Iridium(III)-Catalyzed Regioselective C7-Amination of N-Pivaloylindoles with Sulfonoazides

Article abstract of DOI:10.1021/acs.joc.6b01856

Direct C7-amination of N-pivaloylindoles has been achieved using a combination of [Cp?IrCl₂]₂, AgNTf₂, and AgOAc as the catalyst and sulfonoazides as the nitrogen source. The reaction proceeded at room temperature to 80 °C to afford 7-sulfonamidoindoles in good to excellent yields. The reaction is broadly applicable to the C7-amination of a wide variety of 3-, 4-, 5-, and 6-substituted N-pivaloylindoles with either alkyl or aryl sulfonoazides.

Full text of DOI:10.1021/acs.joc.6b01856

Subscriber access provided by CORNELL UNIVERSITY LIBRARY
Article
Iridium (III)-Catalyzed Regioselective C7-
Amination of N-Pivaloylindoles with Sulfonoazides
Lanting Xu, Lushi Tan, and Dawei Ma
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01856 • Publication Date (Web): 29 Aug 2016
Downloaded from http://pubs.acs.org on August 31, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 34
The Journal of Organic Chemistry
1
2
3
4
5
Iridium (III)-Catalyzed Regioselective C7-Amination of
6
7
N-Pivaloylindoles with Sulfonoazides
8
9
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Lanting Xu,a Lushi Tan,b* and Dawei Maa*#
aState Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu,
Shanghai 200032, China
bMerck Research Laboratories, P.O. Box 2000, RY800-D280, Rahway, NJ 07065-0900,
USA
lushi_tan@merck.com, madw@sioc.ac.cn
Abstract
Direct C7ꢀamination of Nꢀpivaloylindoles has been achieved using a combination of
[Cp*IrCl2]2, AgNTf2, and AgOAc as the catalyst and sulfonoazides as the nitrogen
source. The reaction proceeded at room temperature to 80 oC to afford
7ꢀsulfonamidoindoles in good to excellent yields. The reaction is broadly applicable
to the C7ꢀamination of a wide variety of 3ꢀ, 4ꢀ, 5ꢀ and 6ꢀsubstituted Nꢀpivaloyl indoles
# ISHC Member
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 34
1
2
3
4
with either alkyl or aryl sulfonoazides.
5
6
7
8
9
Introduction
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
7ꢀSulfonamidoindole moiety is a key substructure found in numerous
biologically important compounds such as the tubulin polymerization and cell
proliferation inhibitors ERꢀ68394 (1)1, Eꢀ7070 (2)2, and compound 33, and the
glucocorticoid receptor antagonist compound 44. Indoles 1, 2, and 3 have potential
for treatment of congestive heart diseases, and 4 lowers LDL while raises HDL in a
hamster model of dyslipidemia (Figure 1). Traditionally, these molecules were
synthesized from substituted 7ꢀnitroindoles.3c,5 Since these special heterocycles are
not conveniently available, development of straightforward and general methods for
assembling 7ꢀsulfonamidoindoles are highly desired.6,7 Recently, we discovered that
regioselective C7ꢀfunctionalization of indoles could be achieved by simply using
Nꢀpivaloyl as a directing group.8,9 As an extension of this work, we explored the
possibility if our substrates are applicable for other C7ꢀfunctionalization reactions,
and discovered that Irꢀcatalyzed direct functionalization of Nꢀpivaloyl indoles with
sulfonazides could proceed smoothly to afford 7ꢀsulfonamidoindoles.10ꢀ15 During the
preparation of this manuscript, similar reactions with different conditions were
disclosed by Chang10a and Antonchick10b groups. Chang and coworkers described that
they could carry out the reaction at room temperature, but needed to use 5 mol %
Cp*Ir(OAc)2 as the catalyst and 10 mol% AgNTf2 as the additive;10a while
o
Antonchick found that the reaction completed at 120 C even using 4 mol %
ACS Paragon Plus Environment

Page 3 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
[Cp*IrCl]2 as the catalyst and 16 mol % AgNTf2 and 40 mol % LiOAc as the
additives.10b In our hand, we discovered that only 1 mol % [Cp*IrCl]2 was required to
7
8
9
o
complete the reaction at rt to 80 C if 4 mol % AgNTf2 and 30 mol % AgOAc were
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
employed as the additives. These relatively practical reaction conditions and expanded
substrate scope, together with preliminary mechanism study, are disclosed here.
Cl
Cl
N
N
H
H
O
O
NH
NH
S
S
O
O
ER-68394 (1) H2NO2S
MeO
Cl
2
F
MeO
Me
Me Me
Ph
Me
N
N
H
Me
H
O
O
NH
NH
N
S
S
Bn
Me
Me
O
O
3
4
Figure 1. Biologically important compounds that contain the 7ꢀsulfonamidoindole
moiety
Results and Discussion
We commenced our amination research by employing our standard olefination
conditions of Nꢀpivaloylindoles by treatment of 5a with tosyl azide 6a in the presence
o
of [Cp*RhCl2]2, AgNTf2 and Cu(OAc)2 in DCE at 80 C.8 However, no desired
product was obtained and 5a was recovered completely. We then turned our attention
to Ir catalysts.13g As indicated in Table 1, In the presence of [Cp*IrCl2]2, AgNTf2, and
NaOAc, the reaction of Nꢀpivaloylindole 5a with tosyl azide 6a took place at room
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 34
1
2
3
4
5
6
7
8
9
temperature but with only trace amount of the desired product 7a owing to poor
conversion (entry 1). Changing one of the additives from NaOAc to pivalic acid or
CsOAc gave similar results (entries 2 and 3). However, when AgOAc was used,
complete conversion was observed, and 7a was obtained in 95% yield (entry 4). If
AgOAc was switched to Cu(OAc)2·H2O or Ag2CO3, the reaction yields were greatly
decreased (entries 5 and 6). Further investigations revealed that the use of AgNTf2 is
critical to the reaction efficiency. No desired product was obtained without AgNTf2 or
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
replacing it with AgO2CCF3 and AgOTs even at 80 C (entries 9ꢀ11). Interestingly,
when AgNTf2 was replaced with either AgSbF6 or AgOTf, poor yields were obtained
o
at room temperature but acceptable yields were realized at 80 C (entries 7 and 8).
Using the combination of [Cp*IrCl2]2, AgNTf2 and AgOAc, we examined several
polar solvents, and found that trifluoromethylbenzene and methylene chloride
afforded 7a in 88ꢀ93% yields (entries 12 and 13), while tꢀAmylOH, MeCN, and
dioxane gave poor yields or no conversion (entries 14ꢀ16). Additionally, we
discovered that Ir catalyst was also essential for this reaction and little conversion was
14
observed when [Cp*RhCl2]2,12 [Ru(pꢀcymene)Cl2]2 and Cp*Co(CO)I215 were used
as the catalyst (entries 17ꢀ19). We were pleased that the catalyst loading could be
reduced to 1 mol % without decreasing the reaction yield with the optimized reaction
conditions (entry 4 vs. 20). Noteworthy is that the combination of two silver salts was
essential to ensure complete conversion because using AgNTf2 or AgOAc alone gave
a poor yield or no conversion (entries 21 and 22).
ACS Paragon Plus Environment

