One-pot synthesis of 4(3H)-quinazolinones from azides, alkynes, anilines, and carbon monoxide

Article abstract of DOI:10.1016/j.tetlet.2012.08.045

A one-pot synthesis of 4(3H)-quinazolinones from terminal alkynes, sulphonyl azide, o-iodoanilines, and carbon monoxide has been developed. This cascade process includes the copper-catalyzed three-component reaction of alkyne, azide and amine, the palladium-catalyzed carbonylation, and the Lewis acid catalyzed hydrolysis of sulfonamide.

Full text of DOI:10.1016/j.tetlet.2012.08.045

One-pot Synthesis of 4(3H)-Quinazolinones from
Azides, Alkynes, Anilines, and Carbon Monoxide
*
Yang Shen, Chao Han, Shuying Cai, Ping Lu and Yanguang Wang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, China
E-mail: pinglu@zju.edu.cn (P. Lu); orgwyg@zju.edu.cn (Y. G. Wang)
Contents
General Considerations
S2
S2
General Procedure for the Synthesis of 4
Characterization of 4
S2-S3
S5-S6
General Procedure for the Synthesis of 5
Characterization of 5
S6-S13
S14
General Procedure for the Synthesis of 6
Characterization of 6
S14-S15
S15-S58
Copies of NMR Spectra of 4, 5 and 6
1

General Considerations
1
Infrared spectra were obtained on a FTIR spectrometer. H NMR spectra were
recorded on 400 MHz spectrometer unless noted otherwise and the chemical shifts
were reported relative to internal standard TMS (0 ppm). The following abbreviations
are used to describe peak patterns where appropriate: b = broad, s = singlet, d =
doublet, t = triplet, q = quartet, m = multiplet. Coupling constants are reported in
1
3
Hertz (Hz). C NMR were recorded on 100 MHz unless noted otherwise and
referenced to the internal solvent signals (central peak is 77.0 ppm for CDCl or 40.0
3
ppm for DMSO-d6). MS and HRMS were obtained using EI ionization. Melting
points were measured with micro melting point apparatus.
General Procedure for the synthesis of amidine 4
To a solution of alkyne 1 (1.2 mmol), azide 2 (1.2 mmol), 2-iodoaniline 3 (1.0
mmol), and CuI (0.1 mmol) in THF (5 mL) was slowly added TEA (1.2 mmol) via a
syringe under nitrogen atmosphere over 3-5 min. The reaction mixture was stirred at
room temperature for 12 h. The solution was diluted with ethyl acetate (20 mL),
washed with water (10 mL) and then brine (10 mL), and dried over sodium sulfate.
The solvent was removed in vacuum and the residue was subject to flash
chromatography on silica gel (petroleum ether/ethyl acetate, 3:1 to 1:2) to afford pure
4
.
2

Characterization of 4
O
N S
CH3
O
HN
I
4a
o
Yellow solid, (446mg, 91%) m.p. 137~138 C; IR 3431, 3232, 1590, 1563, 1524, 1280,
-1 1
1
143, 1096 cm ; H NMR (CDCl
3
, 500 MHz): δ 8.09-7.40 (m, 7H), 7.29 (d, J=8.0Hz,
1
3
2
H), 7.22-6.80 (m, 4H), 4.52 (s, 1.4H), 3.49 (s, 0.5H), 2.42 (s, 3H) ppm; C NMR
(
CDCl , 125 MHz): δ 164.1, 142.7, 140.1, 139.0, 137.4, 132.4, 131.1, 129.9, 129.4,
3
-
1
28.9, 128.7, 127.2, 126.5, 123.5, 90.9, 40.9, 21.6 ppm; MS (ESI) m/z 489 ([M-H] );
+
HRMS (EI): m/z calcd for C21
H
19
N O
2 2
SI ([M] ): 490.0212; found: 490.0209.
o
Yellow solid, (470mg, 88%) m.p. 150~151 C; IR 3414, 3265, 1530, 1349, 1286, 1146,
-
1 1
1
7
1
1
087, 760 cm ; H NMR (CDCl , 500 MHz): δ 9.91 (s, 0.6H), 8.28-7.66 (m, 6H),
3
1
3
3
.39-6.85 (m, 6H), 4.63 (s, 0.6H), 3.58 (s, 1H), 2.44 (s, 3H) ppm; C NMR (CDCl ,
25 MHz): δ 164.0, 162.0, 151.0, 147.2, 147.2, 143.6, 141.1, 140.0, 139.0, 138.5,
36.9, 131.6, 130.5, 129.5, 129.0, 127.6, 126.7, 124.6, 124.0, 123.5, 99.3, 40.5, 21.6
-
+
ppm; MS (ESI) m/z 534.7 ([M-H] ); HRMS (EI): m/z calcd for C21
18 3 4
H N O SI ([M] ):
5
35.0063; found: 535.0073.
3

