ars.els-cdn.com · Web viewChemical shifts for 1H NMR spectra are reported as d in units of parts per million (ppm) downfield from SiMe 4 (0.0ppm) and relative to the signal of chloroform

Nickel Catalysed Carbonylative Sonogashira Reaction for the Synthesis of Diarylalkynones and 2-Substituted Flavones

Renuka Cha,b, Markandeya Sarma Va,b, Sridhar Chidaraa , Korupolu Raghu Babub

a Department of Medicinal Chemistry, GVK Biosciences Pvt. Ltd, IDA, Nacharam, Hyderabad, Telangana, India-500076

bDepartment of Engineering Chemistry, Andhra University, Visakhapatnam , A.P., India-530003

Corresponding author. Tel.: +918008804254; fax: +91-40 67483400;

E-mail: [email protected]

List of Contents

1) General Experimental details S2

2) Characteristic data for compounds S3

3) 1H NMR spectra of obtained compounds (3a-3u & 4a to 4j) S16-S45

4) References S46

Experimental Section

General Experimental Details

Corresponding author. Tel.: +918008804254; fax: +91-40 67483400; e-mail: [email protected]

1

Most of the chemical reagents were purchased from Aldrich and all cases, were used without

further purification. Thin layer chromatography (TLC) was performed using Merck 60 F254

precoated silica gel plate (0.2 mm thickness). Subsequent to elution, plates were visualized

using UV radiation (254 NM). Further visualization was carried out by staining with an

ethanolic solution of ninhydrin. Flash-column chromatography was performed using silica

gel (100-200 mesh) with commercially available solvents. 1H NMR spectra were recorded on

Bruker avance III HD, 400 and 500 MHZ spectrophotometers using TMS as an internal

standard. Chemical shifts for 1H NMR spectra are reported as d in units of parts per million

(ppm) downfield from SiMe4 (0.0ppm) and relative to the signal of chloroform-d (7.26ppm).

DMSO-d6 (2.50ppm) multiplicities were given as: s (singlet); d (doublet); t (triplet); q

(quartet); or m (multiplet). Coupling constants are reported as a J value in hertz. Melting

points were recorded on a Büchi Melting Point B-545.Experimental procedure for the synthesis of substituted aryl and α, β-alkynyl ketones:

A mixture of aryl iodide (2 mmol), aryl alkyne (2.4 mmol), Ni(OAc) 2 (10 mol %), Et3N (6

mmol) and 1,4-dioxane (15 mL) were charged into the reactor (steel bomb). The reactor was

closed and pressurized to ~2bar CO and then stirred at 100 °C for 4 h. The reaction Progress

was monitored by TLC. The reaction mixture was cooled to room temperature, before being

filtered through a pad of Celite. The filtrate was concentrated and purified by silica gel with a

mixture of hexane and ethyl acetate to give the pure product.

For all examples, reactions were performed on 100 mg scale of corresponding aryl iodides.

Characteristic data for compounds 1-(4-nitrophenyl)-3-phenylprop-2-yn-1-one 6(3a)

2

The product was purified by flash chromatography to give 88 mg (88%) as a pale yellow

solid. m.p. 158-160 ℃. 1H NMR (500 MHz, TFA-d) δ=8.59 (d, J = 7 Hz, 2H), 8.52 (d, J = 7

Hz, 2H), 7.78 (d, J = 8 Hz, 2H), 7.64 (t, J = 16.5 Hz, 1H), 7.53 (t, J = 15.5 Hz, 2H). HRMS

(ESI-TOF) m/z calcd. for C15H10NO3 [M+H]+ 252.0661, found: 252.0658.

1-(3, 5-dimethylphenyl)-3-phenylprop-2-yn-1-one1 (3b)

The product was purified by flash chromatography to give 83 mg (82%) as a viscous liquid.

1H NMR (500 MHz, DMSO-d6 ) δ = 8.22 (d, J = 8 Hz, 1H), 7.76 (d, J = 7Hz, 2H), 7.60 (t, J

= 14.5Hz, 1H), 7.5 ( t, J = 8 Hz, 2H), 7.29 (d, J = 8Hz, 1H), 7.20 (s, 1H), 2.55 (s, 3H), 2.37

(s, 3H). HRMS (ESI-TOF) m/z calcd. for C17H15O [M + H] + 235.1123, found: 235.1118.

