thieme · supporting information copper-catalyzed direct c-5 fluorination of 8-aminoquinolines by...

Thieme

Supporting Information for DOI: 10.1055/s-0037-1610130

© Georg Thieme Verlag KG Stuttgart · New York 2018

Supporting Information Copper-catalyzed direct C-5 fluorination of 8-aminoquinolines by remote C-H

activation Si-Si Luoa, Lan-Jun Sua, Yue Jianga, Xiao-Bao Lib, Zheng-Hui Lia, Huan Suna* and Ji-Kai Liua*

a: School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan, 430074, P. R.

China

*Email: sunh15@163.com

*Email: jkliu@mail.kib.ac.cn

b: Department of Civil and Environmental Engineering, Northwestern University. Evanston, IL, USA.

60060.

Table of Contents: General inforamtion 2

Characterization data of products 3

References 7

NMR Spectra Images of Products 8

2

General information:

All reactions were carried out under an N2 atmosphere (balloon) with dry solvents under anhydrous

conditions. All reagents were purchased from Adamas and used without further purification unless

specified otherwise. Solvents for chromatography were technical grade and distilled prior to use. Flash

chromatography was performed using 200-300 mesh silica gel with the indicated solvent system

according to standard techniques. Analytical thin-layer chromatography (TLC) was performed on

pre-coated, glass-backed silica gel plates. Visualization of the developed chromatogram was performed

by UV absorbance (254 nm). 1H NMR and 13C NMR data were recorded on Bruker 600 M nuclear

resonance spectrometers unless otherwise specified, respectively. Chemical shifts (δ) in ppm are

reported as quoted relative to the residual signals of chloroform (1H 7.26 ppm or 13C 77.16 ppm).

Multiplicities are described as: s (singlet), bs (broad singlet), d (doublet), t (triplet), q (quartet), m

(multiplet); and coupling constants (J) are reported in Hertz (Hz). 13C NMR spectra were recorded

with total proton decoupling. HRMS (ESI) analysis was performed by The Analytical Instrumentation

Center at School of Pharmaceutical Sciences, South-Central University for Nationalities, and (HRMS)

data were reported with ion mass/charge (m/z) ratios as values in atomic mass units.

3

Characterization data of products

8-aminoquinoline deravitives 11 (0.1 mmol, 1.0 eq.), Cu(OAc)2 (0.02 mmol, 0.2 eq.), Selectfluoro (0.15 mmol, 1.5

eq.), KH2PO4 (0.2 mmol, 2.0 eq.), and Na2SO4 (50 mg) were weighed into an oven dried Schlenk tube, and MeOH

(1mL) was added. The reaction vessel was capped and vacuum-flushed with N2 three times. The reaction was

stirred under N2 atmosphere at 80 °C and the progress of the fluorination was monitored by TLC. Upon complete

consumption of 1, the reaction was cooled to room temperature. Volatile solvent and reagents were removed by

rotary evaportion and the residue was purified by selica gel flsh chromatography using petroleum ether/EtOAc

(100:1 to 20:1) to afford fluorinated product 22.

N-(5-fluoroquinolin-8-yl)-4-methylbenzamide (2a): 45% yield, white solid. 1H NMR (600 MHz, Chloroform-d) δ

10.52 (s, 1H), 8.94-8.85 (m, 2H), 8.47 (dd, J = 8.4, 1.7 Hz, 1H), 8.01-7.94 (m, 2H), 7.56 (dd, J = 8.4, 4.2 Hz, 1H),

7.40-7.33 (m, 2H), 7.30-7.27 (m, 1H), 2.46 (s, 3H). 13C NMR (151 MHz, Chloroform-d) δ 165.48, 153.87 (d,

J=250.7 Hz), 149.22, 142.55, 139.09 (d, J=3.0 Hz), 132.28, 131.35 (d, J=3.0 Hz), 129.98 (d, J=3.0 Hz), 129.62,

127.37, 121.87 (d, J=3.0 Hz), 119.00 (d, J=3.0 Hz), 116.09 (d, J=7.6 Hz), 110.72 (d, J=19.6 Hz), 21.71. 19F NMR

(565 MHz, CDCl3) δ -129.22. HRMS (ESI): m/z = 281.1086, calcd. for C17H14ON2F ([M+H]+) 281.1090.