o
Pale purple solid, (455mg, 87%) m.p. 147~148 C; IR 3435, 3311, 1600, 1566, 1520,
-1 1
1
3
283, 1150, 715, 701 cm ; H NMR (CDCl , 500 MHz): δ 8.04-6.84 (m, 12H), 4.52
1
3
(
s, 1.6H), 3.48 (s, 0.3H), 2.43 (s, 3H) ppm; C NMR (CDCl
3
, 125 MHz): δ 164.1,
1
1
42.9, 139.9, 138.1, 136.2, 132.2, 131.2, 131.0, 129.9, 129.4, 128.9, 128.8, 126.5,
-
23.7, 90.7, 40.8, 21.6 ppm; MS (ESI) m/z 523.5 ([M-H] ); HRMS (EI): m/z calcd for
+
C
21
H
18
N
2
O
2
SClI ([M] ): 523.9822; found: 523.9826.
O
N S
O
CH3
HN
Br
4d
o
White solid, (398mg, 90%) m.p. 100~101 C; IR 3446, 3324, 1601, 1572, 1536, 1438,
-
1 1
1
1
1
4
3
280, 1143, 1090 cm ; H NMR (CDCl , 500 MHz): δ 8.22-6.82 (m, 13H), 4.53 (s,
1
3
3
.6H), 3.52 (s, 0.3H), 2.43 (s, 3H) ppm; C NMR (CDCl , 125 MHz): δ 163.9, 142.7,
40.1, 134.8, 132.4, 130.8, 129.8, 129.4, 128.7, 128.1, 126.5, 126.4, 123.2, 114.8,
+
0.9, 21.6 ppm; MS (ESI) m/z 445.1 ([M+H] ); HRMS (EI): m/z calcd for
+
C
21
H
19
N
2
O
2
SBr ([M] ): 442.0351; found: 442.0354.
4

General Procedure for the Synthesis of 5
2 3
A mixture of 4 (1.0 mmol), Pd(OAc) (0.05 mmol), dppb (0.1 mmol), Et N (3.0
mmol) and tetrahydrofuran (10 mL) were sequentially added to a 25 mL beaker with a
magnetic bar in it. Then put the beaker into a 50ml autoclave. The autoclave was
closed, purged three times with carbon monoxide, pressurized with 20 atm of CO, and
then heated at 100°C for 12 h. The autoclave was removed from the oil bath and
cooled to room temperature prior to the release of excess carbon monoxide. The
reaction mixture was filtered and the filtrate was concentrated by rotary evaporation.
The residue was purified by flash chromatography on silica gel with a mixture of
hexane and ethyl acetate (2:1 to 1:1) as the eluent to afford the desired products 5.
General Procedure for the One-pot Synthesis of 5
To a solution of alkyne 1 (1.2 mmol), azide 2 (1.2 mmol), 2-iodoaniline 3 (1.0
mmol), and CuI (0.1 mmol) in THF (10 mL) was slowly added TEA (1.2 mmol) via a
syringe under nitrogen atmosphere over 3-5 min. The reaction mixture was stirred at
room temperature for 12 h. The reactions mixture was added Pd(OAc) (0.05 mmol),
2
3
dppb (0.1 mmol) and Et N (1.8 mmol). Then put the flask into a 50ml autoclave. The
autoclave was closed, purged three times with carbon monoxide, pressurized with 20
atm of CO, and then heated at 100°C for 12 h. The autoclave was removed from the
oil bath and cooled to room temperature prior to the release of excess carbon
monoxide. The reaction mixture was filtered and the filtrate was concentrated by
5

