Palladium-Catalyzed Oxidative Sulfenylation of Indoles and Related Electron-Rich Heteroarenes with Aryl Boronic Acids and Elemental Sulfur

Article abstract of DOI:10.1021/acs.joc.6b01428

An efficient and convenient palladium-catalyzed C-H bond oxidative sulfenylation of indoles and related electron-rich heteroarenes with aryl boronic acids and elemental sulfur has been described. This procedure provides a useful and direct approach for the assembly of a wide range of structurally diverse 3-sulfenylheteroarenes with moderate to excellent yields from simple and readily available starting materials. Moreover, this synthetic protocol is suitable for N-protected and unprotected indoles. Notably, the construction of two C-S bonds in one step was also achieved in this transformation.

Full text of DOI:10.1021/acs.joc.6b01428

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Article
Palladium-Catalyzed Oxidative Sulfenylation of Indoles and Related
Electron-Rich Heteroarenes with Aryl Boronic Acids and Elemental Sulfur
Jianxiao Li, Chunsheng Li, Shaorong Yang, Yanni An, Wanqing Wu, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01428 • Publication Date (Web): 08 Aug 2016
Downloaded from http://pubs.acs.org on August 10, 2016
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Palladium-Catalyzed Oxidative Sulfenylation of Indoles and
Related Electron-Rich Heteroarenes with Aryl Boronic Acids
and Elemental Sulfur
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Jianxiao Li, Chunsheng Li, Shaorong Yang, Yanni An, Wanqing Wu* and Huanfeng
Jiang*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of
Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640,
China
Fax: (+86) 20ꢀ8711ꢀ2906; Eꢀmail: cewuwq@scut.edu.cn, jianghf@scut.edu.cn
Abstract: An efficient and convenient palladiumꢀcatalyzed CꢀH bond oxidative
sulfenylation of indoles and related electronꢀrich heteroarenes with aryl boronic acids
and elemental sulfur has been described. This procedure provides a useful and direct
approach for the assembly of
a
wide range of structurally diverse
3ꢀsulfenylheteroarenes with moderate to excellent yields from simple and readily
available starting materials. Moreover, this synthetic protocol is suitable for
Nꢀprotected and unprotected indoles. Notably, the construction of two CꢀS bonds in
one step was also achieved in this transformation.
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INTRODUCTION
The development of practical and efficient synthetic methods for the synthesis of
complex molecular skeletons from readily accessible starting materials has aroused
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substantial attention in recent years. In this regard, transition metalꢀcatalyzed
crossꢀcoupling reaction has emerged as an attractive and powerful tool for the
construction of carbonꢀcarbon and/or carbonꢀheteroatom bonds in an atomꢀ and
2
stepꢀeconomical manner over the past decades. Most notably, palladiumꢀcatalyzed
processes play a significant role in this field, since they usually proceed under mild
reaction conditions, great functional group tolerance and high chemoꢀ, regioꢀ, and
3
stereoselectivity. Consequently, considerable efforts have been made to develop
efficient methods for the construction of C ꢀ C, C ꢀ O, C ꢀ N and other Cꢀheteroatom
bonds in recent years. Despite of the overall efficiency and versatility of this
transformation, the development of practical and environmentally friendly synthetic
4
methods for the straightforward construction of CꢀS bond is less explored, and still
highly desirable.
In addition, substituted indoles are versatile and important heterocyclic scaffolds
5
in organic synthesis, and found in many natural products and pharmaceuticals. As a
subclass, 3ꢀsulfenylindoles exhibit a broad spectrum of biological activities, which are
important drugs assessed for the treatment of bacterial infection, cancer, HIV, obesity,
6
heart diseases, and allergies. Consequently, many representative synthetic methods
have been developed for constructing this heterocyclic scaffolds. Generically, two
strategies are typically employed. Undoubtedly, 2ꢀalkynylanilines are the most
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commonly used precursors to prepare this functionalized core backbone (Scheme 1a)
.
For instance, Larock and coꢀworkers reported a novel procedure for the synthesis of
3
ꢀsulfenylindoles
via
nꢀBu
4
NIꢀinduced
electrophilic
cyclization
of
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N,Nꢀdialkylꢀ2ꢀ(1ꢀalkynyl)anilines with arylsulfenyl chlorides. Subsequently, Li and
Zhang reported that 3ꢀsulfenylindoles were synthesized by metalꢀinvolved annulations
8
of 2ꢀ(1ꢀalkynyl)benzenamines with disulfides. On the other hand, direct CꢀH bond
sulfenylation of the preexisting indole ring is a more convenient method for the
9
formation of 3ꢀsulfenylindoles. Among them, metal complexes of vanadium,
1
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12
13
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magnesium, iron, cerium, copper and ruthenium have been identified as
extremely efficient catalysts for constructing these heterocyclic scaffolds. Various
sulfenylating agents such as thiols, disulfides, arylsulfonyl chlorides and Nꢀthioimides
are employed (Scheme 1b). Despite the significances, many of these approaches
require foulsmelling, toxic and unstable sulfenylating agents as starting materials.