Page 5 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
Table 1. Condition screening for reaction of Nꢀpivaloylindole with tosyl azidea
8
9
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
entry
catalyst (mol %)
additives (mol %)
solvent
yield
(%)b
2
1
2
3
4
5
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
AgNTf2 (16)/NaOAc (30)
AgNTf2 (16)/PivOH (30)
AgNTf2 (16)/CsOAc (30)
AgNTf2 (16)/AgOAc (30)
AgNTf2
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
0
0
95
55
(16)/Cu(OAc)2·H2O (30)
6
7
8
9
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
AgNTf2 (16)/Ag2CO3 (30) 1,2ꢀDCE
25
AgSbF6 (16)/AgOAc (30)
AgOTf (16)/AgOAc (30)
AgO2CCF3 (16)/AgOAc
(30)
1,2ꢀDCE 30 (73)c
1,2ꢀDCE 45 (81)c
1,2ꢀDCE
0 (0)c
10
11
12
13
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
AgOTs (16)/AgOAc (30)
AgNTf2 (0)/AgOAc (30)
AgNTf2 (16)/AgOAc (30)
AgNTf2 (16)/AgOAc (30)
1,2ꢀDCE
1,2ꢀDCE
C6H5CF3
CH2Cl2
0 (0)c
0 (0)c
88
93
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 34
1
2
3
4
5
6
7
8
9
14
15
16
17
18
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*RhCl2]2
AgNTf2 (16)/AgOAc (30)
AgNTf2 (16)/AgOAc (30)
AgNTf2 (16)/AgOAc (30)
AgNTf2 (16)/AgOAc (30)
tꢀAmOH
15
0
MeCN
dioxane
1,2ꢀDCE
1,2ꢀDCE
5
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
0
[Ru(pꢀcymene)Cl2 AgNTf2 (16)/AgOAc (30)
9
]
2
19
20
21
22
Cp*Co(CO)I2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
AgNTf2 (16)/AgOAc (30)
AgNTf2 (4)/AgOAc (30)
AgNTf2 (4)/ AgOAc (0)
AgNTf2 (0)/ AgOAc (30)
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
1,2ꢀDCE
0
93d
5d
0d
a5a (0.2 mmol), 6a (0.3 mmol), catalyst (4.0 mol%), and DCE (1.0 mL) at room
b
1
temperature for 24 h. Yields based on H NMR analysis of the crude mixture
c
o
(1,3,5ꢀtrimethoxybenzene; internal standard). Reaction temperature was 80 C.
d[Cp*IrCl2]2 (1.0 mol%) and DCE (0.2 mL) was used.
With the optimized conditions in hand, we next explored the substrate scope
using different substituted indoles. As summarized in Table 2, indoles bearing an
electronꢀdonating group at the 4ꢀ, or 5ꢀ position worked well at room temperature,
leading to the formation of 7bꢀ7d and 7hꢀ7j in 87ꢀ95% yields. Halogenꢀsubstituted
o
indoles were less reactive, and required increased reaction temperature (80 C) to
afford 7e, 7f and 7kꢀ7m in good yields. However, more electronꢀdeficient substrates
like 4ꢀcyanoꢀNꢀpivaloylindole and 5ꢀnitroꢀNꢀpivaloylindole gave no conversion even
ACS Paragon Plus Environment

Page 7 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
at 80 oC. The present reaction is very sensitive to the steric hindrance of the 6ꢀposition
in Nꢀpivaloylindoles. No product was obtained when 6ꢀmethylꢀNꢀpivaloylindole or
6ꢀchloroꢀNꢀpivaloylindole was utilized as the substrates. In contrast,
6ꢀfluoroꢀNꢀpivaloylindole that possesses a small F at the 6ꢀposition delivered the
amination product 7q in 85% yield.
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Substrate Scope of Indolesa
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 34
1
2
3
4
5
6
7
8
9
Me
NH
OBn
OMe
N
N
N
NH
O
7d (90%)
NH
O
7c (96%)
Ts
t-Bu
O
Ts
Ts
t-Bu
Ts
t-Bu
t-Bu
7b (95%)
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Cl
Br
CN
N
N
N
NH
O
7e (78%)b
NH
O
7f (82%)b
NH
O
7g (0%)b
Ts
t-Bu
Ts
t-Bu
PivO
BnO
MeO
N
N
N
NH
NH
NH
Ts
t-Bu
t-Bu
O
Ts
t-Bu
t-Bu
t-Bu
O
Ts
t-Bu
O
7h (88%)
7j (90%)
7i (87%)
F
Cl
Br
N
N
N
NH
O
NH
O
NH
O
Ts
t-Bu
Ts
Ts
7k (80%)b
7m (85%)b
7l (82%)b
O2N
N
Me
t-Bu
N
Cl
N
NH
NH
NH
Ts
O
Ts
Ts
N
t-Bu
O
O
7n (0%)b
7o (0%)b
7p (0%)b
Me
CO2Et
F
N
N
NH
NH
NH
Ts
t-Bu
O
Ts
t-Bu
Ts
O
t-Bu
O
7q (85%)b
c
7r (87%)
PhthN
7s
(70%)
TBSO
N
Me
t-Bu
N
N
NH
O
7v (0%)b
Ts
NH
NH
Ts
t-Bu
O
Ts
t-Bu
O
7t (78%)c
7u (90%)
a5 (0.2 mmol), 6a (0.3 mmol), DCE (0.2 mL) at room temperature for 24ꢀ36 h. bAt 80
oC. cAt 50 oC.
ACS Paragon Plus Environment

Page 9 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
In addition, substrates with both simple and functionalized alkyl substituents at
the 3ꢀposition of Nꢀpivaloylindoles underwent the amination smoothly, producing
7rꢀ7u in 70ꢀ90% yields. The additional functional groups in the side chain of these
products should be useful for further conversion to pharmaceutically important
molecules. However, 2ꢀmethylꢀNꢀpivaloylindole was inert under the present reaction
conditions, presumably because the steric hindrance at this position could inhibit the
formation of the active metal complex intermediates.
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The reaction was successfully conducted on gram scale without any difficulty.
Thus 1.6 g of the desired amination product 7w was obtained in 88% yield from the
tryptophan derivative 5w (Scheme 1). Interestingly, the phthoyl protecting group in
5w was essential for this transformation, as Bocꢀprotected tryptophan derivative 5x
and dipeptide 5y were inert under the same reaction conditions. This phenomenon
indicated that the free NH moiety in the substrates might bond to the metal in a way
that blocked the catalytic reaction.
Scheme 1. Gramꢀscale reaction of a tryptophan derivative
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 34
1
2
3
4
5
6
7
8
9
We also evaluated the reaction scope using different sulfonyl azides and the
results were summarized in Table 3. Aryl sulfonyl azides with electronꢀdonating
groups, in general, were more reactive, giving complete conversion and excellent
yields at room temperature, while aryl sulfonyl azides with electronꢀwithdrawing
groups required elevated temperature to reach complete conversion. Alkyl sulfonyl
azides also worked well, and 8k and 8l were obtained in 88% and 81% yields,
respectively. Using methylsulfonyl azide as the reagent, we examined several
substituted Nꢀpivaloylindoles, and were pleased that all of them proceeded smoothly
to afford the desired products 8oꢀ8s in good to excellent yields.
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 3. Scope of Sulfonyl Azidesa
ACS Paragon Plus Environment

Page 11 of 34
The Journal of Organic Chemistry
1
2
3
Cl
4
5
6
7
8
N
N
O
O
NH
NH
S
Bu-t
O
S
Bu-t
8m (60%)
Cl
O
R
4-MeOC6H4
O
O
8a: R = Ph, 89%b
9
8b: R = 4-FC6H4, 88%c
8c: R = 4-ClC6H4, 90%c
8d: R = 4-BrC6H4, 78%c
8e: R = 4-NCC6H4, 70%
8f: R = 4-AcC6H4, 79%
8g: R = 3,5-Cl2C6H3, 79%c
8h: R = 2,4-F2C6H3, 83%
8i: R = 4-MeOC6H4, 88%b
8j: R = 2-Naphth, 85%c
8k: R = Me, 88%d
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
O
NH
S
Bu-t
O
4-MeOC6H4
Cl
O
8n (73%)
N
NH
8l: R = n-C8H17, 81%d
Ms
Bu-t
8o (63%)d
O
Me
Me
Me
Ph
N
F
N
NH
Ms
Bu-t
8p (91%)d
O
NH
Ms
NH
Bu-t
8q (77%)d
O
Me
Ph
n-Pr
CO2Me
NPhth
N
N
NH
Ms
Bu-t
O
Ms
O
Bu-t
8r (83%)d
8s (77%)d
a5 (0.2 mmol), 6 (0.3 mmol), DCE (0.2 mL) at 80 C for 24ꢀ36 h in pressure tubes.
o
c
o
d
bAt room temperature. At 50 C. [IrCp*Cl2]2 (4 mol %), AgNTf2 (16 mol %), DCE
(1.0 mL) were used at 80 oC.
The application of the current methodology is demonstrated by the successful
preparation of a known tubulin polymerization and cell proliferation inhibitor 1
(ERꢀ68394)1 and 9, a compound with interesting activity against congestive heart
diseases.3 Thus, treatment of 8m and 8q, prepared as discussed above, with our
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 34
1
2
3
4
5
6
standard mild deprotection condition (Et3N in MeOH, room temperature)8 afforded 1
and 9 in 92% and 90% yield respectively (Scheme 2).
7
8
9
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. Deprotection of the amidation products
To obtain mechanistic insights into the present Irꢀcatalyzed direct CꢀH amination,
we conducted some deuteration experiments as depicted in Scheme 3. No significant
H/D exchange was observed when 5a was treated with CD3OD in the presence of
[IrCp*Cl2]2, AgNTf2 and AgOAc, indicating that the CꢀH activation step might be
irreversible. Additionally, kinetic isotope effect (KIE) experiments on parallel
reactions of 6a with 5a and [D]4ꢀ5a in separate vessels were carried out under the
standard reaction conditions, giving the KIE value of kH/kD = 6.5. This result implied
that the CꢀH bond cleavage might occur in the rateꢀlimiting stage.
ACS Paragon Plus Environment

