

4016

.47

6.86

6.40

16.4

76.

4016

.01

6.40

6.86

7.32

7.32

7.32

6.86

2.88

2.18

1.92

1.11

1.08

1.04

1.03

1.00

13C NMR spectrum

(Tho

usan

ds)

02.

04.

06.

08.

010

.012

.014

.016

.018

.020

.022

.024

.026

.028

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

167

.193

140

.246

133

.893

127

.884

127

.817

127

.750

127

.673

127

.587

127

.348

124

.914

124

.540

123

.783

122

.240

121

.991

114

.766

114

.430

114

.085

113

.750

110

.750

107

.856

60.

297

14.

176

6.74

6.74

7.71

268.

7626

8.76

33.7

234

.68

33.7

2

(E)-5-methyl-2-(3,3,3-trifluoroprop-1-enyl)-1H-indole 4h

NH

CF3

S55

1H NMR spectrum

(Mill

ions

)0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

2.2

2.4

2.6

2.8

3.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

8.

060

7.

392

7.

240

7.

102

7.

098

6.

666

5.

997

5.

981

5.

965

5.

957

5.

948

5.

941

5.

924

5.

908

2.

431

2.29

1.83

1.83

16.4

716

.01

16.0

116

.47

1.83

1.83

2.29

1.37

8.23

8.23

1.37

6.40

16.0

16.

4016

.01

6.86

6.40

16.4

76.

8616

.01

6.40

3.00

1.97

1.02

0.94

0.87

0.80

0.35

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.040

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

135

.800

131

.967

130

.050

128

.555

128

.220

128

.181

128

.143

128

.076

128

.009

127

.597

126

.227

124

.923

122

.250

120

.966

119

.576

113

.434

113

.089

112

.744

112

.399

110

.712

107

.521

21.

372

7.71

6.74

6.74

268.

7626

8.76

268.

76

34.6

834

.68

34.6

8

(E)-5-methoxy-2-(3,3,3-trifluoroprop-1-enyl)-1H-indole 4i

NH

CF3

O

S56

1H NMR spectrum

13C NMR spectrum

(E)-1-(2-(3,3,3-trifluoroprop-1-enyl)-1H-indol-7-yl)ethanone 4k

NH

CF3

O

S57

1H NMR spectrum

(Mill

ions

)0

1.0

2.0

3.0

4.0

5.0


12.0 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 0 -1.0 -2.0

7.

874

7.

872

7.

870

7.

350

7.

328

7.

323

6.

620

6.

598

6.

460

6.

130

6.

113

6.

096

6.

090

6.

079

6.

073

6.

056

1.37

2.29

8.69

8.23

1.83

8.69

2.29

2.29

2.29

16.0

116

.01

16.0

116

.01

2.29

2.29

2.29

6.86

16.0

16.

8616

.01

6.86

6.86

16.0

16.

8616

.01

6.86

3.75

3.00

0.99

0.93

0.91

13C NMR spectrum

(Tho

usan

ds)

010

.020

.030

.0


220.0 210.0 200.0 190.0 180.0 170.0 160.0 150.0 140.0 130.0 120.0 110.0 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0 -10.0 -20.0

200

.119

150

.797

137

.199

136

.528

126

.073

125

.738

124

.090

121

.406

119

.097

117

.861

117

.420

108

.546

96.

817

82.

654

27.

630

33.7

233

.72

33.7

226

9.73

269.

737.

717.

717.

71

sonogashira cross-coupling reaction of 2 …different approach to 2-iodo-4-methoxyanisidine s2-3...

Documents