Considering the synthetic simplicity as well as environmentally benign process,
providing the direct strategy for the synthesis of 3ꢀsulfenylindoles via a transition
metalꢀfree protocol is still an urgent need. In recent years, several approaches for
direct sulfenylation of indoles with activated sulfur reagents under transition
15
metalꢀfree conditions have been developed (Scheme 1c)
.
For instance, Tian and
coꢀworkers reported a nice protocol of iodineꢀcatalyzed regioselective sulfenylation of
15e
indoles with sulfonyl hydrazides. Subsequently, Deng and coꢀworkers developed
15g
the iodineꢀcatalyzed sulfenylation of free indoles with sodium sulfinates. And then,
Braga and coꢀworkers described a solvent and metalꢀfree procedure for the synthesis
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of 3ꢀsulfenylindoles from indoles using DMSO as an oxidant. However, thiols,
disulfides, sulfonyl hydrazides, arylsulfonyl chlorides and sodium sulfinates are still
employed as sulfenylating agents. Therefore, the development of convenient and
efficient synthetic methodologies for the construction of this heterocyclic motif under
environmentally friendly reaction condition is still highly desirable. Inspired by the
aforementioned background and our longstanding interest in Pdꢀcatalyzed coupling
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reactions in ionic liquids, herein we disclose an efficient and concise route for the
synthesis of 3ꢀsulfenylindoles via palladiumꢀcatalyzed oxidative sulfenylation of
indoles with aryl boronic acids and elemental sulfur (Scheme 1d).
Scheme 1. Representative methods for the synthesis of 3ꢀsulfenylindoles
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RESULTS AND DISCUSSION
Table 1. Optimization of the reaction conditions
a
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b
Entry
Catalyst
CuX
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuCl
CuBr
CuCN
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
ꢀ
Oxidant
BQ
Base
Solvent
DMF
Yield
24
13
37
52
36
28
17
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1
2
3
4
5
6
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8
9
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
PdCl2
2
K
2
K
2
K
2
K
2
CO
CO
CO
CO
3
3
3
3
2
2
2
DDQ
DMF
AgNO
Ag CO
Ag CO3
3
DMF
2
3
DMF
K CO3
2
DMF
2
2
Pd(PhCN) Cl
2
Ag
Ag
Ag
Ag
2
2
2
2
CO
CO
CO
CO
3
3
3
3
K
2
K
2
K
2
K
2
CO
CO
CO
CO
3
3
3
3
DMF
Pd(TFA)
Pd(OAc)
Pd(OAc)
2
2
2
DMF
DMF
DMF
21
10
Pd(OAc)2
Ag CO3
2
K CO3
DMF
trace
45
2
11
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
2
Ag
Ag
Ag
Ag
2
2
2
2
CO
CO
CO
CO
3
3
3
3
K PO
3 4
DMF
12
13
14
KF
DMF
36
Cs
2
2
CO
3
DMF
64
Cs
CO
3
DMSO
Toluene
1,4ꢀdioxane
[Bmim]Cl
[Bmim]Cl
[Bmim]Cl
[Bmim]Cl
[Bmim]Cl
[Bmim]Cl
[Bmim]Cl
[Bmim]Cl
[Bmim]Cl
[Bmim]Cl
72
15
Pd(OAc)2
Ag CO3
Cs CO3
40
2
2
1
1
1
6
7
8
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
ꢀ
2
2
2
2
Ag
Ag
Ag
Ag
2
2
2
2
CO
CO
CO
CO
3
3
3
3
Cs
2
2
CO
CO
ꢀ
3
38
Cs
3
89 (81)
26
c
19
Cs
2
CO
3
83
2
2
2
0
Ag CO3
Cs CO3
N.D.
N.D.
N.D.
N.D.
N.D.
N.D.
trace
2
2
1
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
2
Ag
2
CO
3
Cs
Cs
Cs
Cs
2
2
2
2
CO
CO
CO
CO
3
3
3
3
2
CuI
ꢀ
O
2
d
e
e
f
23
Ag
2
CO
3
3
2
4
5
ꢀ
Ag
2
CO
2
Pd(OAc)2
Pd(OAc)
CuI
CuI
Ag CO3
Cs CO3
2
2
26
2
Ag
2
CO
3
2 3
Cs CO
a
8
Unless otherwise noted, reactions were performed with 1a (0.10 mmol), 2 (0.20 mmol), S (0.30
mmol), catalyst (5 mol %), CuX (0.10 mmol), Phen (1,10ꢀphenanthroline, 0.11 mmol), oxidant
o
(
0.20 mmol), base (0.20 mmol) and solvents (1 mL) under N at 80 C for 6 h. [Bmim]Cl:
2
b
1
ꢀbutylꢀ3ꢀmethylimidazolium chloride. Determined by GC using dodecane as the internal
c
o
d
standard. The value in parentheses is the yield of isolated product. Performed at 100 C.