1-(2, 6-dichloropyridin-4-yl)-3-phenylprop-2-yn-1-one 2 (3c)

The product was purified by flash chromatography to give 65 mg (65%) as pale yellow

viscous liquid. 1H NMR (500 MHz, DMSO-d6) δ= 8.08 (s, 2H), 7.90 (d, J = 7 Hz, 2H), 7.66

(t, J = 15.5 Hz, 1H), 7.58 (t, J = 15.5 Hz, 2H). HRMS (ESI-TOF) m/z calcd. for C14H8Cl2NO

[M + H] + 275.9982, found: 275.9980

4-(3-phenylpropioloyl) benzonitrile3 (3d)

3

The product was purified by flash chromatography to give 74 mg (72%) as an off-white solid.

m. p. 138-140 °C. 1H NMR (500 MHz, DMSO-d6) δ= 8.34 (d, J = 7 Hz, 2H), 8.11 (d, J = 7

Hz, 2H), 7.87 (d, J = 7 Hz, 2H), 7.66 (t, J = 13.5 Hz, 1H), 7.57 (t, J = 15 Hz, 2H). HRMS

(ESI-TOF) m/z calcd. for C16H10NO [M + H] + 232.0762, found: 232.0763.

4-(3-(4-tert-butylphenyl) propioloyl) benzonitrile (3e)

The product was purified by flash chromatography to give 92 mg (74%) as a white solid. m.

p. 134-136 ℃. 1H NMR (500 MHz, DMSO-d6) δ= 8.33 (d, J = 8.5 Hz, 2H), 8.11 (d, J =

8.5Hz, 2H), 7.79 (d, J = 8.5Hz, 2H), 7.58 (d, J = 8.5Hz, 2H), 1.31 (s, 9H). HRMS (ESI-TOF)

m/z calcd. for C20H18NO [M + H] + 288.1312, found: 288.1314.

Methyl 4-(3-(4-tert-butylphenyl) propioloyl) benzoate (3f)

The product was purified by flash chromatography to give 96 mg (79%) as an off- white

solid. m. p. 92-94 ℃. 1H NMR (500 MHz, DMSO-d6) δ= 8.31 (d, J = 8 Hz, 2H), 8.18 (d, J =

8 Hz, 2H), 7.79 (d, J = 8.5 Hz, 2H), 7.58 (d, J = 8.5 Hz, 2H), 3.91 (s, 3H), 1.33 (s, 9H).

HRMS (ESI-TOF) m/z calcd. for C21H21 O3 [M + H] + 321.1491, found: 321.1482.

1-(4-nitrophenyl)-3-(pyridin-3-yl) prop-2-yn-1-one4 (3g)

4

The product was purified by flash chromatography to give 69 mg (69%) as a yellow solid. m.

p. 170-172 ℃. 1H NMR (500 MHz, DMSO-d6) δ= 9.06 (d, J = 2 Hz, 1H), 8.79 (dd, J =

1.5Hz, 5 Hz, 1H), 8.47 (d, J = 9 Hz, 2H), 8.41 (d, J = 8.5 Hz, 2H), 8.32 (td, 1H), 7.62 (dd, J =

5 Hz, 8Hz, 1H). HRMS (ESI-TOF) m/z calcd. for C14H9N2O3 [M + H] + 253.0613, found:

253.0607.

1-(4-isopropylphenyl)-3-(2-methoxyphenyl) prop-2-yn-1-one (3h)

The product was purified by flash chromatography to give 88 mg (78%) as viscous liquid. 1H

NMR (500 MHz, DMSO-d6) δ= 8.16(d, J = 8.5 Hz, 2H), 7.72 (d, J = 7.5 Hz, 1H) , 7.60 (t, J =

16 Hz, 1H ), 7.52 (d, J = 8 Hz, 2H), 7.21 (d, J = 8Hz, 1H ), 7.08 (t, J = 15 Hz, 1H) , 3.97 (s,

3H), 3.04-2.99 (m, 1H), 1.25 (d, J=7 Hz, 6H). HRMS (ESI-TOF) m/z calcd. for C19H19O2 [M

+ H] + 279.1385, found: 279.1375.

