Gold or no gold: One-pot synthesis of tetrahydrobenz[b]azepin-4-ones from tertiary n-(but-3-ynyl)anilines

Article abstract of DOI:10.1021/ol900027h

Depending on the tertiary aniline substrates, an efficient, one-pot synthesis of tetrahydrobenz[b]azepin-4-ones needs either gold catalysts or no catalyst at all. In the reaction, the aniline nitrogen plays a unique role in relaying "O" from m-CPBA to a tethered C-C triple bond, which is inert to the oxidant under the mild reaction conditions.

Full text of DOI:10.1021/ol900027h

Supporting Information
Gold or No Gold: One-Pot Synthesis of Tetrahydrobenz[b]azepin-4-ones from
tertiary N-(But-3-ynyl)anilines
Li Cui, Guozhu Zhang, Yu Peng and Liming Zhang
Department of Chemistry/216, University of Nevada, Reno
1
664 North Virginia Street, Reno, Nevada 89557
SI-1

General. Ethyl acetate (ACS grade), hexanes (ACS grade) and diethyl ether (ACS grade)
were purchased from Fisher Scientific and used without further purification. Anhydrous
dichloromethane (HPLC grade) was purified by distillation over calcium hydride.
Anhydrous tetrahydrofuran in Pure-Pac™ from Aldrich was used directly without further
purification. Commercially available reagents were used without further purification.
Reactions were monitored by thin layer chromatography (TLC) using whatman precoated
silica gel plates. Flash column chromatography was performed over silicycle silica gel
1
13
(
230-400 mesh). H NMR and C NMR spectra were recorded on a Varian 500 MHz
Unity plus spectrometer and a Varian 400 MHz spectrometer using residue solvent peaks
as internal standards. Infrared spectra were recorded with a Perkin Elmer FT-IR spectrum
-1
2
000 spectrometer and are reported in reciprocal centimeter (cm ). Mass spectra were
recorded with Waters micromass ZQ detector using electron spray method.
Me
N
H
N
I
Me
K2CO3
4
4
-Iodobut-1-yne (1 mmol) was added to a mixture of N-methylaniline (2 mmol) and
K CO (2 mmol) without solvents. The reaction was heated at 80 ºC for 6 h and then
2
3
cooled to room temperature. The reaction mixture was diluted with CH
2
Cl (10 mL/
2
mmol), and the solid was filtered off. The filtrate was concentrated under vacuum, and
the residue was purified through silica gel flash column chromatography (eluents:
hexanes: ethyl acetate = 25:1, then hexanes: ethyl acetate = 10:1) to afford compound 4
1
in 72 % yield. H NMR (400 MHz, CDCl
3
) δ 7.22 − 7.26 (m, 2H), 6.70 − 6.73 (m, 3H),
3
.56 (t, 2H, J = 7.2 Hz), 2.96 (s, 3H), 2.69 (td, 2H, J = 7.2, 2.8 Hz), 1.99 (t, 1H, J = 2.8
13
Hz); C NMR (125 MHz, CDCl ) δ 148.4, 129.3, 116.6, 112.2, 82.2, 69.6, 51.8, 38.4,
3
1
9
6.4; IR (neat):3289, 2911, 2115, 1601, 1501, 1356, 1282, 1228, 1356, 1193, 1115, 1037,
+
+
91; MS (ES ) Calculated for [C11
H
14N] : 160.1; Found: 160.0.
SI-2

H
N
Me
N
NH2
MeI, K CO3
I
2
Br
MeCN
Br
Br
K2CO3
6
a
4
-Iodobut-1-yne (1 mmol) was added to a mixture of 4-bromophenylamine (2 mmol) and
CO (2 mmol) without solvents. The reaction was heated at 80 ºC overnight and then
cooled to room temperature. The reaction mixture was diluted with CH Cl (10 mL/
K
2
3
2
2
mmol), and the solid was filtered off. The filtrate was concentrated under vacuum, and
the residue was purified through silica gel flash column chromatography (eluents:
hexanes: ethyl acetate = 15:1) to afford (4-bromophenyl)but-3-ynylamine.
Iodomethane (2 mmol) was added to a mixture of (4-bromophenyl)but-3-ynylamine (1
mmol) and K
heated at 60 ºC overnight and then cooled to room temperature. The reaction mixture was
diluted with CH Cl (10 mL/ mmol), and the solid was filtered off. The filtrate was
2
CO (1 mmol) in anhydrous acetonitrile (5 mL/ mmol). The reaction was
3
2
2
concentrated under vacuum, and the residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate = 15:1) to afford compound 6a in 45 %
1
yield in 2 steps. H NMR (500 MHz, CDCl
3
) δ 7.30 (d, 2H, J = 9 Hz), 6.57 (d, 2H, J = 9
Hz), 3.53 (t, 2H, J = 7 Hz), 2.95 (s, 3H), 2.41 (td, 2H, J = 7.5, 2.5 Hz), 2.00 (t, 1H, J =
1
3
2
1
.5 Hz); C NMR (125 MHz, CDCl
3
) δ 147.4, 131.9, 113.8, 108.5, 81.8, 69.9, 51.7, 38.5,
+
6.4; IR (neat): 3293, 2914, 2360, 1590, 1497, 1365, 1189, 1113; MS (ES ) Calculated
+
for [C11
H13BrN] : 238.0; Found: 237.8.
H
N
Me
N
NH2
MeI, K CO3
I
2
Me
MeCN
I
K2CO
I
I
3
6
b
Iodomethane (1 mmol) was added to a mixture of 4-iodophenylamine (1 mmol) and
CO (1 mmol) in anhydrous acetonitrile (5 mL/ mmol). The reaction was heated at 80
K
2
3
ºC overnight and then cooled to room temperature. The reaction mixture was diluted with
SI-3

CH
2
Cl (10 mL/ mmol), and the solid was filtered off. The filtrate was concentrated
2
under vacuum, and the residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate = 15:1) to afford (4-iodo-
phenyl)methylamine.
4
-Iodobut-1-yne (1 mmol) was added to a mixture of (4-iodo-phenyl)-methylamine (1
mmol) and K CO (1 mmol) without solvents. The reaction was heated at 80 ºC for 2d
and then cooled to room temperature. The reaction mixture was diluted with CH Cl (10
2
3
2
2
mL/ mmol), and the solid was filtered off. The filtrate was concentrated under vacuum,
and the residue was purified through silica gel flash column chromatography (eluents:
1
hexanes: ethyl acetate = 15:1) to afford compound 6b in 35 % yield in 2 steps. H NMR
(
400 MHz, CDCl
3
) δ 7.45 (d, 2H, J = 9.2 Hz), 6.46 (d, 2H, J = 9.2 Hz), 3.51 (t, 2H, J =
1
3
7
.2 Hz), 2.94 (s, 3H), 2.40 (td, 2H, J = 7.2, 2.8 Hz), 2.00 (t, 1H, J = 2.8 Hz); C NMR
(
125 MHz, CDCl
3
) δ 147.8, 137.7, 114.3, 81.8, 77.4, 69.9, 51.5, 38.4, 16.3; IR (neat):
+
3
294, 2927, 2347, 2117, 1589, 1495, 1374, 1194, 1114, 963, 875, 824; MS (ES )
+
Calculated for [C11
H
13IN] : 286.0; Found: 285.9.
Me
N
H
N
MeI, K CO
NH2
2
3
I
MeCN
MeO
MeO
K2CO3
MeO
6
c
4
-Iodobut-1-yne (1 mmol) was added to a mixture of 4-methoxyphenylamine (2 mmol)
and K CO (2 mmol) without solvents. The reaction was heated at 80 ºC for 5 h and then
cooled to room temperature. The reaction mixture was diluted with CH Cl (10 mL/
2
3
2
2
mmol), and the solid was filtered off. The filtrate was concentrated under vacuum, and
the residue was purified through silica gel flash column chromatography (eluents:
hexanes: ethyl acetate = 25:1) to afford but-3-ynyl(4-methoxyphenyl)amine.
Iodomethane (1.2 mmol) was added to a mixture of but-3-ynyl-(4-methoxyphenyl)-amine
(
1 mmol) and K
2
CO (1 mmol) in anhydrous acetonitrile (5 mL/ mmol). The reaction was
3
heated at 60 ºC overnight and then cooled to room temperature. The reaction mixture was
SI-4