Page 13 of 34
The Journal of Organic Chemistry
1
2
3
4
(a) H/D Exchange Study
<5% D
<5% D
1 mol % [Cp*IrCl2]2
4 mol % AgNTf2
H/D
H/D
5
6
7
8
CD3OD
+
30 mol % AgOAc
1,2-DCE, rt, 24h
N
N
H/D
Bu-t
Bu-t
O
O
9
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
<5% D
5a
[D]n-5a
(b) Kinetic Isotope Effects
H/D
H/D
H/D
H/D
H/D
1 mol % [Cp*IrCl2]2
4 mol % AgNTf2
+
TsN3
N
30 mol % AgOAc
1,2-DCE, rt
H/D
N
6
NH
H/D
Ts
Bu-t
O
O
Bu-t
kH/kD = 6.5
5a/[D]4-5a
8a/[D]3-8a
Scheme 3. Preliminary Mechanistic Studies.
On the basis of the above mechanistic studies and known reports on
metalꢀcatalyzed directing group assisted CꢀH amidation,11ꢀ15 a plausible mechanism is
proposed as shown in Scheme 4. First, treatment of the dimeric precursor [IrCp*Cl2]2
with AgNTf2 and AgOAc generates the cationic Ir(III) catalyst A. The coordination of
A to the Nꢀpivaloyl group of 5a forms B, which accordingly undergoes an irreversible
CꢀH activation at the C7 position of indole substrate to result the sixꢀmembered
iridacycle C. The latter step may be the rateꢀlimiting step based on KIE studies. Next,
coordination of sulfonoazide gives the complex D, which may undergo release of N2
to provide a metalꢀnitrenoid intermediate E. The subsequent intramolecular insertion
of nitrenoid moiety into iridacycle forms a new CꢀN bond to deliver complex F, upon
coordination with acetic acid. Finally, protonolysis of F affords the desired product 7a
and regenerate the catalyst A. Further efforts to explore the detailed mechanistic
insights of the present regioselective amination reaction are ongoing in our group.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 34
1
2
3
4
5
6
1/2 [Cp*IrCl2]2
7
AgNTf2, AgOAc
AgCl
8
9
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Cp*Ir(OAc)(NTf2)
7a
5a
A
Cp*
[NTf2]-
Cp*
+
Ir
+
Ir
[NTf2]-
O
OAc
O
Ts
N
Y
HO
O
N
N
Y
B
F
HOAc
Cp*
Ts
N
Cp*
[NTf2]-
O
O
[NTf2]-
O
+
Ir
+
OH
Ir
Y
N
Y
N
C
E
Ts
N
Cp*
Ts-N3
[NTf2]-
O
+
N2
N2
Ir
HOAc
Y
N
Y = t-Bu
D
Scheme 4. Proposed mechanistic pathway
In summary, we have developed a straightforward and general method for
preparing 7ꢀsulfonamidoindoles from conveniently available starting materials
through Irꢀcatalyzed CꢀH activation. The key is an iridium(III)ꢀcatalyzed, C7ꢀselective
amidation of Nꢀpivaloyindole derivatives. High efficiency and regioselectivity are
achieved even at room temperature with considerably low catalyst loading. A number
ACS Paragon Plus Environment

Page 15 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
of functional groups are tolerated under these reaction conditions, and thus allows
synthesizing 7ꢀsulfonamidoindoles in a diverse manner. The usage of this method has
been illustrated by quick access to some pharmaceutically important molecules.
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Experimental
General Information. All the reactions were carried out under inert atmosphere. All
the solvents used for the reactions were dried according to standard procedures. All
commercial materials were used as received unless otherwise noted. All the Nꢀpivalyl
indoles were synthesized according to the literature procedure.[16,17] All the
sulfonoazides were synthesized according to the literature procedure.[18] All the
reactions were monitored by thin layer chromatography (TLC, Silica gel Merck 60
F254); The spots were visualized by UV light. Purification of products was conducted
by flash chromatography on silica gel (particle size 40ꢀ63 ꢁm, 230ꢀ400 mesh
SiliaFlash® P60 (Silicycle Inc.)). Optical rotations were measured at room
temperature with a digital polarimeter. CDCl3 was used as NMR solvents. Chemical
shifts were given relative to CDCl3 (7.24 ppm for 1H NMR, 77.23 ppm for 13C NMR);
For the characterization of the observed signal multiplicities, the following
abbreviations were applied: s (singlet), d (doublet), dd (double doublet), t (triplet), td
(triple doublet), q (quartet), m (multiplet), as well as br (broad). Highꢀresolution mass
spectra were acquired using ESIꢀFTMS method. Melting point was measured with
Xꢀ4 Meltingꢀpoint apparatus with microscope.
General procedure for the Ir-catalyzed amidation with sulfonoazides: A sealed
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 34
1
2
3
4
5
6
7
8
9
tube was charged with indole substrates (0.2 mmol), [IrCp*Cl2]2 (1.6 mg, 0.002
mmol), AgOAc (10.0 mg, 0.06 mmol), AgNTf2 (2.0 mg, 0.008 mmol), sulfonoazides
(0.3 mmol). The tube was evacuated and backfilled with argon before 0.2 mL
1,2ꢀDCE was added. The reaction mixture was stirred for 24ꢀ36 h at indicated
temperatures. After cooling to room temperature, the mixture was diluted with
dichloromethane, filtered through a plug of diatomite, concentrated under vacuum and
the residue was purified by chromatography on silica with a gradient eluent of
petroleum ether and ethyl acetate to give the corresponding 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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Large scale preparation of 7w: A sealed tube was charged with indole 5e (1.3 g, 3.0
mmol), [IrCp*Cl2]2 (23.9 mg, 0.03 mmol), AgOAc (150 mg, 0.9 mmol), AgNTf2
(30.7 mg, 0.12 mmol), pꢀtoluenesulfonyl azide (887 mg, 4.5 mmol). The tube was
evacuated and backfilled with argon before 3.0 mL 1,2ꢀDCE was added. The reaction
mixture was stirred at room temperature for 40 h. Then the mixture was diluted with
dichloromethane, filtered through a plug of diatomite, concentrated under vacuum and
the residue was purified by chromatography on silica with a gradient eluent of
petroleum ether and ethyl acetate to give 1.6 g (88%) of 7w.
4-Methyl-N-(1-pivaloyl-1H-indol-7-yl)benzenesulfonamide (7a): White solid (67
mg, 90%); m.p. 119ꢀ121 oC; 1H NMR (400 MHz, CDCl3) δ 9.21 (s, 1H), 7.52ꢀ7.48 (m,
2H), 7.39ꢀ7.35 (m, 3H), 7.30 (t, J = 7.7 Hz, 1H), 7.07 (d, J = 8.0 Hz, 2H), 6.56 (d, J =
13
3.9 Hz, 1H), 2.28 (s, 3H), 1.35 (s, 9H); C{1H} NMR (100 MHz, CDCl3) δ 179.5,
143.3, 137.7, 132.4, 129.6, 129.5, 127.0, 126.7, 125.4, 125.4, 123.0, 119.0, 109.5,
41.8, 29.2, 21.6; HRMS (ESI) m/e calcd for C20H23N2O3S (M + H)+ 371.1424, found
ACS Paragon Plus Environment