1-(3, 5-dimethylphenyl)-3-(4-nitrophenyl) prop-2-yn-1-one (3i)

The product was purified by flash chromatography to give 91 mg (75%) as a pale yellow

solid. m.p. 151-152 ℃. 1H NMR (500 MHz, DMSO-d6) δ= 8.33 (d, J =8.5 Hz, 2H), 8.26 (d,

5

J =8 Hz, 1H), 8.04 (d, J =9 Hz, 2H), 7.30 (d, J =8 Hz, 1H), 7.22 (s, 1H), 2.56 (s, 3H), 2.38

(s, 3H). HRMS (ESI-TOF) m/z calcd. for C17H14NO3 [M + H] + 280.0974, found: 280.0969.

3-(2-methoxyphenyl)-1-m-tolylprop-2-yn-1-one (3j)

The product was purified by flash chromatography to give 94 mg (82%) as a pale yellow

solid. m.p. 52-54 °C. 1H NMR (500 MHz, DMSO-d6 ) δ= 8.04 (s, 1H), 8.03 (d, J = 7.5 Hz,

1H), 7.72 (d, J = 7.5Hz, 1H), 7.61 (d, 9Hz, 1H), 7.58 (t, J = 6.5Hz, 1H), 7.54(t, J = 15Hz, 1H)

,7.22(d, J = 8.5Hz, 1H),7.09 (t, J = 15Hz, 1H), 3.97 (s, 3H), 2.44 (s, 3H). HRMS (ESI-TOF)

m/z calcd. for C17H15O2 [M + H] + 251.1072, found: 251.1067.

Methyl 4-(3-phenylpropioloyl) benzoate5 (3k)

The product was purified by flash chromatography to give 77 mg (77%) as off white solid. m.

p. 106-108 °C. 1H NMR (500 MHz, DMSO-d6) δ= 8.32 (d, J = 7Hz, 2H), 8.18 (d, J = 6.5Hz,

2H), 7.86 (d, J = 7Hz, 2H), 7.65 (t, J = 16Hz, 1H), 7.57 (t, J = 15Hz, 2H), 3.91 (s, 3H).

HRMS (ESI-TOF) m/z calcd. for C17H13O3 [M + H] + 265.0865, found: 265.0862.

3-phenyl-1-(4-(trifluoromethyl) phenyl) prop-2-yn-1-one 3(3l)

6

The product was purified by flash chromatography to give 78 mg (78%) as pale yellow solid.

m.p. 74-78 °C. 1 HNMR (500 MHz, DMSO-d6) δ= 8.39 (d, J = 8Hz, 2H), 8.01 (d, J = 8.5Hz,

2H), 7.86 (d, J = 7Hz, 2H), 7.64 (t, J = 7.5Hz, 1H), 7.58 (t, J = 15Hz, 2H). HRMS (ESI-TOF)

m/z calcd. for C16H10F3O [M + H] + 275.0684, found: 275.0675.

1-(4-chlorophenyl)-3-o-tolylprop-2-yn-1-one (3m)

The product was purified by flash chromatography to give 75 mg (71%) as pale yellow solid.

m.p. 88-90 °C. 1H NMR (500 MHz, DMSO-d6) δ= 8.19 (d, J = 9 Hz, 2H), 7.78 (d, J = 7.5Hz,

1H), 7.72 (d, J = 9Hz, 2H), 7.52 (t, J = 16Hz, 1H), 7.44 (d, J = 7.5 Hz, 1H), 7.36 (t, J = 15Hz,

1H), 2.51 (s, 3H). HRMS (ESI-TOF) m/z calcd. for C16H12ClO [M + H] + 255.0577, found:

255.0573.

1-(2-aminophenyl)-3-(pyridin-3-yl) prop-2-yn-1-one (3n)

The product was purified by flash chromatography to give 80 mg (79%) as pale yellow solid.

m.p. 116-118 °C. 1H NMR (500 MHz, DMSO-d6) δ= 8.94 (dd, J = 0.5Hz, 2Hz, 1H), 8.72 (dd,

J = 1.5Hz, 5Hz, 1H), 8.20 (dt, 1H), 8.10 (d, J = 8.5Hz, 1H), 7.56 (dd, J = 8Hz, 5Hz, 1H),

7.49 (bs, 2H), 7.374 ( t, J = 17Hz, 1H), 6.84 (d, J = 8.5Hz, 1H), 6.67 (t, J =16Hz, 1H).