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e
f
PhB(OH) (2a) was replaced by Ph B (2b). PhB(OH) (2a) was replaced by KPhBF (2c).
2
3
2
3
PhB(OH)
2
(2a) was replaced by phenylboronic acid pinacol ester (2d).
The reaction of indole (1a), phenylboronic acid (2a) and elemental sulfur (S
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) was
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employed as a model reaction to screen for the optimal reaction conditions, and the
results are summarized in Table 1. Initially, several oxidants such as BQ, DDQ,
AgNO
Ag CO
catalysts were also examined. Other Pd catalysts, PdCl
3
and Ag
was the best oxidant for this transformation. Subsequently, palladium
, Pd(PhCN) Cl and Pd(TFA)
2 3
CO were tested for the reaction (Table 1, entries 1ꢀ4), we found that
2
3
2
2
2
2
were tested, and they were less effective than Pd(OAc) (Table 1, entries 4ꢀ7).
2
Furthermore, different copper salts were examined, including CuCl, CuBr, CuCN and
CuI, and CuI was the most effective catalyst for this transformation (Table 1, entries
7
ꢀ10). As revealed in Table 1, the bases such as K
2
CO , K
3 3
PO
4
, KF, and Cs
2 3
CO were
investigated (Table 1, entries 10ꢀ13). It was found that Cs
2
CO
3
was the best base for
the present sulfenylation reaction. Finally, different solvents were then screened to
study the efficiency of this reaction (Table 1, entries 13ꢀ17). Notably, [Bmim]Cl was
identified as the optimal solvent for the formation of 3aa (Table 1, entry 17). Without
Pd(OAc)
1). When the reaction was carried out under oxygen atmosphere, no product 3aa was
obtained (entry 22). Several kinds of borates and boronates were further investigated
Table 1, entries 23ꢀ26), however, only trace desired 3aa was detected by GCꢀMS
2
or CuI catalyst, the reaction could not occur at all (Table 1, entries 20 and
2
(
when phenylboronic acid pinacol ester (2d) was used (Table 1, entry 26).
a
Table 2. Sulfenylation of indoles with phenylboronic acid and S
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H
S
Ph
R2
Pd(OAc) (5 mol %), CuI (1 equiv)
2
Phen (1.1 equiv)
R1
R2
S8
R1
PhB(OH)2
Cs CO (2 equiv), Ag CO (2 equiv)
N
N
2
3
2
3
2a
o
[
Bmim]Cl (1 mL), 80 C, 6 h
3
1
H
H
S
Ph
R
S Ph
S
Ph
R = OMe, 82%, 3ab;
R = OBn, 87%, 3ac;
R = F, 78%, 3ad;
R
R = Me, 92%, 3ag;
R = F, 84%, 3ah;
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N
N
N
R = OCOMe, 65%, 3ae;
H
R = CO Me, 68%, 3af;
H
H
2
3
aa, 81%
S
Ph
S
Ph
S Ph
R =OMe, 82%, 3ai;
X
Y
X = F; Y = F, 76%, 3ao;
X = F; Y = Cl, 81%, 3ap;
X = F; Y = Br,
74%, 3aq;
X = Cl; Y = Cl, 70%, 3ar;
X = Br; Y = Cl, 73%, 3as;
R = OCF , 70%, 3aj;
3
R = Cl, 82%, 3ak;
R = Br, 77%, 3al;
N
N
N
R
H
F
3
H
H
R = NO , 61%, 3am;
2
an, 80%
Cl
S
Ph
S
Ph
Me
S
Ph
Me
S
Ph
R
COOEt
N
N
H
Br
N
N
H
H
3
au, 90% H
3
at, 76%
R = OMe, 87%, 3av;
R = Cl, 73%, 3aw;
3ax, 67%
S
Ph
S
Ph
S
Ph
O
S
Ph
R
N
N
Me
N
H
H N
2
N
H
H
H
R = F, 84%, 3ay;
R = Cl, 82%, 3az;
3
ba, 58%
3bc, 46%
3bb, 87%
a
8 2
Reactions were performed with 1 (0.20 mmol), 2a (0.4 mmol), S (0.60 mmol), Pd(OAc) (5
2 3 2 3
mol %), CuI (0.20 mmol), Phen (0.22 mmol), Ag CO (0.4 mmol), Cs CO (0.4 mmol) and
o
[Bmim]Cl (1 mL) under N
2
at 80 C for 6 h. Yields referred to isolated yield.