diluted with CH
2
Cl (10 mL/ mmol), and the solid was filtered off. The filtrate was
2
concentrated under vacuum, and the residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate = 15:1) to afford compound 6c in 28 %
yield in 2 steps.
1H NMR (500 MHz, CDCl
.48 (t, 2H, J = 7.5 Hz), 2.90 (s, 3H), 2.39 (td, 2H, J = 7.5, 2.5 Hz), 1.99 (t, 1H, J = 2.5
) δ 6.84 (d, 2H, J = 9 Hz), 6.71 (d, 2H, J = 9 Hz), 3.76 (s, 3H),
3
3
13
Hz); C NMR (125 MHz, CDCl ) δ 151.9, 143.4, 114.8, 114.5, 82.4, 69.5, 55.8, 52.9,
3
+
3
8.9, 16.2; IR (neat): 3296, 2926, 2862, 1605, 1496, 1450, 1403, 1246, 1051; MS (ES )
+
Calculated for [C12
H16NO] : 190.1; Found: 190.0.
H
N
Me
N
O N
NH2
O
2
N
MeI, K CO
O N
2
2
2
3
I
MeCN
K2CO3
6d
4
-Iodobut-1-yne (1 mmol) was added to a mixture of 3-nitrophenylamine (2 mmol) and
K CO (2 mmol) without solvents. The reaction was heated at 90 ºC for 2 d and then
2
3
cooled to room temperature. The reaction mixture was diluted with CH
2
Cl (10 mL/
2
mmol), and the solid was filtered off. The filtrate was concentrated under vacuum, and
the residue was purified through silica gel flash column chromatography (eluents:
hexanes: ethyl acetate = 25:1, then hexanes: ethyl acetate = 15:1) to afford but-3-ynyl(3-
nitrophenyl)amine.
Iodomethane (4mmol) was added to a mixture of but-3-ynyl-(3-nitrophenyl)amine (1
mmol) and K
heated at 80 ºC for 1 d and then cooled to room temperature. The reaction mixture was
diluted with CH Cl (10 mL/ mmol), and the solid was filtered off. The filtrate was
2
CO
3
(1 mmol) in anhydrous acetonitrile (5 mL/ mmol). The reaction was
2
2
concentrated under vacuum, and the residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate = 15:1) to afford compound 6d in 62 %
1
yield in 2 steps. H NMR (500 MHz, CDCl
3
) δ 7.49- 7.53 (m, 2H), 7.33 (t, 1H, J = 8.5
SI-5

Hz), 6.97 (dd, 1H, J = 8, 2.5 Hz), 3.63 (t, 2H, J = 7 Hz), 3.07 (s, 3H), 2.47 (td, 2H, J = 7,
2
1
1
2
.5 Hz), 2.02 (t, 1H, J = 2.5 Hz); 13C NMR (125 MHz, CDCl ) δ 149.7,149.0, 129.7,
3
17.4, 110.9, 106.0, 81.4, 70.2, 51.4, 38.7, 16.6; IR (neat):3293, 2910, 2360, 2118, 1617,
+
O
Na]+:
525, 1345, 1228, 1198, 1122, 991, 846; MS (ES ) Calculated for [C11
27.1; Found: 226.9.
H
12
N
2
2
Me
N
H
N
MeI, K CO3
Me
Me
NH2
Me
2
I
MeCN
K2CO3
6
e
4
-Iodobut-1-yne (1 mmol) was added to a mixture of m-toluidine (3 mmol) and K CO (3
2
3
mmol) without solvents. The reaction was heated at 60 ºC for 4 h and then cooled to room
temperature. The reaction mixture was diluted with CH Cl (10 mL/ mmol), and the solid
2
2
was filtered off. The filtrate was concentrated under vacuum, and the residue was purified
through silica gel flash column chromatography (eluents: hexanes: ethyl acetate = 15:1)
to afford but-3-ynyl-m-tolylamine.
Iodomethane (1.2 mmol) was added to a mixture of but-3-ynyl-m-tolylamine (1 mmol)
and K
2
CO
3
(1 mmol) in anhydrous acetonitrile (5 mL/ mmol). The reaction was stirred at
Cl (10 mL/ mmol),
room temperature for 1 d. The reaction mixture was diluted with CH
2
2
and the solid was filtered off. The filtrate was concentrated under vacuum, and the
residue was purified through silica gel flash column chromatography (eluents: hexanes:
1
ethyl acetate = 15:1) to afford compound 6e in 45 % yield in 2 steps. H NMR (400 MHz,
CDCl
H), 2.43 (td, 2H, J = 7.6, 2.8 Hz), 2.32 (s, 3H), 2.00 (t, 1H, J = 2.8 Hz); C NMR (125
MHz, CDCl ) δ 148.5, 139.0, 129.1, 117.6, 113.0, 109.4, 82.3, 69.6, 51.8, 38.5, 21.9,
3
) δ 7.13 (t, 1H, J = 9.0 Hz), 6.53- 6.56 (m, 3H), 3.55 (t, 2H, J = 7.2 Hz), 2.97 (s,
1
3
3
3
1
6.4; IR (neat): 3289, 2910, 2360, 2115, 1601, 1495, 1358, 1172, 1089, 1042, 998 ; MS
+
+
(
ES ) Calculated for [C H N] : 174.1; Found: 174.0.
1
2
16
SI-6

Me
N
Me
NH
NH2
MeI, K CO3
I
2
MeCN
K2CO
EtO C
2
EtO C
EtO C
3
2
2
6
f
Iodomethane (1.2 mmol) was added to a mixture of 4-aminobenzoicacid ethylester (1
mmol) and K CO (1 mmol) in anhydrous acetonitrile (5 mL/ mmol). The reaction was
2
3
heated at 80 ºC for 6 h and then cooled to room temperature. The reaction mixture was
diluted with CH Cl (10 mL/ mmol), and the solid was filtered off. The filtrate was
2
2
concentrated under vacuum, and the residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate = 25:1, then hexanes: ethyl acetate =
1
0:1) to afford ethyl 4-methylaminobenzoate.
4
-Iodobut-1-yne (1.2 mmol) was added to a mixture of 4-methylamino-benzoicacid
ethylester (1 mmol) and K
ºC for 4 h and then cooled to room temperature. The reaction mixture was diluted with
CH Cl (10 mL/ mmol), and the solid was filtered off. The filtrate was concentrated
2
CO
3
(2 mmol) without solvents. The reaction was heated at 90
2
2
under vacuum, and the residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate = 25:1, then hexanes: ethyl acetate =
1
1
0:1) to afford compound 6f in 31 % yield in 2 steps. H NMR (500 MHz, CDCl
3
) δ 7.91
(
d, 2H, J = 9 Hz), 6.65 (d, 2H, J = 9 Hz), 4.32 (q, 2H, J = 7 Hz), 3.61 (t, 2H, J = 7 Hz),
13
3
.06 (s, 3H), 2.46 (td, 2H, J = 7, 3 Hz), 2.01 (t, 1H, J = 3 Hz), 1.36(t, 3H, J = 7 Hz); C
) δ 166.8, 151.5, 131.4, 117.8, 110.6, 81.5, 70.1, 60.1, 51.2, 38.6,
6.7, 14.1; IR (neat): 3289, 2977, 2368, 2114, 1699, 1604, 1523, 1384, 1276, 1183, 1106,
NMR (125 MHz, CDCl
3
1
1
+
+
026, 961, 827; MS (ES ) Calculated for [C H NO Na] : 254.1; Found: 253.9.
1
4
17
2
Me
N
Me
NH
NH2
MeI, K CO3
I
2
MeCN
K2CO
3
Me
Me
Me
6
g
Iodomethane (1.2 mmol) was added to a mixture of p-toluidine (1 mmol) and K
2
CO (1
3
mmol) in anhydrous acetonitrile (5 mL/ mmol). The reaction was stirred at room
temperature overnight.. The reaction mixture was diluted with CH Cl (10 mL/ mmol),
2
2
SI-7