N-(7-fluoroquinolin-8-yl)-4-methylbenzamide: white solid. 1H NMR (600 MHz, Chloroform-d) δ 9.15 (s, 1H), 8.84

(dd, J = 4.2, 1.7 Hz, 1H), 8.19 (dd, J = 8.3, 1.7 Hz, 1H), 8.02 (d, J = 8.3 Hz, 2H), 7.69 (dd, J = 9.1, 5.2 Hz, 1H),

7.50 (t, J = 9.5 Hz, 1H), 7.44 (dd, J = 8.3, 4.2 Hz, 1H), 7.34 (d, J = 7.9 Hz, 2H), 2.46 (s, 3H). 13C NMR (151 MHz,

Chloroform-d) δ 165.42, 153.50 (d, J=255.2 Hz), 150.02, 142.81, 142.76, 136.37, 131.42, 129.50, 128.13, 125.24

(d, J=7.6 Hz), 125.13, 121.00 (d, J=1.5 Hz), 120.34 (d, J=12.1 Hz), 118.64 (d, J=24.2 Hz), 21.75. 19F NMR (565

MHz, CDCl3) δ. -108.41 HRMS (ESI): m/z =281.1084, calcd. for C17H14ON2F ([M+H]+) 281.1090.

N-(5,7-difluoroquinolin-8-yl)-4-methylbenzamide: white solid. 1H NMR (600 MHz, Chloroform-d) δ 8.90 (dd, J =

4.3, 1.7 Hz, 1H), 8.86 (s, 1H), 8.43 (dd, J = 8.4, 1.7 Hz, 1H), 7.98 (d, J= 8.2 Hz, 2H), 7.50 (dd, J = 8.4, 4.2 Hz,

1H), 7.34 (d, J = 7.9 Hz, 2H), 7.23 (t, J = 9.8 Hz, 1H), 2.46 (s, 3H). 19F NMR (565 MHz, CDCl3) δ. -106.45,

-123.32. HRMS (ESI): m/z =299.0990, calcd. for C17H13ON2F2 ([M+H]+) 299.0996.

Formatted: Superscript

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Superscript

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font color: Auto

Formatted: Superscript

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font: Italic

Formatted: Font color: Auto

Formatted: English (United States)

Formatted: English (United States), Subscript

Formatted: English (United States)

Formatted: Font: Font color: Red, (Asian) Chinese (PRC)

4

N-(5-fluoroquinolin-8-yl)benzamide (2b): 42% yield, white solid. 1H NMR (600 MHz, Chloroform-d) δ 10.55 (s,

1H), 8.95-8.87 (m, 2H), 8.48 (dt, J = 8.4, 1.7 Hz, 1H), 8.10-8.05 (m, 2H), 7.63-7.54 (m, 4H), 7.31-7.27 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 165.38, 153.86 (d, J=250.7 Hz), 149.16, 138.99 (d, J=1.5 Hz), 135.00,

131.92, 131.14 (d, J=4.5 Hz), 129.91 (d, J=3.0 Hz), 128.85, 127.26, 121.80 (d, J=3.0 Hz), 118.91 (d, J=18.1 Hz),

116.09 (d, J=7.6 Hz), 110.62 (d, J=19.6 Hz). 19F NMR (565 MHz, CDCl3) δ -128.95. HRMS (ESI): m/z =267.0927,

calcd. for C16H12ON2F ([M+H]+) 267.0934.

N-(5-fluoroquinolin-8-yl)-4-methoxybenzamide (2c): 28% yield, white solid. 1H NMR (600 MHz, Chloroform-d) δ

10.48 (s, 1H), 8.93-8.83 (m, 2H), 8.47 (dd, J = 8.4, 1.6 Hz, 1H), 8.08-7.99 (m, 2H), 7.56 (dd, J = 8.4, 4.3 Hz, 1H),

7.30-7.24 (m, 1H), 7.10-6.98 (m, 2H), 3.91 (s, 3H). 13C NMR (151 MHz, Chloroform-d) δ 164.92, 162.53, 153.68

(d, J=250.7 Hz), 149.07, 138.96 (d, J=3.0 Hz), 131.32 (d, J=4.5 Hz), 129.88 (d, J=3.0 Hz), 129.14, 127.27, 121.74

(d, J=3.0 Hz), 118.89 (d, J=3.0 Hz), 115.86 (d, J=7.6 Hz), 114.01, 110.63 (d, J=19.6 Hz), 55.51. 19F NMR (565

MHz, CDCl3) δ -129.42. HRMS (ESI): m/z = 297.1034, calcd. for C17H14O2N2F ([M+H]+) 297.1039.