With the optimized reaction conditions in hand, the scope and generality of the
sulfenylation reaction was investigated using several structurally diverse indoles,
phenylboronic acid (2a) and elemental sulfur (S
summarized in Table 2. Generally, both electronꢀdonating (Me, OMe, OBn) and
electronꢀwithdrawing (F, Cl, Br, CO Me, NO ) substituents on the indole ring were
transferred into the desired products in good to excellent yields (3aaꢀ3aw). Pleasingly,
8
). Representative results are
2
2
5
,6ꢀdisubstituted (1oꢀ1s) and 4,6ꢀdisubstituted (1t) indoles could also undergo this
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transformation to furnish the corresponding 3ꢀphenylthioindoles in good yields
(3aoꢀ3at). Gratifyingly, this transformation was compatible with the Clꢀ and
Brꢀsubstituted indole ring, which might allow for further synthetic transformations by
transition metalꢀcatalyzed coupling reactions. Additionally, Cꢀ2 substituted indoles
proceeded smoothly to afford the corresponding 3ꢀphenylthioindoles (3auꢀ3bb) in
moderate to good yields. Remarkably, 2ꢀmethylꢀ6,7ꢀdihydroꢀ1Hꢀindolꢀ4(5H)ꢀone
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could be converted into the corresponding product 3bc in 46% yield as well.
a
Table 3. Sulfenylation of Nꢀsubstituted indoles with phenylboronic acid and S
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H
S
Ph
Pd(OAc) (5 mol %), CuI (1 equiv)
2
Phen (1.1 equiv)
R1
R2
S8
R1
R2
PhB(OH)2
Cs CO (2 equiv), Ag CO (2 equiv)
N
R3
N
R3
2
3
2
3
2a
o
[Bmim]Cl (1 mL), 80 C, 6 h
5
4
S
Ph
S
Ph
S
Ph
S
Ph
S
Ph
O N
2
Ph
N
N
N
N
N
Me
0%, 5a
Me
85%, 5b
Ph
Boc
Me
6
5%, 5c
86%, 5d
Ph
0%, 5e
9
R = 4-Me, 91%, 5h;
S
Ph
S
S
Ph
t
R = 4- Bu, 87%, 5i;
Br
R = 4-Ph, 80%, 5j;
R = 4-F, 83%, 5k;
R = 3-Cl, 76%, 5l;
R = 4-Br, 81%, 5m;
N
N
N
R
Bn
Ac
0%, 5f
80%, 5g
R = 4-CF , 70%, 5n;
3
S
Ph
R = 4-CN, 77%, 5o;
S
Ph
S
Ph
N
Me
N
N
8
3%, 5p
8
5%, 5q
8
4%, 5r
Me
a
8 2
Reactions were performed with 4 (0.20 mmol), 2a (0.4 mmol), S (0.60 mmol), Pd(OAc) (5
mol %), CuI (0.20 mmol), Phen (0.22 mmol), Ag CO (0.4 mmol), Cs CO (0.4 mmol) and
2
3
2
3
o
[
Bmim]Cl (1 mL) under N
2
at 80 C for 6 h. Yields referred to isolated yield.
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The sulfenylation reactions of several Nꢀsubstituted indoles were then explored,
which showed high tolerance to this reaction. Representative results are summarized
in Table 3. To our delight, Nꢀsubstituted indoles with methyl and phenyl groups, could
convert to the corresponding products 5aꢀ5d in moderate to good yields.
Unfortunately, under the optimized conditions, Nꢀacetylindole (4e) and N ꢀBocꢀindole
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
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28
29
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32
33
34
35
36
37
38
39
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41
42
43
44
45
46
47
48
49
50
51
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53
54
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56
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(
4f) failed to afford the desired products. The main reason is that acetyl and Boc
groups are readily detached from indoles under basic conditions. Furthermore, various
Nꢀbenzylindoles reacted well with phenylboronic acid (2a) and S under the standard
8
conditions to afford the target products 5h-5r in moderate to good yields.