and the solid was filtered off. The filtrate was concentrated under vacuum, and the
residue was purified through silica gel flash column chromatography (eluents: hexanes:
ethyl acetate = 25:1, then hexanes: ethyl acetate = 10:1) to afford methyl-p-tolylamine.
4
-Iodobut-1-yne (1.2 mmol) was added to a mixture of methyl-p-tolylamine (1 mmol)
and K CO (2 mmol) without solvents. The reaction was heated at 90 ºC for 4 h and then
cooled to room temperature. The reaction mixture was diluted with CH Cl (10 mL/
2
3
2
2
mmol), and the solid was filtered off. The filtrate was concentrated under vacuum, and
the residue was purified through silica gel flash column chromatography (eluents:
hexanes: ethyl acetate = 50:1, then hexanes: ethyl acetate = 25:1) to afford compound 6g
1
in 49 % yield in 2 steps. H NMR (400 MHz, CDCl
3
) δ 7.04 (d, 2H, J = 7.2 Hz), 6.64 (d,
2
H, J = 7.2 Hz), 3.52 (t, 2H, J = 7.2 Hz), 2.93 (s, 3H), 2.41 (td, 2H, J = 7.2, 2.8 Hz), 2.25
(
s, 3H), 1.98 (t, 1H, J = 2.8 Hz); 13C NMR (125 MHz, CDCl
3
) δ 146.4, 129.8, 125.9,
1
12.6, 82.3, 69.5, 52.1, 38.5, 20.2, 16.2; IR (neat): 3301, 2914, 2368, 2113, 1617, 1519,
+
+
1
356, 1185, 1111, 1039; MS (ES ) Calculated for [C12
H16N] : 174.1; Found: 174.0.
Me
N
H
N
MeI, K CO3
NH2
2
I
N
Ts
N
Ts
MeCN
N
Ts
K2CO3
6
h
4
5
6
-Iodobut-1-yne (1.2 mmol) was added to a mixture of 1-(toluene-4-sulfonyl)-1H-indol-
-ylamine (1 mmol) and K CO (1 mmol) without solvents. The reaction was heated at
0 ºC overnight and then cooled to room temperature. The reaction mixture was diluted
2
3
with CH Cl (10 mL/ mmol), and the solid was filtered off. The filtrate was concentrated
2
2
under vacuum, and the residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate = 7:1) to afford but-3-ynyl[1-(toluene-4-
sulfonyl)-1H-indol-5-yl]amine.
Iodomethane (1.2 mmol) was added to a mixture of but-3-ynyl-[1-(toluene-4-sulfonyl)-
1
H-indol-5-yl]-amine (1 mmol) and K CO (1 mmol) in anhydrous acetonitrile (5 mL/
2
3
mmol). The reaction was stirred at 60 ºC overnight and then cooled to room temperature.
SI-8

The reaction mixture was diluted with CH
2
Cl (10 mL/ mmol), and the solid was filtered
2
off. The filtrate was concentrated under vacuum, and the residue was purified through
silica gel flash column chromatography (eluents: hexanes: ethyl acetate = 5:1) to afford
1
compound 6h in 50 % yield in 2 steps. H NMR (400 MHz, CDCl
3
) δ 7.82 (d, 1H, J = 9.2
Hz), 7.71 (d, 2H, J = 8 Hz), 7.43 (d, 1H, J = 3.6 Hz), 7.18 (d, 2H, J = 8 Hz), 6.82 (dd, 1H,
J = 9.2, 2.4 Hz), 6.75 (d, 2H, J = 2.4 Hz), 6.51 (d, 1H, J = 3.6 Hz), 3.54 (t, 2H, J = 7.2
1
3
Hz), 2.95 (s, 3H), 2.40 (td, 2H, J = 7.2, 2.4 Hz), 2.32 (s, 3H), 1.98 (t, 1H, J = 2.4 Hz); C
NMR (125 MHz, CDCl ) δ145.7, 144.6, 135.4, 132.2, 129.8, 127.0, 126.8, 126.7, 114.3,
12.0, 109.3, 103.7, 82.2, 69.7, 52.8, 39.0, 21.5, 16.4; IR (neat): 3294, 2925, 2861, 2345,
3
1
2
+
115, 1612, 1558, 1495, 1366, 1259, 1132, 1050, 876, 824; MS (ES ) Calculated for
+
[C
20
H
21
N
2
O
2
S] : 353.1; Found: 353.4.
NH2
I
HN
N
BnBr
K2CO3
6
i
4
-Iodobut-1-yne (1 mmol) was added to a mixture of aniline (2 mmol) and K CO (2
2
3
mmol) without solvents. The reaction was heated at 80 ºC for 6 h and then cooled to room
temperature. The reaction mixture was diluted with CH Cl (10 mL/ mmol), and the solid
2
2
was filtered off. The filtrate was concentrated under vacuum, and the residue was purified
through silica gel flash column chromatography (eluents: hexanes: ethyl acetate = 15:1)
to afford but-3-ynylphenylamine.
Benzyl bromide (1.2 mmol) was added to a mixture of but-3-ynylphenylamine (2 mmol)
without solvents. The reaction was heated at 60 ºC for 20 min. The reaction mixture was
diluted with CH
2
Cl (10 mL/ mmol), and the solid was filtered off. The filtrate was
2
concentrated under vacuum, and the residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate = 50:1) to afford compound 6i in 43 %
1
yield in 2 steps. H NMR (400 MHz, CDCl
3
) δ 7.18 − 7.31 (m, 7H), 6.69− 6.72 (m, 3H),
4
.60 (s, 2H), 3.65 (t, 2H, J = 7.6 Hz), 2.52 (td, 2H, J = 7.6, 2.8 Hz), 2.00 (t, 1H, J = 2.8
Hz); 13C NMR (125 MHz, CDCl
) δ 147.7, 138.6, 129.3, 128.6, 126.9, 126.5, 116.7,
3
SI-9