HRMS (ESI-TOF) m/z calcd. for C14H11N2O [M + H] + 223.0871, found: 223.0867.

1-(2-aminophenyl)-3-phenylprop-2-yn-1-one 6 (3o)

7

The product was purified by flash chromatography to give 86 mg (85%) as pale yellow solid.

m.p. 63 -65 °C. 1H NMR (500 MHz, DMSO-d6) δ= 8.08 (dd, J = 1.5Hz, 8 Hz, 1H), 7.76 (d,

7Hz, 2H), 7.59 (t, J = 13.5Hz, 1H), 7.55 (t, J = 29Hz, 2H), 7.46 (bs, 2H), 7.36 (t, J = 10Hz,

1H), 6.83 (d, 8.5Hz, 1H), 6.67 (t, J = 9Hz, 1H). HRMS (ESI-TOF) m/z calcd. for C15H12NO

[M + H] + 222.0919, found: 222.0917.

Methyl 4-(3-(2-methoxyphenyl) propioloyl) benzoate (3p)

The product was purified by flash chromatography to give 96 mg (86%) as off-white solid.

m. p. 128-130 °C. 1H NMR (500 MHz, DMSO-d6) δ= 8.34 (d, J = 8Hz, 2H), 8.20 (d, J = 8.5,

2H), 7.76 (d, J = 7.5Hz, 1H), 7.63 (t, J = 15.5Hz, 1H), 7.23 (d, J = 8.5 Hz, 1H ), 7.10 (t, J =

15 Hz, 1H), 3.98 (s, 3H), 3.91 (s, 3H). HRMS (ESI-TOF) m/z calcd. for C18H15O4 [M + H] +

295.0970, found: 295.0962.

3-(2-methoxyphenyl)-1-(naphthalen-2-yl) prop-2-yn-1-one (3q)

The product was purified by flash chromatography to give 81 mg (72%) as pale yellow solid.

m. p.76-78 °C. 1H NMR (500 MHz, DMSO-d6) δ= 9.13 (d, J = 8.5Hz, 1H), 8.81 (d, J = 7Hz,

1H), 8.33 (d, J = 8.5 Hz ,1H), 8.11 (d, J = 8Hz, 1H), 7.81 (t, J = 15.5Hz, 1H), 7.76 (t, J

=15.5Hz, 2H), 7.68 (t, J = 14.5Hz, 1H), 7.60 (t, J = 15.5Hz, 1H) 7.22 (d, J = 8.5Hz, 1H), 7.09

(t, J = 15Hz, 1H), 3.97 (s, 3H). HRMS (ESI-TOF) m/z calcd. for C20H15O2 [M + H] +

287.1072, found: 287.1063.

Methyl 4-(3-o-tolylpropioloyl) benzoate (3r)

8

The product was purified by flash chromatography to give 107 mg (88%) as pale brown

viscous liquid. 1H NMR (500 MHz, DMSO-d6) δ= 8.12 (d, J = 8Hz, 2H), 7.74 (d, J = 8.5Hz,

2H), 7.66 (d, J = 8.5Hz , 2H), 7.57 (d, J = 8Hz, 2H), 1.33 (s, 18H). HRMS (ESI-TOF) m/z

calcd. for C23H27O [M + H] + 319.2062, found: 319. 2050.

1-(4-bromophenyl)-3-(pyridin-3-yl) prop-2-yn-1-one7 (3s)

The product was purified by flash chromatography to give 73 mg (73%) as a dark red solid.

m.p. 62-64 °C. 1H NMR (500MHz, DMSO-d6) δ= 8.95 (d, J = 1.5Hz, 1H), 8.75 (dd, J =

1.5Hz, 5 Hz, 1H), 8.23 (t, J = 15 Hz, 2H), 7.84 (d, J = 7.5Hz, 1H), 7.64-7.55 (m, 4H). HRMS

(ESI-TOF) m/z calcd. for C14H9BrNO [M + H] + 285.9868, found: 285.9859.

Methyl 4-(3-o-tolylpropioloyl) benzoate (3t)

The product was purified by flash chromatography to give 98 mg (86%) as a pale yellow

solid. m. p. 139-141 °C. 1H NMR (500 MHz, DMSO-d6) δ= 8.33 (d, J = 7 Hz, 2H), 8.09 (d, J

= 7.5 Hz, 2H), 7.84 (d, J = 7 Hz, 2H), 7.11 (d, J = 7.5 Hz, 2H), 3.86 (s, 3H). HRMS (ESI-

TOF) m/z calcd. for C17H12NO2 [M + H] + 262.0868, found: 262.0872.