a
Table 4. Sulfenylation of 1a with aryl boronic acids 2 and S
8
H
S
Ar
Pd(OAc) (5 mol %), CuI (1 equiv)
2
Phen (1.1 equiv)
ArB(OH)2
S8
Cs CO (2 equiv), Ag CO (2 equiv)
N
N
H
2
3
2
3
2
o
[Bmim]Cl (1 mL), 80 C, 6 h
6
1a
H
S
S
Et
tBu
S
OMe
S
Me
7%, 6a
8
89%, 6b
82%, 6c
81%, 6d
N
H
N
N
N
H
H
H
S
S
F
S
Cl
S
F
Cl
N
N
N
78%,
6h
85%, 6f
N
83%, 6e
8
3%, 6g
H
H
H
H
S
S
S
Br
S
CN
Cl
Cl
Br
N
N
72%, 6i
N
75%, 6j
N
H
62%, 6k
71%, 6l
H
H
H
Cl
S
S
N
S
S
Cl
Cl
N
64%, 6n
N
H
N
53%, 6o
73%, 6m
H
H
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
a
Reactions were performed with 1a (0.20 mmol), 2 (0.4 mmol), S (0.60 mmol), Pd(OAc) (5
8
2
mol %), CuI (0.20 mmol), Phen (0.22 mmol), Ag
2
CO
3
(0.4 mmol), Cs
2
CO
3
(0.4 mmol) and
o
[Bmim]Cl (1 mL) under N
2
at 80 C for 6 h. Yields referred to isolated yield.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
To further explore the generality and scope of this reaction, a wide array of aryl
boronic acids were examined, and the results are summarized in Table 4. In general,
under the optimized conditions, aryl boronic acids with either an electronꢀdonating or
electronꢀwithdrawing group on the benzene ring were able to generate the
corresponding 3ꢀsulfenylindoles 6a-6m in moderate to good yields. Gratifyingly,
various functional groups, such as alkyl, fluoro, chloro, bromo and cyano groups,
were compatible with the reaction conditions. Remarkably, the electronic properties of
the substituents on the benzene ring of aryl boronic acids did not have a significant
influence on the reaction efficiency. Moreover, the heteroaryl boronic acids, such as
thiophenꢀ3ꢀylboronic acid (2n) and pyridinꢀ4ꢀylboronic acid (2o), could be converted
into the corresponding products 6n and 6o in 64% and 53% yields, respectively.
Scheme 2. The sulfenylation of 1H,1'Hꢀ2,2'ꢀbiindole
Furthermore, the present synthetic route to 3ꢀarylthioindoles was successfully
applied to the synthesis of 3,3'ꢀbis(phenylthio)biindole. For instance, under the
optimized conditions, the bissulfenylation of 1H,1'Hꢀ2,2'ꢀbiindole (7) provided the
desired product 8 in 41% yield (Scheme 2).
More importantly, other kinds of electronꢀrich heteroarenes were also tested under
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the present optimized conditions, and the results were listed in Table 5. Similarly, all
the tested imidazo[1,2ꢀa]pyridine substrates could be converted into the desired
17
sulfenylation products (10aꢀ10h) in moderate to good yields. However, when
pyrrole (9i) was subjected to the standard conditions, only a trace amount of the
desired product 10i was detected by GCꢀMS. Unfortunately, when furan was
employed, no desired sulfenylation product 10j was observed in the current condition.
To our delight, 2ꢀphenylbenzofuran (9k) was found to be compatible with this
protocol, thus providing 10k in 46% 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
a
Table 5. Sulfenylation of 9 with aryl boronic acids 2 and S8
a
8 2
Reactions were performed with 9 (0.20 mmol), 2 (0.4 mmol), S (0.60 mmol), Pd(OAc) (5
2 3 2 3
mol %), CuI (0.20 mmol), Phen (0.22 mmol), Ag CO (0.4 mmol), Cs CO (0.4 mmol) and
o
[
Bmim]Cl (1 mL) under N
2
at 80 C for 6 h. Yields referred to isolated yield. N.D = not
determined.
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9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Scheme 3. NꢀArylation of 3ꢀphenylthioindole 3aw
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
To demonstrate the efficiency and practicability of this protocol, we further
examined the Nꢀarylation reaction of the resultant products under basic conditions
(Scheme 3). For instance, under mild condition, 3ꢀphenylthioindole 3aw with benzyl
18
bromide delivered Nꢀbenzyl 3ꢀphenylthioindole 11 in 83% yield. Further, Nꢀphenyl
3ꢀphenylthioindole (12) could also be achieved from 3aw with iodobenzene by using
19
2
Cu O as catalyst.
Scheme 4. Control Experiments
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To gain some insights into the mechanism of this transformation, several control
experiments have been also conducted (Scheme 4). Under the standard conditions,
when 3ꢀmethylꢀ1Hꢀindole (13) was employed to react with phenylboronic acid (2a)
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
and S , however, the desired product 14 was obtained in 8% GC yield (eq 1). This
8
result indicated that the sulfenylation of indoles mainly occurred at the 3ꢀposition.