1
1
2
12.2, 82.0, 69.8, 54.5, 50.2, 29.7, 17.0; IR (neat): 3278, 2918, 2360, 1595, 1504, 1449,
+
+
360, 1246, 1213, 1165, 1026, 996; MS (ES ) Calculated for [C17
H18N] : 236.1; Found:
35.9.
Me Me
N
Me
Me
H
N
NH2
2
MeI, K CO3
I
MeCN
K2CO3
4
-Iodobut-1-yne (1 mmol) was added to a mixture of o-toluidine (2 mmol) and K
2
CO (2
3
mmol) without solvents. The reaction was heated at 60 ºC for 2 d and then cooled to room
temperature. The reaction mixture was diluted with CH Cl (10 mL/ mmol), and the solid
2
2
was filtered off. The filtrate was concentrated under vacuum, and the residue was purified
through silica gel flash column chromatography (eluents: hexanes: ethyl acetate = 25:1,
then hexanes: ethyl acetate = 15:1) to afford but-3-ynyl-o-tolylamine.
Iodomethane (1.2 mmol) was added to a mixture of but-3-ynyl-o-tolylamine (1 mmol)
and K
2
CO
3
(1 mmol) in anhydrous acetonitrile (5 mL/ mmol). The reaction was heated at
8
0 ºC overnight and then cooled to room temperature. The reaction mixture was diluted
with CH
2
Cl
2
(10 mL/ mmol), and the solid was filtered off. The filtrate was concentrated
under vacuum, and the residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate = 15:1) to afford desired product in 53 %
1
yield in 2 steps. H NMR (500 MHz, CDCl
3
) δ 7.16- 7.21 (m, 2H), 7.07 (d, 1H, J = 7.5),
7
2
1
1
1
.00 (t, 1H, J = 7), 3.14 (t, 2H, J = 7.5 Hz), 2.74 (s, 3H), 2.40 (td, 2H, J = 7.5, 2.5 Hz),
1
3
.35 (s, 3H), 1.98 (t, 1H, J = 2.5 Hz); C NMR (125 MHz, CDCl
3
) δ 151.1, 133.4, 131.1,
26.3, 123.3, 120.2, 82.6, 69.1, 54.8, 41.6, 18.2, 17.3;

+
+
493, 1369, 1169, 1094, 1037, 944; MS (ES ) Calculated for [C H N] : 174.1; Found:
1
2
16
74.0.
SI-10

Me
N
Cl
OH
mCPBA (1 equiv.) was added into a solution of a N-(but-3-ynyl)aniline (1 equiv.) and
NaHCO (1 equiv.) in CH Cl (0.05 M) under N at 0 ºC. The reaction was stirred at 0 ºC
for 0.5 h. The N-oxide purified directly through silica gel flash column chromatography
eluents: DCM: MeOH = 2: 1). The anhydrous hydrogen chloride gas was bubbled into
3
2
2
2
(
the eluent containing N-oxide then concentrated under vacuum to afford the desired
1
product in 80 % yield. H NMR (400 MHz, CDCl ) δ 7.94- 7.92 (m, 2H), 7.67- 7.57 (m,
3
3
H), 4.71- 4.63 (m, 1H), 4.44-4.36 (m, 1H), 4.21 (s, 3H), 2.92- 2.85 (m, 1H), 2.41- 2.34
(
m, 1H), 2.03 (t, 1H, J = 2.8 Hz); 13C NMR (125 MHz, CDCl
3
) δ145.8,131.1, 130.4,

1
1
20.0, 77.1, 72.0, 69.2, 60.2, 13.9; IR (neat):2923, 2859, 2253, 1713, 1605, 1555, 1497,
+
+
452, 1401; MS (ES ) Calculated for [C11
H14NO] : 176.1; Found: 176.1.
General procedure A: Preparation of tetrahydrobenz[b]azepin-4-ones
mCPBA (1 equiv.), NaHCO (1 equiv.)
Me
Me
N
3
o
CH Cl , 0 C
N
2
2
R
R
then Ph PAuNTf (5 mol %)
3
2
o
-
20 C
O
6
7
mCPBA (0.2 mmol) was added into a solution of a N-(but-3-ynyl)aniline (0.2 mmol) and
NaHCO (0.2 mmol) in CH Cl (0.05 M) under N at 0 ºC. The N-oxide formation was
monitored by TLC. After completion of the N-oxide formation, Ph3PAuNTf (5 mol %)
3
2
2
2
2
was added into the reaction at -20 ºC. Upon completion, the reaction was diluted with
CH Cl (25 mL) and washed with 5 % aqueous Na S O (10 mL), 10 % aqueous
2
2
2
2
3
NaHCO
3
(10 mL) and water. The organic layer was washed with brine, dried with
MgSO , and concentrated under vacuum. The residue was purified through silica gel flash
4
column (eluents: hexanes: ethyl acetate = 15:1).
SI-11

Me
N
O
5
Compound 5 was prepared in 79 % yield according to the general procedure A. The
1
reaction time is 30 min for the formation of N-oxide and 30 min for Au catalysis. H
NMR (500 MHz, CDCl ) δ 7.27 (t, 1H, J = 6 Hz), 7.08 (d, 1H, J = 7.5 Hz), 7.01 (d, 1H, J
3
=
8 Hz), 7.00 (t, 1H, J = 6.5 Hz), 3.68(s, 2H), 3.26 (t, 2H, J = 6.5 Hz), 2.87 (s, 3H), 2.55
1
3
(
t, 2H, J = 6.5 Hz); C NMR (125 MHz, CDCl
3
) δ 208.8, 149.3, 129.6, 129.4, 128.3,
1
1
22.2, 118.2, 53.9, 48.7, 41.6, 41.5; IR (neat): 2940, 2806, 2360, 1716, 1651, 1554, 1495,
+
+
465, 1323, 1183, 1052; MS (ES ) Calculated for [C H ONa] : 198.1; Found: 198.0.
1
1
13
Me
N
Br
O
7
a
Compound 7a was prepared in 73 % yield according to the general procedure A. The
1
reaction time is 30 min for the formation of N-oxide and 30 min for Au catalysis. H
NMR (400 MHz, CDCl
3
) δ 7.36 (dd, 1H, J = 8.8, 2.4 Hz), 7.21 (d, 1H, J = 2.4 Hz), 6.86
(
d, 1H, J = 8.4 Hz), 3.64 (s, 2H), 3.26 (t, 2H, J = 6.8 Hz), 2.85 (s, 3H), 2.55 (t, 2H, J =
1
3
6
5
.8 Hz); C NMR (125 MHz, CDCl ) δ 207.5, 148.3, 132.3, 131.3, 131.1, 119.8, 114.5,
3
3.6, 48.3, 41.6, 41.3; IR (neat): 2951, 2810, 2364, 2334, 1718, 1491, 1324, 1271, 1098;
+
+
MS (ES ) Calculated for [C11
H
12BrNONa] : 276.0; Found: 275.9.
Me
N
I
O
7b
Compound 7b was prepared in 68 % yield according to the general procedure A. The
1
reaction time is 2 h for the formation of N-oxide and 30 min for Au catalysis. H NMR
SI-12