rotary evaporation. The residue was purified by flash chromatography on silica gel
with a mixture of hexane and ethyl acetate (4:1 to 1:1) as the eluent to afford the
desired products 5.
Gram Scale for the One-pot Synthesis of 5a
To a solution of phenyl acetylene 1a (7.2 mmol, 0.734g), tosyl azide 2 (7.2 mmol,
1
.418g), 2-iodoaniline 3a (6.0 mmol, 1.314g), and CuI (0.6 mmol, 0.114g) in THF (50
mL) was slowly added TEA (7.2 mmol, 1.0ml) via a syringe under nitrogen
atmosphere over 15 min. The reaction mixture was stirred at room temperature for 12
h. The reactions mixture was added Pd(OAc)
(0.3 mmol, 0.067g), dppb (0.6 mmol,
2
0
.247g) and Et N (10.8 mmol, 1.5ml). Then put the flask into a 50ml autoclave. The
3
autoclave was closed, purged three times with carbon monoxide, pressurized with 20
atm of CO, and then heated at 100°C for 12 h. The autoclave was removed from the
oil bath and cooled to room temperature prior to the release of excess carbon
monoxide. The reaction mixture was filtered and the filtrate was concentrated by
rotary evaporation. The residue was purified by flash chromatography on silica gel
with a mixture of hexane and ethyl acetate (4:1 to 1:1) as the eluent to afford the
desired products 5a in 69% yield, 983mg.
Characterization of 5
o
White solid, (174mg, 74%) m.p. 254~255 C; IR 2917, 1679, 1615, 1466, 1158, 1000,
-
1 1
7
8
1
76, 716 cm ; H NMR (d
6
-DMSO, 500 MHz): δ 8.11-8.10 (m, 1H), 7.79-7.34 (m,
1
3
H), 3.97 (s, 2H) ppm; C NMR (d -DMSO, 125 MHz): δ 162.3, 156.3, 149.4, 137.0,
6
34.9, 129.4, 129.0, 127.4, 127.3, 126.7, 126.2, 121.2, 41.3 ppm; HRMS (EI): m/z
6

+
calcd for C15H
12
N
2
O ([M] ): 236.0950; found: 236.0951.
o
Yellow solid, (145mg, 58%) m.p. 225~227 C; IR 2895, 1682, 1622, 1466, 1338, 1191,
-
1 1
1
1
000, 769 cm ; H NMR (d
6
-DMSO, 500 MHz): δ 12.38 (s, 1H), 8.10 (d, J = 8.0 Hz,
H), 7.77-7.74 (m, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.23-7.14
1
3
(
m, 4H), 3.97 (s, 2H), 2.35 (s, 3H) ppm; C NMR (d -DMSO, 125 MHz): δ 161.9,
6
155.8, 148.8, 136.6, 135.1, 134.3, 130.0, 129.2, 126.9, 126.8, 126.1, 125.9, 125.7,
-
1
20.8, 38.3, 19.5 ppm; MS (ESI) m/z 249.2 ([M-H] ); HRMS (EI): m/z calcd for
+
C
16
H
14
N
2
O ([M] ): 250.1106; found: 250.1102.
o
Yellow solid, (190mg, 76%) m.p. 202~203 C; IR 2921, 1673, 1612, 1469, 1328, 1178,
-
1 1
7
1
7
72, 691 cm ; H NMR (d
6
-DMSO, 500 MHz): δ 12.38 (s, 1H), 8.10 (d, J =8.0Hz,
H), 7.78 (t, J = 6.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.47 (t, J = 6.0 Hz, 1H),
1
3
.23-7.19 (m, 3H), 7.07-7.05 (m, 1H), 3.92 (s, 2H), 2.28 (s, 1H) ppm; C NMR
(
d6-DMSO, 125 MHz): δ 162.3, 156.4, 149.4, 138.0, 136.9, 134.8, 129.9, 128.8,
27.9, 127.4, 126.6, 126.4, 126.1, 121.2, 41.2, 21.4 ppm; MS (ESI) m/z 250.9
1
+
+
(
14 2
[M+H] ); HRMS (EI): m/z calcd for C16H N O ([M] ): 250.1106; found: 250.1107.
7