1-m-tolyl-3-p-tolylprop-2-yn-1-one (3u)

9

The product was purified by flash chromatography to give 93 mg (88%) as pale yellow solid.

m. p. 110-112 °C. 1H NMR (500 MHz, DMSO-d6) δ= 8.13 (d, J = 8 Hz, 2H), 7.72 (dd, J =

1.5Hz, 7.5Hz, 1H), 7.60 (t, J = 16Hz, 1H), 7.45 (d, J = 8Hz, 2H), 7.21 (d, J = 8.5Hz, 1H),

7.08(t, J = 14Hz, 1H), 3.96 (s, 3H), 2.43 (s, 3H). HRMS (ESI-TOF) m/z calcd. for C18H15O3

[M + H] + 279.0943, found: 279.0945.

2-phenyl-4H-chromen-4-one (4a) 8

The product was purified by flash chromatography to give 85 mg (85%) as off-white solid.

m.p. 101-103 °C. 1H NMR (500 MHz, DMSO-d6) δ = 8.12-8.11 (m, 2H), 8.07 (dd, J = 8Hz,

1.5Hz, 1H), 7.86-7.83 (m, 1H), 7.81(dd, J = 8.5Hz, 0.5Hz, 1H), 7.62-7.58(m, 3H), 7.53(t,

J=16 Hz, 1H), 7.04 (s, 1H). HRMS (ESI-TOF) m/z calcd. for C15H11O2 [M + H] + 223.0759,

found: 223.0751.

2- (pyridine-3-yl)-4H-chromen-4-one (4b) 9

The product was purified by flash chromatography to give 76 mg (75%) as pale brown solid.

m. p. 116-118 °C. 1H NMR (500 MHz, DMSO-d6) δ= 9.32 (d, J = 2 Hz, 1H), 8.79 (dd, J =5

Hz, J = 1.5Hz, 1H), 8.51(dt, J =2Hz, 2H), 8.08(dd, J = 8Hz 1H), 7.88(m, 1H) ,7.64-7.44(dd,

J = 4.5Hz, 0.5Hz, 2H), 7.54(td, 1H), 7.18 (s, 1H). HRMS (ESI-TOF) m/z calcd. for

C14H10NO2 [M + H] + 224.0712, found: 224.0704.

10

2- Butyl -4H-chromen-4-one (4c) 10

The product was purified by flash chromatography to give 66 mg (72%) as pale yellow

viscous liquid. 1H NMR (500 MHz, DMSO-d6) δ = 8.01(dd, J = 8Hz, 1.5Hz, 1H), 7.79-7.76

(m, 1H), 7.62 (dd, J = 8.5Hz, 0.5 Hz, 1H), 7.47-7.44( m, 1H), 6.24 (s, 1H) , 2.68 (t, J = 15Hz,

2H), 1.70-1.64(m ,2H), 1.41-1.34(m, 2H) 0.93 (t, J = 14.5Hz, 3H). HRMS (ESI-TOF) m/z

calcd. for C13H15O2 [M + H] + 203.1072, found: 203.1065.

2-(4- amino phenyl)-4H-chromen-4-one (4d) 11

The product was purified by flash chromatography to give 85 mg (80%) as a pale brown

solid. m.p. 154-156°C. 1H NMR (500 MHz, DMSO-d6) δ= 8.06 (dd, J = 6.5 Hz, 1.5 Hz, 1H),

7.85-7.82 (m, 1H), 7.73 (d, J = 8Hz ,1H), 7.52-7.49(m, 1H), 7.24 (d, J = 1.5Hz, 1H), 7.21-

7.19(m, 2H), 6.80 (s,1H), 6.79-6.78(m, 1H), 5.40 (brs, 2H). HRMS (ESI-TOF) m/z calcd. for

C15H12NO2 [M + H] + 238.0868, found: 238.0860.

2-(4- Nitro phenyl)-4H-chromen-4-one (4e) 12

The product was purified by flash chromatography to give 78 mg (65%) as yellow solid. m.p.