(
400 MHz, CDCl
3
) δ 7.36 (d, 1H, J = 8.4 Hz), 7.38 (s, 1H), 6.74 (d, 1H, J = 8.4 Hz), 3.63
1
3
(
s, 2H), 3.28 (t, 2H, J = 7.2 Hz), 2.85 (s, 3H), 2.56 (t, 2H, J = 7.2 Hz); C NMR (125
MHz, CDCl
3
) δ 207.4, 149.0, 138.1, 137.2, 131.3, 120.2, 84.6, 53.5, 48.1, 41.5, 41.4; IR
+
(neat): 2934, 2856, 2364, 2334, 1717, 1491, 1322, 1269, 1093; MS (ES ) Calculated for
+
[C
11
H13INO] : 302.0; Found: 301.7.
Me
N
MeO
O
7
c
Compound 7c was prepared in 73 % yield according to the general procedure A. The
1
reaction time is 15 min for the formation of N-oxide and 15 min for Au catalysis. H
NMR (400 MHz, CDCl
3
) δ 6.98 (d, 1H, J = 6 Hz), 6.81 (dd, 1H, J = 8.8, 3.2 Hz), 6.69 (d,
1
2
1
1
H, J = 2.8 Hz), 3.78 (s, 3H), 3.62 (s, 2H), 3.15 (t, 2H, J = 6.4 Hz), 2.81 (s, 3H), 2.51 (t,
1
3
H, J = 6.4 Hz); C NMR (125 MHz, CDCl ) δ 209.2, 155.2, 142.7, 131.9, 119.3, 115.5,
3
12.7, 55.5, 54.9, 48.6, 41.9, 41.4; IR (neat): 2940, 2799, 1716, 1608, 1501, 1252, 1124,
+
+
042; MS (ES ) Calculated for [C12
H15NO
2
Na] : 228.1; Found: 227.9.
O
Me
N
O N
2
O N
2
N
Me
O
ortho-
para-
7
d
Compound 7d was prepared in 58 % yield (ortho: para= 1.35 :1) according to the general
procedure A. The reaction time is 2 h for the formation of N-oxide and 30 min for Au
1
catalysis. H NMR (500 MHz, CDCl
3
) δ 7.79 (d, 1H, para, J = 2 Hz,), 7.77 (dd, 1H, para,
J = 8, 2 Hz), 7.44 (d, 1H, ortho, J = 8 Hz), 7.37 (t, 1H, ortho, J = 8 Hz), 7.23 (d, 1H, para,
J = 7.5 Hz), 7.20 (d, 1H, ortho, J = 8 Hz), 3.83 (s, 3H, ortho), 3.81 (s, 3H, para), 3.41 (t,
2H, para, J = 6 Hz), 3.35 (t, 2H, ortho, J = 6.8 Hz), 2.99 (s, 3H, para), 2.93 (s, 3H, ortho),
SI-13

13
2
.61 (t, 2H, para, J = 6.4 ), 2.59 (t, 2H, ortho, J = 6.8 Hz); C NMR (125 MHz, CDCl
3
)
δ 205.7, 204.7, 151.0, 150.5, 150.1, 148.4, 135.2, 130.3, 128.4, 123.6, 122.4, 1117.3,
1
16.4, 112.5, 53.2, 52.9, 48.8, 43.7, 41.7, 41.6, 41.5, 40.8; IR (neat): 2914, 2855, 2360,
+
+
1
718, 1525, 1345, 1109; MS (ES ) Calculated for [C H NO Na] : 228.1; Found: 227.9.
1
2
15
2
O
Me
N
Me
Me
N
Me
O
ortho
para
7
e
Compound 7e was prepared in 70 % yield (ortho: para= 1:1) according to the general
procedure A. The reaction time is 30 min for the formation of N-oxide and 30 min for Au
1
catalysis. H NMR (400 MHz, CDCl ) δ 7.17 (t, 1H,ortho, J = 7.6 Hz), 6.96 (d, 1H, para,
3
J = 7.6 Hz), 6.91 (d, 1H, J = 8 Hz), 6.88 (d, 1H, J = 7.6 Hz), 6.83 (s, 3H, para), 6.76 (d,
1
3
2
2
5
1
H, para, J = 7.6 Hz), 3.71 (s, 2H), 3.64 (s, 2H, para), 3.25 (t, 2H, para, J = 6.8 Hz),
.21 (t, 2H, J = 6 Hz), 2.86 (s, 3H, para), 2.85 (s, 3H), 2.55 (t, 2H, para, J = 6.8 Hz),
13
.50 (t, 2H, J = 6 Hz), 2.34 (s, 3H, para), 2.29 (s, 3H); C NMR (125 MHz, CDCl ) δ
3
09.2, 208.8, 149.5, 149.1, 138.1,136.2, 129.4, 128.7, 126.3, 124.7, 122.8, 119.0, 116.3,
4.0, 48.3, 44.3, 41.9, 41.6, 41.5, 40.9, 21.4, 20.4; IR (neat): 2925, 2806, 2360, 1718,
+
+
577, 1454, 1324, 1174; MS (ES ) Calculated for [C12
H
15NONa] : 212.1; Found: 211.9.
1
Compound Para- 7e: H NMR (400 MHz, CDCl
3
) δ 7.17 (t, 1H, J = 7.6 Hz), 6.91 (d, 1H,
J = 8 Hz), 6.88 (d, 1H, J = 7.6 Hz), 3.71 (s, 2H), 3.21 (t, 2H, J = 6 Hz), 2.85 (s, 3H), 2.50
1
3
(
t, 2H, J = 6 Hz), 2.29 (s, 3H); C NMR (125 MHz, CDCl ) δ 208.8, 149.5, 136.2, 128.7,
3
1
1
27.5, 124.7, 116.3, 54.0, 44.3, 41.9, 40.9, 20.4; IR (neat): 2925, 2806, 2360, 1718, 1577,
+
+
454, 1324, 1174; MS (ES ) Calculated for [C12
H15NONa] : 212.1; Found: 211.9.
SI-14

Me
N
EtO C
2
O
7
f
Compound 7f was prepared in 40 % yield according to the general procedure A. The
1
reaction time is 30 min for the formation of N-oxide and 30 min for Au catalysis. H
NMR (500 MHz, CDCl ) δ 7.90 (dd, 1H, J = 8.4, 2.4 Hz), 7.72 (d, 1H, J = 2 Hz), 6.89 (d,
3
1
2
1
H, J = 8.4 Hz), 4.34 (q, 2H, J = 7.2 Hz) 3.80 (s, 2H), 3.50 (t, 2H, J = 6 Hz), 2.99 (s, 3H),
1
3
.64 (t, 2H, J = 6.4 Hz), 1.37 (t, 3H, J = 7.2 Hz); C NMR (125 MHz, CDCl ) δ 207.1,
3
66.4, 152.9, 131.7, 130.2, 125.3, 122.2, 116.4, 60.6, 52.2, 48.9, 41.7, 41.4, 14.4; IR
+
(
neat): 2914, 2360, 2338, 1705, 1603, 1508, 1363, 1274, 1183, 1113, 1029; MS (ES )
+
Calculated for [C14
H17NO
3
Na] : 270.1; Found: 269.9.
Me
N
Me
O
7
g
Compound 7g was prepared in 70 % yield according to the general procedure A. The
1
reaction time is 30 min for the formation of N-oxide and 30 min for Au catalysis. H
NMR (500 MHz, CDCl ) δ 7.07 (dd, 1H, J = 8.4, 1.6 Hz), 6.91- 6.94 (m, 2H), 3.63 (s,
3
1
3
2
H), 3.20 (t, 2H, J = 6.8 Hz), 2.83 (s, 3H), 2.53 (t, 2H, J = 6.8 Hz), 2.28 (s, 3H); C
NMR (125 MHz, CDCl ) δ 209.2, 146.9, 131.8, 130.3, 129.7, 128.7, 118.1, 54.4, 48.6,
3
4
1.7, 41.5, 20.5; IR (neat): 2940, 2364, 2323, 1718, 1504, 1326, 1274, 1178, 1089, 1035;
+
+
MS (ES ) Calculated for [C12
H15NONa] : 212.1; Found: 211.9.
O
Me
N
N
Me
N
Ts
N
Ts
O
ortho-7h
para-7h’
SI-15