Page 17 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
371.1426.
4-Methyl-N-(4-methyl-1-pivaloyl-1H-indol-7-yl)benzenesulfonamide (7b): White
7
8
9
o
1
solid (73 mg, 95%); m.p. 162ꢀ164 C; H NMR (400 MHz, CDCl3) δ 8.95 (s, 1H),
7.47 (d, J = 3.9 Hz, 1H), 7.40ꢀ7.35 (m, 3H), 7.10ꢀ7.04 (m, 3H), 6.58 (d, J = 3.9 Hz,
1H), 2.45 (s, 3H), 2.28 (s, 3H), 1.33 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ
179.5, 143.2, 137.8, 131.6, 129.6, 129.5, 128.6, 127.0, 126.0, 125.8, 123.7, 122.9,
107.7, 41.8, 29.2, 21.6, 18.3; HRMS (ESI) m/e calcd for C21H25N2O3S (M + H)+
385.1580, found 385.1586.
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N-(4-Methoxy-1-pivaloyl-1H-indol-7-yl)-4-methylbenzenesulfonamide (7c): White
o
1
solid (77 mg, 96%); m.p. 155ꢀ157 C; H NMR (400 MHz, CDCl3) δ 8.64 (s, 1H),
7.44 (d, J = 8.6 Hz, 1H), 7.35 (d, J = 3.9 Hz, 1H), 7.30 (d, J = 8.3 Hz, 2H), 7.04 (d, J
= 8.0 Hz, 2H), 6.76 (d, J = 8.6 Hz, 1H), 6.68 (d, J = 3.9 Hz, 1H), 3.92 (s, 3H), 2.27 (s,
3H), 1.29 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 179.3, 151.7, 143.2, 137.7,
131.5, 129.5, 127.0, 125.8, 125.0, 122.0, 118.02, 106.2, 105.4, 55.9, 41.7, 29.1, 21.6.
HRMS (ESI) m/e calcd for C21H25N2O4S (M + H)+ 401.1530, found 401.1532.
N-(4-(Benzyloxy)-1-pivaloyl-1H-indol-7-yl)-4-methylbenzenesulfonamide (7d): Br
own solid (86 mg, 90%); m.p. 156ꢀ158 oC; 1H NMR (400 MHz, CDCl3) δ 8.66 (s, 1H),
7.46ꢀ7.29 (m, 9H), 7.05 (d, J = 8.0 Hz, 2H), 6.83 (d, J = 8.6 Hz, 1H), 6.74 (d, J = 3.9
Hz, 1H), 5.18 (s, 2H), 2.27 (s, 3H), 1.30 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ
179.3, 150.7, 143.2, 137.6, 136.9, 131.5, 129.5, 128.8, 128.3, 127.6, 127.0, 125.6,
125.1, 122.4, 118.2, 106.9, 106.3, 70.5, 41.7, 29.0, 21.5; HRMS (ESI) m/e calcd for
C27H29N2O4S (M + H)+ 477.1843, found 477.1844.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 34
1
2
3
4
N-(4-Chloro-1-pivaloyl-1H-indol-7-yl)-4-methylbenzenesulfonamide (7e): White
5
6
o
1
solid (63 mg, 78%); m.p. 144ꢀ146 C; H NMR (400 MHz, CDCl3) δ 8.97 (s, 1H),
7.54 (d, J = 3.9 Hz, 1H), 7.44ꢀ7.39 (m, 3H), 7.29 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 8.0
Hz, 2H), 6.70 (dd, J = 3.9, 0.9 Hz, 1H), 2.29 (s, 3H), 1.35 (s, 9H); 13C{1H} NMR (100
MHz, CDCl3) δ 179.7, 143.6, 137.4, 130.7, 130.2, 129.6, 127.2, 126.9, 124.9, 124.1,
124.0, 123.8, 107.5, 41.9, 29.0, 21.6; HRMS (ESI) m/e calcd for C20H22N2O3SCl (M
+ H)+ 405.1034, found 405.1038.
7
8
9
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N-(4-Bromo-1-pivaloyl-1H-indol-7-yl)-4-methylbenzenesulfonamide (7f): Brown
o
1
solid (74 mg, 82%); m.p. 141ꢀ143 C; H NMR (400 MHz, CDCl3) δ 8.99 (s, 1H),
7.55 (d, J = 3.9 Hz, 1H), 7.44ꢀ7.35 (m, 4H), 7.10 (d, J = 8.0 Hz, 2H), 6.66 (d, J = 3.9
Hz, 1H), 2.29 (s, 3H), 1.35 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 179.8, 143.6,
137.5, 132.6, 130.0, 129.7, 128.2, 127.2, 127.0, 124.7, 123.9, 112.4, 109.4, 42.0, 29.1,
21.6; HRMS (ESI) m/e calcd for C20H22N2O3BrS (M + H)+ 449.0529, found
449.0525.
N-(5-Methoxy-1-pivaloyl-1H-indol-7-yl)-4-methylbenzenesulfonamide
(7h):
o
1
White solid (70 mg, 88%); m.p. 125ꢀ127 C; H NMR (400 MHz, CDCl3) δ 9.63 (s,
1H), 7.48ꢀ7.45 (m, 3H), 7.14 (d, J = 2.5 Hz, 1H), 7.09 (d, J = 8.1 Hz, 2H), 6.79 (d, J =
2.5 Hz, 1H), 6.47 (d, J = 3.9 Hz, 1H), 3.82 (s, 3H), 2.28 (s, 3H), 1.35 (s, 9H); 13C{1H}
NMR (100 MHz, CDCl3) δ 179.0, 157.6, 143.4, 137.5, 133.3, 129.5, 127.5, 127.0,
126.2, 123.8, 109.6, 109.5, 102.0, 55.9, 41.7, 29.2, 21.6; HRMS (ESI) m/e calcd for
C21H25N2O4S (M + H)+ 401.1530, found 401.1534.
N-(5-(Benzyloxy)-1-pivaloyl-1H-indol-7-yl)-4-methylbenzenesulfonamide
(7i):
ACS Paragon Plus Environment