4-chloro-N-(5-fluoroquinolin-8-yl)benzamide (2d): 35% yield, white solid. 1H NMR (600 MHz, Chloroform-d) δ

10.51 (s, 1H), 8.91 (dt, J = 4.1, 1.9 Hz, 1H), 8.89-8.84 (m, 1H), 8.47 (dq, J = 8.4, 1.7 Hz, 1H), 8.01 (dt, J = 8.5, 1.7

Hz, 2H), 7.57 (dt, J = 6.1, 2.9 Hz, 1H), 7.55-7.50 (m, 2H), 7.30-7.24 (m, 1H). 13C NMR (151 MHz, Chloroform-d)

δ 164.22, 153.97 (d, J=252.2 Hz), 149.22, 138.93 (d, J=3.0 Hz), 138.20, 133.35, 130.88 (d, J=4.5 Hz), 129.97 (d,

J=3.0 Hz), 129.11, 128.68, 121.87 (d, J=3.0 Hz), 118.91 (d, J=18.1 Hz), 116.16 (d, J=7.6 Hz), 110.60 (d, J=19.6

Hz). 19F NMR (565 MHz, CDCl3) δ -128.55. HRMS (ESI): m/z = 301.0539, calcd. for C16H11ON2FCl ([M+H]+)

301.0544.

N-(5-fluoroquinolin-8-yl)-3-methylbenzamide (2e): 32% yield, white solid. 1H NMR (600 MHz, Chloroform-d) δ

10.50 (s, 1H), 8.94-8.86 (m, 2H), 8.46 (dd, J = 8.4, 1.7 Hz, 1H), 7.87 (s, 1H), 7.86 (d, J=7.8 Hz, 1H), 7.55 (dd, J =

8.4, 4.2 Hz, 1H), 7.47-7.37 (m, 2H), 7.26 (d, J = 5.3 Hz, 1H), 2.49 (s, 3H). 13C NMR (151 MHz, Chloroform-d) δ

5

165.61, 153.82 (d, J=252.2 Hz), 149.14, 138.99 (d, J=3.0 Hz), 138.73, 135.00, 132.68, 131.20 (d, J=4.5 Hz),

129.88(d, J=4.5 Hz), 128.69, 128.03, 124.17, 121.77(d, J=3.0 Hz), 118.89 (d, J=18.1 Hz), 116.07 (d, J=7.6 Hz),

110.60 (d, J=19.6 Hz), 21.53. 19F NMR (565 MHz, CDCl3) δ -129.06. HRMS (ESI): m/z = 281.1084, calcd. for

C17H14ON2F ([M+H]+) 281.1090.

3-chloro-N-(5-fluoroquinolin-8-yl)benzamide (2f): 30% yield, white solid. 1H NMR (600 MHz, Chloroform-d) δ

10.50 (s, 1H), 8.93 (dd, J = 4.2, 1.6 Hz, 1H), 8.87 (dd, J = 8.6, 5.3 Hz, 1H), 8.48 (dd, J = 8.4, 1.6 Hz, 1H), 8.05 (t, J

= 1.9 Hz, 1H), 7.94 (d, J = 7.7, 1H), 7.62-7.54 (m, 2H), 7.50 (t, J = 7.8 Hz, 1H), 7.31-7.27 (m, 1H). 13C NMR (151

MHz, Chloroform-d) δ 163.93, 154.05 (d, J=252.2 Hz), 149.28, 138.95(d, J=3.0 Hz), 136.78, 135.06, 131.96,

130.80 (d, J=4.5Hz), 130.15, 129.98 (d, J=3.0 Hz), 127.67, 125.25, 121.90 (d, J=3.0 Hz), 118.92 (d, J=3.0 Hz),

116.29 (d, J=7.6 Hz), 110.59 (d, J=19.6 Hz). 19F NMR (565 MHz, CDCl3) δ -128.38. HRMS (ESI): m/z =

301.0539, calcd. for C16H11ON2FCl ([M+H]+) 301.0544.