o
White solid, (192mg, 77%) m.p. 231~233 C; IR 2919, 1679, 1611, 1468, 1161, 1003,
-1 1
8
85, 773 cm ; H NMR (d
6
-DMSO, 500 MHz): δ 12.40 (s, 1H), 8.08 (d, J = 8.0 Hz,
1H), 7.77 (t, J = 8.0 Hz, 1H), 7.61 (d, J = 8.5 Hz, 1H), 7.46 (t, J = 7.5 Hz, 1H), 7.27
1
3
(
(
d, J = 8.0 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 3.89 (s, 2H), 2.25 (s, 3H) ppm; C NMR
d6-DMSO, 125 MHz): δ 161.9, 156.1, 148.9, 135.8, 134.3, 133.5, 129.0, 128.7, 126.9,
-
1
26.1, 125.7, 120.7, 40.4, 20.6 ppm; MS (ESI) m/z 249.9 ([M-H] ); HRMS (EI): m/z
+
calcd for C16H
14
N
2
O ([M] ): 250.1106; found: 250.1109.
o
Yellow solid, (178mg, 67%) m.p. 160~161 C; IR 2968, 1654, 1608, 1470, 1331, 1153,
-1 1
1
006, 779 cm ; H NMR (CDCl , 500 MHz): δ 9.69 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H),
3
7.72-7.68 (m, 2H), 7.43-7.27 (m, 3H), 6.98-6.95 (m, 2H), 4.06 (s, 2H), 3.94 (s, 3H)
1
3
ppm; C NMR (CDCl , 125 MHz): δ 162.3, 157.0, 155.2, 149.2, 134.7, 131.6, 129.6,
3
1
2
2
27.4, 126.64, 126.57, 123.4, 121.8, 121.2, 111.4, 56.0, 37.6 ppm; MS (ESI) m/z
+
66.9 ([M+H]+); HRMS (EI): m/z calcd for C16
66.1055.
H
14
N
2
O
2
([M] ): 266.1055; found:
8

o
Yellow solid, (234mg, 88%) m.p. 219~220 C; IR 2917, 1681, 1611, 1511, 1252, 1033,
-
1 1
8
1
9
20, 771 cm ; H NMR (d
6
-DMSO, 500 MHz): δ 12.40 (s, 1H), 8.12 (d, J = 7.5 Hz,
H), 7.80-7.76 (m, 1H), 7.64 (d, J = 7.5 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H), 7.35 (d, J =
1
3
.0 Hz, 2H), 6.91 (d, J = 9.0 Hz, 2H), 3.90 (s, 2H), 3.73 (s, 3H) ppm; C NMR
(
d6-DMSO, 125 MHz): δ 162.4, 158.7, 156.8, 149.5, 134.8, 130.4, 128.9, 127.4,
+
1
26.6, 126.2, 121.2, 114.4, 55.5, 40.5 ppm; MS (ESI) m/z 266.9 ([M+H] ); HRMS
+
(
EI): m/z calcd for C16
H
14
N
2
O
2
([M] ): 266.1055; found: 266.1057.
o
Pale white solid, (216mg, 82%) m.p. 229~231 C; IR 2964, 2921, 1676, 1161, 1469,
-
1 1
1
7
1
6
332, 1002, 770 cm ; H NMR (d -DMSO, 500 MHz): δ 12.39 (s, 1H), 8.10 (d, J =
.5 Hz, 1H), 7.77 (t, J = 7.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.47 (t, J = 7.5 Hz,
H), 7.32 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 3.91 (s, 2H), 2.56 (q, J = 7.5
1
3
Hz, 2H), 1.14 (t, J = 7.5 Hz, 3H) ppm; C NMR (d
6
-DMSO, 125 MHz): δ 162.3,
1
1
56.6, 149.4, 142.7, 134.8, 134.2, 129.2, 128.3, 127.4, 126.6, 126.1, 121.2, 40.9, 28.2,
+
6.0 ppm; MS (ESI) m/z 264.9 ([M+H] ); HRMS (EI): m/z calcd for C H N O
1
7
16
2
+
(
[M] ): 264.1263; found: 264.1258.
9