Page 19 of 34
The Journal of Organic Chemistry
1
2
3
4
o
1
White solid (83 mg, 87%); m.p. 157ꢀ159 C; H NMR (400 MHz, CDCl3) δ 9.64 (s,
5
6
7
1H), 7.47ꢀ7.41 (m, 5H), 7.38ꢀ7.29 (m, 3H), 7.26 (d, J = 2.4 Hz, 1H), 7.07 (d, J = 8.0
8
9
13
Hz, 2H), 6.86 (d, J = 2.5 Hz, 1H), 5.10 (s, 2H), 2.28 (s, 3H), 1.35 (s, 9H); C{1H}
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NMR (100 MHz, CDCl3) δ 179.0, 156.7, 143.4, 137.5, 137.0, 133.2, 129.5, 128.8,
128.2, 127.7, 127.5, 127.1, 126.3, 124.0, 110.2, 109.6, 103.5, 70.7, 41.7, 29.2, 21.6;
HRMS (ESI) m/e calcd for C27H29N2O4S (M + H)+ 477.1843, found 477.1849.
7-(4-Methylphenylsulfonamido)-1-pivaloyl-1H-indol-5-yl pivalate (7j): White
o
1
solid (85 mg, 90%); m.p. 145ꢀ147 C; H NMR (400 MHz, CDCl3) δ 9.39 (s, 1H),
7.51 (d, J = 3.9 Hz, 1H), 7.43 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 2.3 Hz, 1H), 7.08ꢀ7.06
13
(m, 3H), 6.50 (d, J = 3.9 Hz, 1H), 2.27 (s, 3H), 1.36 (s, 9H), 1.34 (s, 9H); C{1H}
NMR (100 MHz, CDCl3) δ 179.3, 177.2, 148.5, 143.5, 137.2, 132.7, 129.5, 127.7,
127.1, 127.0, 126.0, 116.3, 111.4, 109.5, 41.8, 39.3, 29.1, 27.3, 21.6; HRMS (ESI)
m/e calcd for C25H31N2O5S (M + H)+ 471.1948, found 471.1951.
N-(5-Fluoro-1-pivaloyl-1H-indol-7-yl)-4-methylbenzenesulfonamide (7k): White
o
1
solid (62 mg, 80%); m.p. 128ꢀ130 C; H NMR (400 MHz, CDCl3) δ 9.56 (s, 1H),
7.57 (d, J = 3.9 Hz, 1H), 7.50 (d, J = 8.1 Hz, 2H), 7.30 (dd, J = 10.6, 2.5 Hz, 1H),
7.12 (d, J = 8.2 Hz, 2H), 6.99 (dd, J = 7.5 Hz, 2.5 Hz, 1H), 6.52 (d, J = 3.9 Hz, 1H),
13
2.30 (s, 3H), 1.38 (s, 9H); C{1H} NMR (100 MHz, CDCl3) δ 179.5, 161.5 (JCꢀF
=
240.8 Hz), 143.7, 137.4, 133.2 (JCꢀF = 11.1 Hz), 129.7, 128.2, 127.1, 126.8 (JCꢀF = 11.9
Hz), 125.5 (JCꢀF = 1.8 Hz), 109.50 (JCꢀF = 32.2 Hz), 109.46, 104.1 (JCꢀF = 23.4 Hz),
42.0, 29.2, 21.6; HRMS (ESI) m/e calcd for C20H22N2O3FS (M + H)+ 389.1330, found
389.1334.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 34
1
2
3
4
N-(5-Bromo-1-pivaloyl-1H-indol-7-yl)-4-methylbenzenesulfonamide (7l): Brown
5
6
o
1
solid (74 mg, 82%); m.p. 165ꢀ167 C; H NMR (400 MHz, CDCl3) δ 9.30 (s, 1H),
7.63 (d, J = 1.9 Hz, 1H), 7.52 (d, J = 3.9 Hz, 1H), 7.47ꢀ7.45 (m, 3H), 7.11 (d, J = 8.0
Hz, 2H), 6.50 (d, J = 3.9 Hz, 1H), 2.30 (s, 3H), 1.36 (s, 9H); 13C{1H} NMR (125
MHz, CDCl3) δ 179.6, 143.7, 137.3, 133.7, 129.7, 128.3, 127.8, 127.0, 126.5, 124.7,
121.3, 118.2, 108.8, 42.0, 29.1, 21.6; HRMS (ESI) m/e calcd for C20H22N2O3BrS (M
+ H)+ 449.0529, found 449.0525.
7
8
9
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N-(5-Chloro-1-pivaloyl-1H-indol-7-yl)-4-methylbenzenesulfonamide (7m): White
o
1
solid (69 mg, 85%); m.p. 149ꢀ151 C; H NMR (400 MHz, CDCl3) δ 9.36 (s, 1H),
7.54 (d, J = 3.9 Hz, 1H), 7.50 (d, J = 2.0 Hz, 1H), 7.47 (d, J = 8.2 Hz, 2H), 7.30 (d, J
= 2.0 Hz, 1H), 7.11 (d, J = 8.1 Hz, 2H), 6.50 (d, J = 3.9 Hz, 1H), 2.30 (s, 3H), 1.36 (s,
9H); 13C{1H} NMR (125 MHz, CDCl3) δ 179.6, 143.7, 137.4, 133.3, 130.8, 129.7,
127.9, 127.8, 127.1, 126.3, 121.9, 118.2, 108.9, 42.0, 29.2, 21.6; HRMS (ESI) m/e
calcd for C20H22N2O3ClS (M + H)+ 405.1034, found 405.1032.
N-(6-Fluoro-1-pivaloyl-1H-indol-7-yl)-4-methylbenzenesulfonamide (7q): White
o
1
solid (66 mg, 85%); m.p. 129ꢀ131 C; H NMR (500 MHz, CDCl3) δ 7.84 (s, 1H),
7.56ꢀ7.53 (m, 3H), 7.40 (dd, J = 8.5, 4.9 Hz, 1H), 7.17 (d, J = 8.0 Hz, 2H), 7.13 (dd, J
= 10.0, 8.6 Hz, 1H), 6.56 (d, J = 3.9 Hz, 1H), 2.35 (s, 3H), 1.40 (s, 9H); 13C{1H}
NMR (125 MHz, CDCl3) δ 179.5, 158.7 (JCꢀF = 245.6 Hz), 143.7, 137.7, 132.9 (JCꢀF
=
3.7 Hz), 129.5, 128.2 (JCꢀF = 1.9 Hz), 127.4, 127.1 (JCꢀF = 3.8 Hz), 120.5 (JCꢀF = 9.8
Hz), 113.8 (JCꢀF = 24.1 Hz), 113.5 (JCꢀF = 17.3 Hz), 108.5 (JCꢀF = 1.4 Hz), 41.8, 29.0,
21.7; HRMS (ESI) m/e calcd for C20H22N2O3FS (M +H)+ 389.1330, found 389.1323.
ACS Paragon Plus Environment

Page 21 of 34
The Journal of Organic Chemistry
1
2
3
4
4-Methyl-N-(3-methyl-1-pivaloyl-1H-indol-7-yl)benzenesulfonamide (7r): Yellow
5
6
7
o
1
solid (67 mg, 87%); m.p. 129ꢀ131 C; H NMR (400 MHz, CDCl3) δ 9.45 (s, 1H),
8
9
7.53 (dd, J = 7.0, 1.9 Hz, 1H), 7.40 (d, J = 8.2 Hz, 2H), 7.30ꢀ7.24 (m, 3H), 7.06 (d, J
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
= 8.0 Hz, 2H), 2.28 (s, 3H), 2.19 (d, J = 1.1 Hz, 3H), 1.33 (s, 9H); C{1H} NMR
(100 MHz, CDCl3) δ 179.0, 143.3, 137.7, 133.4, 129.8, 129.5, 127.0, 125.4, 125.1,
123.5, 122.8, 118.3, 116.7, 41.7, 29.1, 21.6, 9.9; HRMS (ESI) m/e calcd for
C21H25N2O3S (M + H)+ 385.1580, found 385.1585.
Ethyl 2-(7-(4-methylphenylsulfonamido)-1-pivaloyl-1H-indol-3-yl)acetate (7s):
Yellow semisolid (64 mg, 70%); 1H NMR (400 MHz, CDCl3) δ 9.34 (s, 1H), 7.62 (s,
1H), 7.53ꢀ7.51 (m, 1H), 7.40 (d, J = 7.0 Hz, 2H), 7.30ꢀ7.28 (m, 2H), 7.07 (d, J = 8.1
Hz, 2H), 4.19 (q, J = 7.1 Hz, 2H), 3.64 (d, J = 1.0 Hz, 2H), 2.28 (s, 3H), 1.36 (s, 9H),
1.27 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) 179.3, 170.7, 143.4, 137.6,
132.2, 129.5 (2C), 126.9 (2C), 125.5, 125.3, 122.9, 116.6, 114.9, 61.3, 41.8, 30.7, 29.1,
21.6, 14.4; HRMS (ESI) m/e calcd for C24H29N2O5S (M + H)+ 457.1792, found
457.1794.
N-(3-(2-((tert-Butyldimethylsilyl)oxy)ethyl)-1-pivaloyl-1H-indol-7-yl)-4-methyl-
1
benzenesulfonamide (7t): Brown semisolid (82 mg, 78%); H NMR (400 MHz,
CDCl3) δ 9.41 (s, 1H), 7.52 (dd, J = 6.7, 2.0 Hz, 1H), 7.39ꢀ7.38 (m, 3H), 7.31ꢀ7.25 (m,
2H), 7.06 (d, J = 8.0 Hz, 2H), 3.87 (t, J = 6.1 Hz, 2H), 2.81 (t, J = 6.0 Hz, 2H), 2.27 (s,
3H), 1.33 (s, 9H), 0.83 (s, 9H), ꢀ0.06 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ
179.1, 143.2, 137.7, 132.9, 129.6, 129.5, 127.0, 125.4, 125.0, 124.3, 122.8, 120.1,
116.7, 62.4, 41.7, 29.1, 28.5, 26.1, 21.6, 18.4, ꢀ5.2; HRMS (ESI) m/e calcd for
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 34
1
2
3
4
C28H40N2O4SSiNa (M + Na)+ 551.2370, found 551.2365.
5
6
7
N-(3-(2-(1,3-Dioxoisoindolin-2-yl)ethyl)-1-pivaloyl-1H-indol-7-yl)-4-methyl-
8
9
o
1
benzenesulfonamide (7u): White solid (98 mg, 90%); m.p. 167ꢀ169 C; H NMR
(400 MHz, CDCl3) δ 9.26 (s, 1H), 7.81ꢀ7.79 (m, 2H), 7.70ꢀ7.68 (m, 2H), 7.50ꢀ7.48 (m,
1H), 7.44ꢀ7.42 (m, 1H), 7.38ꢀ7.36 (m, 3H), 7.31 (t, J = 7.8 Hz, 1H), 7.06 (d, J = 8.1
Hz, 1H), 3.98 (t, J = 7.2, 2H), 3.06 (t, J = 7.2 Hz, 2H), 2.26 (s, 3H), 1.29 (s, 9H);
13C{1H} NMR (100 MHz, CDCl3) δ 179.2, 168.4, 143.3, 137.7, 134.4, 132.3, 132.1,
129.8, 129.5, 126.9, 125.4, 125.3, 123.7, 123.5, 123.1, 118.8, 116.7, 41.7, 37.2, 29.0,
24.1, 21.6; HRMS (ESI) m/e calcd for C30H30N3O5S (M + H)+ 544.1901, found
544.1902.
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(S)-Methyl
2-(1,3-dioxoisoindolin-2-yl)-3-(7-(4-methylphenylsulfonamido)-1-
pivaloyl-1H-indol-3-yl)propanoate (7w): White semisolid (1.6 g, 88%); [α]D ꢀ101.9
1
(c 0.2, CH3OH); H NMR (500 MHz, CDCl3) δ 9.23 (s, 1H), 7.77ꢀ7.75 (m, 2H),
7.70ꢀ7.68 (m, 2H), 7.46 (d, J = 7.8 Hz, 1H), 7.34ꢀ7.23 (m, 5H), 7.01 (d, J = 8.0 Hz,
2H), 5.21ꢀ5.18 (m, 1H), 3.76 (s, 3H), 3.62ꢀ3.59 (m, 2H), 2.22 (s, 3H), 1.19 (s, 9H);
13C{1H} NMR (125 MHz, CDCl3) δ 179.1, 169.2, 167.6, 143.2, 137.7, 134.6, 132.0,
131.7, 129.7, 129.5, 126.9, 125.5, 125.3, 124.5, 123.7, 123.1, 117.6, 116.3, 53.3, 51.3,
41.6, 28.9, 24.6, 21.5.; HRMS (ESI) m/e calcd for C32H32N3O7S (M + H)+ 602.1955,
found 602.1945.
N-(1-Pivaloyl-1H-indol-7-yl)benzenesulfonamide (8a): White solid (63 mg, 89%);
o
1
m.p. 125ꢀ127 C; H NMR (400 MHz, CDCl3) δ 9.26 (s, 1H), 7.54ꢀ7.48 (m, 4H),
7.42ꢀ7.36 (m, 2H), 7.31ꢀ7.25 (m, 3H), 6.55 (d, J = 3.9 Hz, 1H), 1.35 (s, 9H); 13C{1H}
ACS Paragon Plus Environment