Subsequently, when treated with indole (1a) with 1,2ꢀdiphenyldisulfane (15) and
benzenethiol (16) under the standard conditions, no desired product 3aa could be
20
detected by GCꢀMS (eq 2). All of these results described above suggested that
neither 15 nor 16 was a possible intermediate in this chemical process. When
3
ꢀiodoꢀindole (17) was used as the substrate under the redoxꢀneutral conditions, the
desired product 3aa was detected by GCꢀMS in 56% yield (eq 3). This result
suggested that Ag CO as the oxidant played a crucial role to complete the catalytic
cycle. Moreover, when equiv. of radical inhibitor
,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy (TEMPO) was added to the reaction under the
2
3
2
2
standard conditions, the desired product 3aa was also detected in 85% GC yield (eq 4).
This observation demonstrated that the reaction should not be a radical pathway.
Although the direct sulfuration reactions of borates and boronates by elemental
21
sulfur have been wellꢀdeveloped, palladiumꢀcatalyzed oxidative sulfenylation
22
reaction using elemental sulfur as sulfurating reagent remains relatively rare. Further,
more traditional nucleophiles boron reagents like potassium phenyltrifluoroborate
(KPhBF
3
, 2c) and phenylboronic acid pinacol ester (2d) were ineffective in our
21
current catalytic system. Additionally, disulfides were not possible intermediate
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9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
2
according to the control experiments and our previous reports. Hence, these
observations indicated that the current protocol is different from the previous
postulated process. As a consequence, based on the above observations and relevant
reports in the literature, a tentative mechanism of this transformation is illustrated in
Scheme 5. Initially, vinylꢀpalladium intermediate I was generated by electrophilic
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
3, 24
palladation of heteroarenes.
intermediate II from aryl boronic acid, S
intermediate I could undergo transmetallation with intermediate II to produce
Simultaneously, the organocopper thiolate complex
2
5
8
, and CuI was formed. Subsequently,
22
intermediate III. On the other hand, organocopper thiolate complex are frequently
20
accompanied by sideꢀreactions to give a handful of thiol derivatives. Finally, a
reductive elimination produced the target products and Ag(I) oxidize Pd(0) to Pd(II)
26
active species to complete the catalytic cycle. Silver mirror reaction was observed
when the reaction was finished.
Scheme 5. Plausible Mechanism
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CONCLUSION
In summary, we have successfully accomplished an efficient and convenient
strategy for the synthesis of structurally diverse 3ꢀsulfenylheteroarenes by a
palladiumꢀcatalyzed CꢀH bond oxidative sulfenylation of indoles and related
electronꢀrich heteroarenes with aryl boronic acids and elemental sulfur. Importantly,
readily available indoles without preactivation, broad substrate scopes, and excellent
functional group compatibility make this protocol practical and attractive. Moreover,
this chemistry described herein represents an efficient synthetic approach for
accessing biologically important 3ꢀsulfenylindole derivatives.
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
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42
43
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48
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50
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52
53
54
55
56
57
58
59
60
EXPERIMENTAL SECTION
General methods. Melting points were measured by a melting point instrument and
1
13
were uncorrected. H and C NMR spectra were recorded by using a 400 MHz NMR
spectrometer. The chemical shifts are referenced to signals at 7.24 and 77.0 ppm,
respectively, and chloroform is used as a solvent with TMS as the internal standard.
IR spectra were obtained either as potassium bromide pellets or as liquid films
between two potassium bromide pellets with an infrared spectrometer. GCꢀMS was
obtained using electron ionization. The data of HRMS was carried out on a
highꢀresolution mass spectrometer (LCMSꢀITꢀTOF). TLC was performed by using
commercially available 100ꢀ400 mesh silica gel plates (GF254). Unless otherwise
noted, all purchased chemicals were used without further purification.
2
General Procedure for Sulfenylation of Indoles: A mixture of Pd(OAc) (5 mol %),
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1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
indoles (0.20 mmol) and [Bmim]Cl (1 mL) was added to an Schlenk tube equipped
with a stirꢀbar and stirred at room temperature for 15 min. A balloon filled with N
2
was connected to the Schlenk tube via the side tube and purged 3 times. Then, aryl
boronic acids (0.4 mmol), elemental sulfur (0.60 mmol), CuI (0.40 mmol), Phen (0.44
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
mmol), Ag
2
CO
3
2 3
(0.4 mmol) and Cs CO (0.4 mmol) were quickly added to the tube
o
under N
2
atmosphere and stirred at 80 C for 6 h. After the reaction was finished, the
N
2
gas was released carefully and the reaction was quenched by water and extracted
with CH Cl three times. The combined organic layers were dried over anhydrous
Na SO and evaporated under vacuum. The residue was purified by flash column
2
2
2
4
chromatography on silica gel (hexanes/ethyl acetate) to afford the desired products.