o
Brown solid, (210mg, 77%) m.p. 242~244 C; IR 2894, 1677, 1676, 1614, 1466, 1329,
-
1 1
1
7
1
1
162, 1011, 773 cm ; H NMR (d
6
-DMSO, 500 MHz): δ 12.44 (s, 1H), 8.08 (d, J =
.5 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 8.5 Hz, 1H), 7.47 (t, J = 7.5 Hz,
1
3
H), 7.42-7.38 (m, 4H), 3.95 (s, 2H) ppm; C NMR (d
6
-DMSO, 125 MHz): δ 161.8,
55.6, 148.8, 135.5, 134.4, 131.5, 130.8, 128.4, 126.9, 126.2, 125.7, 120.8, 40.0 ppm;
-
+
MS (ESI) m/z 269.0 ([M-H] ); HRMS (EI): m/z calcd for C H N OCl ([M] ):
1
5
11
2
2
70.0560; found: 270.0562.
o
Yellow solid, (160mg, 63%) m.p. 227~229 C; IR 2915, 1676, 1612, 1505, 1465, 1223,
-
1 1
1
1
9
158, 770 cm ; H NMR (d -DMSO, 500 MHz): δ 12.42 (s, 1H), 8.08 (d, J = 7.5 Hz,
6
H), 7.77 (t, J = 7.5 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.48-7.42 (m, 3H), 7.16 (t, J =
1
3
.0 Hz, 2H), 3.94 (s, 2H) ppm; C NMR (d -DMSO, 125 MHz): δ 161.8, 161.2 (d, J
6
=
241.2 Hz), 155.8, 156.8, 148.8, 134.4, 132.6 (d, J = 3.25 Hz), 130.8 (d, J = 8.13
Hz), 126.9, 126.2, 125.7, 120.7, 115.3, 115.1, 39.9 ppm; MS (ESI) m/z 254.9
+
+
(
[M+H] ); HRMS (EI): m/z calcd for C H N OF ([M] ): 254.0855; found:
15 11 2
2
54.0857.
10

o
Yellow solid, (205mg, 72%) m.p. 242~243 C; IR 3037, 1677, 1612, 1468, 1321, 1157,
-1 1
1
000, 769 cm ; H NMR (d
6
-DMSO, 500 MHz): δ 12.50 (s, 1H), 8.24 (d, J = 8.0 Hz,
1H), 8.11 (d, J = 7.5 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.73
(
t, J = 7.5 Hz, 1H), 7.56-7.54 (m, 1H), 7.52-7.50 (m, 3H), 7.48-7.46 (m, 2H), 4.46 (s,
1
3
2
1
3
6
H) ppm; C NMR (d -DMSO, 125 MHz): δ 161.8, 155.8, 148.7, 134.3, 133.4,
32.7, 131.7, 128.5, 127.4, 127.3, 126.9, 126.2, 125.8, 125.7, 125.6, 124.1, 120.8,
+
8.1 ppm; MS (ESI) m/z 287.1 ([M+H] ); HRMS (EI): m/z calcd for C16
H
14
2
N O
+
(
[M] ): 286.1106; found: 286.1103.
o
Brown solid, (203mg, 71%) m.p. 234~235 C; IR 2917, 1678, 1611, 1468, 1321, 1000,
-
1 1
8
1
6
1
1
82, 769 cm ; H NMR (d -DMSO, 500 MHz): δ 12.50 (s, 1H), 8.25 (d, J = 8.5 Hz,
6
H), 8.13-8.11 (m, 1H), 7.95 (d, J = 7.5 Hz, 1H), 7.75-7.72 (m, 1H), 7.58-7.46 (m,
1
3
H), 4.47 (s, 2H), ppm; C NMR (d -DMSO, 125 MHz): δ 162.3, 156.3, 149.2,
6
34.8, 133.9, 133.2, 132.2, 129.0, 127.9, 127.8, 127.4, 126.7, 126.24, 126.18, 126.1,
-
24.6, 121.3, 38.6 ppm; MS (ESI) m/z 284.9 ([M-H] ); HRMS (EI): m/z calcd for
+
C
19
H
14
N
2
O ([M] ): 286.1106; found: 286.1110.
11