Page 23 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
NMR (100 MHz, CDCl3) δ 179.5, 140.5, 132.6, 132.4, 129.6, 128.9, 126.9, 126.7,
125.4, 125.2, 123.1, 119.1, 109.5, 41.8, 29.2; HRMS (ESI) m/e calcd for C19H21N2O3S
(M + H)+ 357.1267, found 357.1269.
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4-Fluoro-N-(1-pivaloyl-1H-indol-7-yl)benzenesulfonamide (8b): White solid (66
mg, 88%); m.p. 116ꢀ118 oC; 1H NMR (400 MHz, CDCl3) δ 9.34 (s, 1H), 7.54ꢀ7.49 (m,
4H), 7.39 (dd, J = 7.7, 1.2 Hz, 1H), 7.31 (t, J = 7.7 Hz, 1H), 6.97ꢀ6.93 (m, 2H), 6.57
13
(d, J = 3.9 Hz, 1H), 1.38 (s, 9H); C{1H} NMR (100 MHz, CDCl3) δ 179.5, 166.4
(JCꢀF = 253.2 Hz), 136.6 (JCꢀF = 2.8 Hz), 132.5, 129.7 (JCꢀF = 9.2 Hz), 129.6, 126.9,
125.5, 125.0, 122.9, 119.2, 116.2 (JCꢀF = 22.3 Hz), 109.7, 41.9, 29.3; HRMS (ESI) m/e
calcd for C19H20FN2O3S (M + H)+ 375.1173, found 375.1181.
4-Chloro-N-(1-pivaloyl-1H-indol-7-yl)benzenesulfonamide (8c): White solid (70
o
mg, 90%); m.p. 112ꢀ114 C; 1H NMR (400 MHz, CDCl3) δ 9.37 (s, 1H), 7.53 (d, J =
3.9 Hz, 1H), 7.51 (dd, J = 7.8, 1.1 Hz, 1H), 7.45ꢀ7.41 (m, 2H), 7.39 (dd, J = 7.7, 1.2
Hz, 1H),7.32 (t, J = 7.7 Hz, 1H), 7.25ꢀ7.23 (m, 2H), 6.58 (d, J = 3.9 Hz, 1H), 1.37 (s,
9H); 13C{1H} NMR (100 MHz, CDCl3) δ 179.5, 139.1, 138.9, 132.5, 129.5, 129.1,
128.4, 126.8, 125.5, 124.9, 123.0, 119.3, 109.7, 41.9, 29.2; HRMS (ESI) m/e calcd for
C19H20N2O3ClS (M + H)+ 391.0878, found 391.0884.
4-Bromo-N-(1-pivaloyl-1H-indol-7-yl)benzenesulfonamide (8d): White solid (68
o
mg, 78%); m.p. 118ꢀ120 C; 1H NMR (400 MHz, CDCl3) δ 9.38 (s, 1H), 7.53 (d, J =
3.9 Hz, 1H), 7.51 (dd, J = 7.8, 0.9 Hz, 1H), 7.42ꢀ7.37 (m, 3H), 7.36ꢀ7.33 (m, 2H),
13
7.32 (t, J = 7.7 Hz, 1H), 6.58 (d, J = 3.9 Hz, 1H), 1.37 (s, 9H); C{1H} NMR (100
MHz, CDCl3) δ 179.5, 139.5, 132.5, 132.1, 129.5, 128.5, 127.6, 126.8, 125.5, 124.8,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 34
1
2
3
4
5
6
123.0, 119.4, 109.7, 41.9, 29.2; HRMS (ESI) m/e calcd for C19H20BrN2O3S (M + H)+
435.0372, found 435.0376.
7
8
9
4-Cyano-N-(1-pivaloyl-1H-indol-7-yl)benzenesulfonamide (8e): Brown semisolid
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
(53 mg, 70%); H NMR (400 MHz, CDCl3) δ 9.58 (s, 1H), 7.64ꢀ7.62 (m, 2H),
7.59ꢀ7.56 (m, 2H), 7.54 (d, J = 3.9 Hz, 1H), 7.49ꢀ7.47 (m, 1H), 7.40ꢀ7.38 (m, 1H),
7.32 (t, J = 7.8 Hz, 1H), 6.59 (d, J = 3.9 Hz, 1H), 1.38 (s, 9H); C{1H} NMR (100
13
MHz, CDCl3) δ 179.7, 144.7, 132.69, 132.65, 129.4, 127.7, 126.9, 125.7, 124.5, 122.5,
119.6, 117.4, 116.3, 109.9, 42.0, 29.3; HRMS (ESI) m/e calcd for C20H20N3O3S (M +
H)+ 382.1220, found 382.1220.
4-Acetyl-N-(1-pivaloyl-1H-indol-7-yl)benzenesulfonamide (8f): Brown semisolid
1
(63 mg, 79%); H NMR (400 MHz, CDCl3) δ 9.49 (s, 1H), 7.83 (d, J = 8.4 Hz, 2H),
7.60 (d, J = 8.4 Hz, 2H), 7.50ꢀ7.48 (m, 2H), 7.37 (d, J = 7.0 Hz, 1H), 7.30ꢀ7.26 (m,
1H), 6.55 (d, J = 3.9 Hz, 1H), 2.52 (s, 3H), 1.34 (s, 9H); C{1H} NMR (100 MHz,
13
CDCl3) δ 196.9, 179.6, 144.3, 139.9, 132.5, 129.4, 128.7, 127.3, 126.8, 125.5, 124.7,
122.5, 119.3, 109.7, 41.9, 29.2, 27.0; HRMS (ESI) m/e calcd for C21H23N2O4S (M +
H)+ 399.1373, found 399.1378.
3,5-Dichloro-N-(1-pivaloyl-1H-indol-7-yl)benzenesulfonamide (8g): Brown solid
(67 mg, 79%); m.p. 108ꢀ110 C; 1H NMR (400 MHz, CDCl3) δ 9.59 (s, 1H), 7.56 (d,
o
J = 3.9 Hz, 1H), 7.52 (dd, J = 7.8, 1.1 Hz, 1H), 7.43 (dd, J = 7.7, 1.2 Hz, 1H),
7.36ꢀ7.31 (m, 4H), 6.61 (d, J = 3.9 Hz, 1H), 1.41 (s, 9H); C{1H} NMR (100 MHz,
13
CDCl3) δ 179.7, 143.1, 135.8, 132.7, 132.5, 129.6, 126.9, 125.7, 125.4, 124.4, 123.0,
119.8, 109.9, 41.9, 29.2; HRMS (ESI) m/e calcd for C19H19N2O3Cl2S (M + H)+
ACS Paragon Plus Environment