1
5d
3-(Phenylthio)-1H-indole (3aa): Yield: 81% (36.5 mg) as a white solid; mp =
1
1
48.4 ꢀ 149.8 °C; R
f
0.32 (hexanes/ethyl acetate 10/1); H NMR (400 MHz, CDCl
3
) δ
8.33 (s, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.48 ꢀ 7.37 (m, 2H), 7.24 (d, J = 9.6 Hz, 1H),
13
7
.18 ꢀ 7.08 (m, 5H), 7.04 (t, J = 6.8 Hz, 1H); C NMR (100 MHz, CDCl ) δ 139.3,
3
136.5, 130.7, 129.1, 128.7, 125.9, 124.8, 123.1, 120.9, 119.7, 111.6, 102.9 ppm;
ꢀ1
ν
max(KBr)/cm 3408, 3026, 1654, 1600, 1454, 1400, 742; MS (EI) m/z 77, 148, 165,
+
193, 225; HRMSꢀESI (m/z): calcd for C14
48.0508.
H
11NNaS, [M+Na] : 248.0504, found
2
4-Methoxy-3-(phenylthio)-1H-indole (3ab): Yield: 82% (41.8 mg) as a yellow solid;
1
mp = 78.4 ꢀ 79.8 °C; R
f
0.28 (hexanes/ethyl acetate 4/1); H NMR (400 MHz, CDCl
3
)
δ 8.33 (s, 1H), 7.23 ꢀ 7.20 (m, 1H), 7.18 ꢀ 7.12 (m, 5H), 7.07 ꢀ 7.01 (m, 1H), 6.97 (d, J
13
=
8.0 Hz, 1H), 6.52 (d, J = 7.6 Hz, 1H), 3.66 (s, 3H); C NMR (100 MHz, CDCl
3
) δ
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54.7, 140.7, 138.5, 129.6, 128.5, 126.5, 124.7, 123.9, 118.6, 104.9, 102.5, 101.6,
ꢀ1
5
5.6 ppm; νmax(KBr)/cm 3410, 3034, 1658, 1604, 1560, 1448, 1280, 1092, 746; MS
+
(EI) m/z 119, 207, 240, 255; HRMSꢀESI (m/z): calcd for C15
H
13NNaOS, [M+Na] :
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
2
4
78.0610, found 278.0609.
-(Benzyloxy)-3-(phenylthio)-1H-indole (3ac): Yield: 87% (57.6 mg) as a green oil;
1
R
f
0.30 (hexanes/ethyl acetate 4/1); H NMR (400 MHz, CDCl
3
) δ 8.30 (s, 1H), 7.23 ꢀ
7
6
1
1
.16 (m, 4H), 7.13 ꢀ 7.05 (m, 7H), 7.01 (t, J = 6.8 Hz, 1H), 6.94 (d, J = 8.0 Hz, 1H),
13
.56 (d, J = 7.6 Hz, 1H), 5.00 (s, 2H); C NMR (100 MHz, CDCl
3
) δ 153.6, 141.1,
38.7, 137.2, 130.3, 128.6, 128.2, 127.4, 127.1, 125.8, 124.4, 123.9, 118.8, 105.1,
ꢀ1
02.6, 101.7, 69.9 ppm; νmax(KBr)/cm 3404, 3028, 1658, 1624, 1560, 1444, 1276,
1042, 753; MS (EI) m/z 91, 207, 240, 298, 331; HRMSꢀESI (m/z): calcd for
+
C
21
H
17NNaOS, [M+Na] : 354.0923, found 354.0925.
1
5a
4-Fluoro-3-(phenylthio)-1H-indole (3ad): Yield: 78% (37.9 mg) as a yellow solid;
1
mp = 137.2 ꢀ 138.5 °C; R 0.40 (hexanes/ethyl acetate 5/1); H NMR (400 MHz,
f
CDCl
3
) δ 8.45 (s, 1H), 7.36 (d, J = 2.4 Hz, 1H), 7.20 ꢀ 7.12 (m, 6H), 7.07 (ddd, J =
13
8
.4, 6.0, 2.8 Hz, 1H), 6.82 ꢀ 6.74 (m, 1H); C NMR (100 MHz, CDCl
3
) δ 156.9 (d, J
= 248.7 Hz), 139.7, 139.4 (d, J = 10.0 Hz), 131.1, 128.8, 126.4, 125.1, 123.7 (d, J =
.7 Hz), 117.7 (d, J = 18.0 Hz), 107.8 (d, J = 4.1 Hz), 106.4 (d, J = 19.0 Hz), 101.4 (d,
7
ꢀ1
J = 2.1 Hz) ppm; νmax(KBr)/cm 3396, 3024, 1656, 1625, 1438, 1404, 740; MS (EI)
+
m/z 95, 122, 166, 211, 243; HRMSꢀESI (m/z): calcd for C14
266.0410, found 266.0406.