o
Light yellow solid, (229mg, 71%) m.p. 177~178 C; IR 2916, 1675, 1613, 1543, 1260,
-1 1
9
86, 774, 693 cm ; H NMR (d
Hz, 1H), 7.78 (d, J = 7.0 Hz, 1H), 7.61 (d, J = 8.5 Hz, 1H), 7.47 (t, J = 7.5 Hz, 1H),
.40-7.28 (m, 6H), 5.00 (s, 2H), 3.49 (q, J = 6.5 Hz, 2H), 2.78 (t, J = 7.0 Hz, 2H)
6
-DMSO, 500 MHz): δ 12.20 (s, 1H), 8.09 (d, J = 8.0
7
1
3
ppm; C NMR (d
6
-DMSO, 125 MHz): δ 161.7, 156.1, 155.3, 148.8, 137.1, 134.2,
1
3
3
28.3, 127.7, 127.6, 126.9, 126.0, 125.6, 121.0, 85.2, 38.0, 34.9 ppm; MS (ESI) m/z
+
+
24.2 ([M+H] ); HRMS (EI): m/z calcd for C H N O ([M] ): 323.1270; found:
1
8
17
3
3
23.1268.
o
Yellow solid, (123mg, 57%) m.p. 153~154 C; IR 2924, 1672, 1612, 1468, 1149, 1003,
-
1 1
8
7
2
91, 765 cm ; H NMR (d -DMSO, 500 MHz): δ 12.18 (s, 1H), 8.09-8.07 (m, 1H),
6
.78-7.73 (m, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 2.60-2.51 (m,
1
3
H), 1.73-1.70 (m, 2H), 1.31-1.28 (m, 4H), 0.86 (t, J = 7.0 Hz, 3H) ppm; C NMR
(
d
6
-DMSO, 125 MHz): δ 161.8, 157.5, 148.9, 134.2, 126.8, 125.8, 125.6, 120.8, 34.5,
+
3
0.7, 26.5, 21.8, 13.8 ppm; MS (ESI) m/z 217.0 ([M+H] ); HRMS (EI): m/z calcd for
+
C
13
H
16
N
2
O ([M] ): 216.1263; found: 216.1266.
12

o
Yellow solid, (136mg, 63%) m.p. 197~198 C; IR 2968, 1654, 1608, 1470, 1331, 1006,
-1 1
7
79, 692 cm ; H NMR (d
6
-DMSO, 500 MHz): δ 8.12 (d, J = 7.5 Hz, 1H), 7.79 (t, J
=
6.5 Hz, 1H), 7.64 (d, J = 8.5 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H), 3.43 (s, 1H), 2.54 (s,
1
3
1
H), 1.03 (s, 9H) ppm; C NMR (d
6
-DMSO, 125 MHz): δ 162.2, 156.0, 149.3, 134.7,
+
1
27.4, 126.4, 121.1, 47.7, 32.4, 29.9 ppm; MS (ESI) m/z 216.9 ([M+H] ); HRMS
+
(
EI): m/z calcd for C13
H
16
N
2
O ([M] ): 216.1263; found: 216.1261.
o
Yellow solid, (151mg, 66%) m.p. 131~133 C; IR 2957, 1670, 1610, 1469, 1337, 1002,
-
1 1
8
1
98, 768 cm ; H NMR (d
6
-DMSO, 500 MHz): δ 12.17 (s, 1H), 8.10 (d, J = 8.0 Hz,
H), 7.79-7.76 (m, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 8.0 Hz, 1H), 2.63-2.59
(
m, 1H), 2.42-2.37 (m, 1H), 2.10-2.08 (m, 1H), 1.35-1.18 (m, 4H), 0.90-0.84 (m, 6H)
1
3
ppm; C NMR (d
6
-DMSO, 125 MHz): δ 162.3, 157.3, 149.4, 134.7, 127.3, 126.3,
1
26.1, 121.2, 42.4, 38.9, 31.7, 19.9, 19.6, 14.5 ppm; HRMS (EI): m/z calcd for
+
C H N O ([M] ): 230.1419; found: 230.1417.
1
4
18
2
13