4-fluoro-N-(5-fluoroquinolin-8-yl)benzamide (2g): 38% yield, white solid. 1H NMR (600 MHz, Chloroform-d) δ

10.50 (s, 1H), 8.91 (dd, J = 4.2, 1.6 Hz, 1H), 8.87 (dd, J = 8.6, 5.3 Hz, 1H), 8.48 (dd, J = 8.4, 1.7 Hz, 1H), 8.12

-8.06 (m, 2H), 7.57 (dd, J = 8.4, 4.2 Hz, 1H), 7.30-7.23 (m, 3H). 13C NMR (151 MHz, Chloroform-d) δ 165.83,

164.23, 164.16, 153.89 (d, J=252.2 Hz), 149.16, 138.92 (d, J=3.0 Hz), 131.16 (d, J=3.0 Hz), 130.96 (d, J=4.5 Hz),

129.95 (d, J=4.5 Hz), 129.64 (d, J=9.1 Hz), 121.82 (d, J=1.5 Hz), 118.90 (d, J=18.1 Hz), 116.07 (d, J=9.1 Hz),

115.97 (d, J=22.6 Hz), 110.59 (d, J=19.6 Hz). 19F NMR (565 MHz, CDCl3) δ -107.51, -128.74. HRMS (ESI): m/z

= 285.0833, calcd. for C16H11ON2F2 ([M+H]+) 285.0839.

4-bromo-N-(5-fluoroquinolin-8-yl)benzamide (2h): 31% yield, white solid. 1H NMR (600 MHz, Chloroform-d) δ

10.51 (s, 1H), 8.91 (dd, J = 4.3, 1.7 Hz, 1H), 8.87 (dd, J = 8.6, 5.3 Hz, 1H), 8.48 (dd, J = 8.4, 1.7 Hz, 1H), 7.96 (d,

J=8.4 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H), 7.57 (dd, J = 8.4, 4.2 Hz, 1H), 7.30-7.27 (m, 1H). 13C NMR (151 MHz,

Chloroform-d) δ 164.34, 153.99 (d, J=252.2 Hz), 149.23, 138.93 (d, J=3.0 Hz), 133.82, 132.09, 130.86 (d, J=4.5

Hz), 129.98 (d, J=3.0 Hz), 128.85, 126.70, 121.88 (d, J=3.0 Hz), 118.92 (d, J=18.1 Hz), 116.19 (d, J=9.1 Hz),

110.61 (d, J=19.6 Hz). 19F NMR (565 MHz, CDCl3) δ -128.51. HRMS (ESI): m/z = 345.0034, calcd. for

C16H11ON2FBr ([M+H]+) 345.0039.

6

N-(5-fluoroquinolin-8-yl)-2,6-dimethoxybenzamide (2i): 34% yield, white solid. 1H NMR (600 MHz,

Chloroform-d) δ 10.10 (s, 1H), 8.99 (dd, J = 7.6, 1.3 Hz, 1H), 8.78 (dd, J = 4.2, 1.7 Hz, 1H), 8.18 (dd, J = 8.2, 1.7

Hz, 1H), 7.61 (t, J = 7.9 Hz, 1H), 7.56 (dd, J = 8.3, 1.4 Hz, 1H), 7.45 (dd, J = 8.2, 4.2 Hz, 1H), 7.14 (dd, J = 11.2,

9.1 Hz, 1H), 6.64 (dd, J = 9.2, 3.3 Hz, 1H), 4.01 (d, J = 1.9 Hz, 3H), 3.83 (s, 3H). 13C NMR (151 MHz,

Chloroform-d) δ 162.92 (d, J=3.0 Hz), 153.18 (d, J=3.0 Hz), 150.80 (d, J=241.6 Hz), 148.35, 145.77 (d, J=12.1 Hz)

138.60, 136.44, 134.76, 128.10, 127.60, 121.97, 121.73, 117.79 (d, J=21.1 Hz), 117.01, 106.10 (d, J=7.6 Hz),

62.32 (d, J=4.5 Hz), 56.49. 19F NMR (565 MHz, CDCl3) δ -139.30, -139.33. HRMS (ESI): m/z = 327.1140, calcd.

for C18H16O3N2F ([M+H]+) 327.1145.

2,3,4,5,6-pentafluoro-N-(5-fluoroquinolin-8-yl)benzamide (2j): 23% yield, white solid. 1H NMR (600 MHz,

Chloroform-d) δ 10.19 (s, 1H), 8.87 (ddd, J = 4.7, 3.0, 1.7 Hz, 1H), 8.83 (ddd, J = 8.9, 5.3, 3.8 Hz, 1H), 8.48 (ddd,

J = 8.4, 4.2, 1.7 Hz, 1H), 7.58 (ddd, J = 8.5, 4.2, 2.9 Hz, 1H), 7.32-7.27 (m, 1H). 13C NMR (151 MHz,

Chloroform-d) δ 155.23, 154.61 (d, J=253.7 Hz), 149.49, 145.35 (m), 143.66 (m), 141.81 (m), 138.65 (m), 136.98

(m), 130.07 (m), 122.08, 118.90 (dd, J=18.4, 3.6 Hz), 116.99 (d, J=9.1 Hz), 116.94 (m), 110.51(dd, J=19.6, 2.8 Hz). 19F NMR (565 MHz, Chloroform-d) δ -126.79 , -139.92 (d, J = 19.0 Hz), -149.94 (d, J = 20.9 Hz), -149.99 ,

-159.64 (t, J = 19.2 Hz). HRMS (ESI): m/z = 357.0457, calcd. for C16H7ON2F6 ([M+H]+) 357.0463.