Compound ortho-7h and para-7h was prepared in 65 % yield in a 1:1 separable mixture
according to the general procedure A. The reaction time is 30 min for the formation of N-
1
oxide and 30 min for Au catalysis. For compound ortho-7h : H NMR (400 MHz,
CDCl
3
) δ 7.86 (d, 2H, J = 8.8 Hz), 7.74 (d, 2H, J = 8.8 Hz), 7.54 (d, 2H, J = 3.6 Hz), 7.21
(
(
d, 2H, J = 8.8 Hz), 7.05 (d, 2H, J = 5.2 Hz), 6.58 (d, 2H, J = 3.6 Hz), 3.78 (s, 2H), 3.23
1
3
t, 2H, J = 6.8 Hz), 2.86 (s, 3H), 2.50 (t, 2H, J = 6.8 Hz), 2.34 (s, 3H); C NMR (125
) δ 208.6, 144.9, 135.3, 130.8, 130.6, 129.9, 127.0, 126.8, 121.6, 116.1,
12.7, 107.1, 54.7, 44.3, 42.0, 41.6, 21.6; IR (neat): 2926, 2861, 2381, 2345, 2327, 1714,
MHz, CDCl
3
1
+
1
597, 1558, 1495, 1451, 1369, 1272, 1172, 1142, 1050, 876, 824; MS (ES ) Calculated
+
1
for [C20
H
20
N
2
O
3
SNa] : 391.1; Found: 391.4. For compound para-7h: H NMR (400
) δ 7.74 (d, 2H, J = 8.4 Hz), 7.71 (s, 1H), 7.49 (d, 1H, J = 3.6 Hz), 7.22 (d,
H, J = 8.8 Hz), 7.17 (s, 1H), 6.57 (d, 1H, J = 3.6 Hz), 3.73 (s, 2H), 3.14 (t, 2H, J = 6.8
MHz, CDCl
3
2
13
Hz), 2.84 (s, 3H), 2.47 (t, 2H, J = 6.8 Hz), 2.34 (s, 3H); C NMR (125 MHz,CDCl
3
)δ
2
4
1
09.1, 145.8, 144.9, 135.4, 130.8, 129.9, 128.7, 126.8, 126.4, 114.0, 110.8, 108.8, 54.7,
9.1, 42.1, 41.1, 21.6; IR (neat): 2925, 2861, 2382, 2347, 2081, 1713, 1607, 1557, 1495,
+
451, 1371, 1260, 1172, 1120, 1092, 105, 875, 824; MS (ES ) Calculated for
+
[C
20
H
20
N
2
O
3
SNa] : 391.1; Found: 391.2.
Ph
N
O
7
i
Compound 7i was prepared in 69 % yield according to the general procedure A. The
1
reaction time is 2h for the formation of N-oxide and 30 min for Au catalysis. H NMR
(500 MHz, CDCl
3
) δ 7.31- 7.36 (m, 4H), 7.23- 7.27 (m, 2H), 7.12 (d, 1H, J = 7.5 Hz),
7
2
1
.07 (d, 1H, J = 8.0 Hz), 6.97 (td, 1H, J = 7.5, 1 Hz), 4.34 (s, 2H), 3.29 (s, 2H), 3.23 (t,
1
3
H, J = 7 Hz), 2.53 (s, 3H), 2.53 (t, 2H, J = 7 Hz); C NMR (125 MHz, CDCl ) δ 208.6,
3
49.1, 138.4, 129.8, 129.4, 128.6, 128.4, 128.0, 127.3, 122.5, 119.4, 58.2, 50.9, 48.9, 41.6;
SI-16

+
IR (neat): 2918, 2843, 2360, 2334, 1716, 1495, 1365, 1224; MS (ES ) Calculated for
+
[C
17
H
17NONa] : 274.1; Found: 273.9.
MeMe
N
O
9
Compound 9 was prepared in 20 % yield according to the general procedure A. The
reaction time is 1 h for the formation of N-oxide and 30 min for Au catalysis. For
1
compound 8: H NMR (400 MHz, CDCl
3
) δ 7.16- 7.23 (m, 2H), 7.05 (s, 1H), 7.03 (s,
13
1
H), 3.22 (t, 4H, J = 6 Hz), 2.61 (t, 2H, J = 6 Hz), 2.39 (s, 3H); C NMR (125 MHz,
CDCl ) δ 208.9, 147.0, 135.5, 131.7, 131.1, 130.8, 124.2, 51.0, 49.2, 41.3, 40.9, 19.2.
3
I
N
NH
K2CO3
1
0
4
-Iodobut-1-yne (1 mmol) was added to a mixture of 1,2,3,4-Tetrahydro-quinoline (2
mmol) and K CO (2 mmol) without solvents. The reaction was heated at 60 ºC for 4 h
2
3
and then cooled to room temperature. The reaction mixture was diluted with CH
2
Cl (10
2
mL/ mmol), and the solid was filtered off. The filtrate was concentrated under vacuum,
and the residue was purified through silica gel flash column chromatography (eluents:
hexanes: ethyl acetate = 25:1, then hexanes: ethyl acetate = 15:1) to afford compound in
1
7
2 % yield. H NMR (400 MHz, CDCl ) δ 7.03 (t, 1H, J = 7.2 Hz), 7.03 (d, 1H, J = 7.2
3
Hz), 6.60− 6.56 (m, 2H), 3.48 (t, 2H, J = 7.6 Hz ), 3.33 (t, 2H, J = 5.6 Hz ), 2.74 (t, 2H, J
6.4 Hz ), 2.45 (td, 2H, J = 8.4 Hz, J = 2.4 Hz), 1.99 (t, 1H, J = 2.4 Hz), 1.97−1.92 (m,
=
1
3
2
5
H); C NMR (125 MHz, CDCl
3
) δ 144.3, 129.3, 127.2, 122.5, 116.0, 110.3, 82.4, 69.5,
+
0.4, 49.6, 28.0, 22.1, 15.9; IR (neat): 3288, 2926, 1600, 1450, 1344; MS (ES )
+
Calculated for [C H N] : 186.1; Found: 186.0.
1
3
16
SI-17

N
O
1
1
Compound 11 was prepared in 57 % yield according to the general procedure A, (2-
t
biphenyl) Bu
2
PAuNTf
2
was used. The reaction temperature for Au-catalysis was room
1
temperature and the reaction time was 40 min. H NMR (400 MHz, CDCl ) δ 6.97 (d, 1H,
3
J = 7.2 Hz ), 6.87 (d, 1H, J = 6.4 Hz), 6.80-6.76 (m, 1H), 3.73 (s, 2H), 3.43 (t, 2H, J = 6.4
Hz), 3.20 (t, 2H, J = 5.6 Hz), 2.77 (t, 2H, J = 6.4 Hz), 2.63 (t, 2H, J = 6.4 Hz),
1
1
1
.90−1.84(m, 2H); 13C NMR (125 MHz, CDCl
) δ 208.6, 144.8, 128.6, 128.5, 128.0,
3
26.3, 120.5, 52.0, 51.7, 49.1, 42.0, 27.8, 19.4; IR (neat): 2936, 2855, 1718, 1595, 1491,
+
+
450, 1317; MS (ES ) Calculated for [C13
H
15NNaO] : 224.1; Found: 224.1.
N
Me
N
O
O
1
3
14
Compound 13 was isolated in 40 % yield along with 14 (26 % yield) according to the
t
general procedure A, (2-biphenyl) Bu
2
PAuNTf was used. The reaction temperature for
2
Au-catalysis was room temperature and the reaction time was 30 min. From compound
1
1
6
=
3: H NMR (400 MHz, CDCl ) δ 7.00 (d, 1H, J = 7.2 Hz ), 6.78 (d, 1H, J = 7.6 Hz),
3
.67-6.63 (m, 1H), 3.90 (s, 2H), 3.43-3.39 (m, 4H), 2.93 (t, 2H, J = 8.4 Hz), 2.83 (t, 2H, J
1
3
5.6 Hz); C NMR (125 MHz, CDCl
3
) δ 207.1, 150.1, 131.0, 128.8, 123.4, 119.2, 114.2,