202-206 °C. 1H NMR (500 MHz, DMSO-d6) δ= 8.34 (d, J = 2 Hz, 2H), 8.29 (d, J = 2Hz,

2H), 7.87-7.83 (m, 2H), 7.59 (d, J = 2Hz, 1H), 7.38 (td, J = 8Hz, 0.5 Hz, 1H), 7.07 (s, 1H).

HRMS (ESI-TOF) m/z calcd. for C15H10NO4 [M + H] + 268.0610, found: 268.0608.

11

2- o-tolyl-4H-chromen-4-one (4f) 13

The product was purified by flash chromatography to give 80 mg (75%) as off-white solid.

m. p. 102-114 °C. 1HNMR (500 MHz, DMSO-d6) δ= 8.18 (d, J = 6 Hz, 1H), 7.83-7.80 (m,

2H), 7.57 (d, J = 8Hz, 1H), 7.38-7.32 (m, 4H), 7.01 (s, 1H), 2.47 (s, 3H). HRMS (ESI-TOF)

m/z calcd. for C16H13O2 [M + H] + 237.0196, found: 238.0916

2, (2-Chloro phenyl)-4H-chromen-4-one (4g) 14

12

The product was purified by flash chromatography to give 99 mg (85%) as pale-yellow solid.

m .p . 115-119 °C. 1H NMR (500 MHz, DMSO-d6) δ= 8.35 (d, J = 7.5 Hz, 1H), 7.86-7.82 (m,

2H), 7.65 (d, J = 8Hz, 1H), 7.59 (d, J = 8.5 Hz, 1H), 7.56 (t, J = 15.5 Hz, 1H), 7.512 (t, J =

15.5 Hz, 1H), 7.37 (t, J = 15.5 Hz, 1H), 7.10 (s, 1H). HRMS (ESI-TOF) m/z calcd. for

C15H10ClO2 [M+H] + 257.0369, found 257.0357.

2-(4-methoxyphenyl)-4H-chromen-4-one (4h) 9

The product was purified by flash chromatography to give 93 mg (82%) as isolated as off-

white solid. m.p. 124-129 °C. 1H NMR (500 MHz, DMSO-d6) δ= 8.09 (d, J = 9Hz, 2H), 8.05

(d, J = 8 Hz, 1H), 7.84 (t, J = 15.5Hz, 1H), 7.79 (d, J = 8Hz, 1H), 7.51 (t, J = 16Hz 1H), 7.14

(d, J = 9 Hz 2H), 6.96 (s, 1H), 3.86 (s, 3H). HRMS (ESI-TOF) m/z calcd. for C16H13O3

[M+H] + 253.0865, found 253.0870.

2- cyclohexyl-4H-chromen-4-one (4i) 15

The product was purified by flash chromatography to give 54 mg (54%) as yellow liquid.

1H NMR (500 MHz, DMSO-d6) δ= 8.01 (dd, J = 1.5 Hz, 8 Hz, 1H), 7.79-7.75 (m, 1H), 7.62

(dd, J=8.5Hz, 1Hz, 1H), 7.47-7.44 ( m, 1H), 6.18 (s, 1H), 2.63 (ttd, 1H), 1.98 (dd , J=1.5Hz,

13Hz, 2H), 1.82 (td, 2H) ,1.71 (m, 1H), 1.49-1.33 (m, 4H), 1.27-1.22(m, 1H). HRMS (ESI-

TOF) m/z calcd. for C15H17O2 [M + H] + 229.1229, found: 229.1218.

13

2- cyclopentyl-4H-chromen-4-one (4j) 12

The product was purified by flash chromatography to give 40 mg (42%) as pale yellow

viscous liquid.1H NMR (400 MHz, CDCl3) δ =8.19 (d, J = 1.6Hz, 1H), 7.66 (t, J=17.2 1H),

7.43 (d, J=8Hz 1H), 7.39 ( t, J=15.2 Hz, 1H), 6.22 (s, 1H) , 3.03-2.99 (m, 1H), 2.09-2.05 (m ,

2H), 1.85-1.71(m, 6H). HRMS (ESI-TOF) m/z calcd. for C14H15O2 [M + H] + 215.1072,

found: 215.1064.