Page 25 of 34
The Journal of Organic Chemistry
1
2
3
4
425.0488, found 425.0487.
5
6
7
2,4-Difluoro-N-(1-pivaloyl-1H-indol-7-yl)benzenesulfonamide
(8h):
White
8
9
1
semisolid (65 mg, 83%); H NMR (400 MHz, CDCl3) δ 9.62 (s, 1H), 7.77ꢀ7.72 (m,
1H), 7.64 (d, J = 3.9 Hz, 1H), 7.47ꢀ7.45 (m, 1H), 7.30ꢀ7.28 (m, 1H), 7.22 (t, J = 7.8
Hz, 1H), 6.82ꢀ6.77 (m, 1H), 6.74ꢀ6.69 (m, 1H), 6.57 (d, J = 3.9 Hz, 1H), 1.51 (s, 9H);
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13C{1H} NMR (100 MHz, CDCl3) δ 179.9, 167.2 (JCꢀF = 256.0, 11.3 Hz), 161.0 (JCꢀF
256.7, 12.7 Hz), 133.0 (JCꢀF = 10.4, 1.4 Hz), 132.6, 128.8, 127.0, 125.4, 124.8, 124.5
(JCꢀF = 26.2, 14.0 Hz), 120.4, 118.7, 112.0 (JCꢀF = 21.7, 3.8 Hz), 109.6, 105.6 (JCꢀF
=
=
25.7, 24.6 Hz), 42.1, 29.3; HRMS (ESI) m/e calcd for C19H19N2O3SF2 (M + H)+
393.1079, found 393.1082.
4-Methoxy-N-(1-pivaloyl-1H-indol-7-yl)benzenesulfonamide (8i): White solid (68
mg, 88%); m.p. 119ꢀ121 oC; 1H NMR (400 MHz, CDCl3) δ 9.19 (s, 1H), 7.48ꢀ7.46 (m,
2H), 7.40 (d, J = 8.8 Hz, 2H),7.33 (d, J = 7.0 Hz, 1H), 7.26ꢀ7.21 (m, 1H), 6.70 (d, J =
8.9 Hz, 2H), 6.53 (d, J = 3.9 Hz, 1H), 3.70 (s, 3H), 1.34 (s, 9H); C{1H} NMR (100
13
MHz, CDCl3) δ 179.5, 162.8, 132.4, 132.1, 129.5, 129.0, 126.7, 125.4, 125.3, 122.9,
118.9, 114.0, 109.5, 55.7, 41.8, 29.2; HRMS (ESI) m/e calcd for C20H23N2O4S (M +
H)+ 387.1372, found 387.1376.
N-(1-Pivaloyl-1H-indol-7-yl)naphthalene-2-sulfonamide (8j): Brown semisolid (69
1
mg, 85%); H NMR (400 MHz, CDCl3) δ 9.39 (s, 1H), 8.14 (s, 1H), 7.77ꢀ7.74 (m,
2H), 7.67 (d, J = 8.6 Hz, 1H), 7.58ꢀ7.48 (m, 3H), 7.37ꢀ7.28 (m, 4H), 6.50 (d, J = 3.9
Hz, 1H), 1.16 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 179.4, 137.4, 134.8, 132.4,
132.2, 129.6, 129.3, 129.0, 128.9, 128.1, 127.9, 127.6, 126.7, 125.4, 125.2, 123.2,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 34
1
2
3
4
5
6
122.3, 119.2, 109.5, 41.6, 28.9; HRMS (ESI) m/e calcd for C23H22N2O3SNa (M +
Na)+ 429.1243, found 429.1250.
7
8
9
N-(1-Pivaloyl-1H-indol-7-yl)methanesulfonamide (8k): White solid (52 mg, 88%);
m.p. 160ꢀ162 oC; 1H NMR (400 MHz, CDCl3) δ 9.03 (s, 1H), 7.72 (d, J = 3.9 Hz, 1H),
7.50 (d, J = 7.8 Hz, 1H), 7.41ꢀ7.39 (m, 1H), 7.32 (t, J = 7.8 Hz, 1H), 6.67 (d, J = 3.9
Hz, 1H), 2.90 (s, 3H), 1.54 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 180.1, 132.9,
129.1, 127.0, 125.6, 125.5, 120.8, 118.8, 109.7, 42.2, 39.9, 29.4; HRMS (ESI) m/e
calcd for C14H18N2O3SNa (M + Na)+ 317.0930, found 317.0928.
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N-(1-Pivaloyl-1H-indol-7-yl)octane-1-sulfonamide (8l): Brown semisolid (64 mg,
81%); 1H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 7.71 (d, J = 3.9 Hz, 1H), 7.51 (dd,
J = 7.8, 1.0 Hz, 1H), 7.38 (dd, J = 7.7, 1.2 Hz, 1H), 7.31 (t, J = 7.8 Hz, 1H), 6.66 (d, J
= 3.9 Hz, 1H), 3.00ꢀ2.96 (m, 2H), 1.78ꢀ1.71 (m, 2H), 1.54 (s, 9H), 1.32ꢀ1.18 (m, 10H),
0.85 (t, J = 6.8 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 180.1, 132.9, 128.9,
127.0, 125.9, 125.5, 120.0, 118.4, 109.7, 52.2, 42.2, 31.8, 29.4, 29.1, 29.0, 28.3, 23.5,
22.7, 14.2; HRMS (ESI) m/e calcd for C21H33N2O3S (M + H)+ 393.2206, found
393.2209.
N-(5-Chloro-1-pivaloyl-1H-indol-7-yl)-4-methoxybenzenesulfonamide
(8m):
o
1
White solid (51 mg, 60%); m.p. 151ꢀ153 C; H NMR (500 MHz, CDCl3) δ 9.34 (s,
1H), 7.56 (d, J = 4.0 Hz, 1H), 7.53 (d, J = 9.0 Hz, 2H), 7.48 (d, J = 2.0 Hz, 1H), 7.29
(d, J = 2.0 Hz, 1H), 6.78 (d, J = 9.0 Hz, 2H), 6.5 (d, J = 4.0 Hz, 1H), 3.75 (s, 3H),
13
1.39 (s, 9H); C{1H} NMR (125 MHz, CDCl3) δ 179.6, 163.1, 133.4, 131.9, 130.8,
129.2, 128.0, 127.8, 126.5, 121.7, 118.1, 114.2, 108.9, 55.8, 42.0, 29.3; HRMS (ESI)
ACS Paragon Plus Environment