5
6.0, 47.9, 45.8, 44.6, 28.7; IR (neat): 2926, 2855, 1713, 1602, 1558, 1494, 1452; MS
+
+
(
ES ) Calculated for [C12
H13NNaO] : 210.1; Found: 209.9. For compound 14 was
isolated in 26 % yield when making the compound 13 according to the general procedure
1
A. H NMR (400 MHz, CDCl
3
) δ 7.62 (d, 1H, J = 8 Hz), 7.33 (d, 1H, J = 8.4 Hz), 7.25-
7
2
.19 (m, 1H), 7.13-7.08 (m, 2H), 6.47 (d, 1H, J = 2.8 Hz), 4.42 (t, 2H, J = 6.4 Hz), 2.94 (t,
1
3
H, J = 6.4 Hz), 2.10 (s, 3H); C NMR (125 MHz, CDCl ) δ 206.2, 135.5, 128.7, 128.2,
3
SI-18

1
21.5, 121.1, 119.4, 109.0, 101.4, 43.4, 40.5, 30.4; IR (neat): 2923, 2855, 1711, 1607,
+
+
1489, 1453, 1399; MS (ES ) Calculated for [C12
H13NNaO] : 210.1; Found: 209.9.
Me
N
Me
N
n-BuLi
H
ClCO
2
Me, THF
CO Me
2
4
15a
Compound 4 (1 mmol) was dissolved in THF (5 mL), and the resulting solution was
cooled to -78 ºC in a dry ice-acetone bath. n-BuLi (1.2 mmol) was added drop-wise over
3
minutes. After stirring at -78 ºC for 0.5 h, The resulting mixture was stirred at -78 ºC for
another 0.5 h. Methyl chloroformate (1.2 mmol) was added in one portion. The reaction
was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was
then quenched with sat. aqueous NH
layer was extracted with diethyl ether (2 x 10 mL). The combined organic layers was
washed with brine (25 mL), dried upon MgSO , filtered and concentrated. The residue
4
Cl. The organic layer was separated. The aqueous
4
was purified through silica gel flash column chromatography (eluents: hexanes: ethyl
1
acetate = 2:1) to yield the desired compound 15a in 60 % yield. H NMR (400 MHz,
CDCl ) δ 7.27− 7.23 (m, 2H), 6.76− 6.70 (m, 3H), 3.77 (s, 3H), 3.63 (t, 2H, J = 7.2 Hz),
3
1
3
2
1
1
.99 (s, 3H), 2.58 (t, 2H, J = 7.2 Hz); C NMR (125 MHz, CDCl ) δ 154.0, 148.0, 129.4,
3
17.0, 112.3, 87.2, 74.0, 52.6, 50.8, 38.5, 16.6; IR (neat): 3028, 2926, 2236, 1715, 1598,
+
15NNaO
]+: 240.1; Found: 240.1.
502, 1433, 1356, 1258; MS (ES ) Calculated for [C13
H
2
Me
N
Me
N
n-BuLi
(MeCO) O, Et O
H
2
2
COMe
4
15b
O (5 mL), and the resulting solution was
Compound 4(1 mmol) was dissolved in Et
2
o
cooled down to -78 C in a dry ice-acetone bath. n-BuLi (1.1 mmol) was added drop-wise
o
over 5 minutes. After stirring at -78 C for 0.5 h. The resulting mixture was stirred at -
SI-19

7
8oC for another 0.5 h. Acetyl chloride (12 mmol) was added in one portion. The reaction
was allowed to warm to room temperature and stirred for 6 hours. The reaction mixture
was then quenched with sat. aqueous NH Cl. The organic layer was separated. The
4
aqueous layer was extracted with diethyl ether (2 x 10 mL). The combined organic layers
was washed with brine (25 mL), dried upon MgSO , filtered and concentrated. The
4
residue was purified through silica gel flash column chromatography (eluents: hexanes:
1
ethyl acetate = 2:1) to yield the desired compound 15b in 60 % yield. H NMR (400 MHz,
CDCl ) δ 7.27− 7.23 (m, 2H), 6.76− 6.71 (m, 3H), 3.63 (t, 2H, J = 7.2 Hz), 2.99 (s, 3H),
3
1
3
2
1
1
.61 (t, 2H, J = 7.2 Hz), 2.29 (s, 3H); C NMR (125 MHz, CDCl ) δ 184.6, 148.1, 129.4,
3
17.0, 112.3, 91.2, 82.3, 50.9, 38.4, 32.6, 16.9; IR (neat): 2923, 2859, 2209, 1674, 1602,
+
+
499, 1356, 1229; MS (ES ) Calculated for [C13
H
15NNaO] : 224.1; Found: 224.1.
Me
N
Me
N
Pd(PPh ) Cl , CuI
3
2
2
H
COPh
ClCOPh, Et N
3
4
15c
To a solution of anhydrous Et N (2 mL) was successively added copper iodide (0.05
3
mmol), dichlorobis(triphenylphosphine)palladium (0.05 mmol). Under nitrogen,
compound 4 (1.32 mmol) and benzoyl chloride (1.5 mmol) were added in succession.
The resulting mixture was stirred at room temperature for 8 h. The reaction was quenched
by filtration through a pad of silica gel using ethyl acetate as eluent. The filtrate was
concentrated, and the residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate = 2:1) to yield the desired compound 15c
1
in 52 % yield. H NMR (400 MHz, CDCl
3
) δ 8.10 (d, 2H, J = 6.8 Hz), 7.59 (t, 1H, J = 7.2
Hz), 7.45 (t, 2H, J = 7.6 Hz), 7.27 (t, 2H, J = 8.8 Hz), 6.77− 6.33 (m, 3H), 3.72 (t, 2H, J
1
3
=
6.8 Hz), 3.02 (s, 3H), 2.75 (t, 2H, J = 6.8 Hz); C NMR (125 MHz, CDCl ) δ 177.9,
3
1
48.1, 136.6, 134.0, 129.5, 129.4, 128.5, 117.0, 112.4, 93.9, 80.7, 50.9, 38.4, 17.3; IR
+
(
[
neat): 3058, 2920, 2196, 1642, 1598, 1502, 1452, 1263; MS (ES ) Calculated for
+
C
18
H
17NNaO] : 286.1; Found: 286.1.
SI-20

Me
N
Me
N
n-BuLi
ClSO Me, THF
H
SO Me
2
2
4
15d
Ccompound 4 (2 mmol) was dissolved in THF (7 mL), and the resulting solution was
o
cooled down to -78 C in a dry ice-acetone bath. n-BuLi (3 mmol) was added drop-wise
over 3 minutes. After stirring at -78 ºC for 1 h. Methanesulfonyl chloride (2.4 mmol) was
added in dropwise. The reaction was allowed to warm to room temperature and stirred for
overnight. The reaction mixture was then quenched with sat. aqueous NH Cl. The
4
organic layer was separated. The aqueous layer was extracted with diethyl ether (2 x 10
mL). The combined organic layers was washed with brine (25 mL), dried upon MgSO4,
filtered and concentrated. The residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate = 2:1) to yield the desired compound
1
1
5d in 18 % yield. H NMR (400 MHz, CDCl
3
) δ 7.28- 7.24 (m, 2H), 6.77- 6.71 (m, 3H),
1
3
3
.67 (t, 2H, J = 6.8 Hz), 3.08 (s, 3H), 2.99 (s, 3H), 2.67 (t, 2H, J = 6.8 Hz); C NMR
(
125 MHz, CDCl
3
) δ 184.6, 148.1, 129.4, 117.0, 112.3, 91.2, 82.3, 50.9, 38.4, 32.6, 16.9;
+
IR (neat): 3018, 2923, 2862, 2202, 1600, 1502, 1450, 1322, 1148; MS (ES ) Calculated
+
for [C12
H15NNaO
2
S] : 260.1; Found: 260.0.
Me
N
N
I
Pd(PPh ) Cl , CuI
3 2 2
+
H
NO2
Et N
3
NO2
4
To a solution of anhydrous Et N (2 mL) was successively added copper iodide(0.03
3
mmol), dichlorobis(triphenylphosphine)palladium (0.015 mmol). Under nitrogen,
compound 4 (0.3 mmol) and 1-iodo-4-nitro-benzene (0.3 mmol) were added in
succession. The resulting mixture was stirred at 80 ºC for 10 min. The reaction was
cooled down to room temperature and quenched by filtration through a pad of silica gel
using ethyl acetate as eluent. The filtrate was concentrated, and the residue was purified
through silica gel flash column chromatography (eluents: hexanes: ethyl acetate = 2:1) to
1
yield the desired compound in 71 % yield. H NMR (400 MHz, CDCl
3
) δ 8.15 (d, 2H, J =
SI-21