N-(5-fluoroquinolin-8-yl)thiophene-3-carboxamide (2m): 25% yield, yellow solid. 1H NMR (600 MHz,

Chloroform-d) δ 10.35 (s, 1H), 8.91 (dd, J = 4.2, 1.7 Hz, 1H), 8.85 (dd, J = 8.6, 5.4 Hz, 1H), 8.47 (dd, J = 8.4, 1.2

Hz, 1H), 8.16 (dd, J = 3.0, 1.3 Hz, 1H), 7.69 (dd, J = 5.1, 1.3 Hz, 1H), 7.57 (dd, J = 8.4, 4.2 Hz, 1H), 7.45 (dd, J =

5.0, 3.0 Hz, 1H), 7.29 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 161.07, 153.93 (d, J=250.7 Hz), 149.27,

138.93 (d, J=3.0 Hz), 138.28, 131.15 (d, J=4.5 Hz), 130.05 (d, J=4.5 Hz), 129.11, 126.95, 126.41, 121.93 (d, J=3.0

Hz), 119.02 (d, J=16.6 Hz), 116.15 (d, J=7.6Hz), 110.76 (d, J=19.6 Hz). 19F NMR (565 MHz, CDCl3) δ -129.07.

HRMS (ESI): m/z = 273.0491, calcd. for C14H10FN2OS ([M+H]+) 273.0498.

7

2-chloro-N-(5-fluoroquinolin-8-yl)benzamide (2n): 41% yield, white solid. 1H NMR (600 MHz, Chloroform-d) δ

10.33 (s, 1H), 8.92 (dd, J = 8.6, 5.4 Hz, 1H), 8.86 (dd, J = 4.2, 1.7 Hz, 1H), 8.47 (dd, J = 8.4, 1.7 Hz, 1H), 7.82 (dd,

J = 7.5, 1.9 Hz, 1H), 7.55 (dd, J = 8.4, 4.2 Hz, 1H), 7.52 (dd, J = 7.8, 1.4 Hz, 1H), 7.44 (m, 2H), 7.32-7.27 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 164.87, 154.22 (d, J=250.7 Hz), 149.38, 139.03 (d, J=3.0 Hz), 135.75,

131.74, 131.28, 131.10 (d, J=4.5 Hz), 131.07, 130.68, 130.26, 129.96 (d, J=3.0 Hz), 127.33, 121.94 (d, J=1.5 Hz),

119.00 (d, J=3.0 Hz), 116.62 (d, J=7.6 Hz), 110.67 (d, J=19.6 Hz). 19F NMR (565 MHz, CDCl3) δ -128.33. HRMS

(ESI): m/z = 301.0541, calcd. for C16H11FN2OCl ([M+H]+) 301.0544.

N-(5-fluoroquinolin-8-yl)-2-methylbenzamide (2o): 34% yield, white solid. 1H NMR (600 MHz, Chloroform-d) δ

10.02 (s, 1H), 8.91 (dd, J = 8.6, 5.4 Hz, 1H), 8.84 (dd, J = 4.2, 1.7 Hz, 1H), 8.47 (dd, J = 8.4, 1.7 Hz, 1H), 7.68 (dd,

J = 7.5, 1.4 Hz, 1H), 7.54 (dd, J = 8.4, 4.2 Hz, 1H), 7.42 (m, 1H), 7.36-7.31 (m, 2H), 7.31-7.27 (m, 1H), 2.61 (s,

3H). 13C NMR (151 MHz, Chloroform-d) δ 168.21, 154.02 (d, J=252.2 Hz), 149.25, 138.99 (d, J=4.5 Hz), 136.84,

136.60, 131.54, 131.41 (d, J=4.5 Hz), 130.53, 129.98 (d, J=3.0 Hz), 127.36, 126.17, 121.89 (d, J=3.0 Hz), 119.01

(d, J=3.0 Hz), 116.18 (d, J=7.6 Hz), 110.67 (d, J=19.6 Hz), 20.36. 19F NMR (565 MHz, CDCl3) δ -128.88. HRMS

(ESI): m/z = 281.1084, calcd. for C17H14ON2F ([M+H]+) 281.1090.