14

1H NMR (500 MHz, TFA-D) analysis of compound 3a

15

1H NMR (500 MHz, DMSO-d6) analysis of compound 3b

16

1H NMR (500 MHz, DMSO-d6) analysis of compound 3c

17

1H NMR (500 MHz, DMSO-d6) analysis of compound 3d

18

1H NMR (500 MHz, DMSO-d6) analysis of compound 3e

19

1H NMR (500 MHz, DMSO-d6) analysis of compound 3f

20

1H NMR (500 MHz, DMSO-d6) analysis of compound 3g

21

1H NMR (500 MHz, DMSO-d6) analysis of compound 3h

22

1H NMR (500 MHz, DMSO-d6) analysis of compound 3i

23

1H NMR (500 MHz, DMSO-d6) analysis of compound 3j

24

1H NMR (500 MHz, DMSO-d6) analysis of compound 3k

25

1H NMR (500 MHz, DMSO-d6) analysis of compound 3l

26

1H NMR (500 MHz, DMSO-d6) analysis of compound 3m

27

28

1H NMR (500 MHz, DMSO-d6) analysis of compound 3n

1H NMR (500 MHz, DMSO-d6) analysis of compound 3o

29

30

1H NMR (500 MHz, DMSO-d6) analysis of compound 3p

31

1H NMR (500 MHz, DMSO-d6) analysis of compound 3q

32

1H NMR (500 MHz, DMSO-d6) analysis of compound 3r

33

1H NMR (500 MHz, DMSO-d6) analysis of compound 3s

34

1H NMR (500 MHz, DMSO-d6) analysis of compound 3t

35

1H NMR (500 MHz, DMSO-d6) analysis of compound 3u

36

1H NMR (500 MHz, DMSO-d6) analysis of compound 4a

37

1H NMR (500 MHz, DMSO-d6) analysis of compound 4b

38

1H NMR (500 MHz, DMSO-d6) analysis of compound 4c

39

1H NMR (500 MHz, DMSO-d6) analysis of compound 4d

40

1H NMR (400 MHz, CDCl3) analysis of compound 4e

41

1H NMR (500 MHz, DMSO-d6) analysis of compound 4f

42

1H NMR (500 MHz, DMSO-d6) analysis of compound 4g

43

1H NMR (500 MHz, DMSO-d6) analysis of compound 4h

44

1H NMR (500 MHz, DMSO-d6) analysis of compound 4i

1H NMR (400 MHz, CDCl3) analysis of compound 4j

45

References and notes

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1. Tang, T.; Fei, X. D.; Ge, Z. Y.; Chen, Z.; Zhu, Y. M.; Ji, S. J. J. Org. Chem. 2013, 78, 3170.

2. Boersch, C.; Merkul, E.; Müller, T. J. Angew. Chem., Int. Ed. 2011, 50, 10448.

3. Bai, C.; Jian, S.; Yao, X.; Li, Y. Catal. Sci. Technol. 2014, 4, 3261.

4. Bakherad, M.; Keivanloo, A.; Bahramian, B.; Jajarmi, S. Synlett. 2011, 311.

5. Tan, C.; Wang, P.; Liu, H.; Zhao, X. L.; Lu, Y.; Liu, Y. Chem. Commun. 2015, 51, 10871.

6. Zhang, C.; Liu, J.; Xia, C. Org. Biomol. Chem. 2014, 12, 9702.

7. Zhao, T.; Xu, B. Org. Lett. 2010, 12, 212.

8. Xue, L.; Shi, L.; Han, Y.; Xia, C.; Huynh, H. V.; Li, F. Dalton Trans. 2011, 40, 7632.

9. Zhu, F.; Li, Y.; Wang, Z.; Wu, X. F. Catal. Sci. Technol. 2016, 6, 2905.

10. Awuah, E.; Capretta, A. Org. Lett. 2009, 11, 3210.

11. Cushman, M.; Nagarathnam, D.; Burg, D. L.; Geahlen, R. L. J. Med. Chem. 1991, 34, 798.

12. Baruah, S.; Kaishap, P. P.; Gogoi, S. Chem. Commun. 2016, 52, 13004.

13. Wu, X. F.; Neumann, H.; Beller, M. Chem. - Eur. J. 2012, 18, 12595

14. Lim, D. S.; Lim, D. H.; Lee, J. H.; Oh, E. T.; Keum, Y. S. J. Agric. Food Chem.

2017, 65, 3056.

15. Wen, S. S.; Wang, J.; Luo, Y. M.; Yang, H. Tetrahedron 2014, 70, 9314.

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