Page 27 of 34
The Journal of Organic Chemistry
1
2
3
4
m/e calcd for C20H22N2O4ClS (M + H)+ 421.0983, found 421.0981.
5
6
7
N-(4-Chloro-1-pivaloyl-1H-indol-7-yl)-4-methoxybenzenesulfonamide
(8n):
8
9
Brown semisolid (61 mg, 73%); 1H NMR (500 MHz, CDCl3) δ 8.95 (s, 1H), 7.56 (d, J
= 4.0 Hz, 1H), 7.46 (d, J = 9.0 Hz, 2H), 7.41 (d, J = 8.5 Hz, 1H), 7.27 (d, J = 8.4 Hz,
1H), 6.76 (d, J = 9.0 Hz, 2H), 6.70 (d, J = 4.0 Hz, 1H), 3.75 (s, 3H), 1.38 (s, 9H);
13C{1H} NMR (125 MHz, CDCl3) δ 179.7, 163.0, 132.0, 130.8, 130.3, 129.1, 127.2,
124.9, 124.1, 124.0, 123.7, 114.2, 107.5, 55.8, 42.0, 29.2; HRMS (ESI) m/e calcd for
C20H22N2O4ClS (M + H)+ 421.0983, found 421.0985.
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N-(5-Chloro-1-pivaloyl-1H-indol-7-yl)methanesulfonamide (8o): White semisolid
(41 mg, 63%)；1H NMR (500 MHz, CDCl3) δ 9.24 (s, 1H), 7.74 (d, J = 4.0 Hz, 1H),
7.48 (d, J = 2.0 Hz, 1H), 7.34 (d, J = 2.0 Hz, 1H), 6.60 (d, J = 4.0 Hz, 1H), 2.96 (s,
3H), 1.53 (s, 9H); 13C{1H} NMR (125 MHz, CDCl3) δ 180.2, 133.8, 131.0, 128.3,
127.2, 126.7, 119.5, 117.9, 109.1, 42.3, 40.2, 29.4. HRMS (ESI) m/e calcd for
C14H17ClN2O3SNa (M + Na)+ 351.0541, found 351.0543.
N-(3-(1-Cyclopropyl-1-(4-fluorophenyl)ethyl)-1-pivaloyl-1H-indol-7-yl)methane-
1
sulfonamide (8p): Brown semisolid (83 mg, 91%); H NMR (400 MHz, CDCl3) δ
9.16 (s, 1H), 7.86 (s, 1H), 7.37 (d, J = 7.8 Hz, 1H), 7.20ꢀ7.17 (m, 2H), 7.05 (t, J = 7.9
Hz, 1H), 6.94 (t, J = 8.7 Hz, 2H), 6.63 (d, J = 7.8 Hz, 1H), 2.93 (s, 3H), 1.58 (s, 12H),
1.49ꢀ1.45 (m, 1H), 0.57ꢀ048 (m, 2H), 0.31ꢀ0.27 (m, 1H), 0.14ꢀ0.11 (m, 1H); 13C{1H}
NMR (125 MHz, CDCl3) δ 179.9, 162.6 (JCꢀF = 243.8 Hz), 140.7 (JCꢀF = 3.2 Hz),
131.5 (JCꢀF = 89.3 Hz), 130.3, 129.3, 129.2, 125.8, 124.8, 124.3, 120.1, 119.2, 115.1
(JCꢀF = 20.9 Hz), 42.3, 41.8, 40.2, 29.5, 25.1, 22.1, 1.8, 1.5; HRMS (ESI) m/e calcd for
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 34
1
2
3
4
C25H29FN2O3SNa (M + Na)+ 479.1775, found 479.1774.
5
6
7
N-(3-(2-Phenylpropan-2-yl)-1-pivaloyl-1H-indol-7-yl)methanesulfonamide (8q):
8
9
1
Brown semisolid (64 mg, 77%); H NMR (400 MHz, CDCl3) δ 9.07 (s, 1H), 7.59 (s,
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1H), 7.38 (dd, J = 0.9, 7.8 Hz, 1H), 7.28ꢀ7.27 (m, 4H), 7.20ꢀ7.18 (m, 1H), 7.07 (t, J =
7.9 Hz, 1H), 6.78 (dd, J = 1.1, 7.9 Hz, 1H), 2.92 (s, 3H), 1.74 (s, 6H), 1.57 (s, 9H);
13C{1H} NMR (100 MHz, CDCl3) δ 179.9, 147.7, 131.7, 131.6, 130.5, 128.6, 126.5,
126.3, 125.7, 124.9, 123.1, 120.3, 119.3, 42.2, 40.2, 39.1, 30.1, 29.5. HRMS (ESI)
m/e calcd for C23H29N2O3S (M + H)+ 413.1893, found 413.1894.
N-(3-(2-Phenylpentan-2-yl)-1-pivaloyl-1H-indol-7-yl)methanesulfonamide (8r):
1
Brown semisolid (73 mg, 83%); H NMR (400 MHz, CDCl3) δ 9.14 (s, 1H), 7.59 (s,
1H), 7.38 (d, J = 7.8 Hz, 1H), 7.29ꢀ7.26 (m, 4H), 7.21ꢀ7.18 (m, 1H), 7.06 (t, J = 7.9
Hz, 1H), 6.75 (d, J = 7.9 Hz, 1H), 2.94 (s, 3H), 2.14ꢀ2.02 (m, 2H), 1.70 (s, 3H), 1.59
(s, 9H), 1.13ꢀ1.10 (m, 2H), 0.90 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3)
δ 179.9, 146.9, 131.7, 130.7, 130.2, 128.5, 126.9, 126.4, 125.6, 124.9, 123.8, 120.1,
119.3, 43.4, 42.5, 42.2, 40.2, 29.5, 27.0, 17.9, 14.9. HRMS (ESI) m/e calcd for
C25H32N2O3SNa (M + Na)+ 463.2026, found 463.2018.
(S)-Methyl 2-(1,3-dioxoisoindolin-2-yl)-3-(7-(methylsulfonamido)-1-pivaloyl-1H-
indol-3-yl) propanoate (8s): White semisolid (81 mg, 77%); [α]D ꢀ140.3 (c 0.2,
1
CH3OH); H NMR (500 MHz, CDCl3) δ 9.09 (s, 1H), 7.78ꢀ7.75 (m, 2H), 7.70ꢀ7.68
(m, 2H), 7.54 (s, 1H), 7.46 (d, J = 7.8 Hz, 1H), 7.38 (dd, J = 1.0, 7.8 Hz. 1H), 7.31 (t,
J = 7.8 Hz, 1H), 5.27ꢀ5.23 (m, 1H), 3.79 (s, 3H), 3.67ꢀ3.65 (m, 2H), 2.83 (s, 3H), 1.38
(s, 9H); 13C{1H} NMR (125 MHz, CDCl3) δ 179.7, 169.2, 167.7, 134.7, 132.5, 131.7,
ACS Paragon Plus Environment

Page 29 of 34
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
129.2, 125.9, 125.6, 124.8, 123.8, 120.9, 117.9, 116.2, 53.4, 51.1, 42.0, 39.9, 29.1,
24.8. HRMS (ESI) m/e calcd for C26H27N3O7SNa (M + Na)+ 548.1462, found
548.1452.
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
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N-(5-Chloro-1H-indol-7-yl)-4-methoxybenzenesulfonamide (1): To a solution of
8m (84 mg, 0.2 mmol) in 1.0 mL of methanol was added Et3N (1.0 mL) dropwise at
room temperature. The reaction mixture was stirred for 24 h before it was
concentrated under vacuum. The residue was purified by chromatography on silica
with a gradient eluent of petroleum ether and ethyl acetate to give 62 mg (92%) of 1
o
as white solid. m.p. 142ꢀ144 C; 1H NMR (400 MHz, CDCl3) δ 9.35 (s, 1H), 7.63 (d,
J = 9.0 Hz, 2H), 7.42 (d, J = 1.3 Hz, 1H), 7.26ꢀ7.25 (m, 1H), 7.15 (s, 1H), 6.85 (d, J =
9.0 Hz, 2H), 6.54 (d, J = 1.6 Hz, 1H), 6.46ꢀ6.44 (m, 1H), 3.79 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 163.7, 130.8, 130.0, 129.7, 129.0, 126.8, 124.8, 121.0, 119.1,
117.5, 114.6, 102.7, 55.8. HRMS (ESI) m/e calcd for C15H14ClN2O3S (M + H)+
337.0408, found 337.0402.
N-(3-(2-Phenylpropan-2-yl)-1H-indol-7-yl)methanesulfonamide (9): Following the
same procedure for preparing 1 from 8m, 9 was obtained in 90% yield (yellow solid，
o
1
59 mg) from 8q. m.p. 161ꢀ163 C; H NMR (400 MHz, CDCl3) δ 9.02 (s, 1H),
7.33ꢀ7.31 (m, 2H), 7.25ꢀ7.21 (m, 2H), 7.18ꢀ7.13 (m, 2H), 6.98 (s, 1H), 6.96 (d, J =
8.0 Hz, 1H), 6.90 (d, J = 7.3 Hz, 1H), 6.82 (t, J = 7.8 Hz, 1H), 3.00 (s, 3H), 1.75 (s,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 149.8, 133.1, 128.6, 128.2, 126.54, 126.53,
125.8, 122.1, 120.9, 119.9, 119.2, 117.5, 39.0, 38.8, 30.8. HRMS (ESI) m/e calcd for
C18H21N2O2S (M + H)+ 329.1318, found 329.1314.
ACS Paragon Plus Environment