N-(5-fluoroquinolin-8-yl)pivalamide (2p): 36% yield, white solid. 1H NMR (600 MHz, Chloroform-d) δ 10.08 (s,

1H), 8.87 (dd, J = 4.3, 1.6 Hz, 1H), 8.76 (dd, J = 8.6, 5.4 Hz, 1H), 8.44 (dd, J = 8.4, 1.7 Hz, 1H), 7.53 (dd, J = 8.4,

4.2 Hz, 1H), 7.21 (t, J = 9.2 Hz, 1H), 1.43 (s, 9H). 13C NMR (151 MHz, Chloroform-d) δ 177.25, 153.67 (d,

J=250.7 Hz), 149.18, 139.09 (d, J=3.0 Hz), 131.36 (d, J=3.0 Hz), 129.90 (d, J=4.5 Hz), 121.74 (d, J=3.0 Hz),

118.91 (d, J=18.1 Hz), 115.78 (d, J=7.6 Hz), 110.62 (d, J=19.6 Hz), 40.40, 27.85. 19F NMR (565 MHz, CDCl3) δ

-129.76. HRMS (ESI): m/z = 247.1241, calcd. for C14H16ON2F ([M+H]+) 247.1247.

N-(5-fluoroquinolin-8-yl)cyclohexanecarboxamide (2q): 30% yield, white solid. 1H NMR (600 MHz,

Chloroform-d) δ 9.70 (s, 1H), 8.87 (dd, J = 4.2, 1.6 Hz, 1H), 8.75 (dd, J = 8.6, 5.4 Hz, 1H), 8.44 (dd, J = 8.4, 1.5

Hz, 1H), 7.53 (dd, J = 8.4, 4.2 Hz, 1H), 7.21 (t, J = 9.2 Hz, 1H), 2.47 (tt, J = 11.8, 3.6 Hz, 1H), 2.13-2.03 (m, 2H),

1.88 (dt, J = 12.9, 3.5 Hz, 2H), 1.64 (m, 3H), 1.39 (m, 2H), 1.32 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ

174.89, 153.66 (d, J=250.7 Hz), 149.07, 138.81 (d, J=3.0 Hz), 131.31 (d, J=4.5 Hz), 129.95 (d, J=4.5 Hz), 121.75

(d, J=1.5 Hz), 118.91 (d, J=18.1 Hz), 116.01 (d, J=7.5 Hz), 110.65 (d, J=19.6 Hz), 46.97, 29.88, 25.90, 25.89. 19F

NMR (565 MHz, CDCl3) δ -129.68. HRMS (ESI): m/z = 273.1396, calcd. for C16H18ON2F ([M+H]+) 273.1403.

8

5-fluoroquinolin-8-amine (2r): 22% yield , yellow solid(a mixture was obtained, the yiled was calculated based on 1H NMR). 1H NMR (600 MHz, Chloroform-d) δ 8.80 (dd, J = 4.2, 1.7 Hz, 1H), 8.09 (dd, J = 8.3, 1.7 Hz, 1H), 7.36

(dd, J = 8.3, 4.2 Hz, 1H), 7.31 (dd, J = 10.5, 8.9 Hz, 1H), 7.13 (dd, J = 8.9, 5.5 Hz, 1H), 4.87 (s, 2H). 13C NMR

(151 MHz, Chloroform-d) 149.46 (d, J=237.1 Hz), 148.36, 139.48 (d, J=9.1 Hz), 136.20, 130.34 (d, J=12.1 Hz),

125.61, 120.50 (d, J=3.0 Hz), 116.99 (d, J=22.6 Hz), 115.47 (d, J=9.1 Hz). 19F NMR (565 MHz, CDCl3) δ

-134.8584. HRMS (ESI): m/z = 163.06660665, calcd. for C9H8N2F ([M+H]+) 163.0672.

References 1. V. G. Zaitsev, D. Shabashov, O. Daugulis, J. Am. Chem. Soc., 2005, 127, 13154. 2. J. Ding, Y. Zhang, J. Li, Org. Chem. Front., 2017, 4, 1528.

Formatted: German (Germany)

Formatted: German (Germany)

Formatted: German (Germany)

Formatted: Font: Italic

Formatted: German (Germany)

Formatted: German (Germany)

Formatted: German (Germany)

9

NMR Spectra Images of Starting Substrates and Products

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42