o
Light yellow solid, (197mg, 79%) m.p. 237~239 C; IR 2923, 1666, 1617, 1489, 1315,
-1 1
1
014, 841, 731 cm ; H NMR (d
6
-DMSO, 500 MHz): δ 12.33 (s, 1H), 7.88 (d, J =
8.5 Hz, 1H), 7.59-7.50 (m, 2H), 7.39-7.24 (m, 5H), 3.93 (s, 2H), 2.41 (s, 3H) ppm;
1
3
C NMR (d
6
-DMSO, 125 MHz): δ 161.8, 155.0, 146.9, 133.6, 135.8, 135.6, 128.8,
+
1
28.4, 126.8, 126.7, 125.0, 120.5, 40.7, 20.7 ppm; MS (ESI) m/z 250.9 ([M+H] );
+
HRMS (EI): m/z calcd for C16
H
14
N
2
O ([M] ): 250.1106; found: 250.1104.
General Procedure for the Synthesis of 6
2 3
A mixture of 4 (1.0 mmol), Pd(OAc) (0.05 mmol), dppb (0.1 mmol), Et N (3.0
mmol) and tetrahydrofuran (10 mL) were sequentially added to a 25 mL beaker with a
magnetic bar in it. Then put the beaker into a 50ml autoclave. The autoclave was
closed, purged three times with carbon monoxide, pressurized with 20 atm of CO, and
then heated at 70°C for 12 h. The autoclave was removed from the oil bath and cooled
to room temperature prior to the release of excess carbon monoxide. The reaction
mixture was filtered and the filtrate was concentrated by rotary evaporation. The
14

residue was purified by flash chromatography on silica gel with a mixture of hexane
and ethyl acetate (2:1 to 1:1) as the eluent to afford the desired products 6.
Characterization of 6
o
Yellow solid, (323mg, 83%) m.p. 111~113 C; IR 3572, 3451, 1715, 1652, 1587, 1366,
-
1 1
1
7
7
173, 771 cm ; H NMR (CDCl , 500 MHz): δ 8.09-8.07 (m, 1H), 7.76-7.73 (m, 1H),
3
.66-7.64 (m, 1H), 7.47 (d, J=9.0 Hz, 2H), 7.44-7.41 (m, 1H), 7.33-7.30 (m, 5H),
1
3
3
.15 (d, J=8.5 Hz, 2H), 4.76 (s, 2H), 2.36 (s, 3H) ppm; C NMR CDCl , 125 MHz):
δ 161.7, 152.4, 145.6, 145.1, 136.7, 136.1, 135.6, 129.3, 129.2, 128.7, 127.8, 127.5,
+
1
27.1, 127.0, 121.5, 43.7, 21.7 ppm; MS (ESI) m/z 412.9 ([M+Na] ); HRMS (EI):
+
m/z calcd for C22
H
18
N
2
O
3
S ([M] ):390.1038; found: 390.1039.
Copies of NMR Spectra of 4, 5 and 6
15

O
S
H C
O
3
O
16

O
S
O
S
H
N
CH3
N
CH3
Ph
Ph
O
O
N
I
HN
I
4a'
4a
17

O
S
O
S
H
N
CH3
N
CH3
Ph
Ph
O
O
N
I
HN
I
4a'
4a
18

O
S
O
S
H
N
CH3
N
CH3
O
O
N
I
HN
I
O2N
O2N
4b'
4b
19

O
S
O
S
H
N
CH3
N
CH3
O
O
N
I
HN
I
O2N
O2N
4b'
4b
20

O
S
O
S
H
N
CH3
N
CH3
O
O
N
I
HN
I
Cl
Cl
4
c'
4
c
21

O
S
O
S
H
N
CH3
N
CH3
O
O
N
I
HN
I
Cl
Cl
4
c'
4
c
22

O
S
O
S
H
N
CH3
N
CH3
O
O
HN
Br
N
Br
4d
4d'
23

O
S
O
S
H
N
CH3
N
CH3
O
O
HN
Br
N
Br
4d
4d'
24

d6-DMSO
H O
2
25

26

27

28

d6-DMSO
H O
2
29

30