7
.2 Hz), 7.47 (d, 2H, J = 7.2 Hz), 7.28− 7.24 (m, 2H), 6.78− 6.72 (m, 3H), 3.68 (t, 2H, J
1
3
=
7.2 Hz), 3.03 (s, 3H), 2.71 (t, 2H, J = 7.2 Hz); C NMR (125 MHz, CDCl ) δ 148.4,
3
1
46.8, 132.2, 130.7, 129.3, 123.5, 116.8, 112.3, 94.0, 80.6, 51.5, 38.4, 17.7; IR (neat):
+
+
2
923, 2855, 2219, 1593, 1506, 1342; MS (ES ) Calculated for [C17
H
16
N
2
O
2
H] : 281.1;
Found: 281.1.
Me
N
O
O N
2
The above compound was prepared in 44 % yield according to the general procedure A.
1
The reaction time is 30 min for the formation of N-oxide and 30 min for Au catalysis. H
NMR (400 MHz, CDCl
3
) δ 7.13 (d, 2H, J = 9.2 Hz ), 7.38-7.33 (m, 3H), 7.20 (d, 1H, J =
7
2
1
.6 Hz), 7.08-7.04 (m, 2H), 4.75 (s, 1H), 3.42−3.35 (m, 1H), 3.18-3.13 (m, 1H),
1
3
.96−2.89(m, 1H), 2.84 (s, 3H), 2.56−2.51 (m, 1H); C NMR (125 MHz, CDCl ) δ 207.8,
3
48.2, 146.2, 133.8, 130.4, 130.0, 129.4, 124.0, 123.4, 120.1, 63.5, 56.0, 41.7, 39.9; IR
+
(
[
neat): 2933, 2859, 1716, 1600, 1517, 1491, 1447, 1346; MS (ES ) Calculated for
C
17
H
16
N
2
NaO
]+: 319.1; Found: 319.0.
3
SI-22

General procedure B: Preparation of EWG substituted tetrahydrobenz[b]azepin-4-
ones
mCPBA (0.2 mmol) was added into a solution of a N-(but-3-ynyl)aniline (0.2 mmol) and
NaHCO
3
(0.2 mmol) in CH
2
Cl
2
(0.05 M) under N at 0 ºC. The product formation was
2
monitored by TLC. Upon completion, Upon completion, the reaction mixture was diluted
with CH Cl (25 mL) and washed with 5 % aqueous Na S O (10 mL), 10 % aqueous
2
2
2
2
3
NaHCO
3
(10 mL), water and brine. The organic layer was dried with MgSO , and
4
concentrated under vacuum. The residue was purified through silica gel flash column
chromatography (eluents: hexanes: ethyl acetate= 2:1).
Me
N
OH
OMe
O
1
6a
Compound 16a was prepared in 73% yield according to the general procedure B, reaction
1
time is 30 min. H NMR (500 MHz, CDCl
3
) δ 13.01(s, 1H), 7.29 (d, 1H, J = 7.5 Hz),
7
.26-7.22 (m, 1H), 7.06-7.01 (m, 2H), 3.76(s, 3H), 3.48-3.45 (m, 1H), 2.80 (s, 3H), 2.34
1
3
(
t, 2H, J = 7 Hz); C NMR (125 MHz, CDCl
3
) δ 177.1, 171.8, 147.6, 131.2, 128.9, 127.5,
1
1
21.6, 118.8, 100.3, 62.2, 52.0, 41.4, 32.2; IR (neat): 2936, 2859, 1646, 1612, 1491, 1443,
+
+
341, 1224; MS (ES ) Calculated for [C H NNaO ] : 256.1; Found: 256.0.
1
3
15
3
SI-23

Me
N
OH
O
Me
16b
Compound 16b was prepared in 76% yield according to the general procedure B, the
1
reaction time was 60 min. H NMR (400 MHz, CDCl
3
) δ 7.29-7.26(m, 1H), 7.11-7.03(m,
3
1
1
1
H), 3.67-3.55(m, 1H), 3.05-2.99 (m, 1H), 2.79(s, 3H), 2.65-2.55 (m, 1H), 2.29-2.23 (m,
H), 2.10 (s, 3H); 13C NMR (125 MHz, CDCl ) δ 197.6, 184.7, 148.3, 131.0, 130.6,
3
28.1, 122.3, 118.9, 112.5, 59.1, 41.4, 37.6, 22.3; IR (neat): 2926, 2859, 1602, 1494,
+
15NNaO
]+: 240.1; Found: 240.0.
450, 1405, 1268; MS (ES ) Calculated for [C13
H
2
Me
N
OH
O
1
6c
Compound 16c was prepared in 82 % yield according to the general procedure B, the
1
reaction time was 1 h. H NMR (400 MHz, CDCl
3
) δ 7.32-7.27 (m, 1H), 7.22-7.16 (m,
5
1
H), 7.08 (d, 1H, J = 8 Hz), 6.71-6.67 (m, 1H), 6.62 (d, 1H, J = 7.6Hz), 3.91-3.86 (m,
1
3
H), 3.15-3.11 (m, 1H), 2.89 (s, 3H), 2.78-2.71 (m, 1H), 2.44-2.41 (m, 1H); C NMR
)δ 198.8, 180.4, 148.2, 135.5, 132.1, 131.4, 130.4, 129.5, 128.1, 127.6,
(125 MHz,CDCl
3
1
22.2, 118.5, 111.7, 58.9, 41.3, 37.9; IR (neat): 2930, 2808, 1725, 1600, 1560, 1494,
+
17NNaO
]+: 302.1; Found: 302.0.
1
455, 1403, 1334; MS (ES ) Calculated for [C18
H
2
SI-24

Me
N
O
O S O
Me
16d
Compound 16d was prepared in 63 % yield according to the general procedure B, the
1
reaction temperature was -20 ºC and reaction time was 4 h. H NMR (400 MHz, CDCl
3
) δ
7
1
1
5
.47-7.43(m, 1H), 7.39(d, 1H, J = 8 Hz), 7.19-7.15(m, 2H), 4.65(s, 1H), 3.52-3.45(m,
H), 3.07-3.02 (m, 1H), 2.99(s, 3H), 2.89-2.83 (m, 1H), 2.79(s, 3H), 2.57-2.52 (m,
1
3
H); C NMR (125 MHz, CDCl ) δ 201.6, 148.8, 133.8, 131.5, 125.4, 124.4, 120.3, 79.1,
3
5.9, 41.4, 40.8, 40.5; IR (neat): 2930, 2862, 1720, 1600, 1556, 1492, 1453, 1403; MS
+
+
(
ES ) Calculated for [C12
H
15NNaO
3
S] : 276.1; Found: 276.0.
SI-25

SI-26

SI-27

SI-28

SI-29

SI-30