H
10FNNaS, [M+Na] :
3
-(Phenylthio)-1H-indol-4-yl acetate (3ae): Yield: 65% (36.8 mg) as a white solid;
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1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
mp = 124.7 ꢀ 126.3 °C; R
f
0.25 (hexanes/ethyl acetate 2/1); H NMR (400 MHz,
CDCl ) δ 8.61 (s, 1H), 7.15 (ddd, J = 4.8, 4.0, 1.6 Hz, 5H), 7.05 (td, J = 7.2, 1.2 Hz,
3
13
3
1
9
H), 6.80 (dd, J = 5.2, 3.2 Hz, 1H), 2.12 (s, 3H); C NMR (100 MHz, CDCl
3
) δ
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
70.6, 143.8, 140.4, 138.7, 132.5, 128.7, 125.2, 124.7, 123.1, 121.0, 114.0, 110.2,
ꢀ1
9.7, 20.8 ppm; νmax(KBr)/cm 3400, 3028, 1686, 1653, 1600, 1540, 1427, 1403, 744;
2
MS (EI) m/z 109, 163, 208, 241, 283; HRMSꢀESI (m/z): calcd for C16H13NNaO S,
+
[
M+Na] : 306.0559, found 306.0564.
Methyl 3-(Phenylthio)-1H-indole-4-carboxylate (3af): Yield: 68% (38.5 mg) as a
1
white solid; mp = 122.3 ꢀ 123.5 °C; R 0.23 (hexanes/ethyl acetate 2/1); H NMR (400
f
MHz, CDCl
7.6 Hz, 1H), 7.13 ꢀ 7.08 (m, 2H), 7.05 ꢀ 6.97 (m, 3H), 3.58 (s, 3H); C NMR (100
MHz, CDCl ) δ 169.7, 140.2, 137.6, 134.0, 128.6, 125.6, 125.4, 125.2, 124.6, 122.2,
122.1, 115.3, 101.9, 51.9 ppm; νmax(KBr)/cm 3408, 3035, 2946, 1683, 1636, 1526,
3
) δ 9.26 (s, 1H), 7.45 (dd, J = 7.6, 3.2 Hz, 2H), 7.36 (s, 1H), 7.20 (t, J =
13
3
ꢀ1
1
425, 763; MS (EI) m/z 111, 152, 196, 223, 283; HRMSꢀESI (m/z): calcd for
+
C
16
H
13NNaO
2
S, [M+Na] : 306.0559, found 306.0565.
15c
5
-Methyl-3-(phenylthio)-1H-indole (3ag): Yield: 92% (43.9 mg) as a white solid;
1
mp = 135.6 ꢀ 137.2 °C; R
CDCl
7.2 Hz, 2H), 7.11 ꢀ 6.99 (m, 4H), 2.40 (s, 3H); C NMR (100 MHz, CDCl ) δ 139.5,
f
0.36 (hexanes/ethyl acetate 10/1); H NMR (400 MHz,
3
) δ 8.22 (s, 1H), 7.39 (d, J = 7.2 Hz, 2H), 7.28 (d, J = 8.0 Hz, 1H), 7.15 (t, J =
13
3
1
34.8, 130.9, 130.5, 129.4, 128.7, 125.7, 124.8, 124.7, 119.2, 111.3, 101.9, 21.5 ppm;
ꢀ1
ν
max(KBr)/cm 3404, 3033, 2915, 1623, 1538, 1447, 1220, 748; MS (EI) m/z 118, 162,
+
2
06, 223, 239; HRMSꢀESI (m/z): calcd for C15
H
13NNaS, [M+Na] : 262.0661, found
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62.0654.
1
5e
5
-Fluoro-3-(phenylthio)-1H-indole (3ah): Yield: 84% (40.8 mg) as a yellow solid;
1
mp = 114.2 ꢀ 115.5 °C; R
f
0.36 (hexanes/ethyl acetate 10/1); H NMR (400 MHz,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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43
44
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46
47
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49
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52
53
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55
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57
58
59
60
DMSO) δ 11.83 (s, 1H), 7.86 (d, J = 2.4 Hz, 1H), 7.67 ꢀ 7.37 (m, 1H), 7.21 (td, J = 8.0,
1
3
1
.6 Hz, 2H), 7.15 ꢀ 6.97 (m, 5H); C NMR (100 MHz, DMSO) δ 157.7 (d, J = 232.6
Hz), 138.8, 134.4, 133.3, 129.3 (d, J = 9.8 Hz), 128.8, 125.4, 124.9, 113.6 (d, J = 9.6
Hz), 110.4 (d, J = 26.0 Hz), 103.0 (d, J = 23.6 Hz), 99.6 (d, J = 4.6 Hz) ppm;
ꢀ1
ν
max(KBr)/cm 3388, 3024, 1653, 1600, 1546, 1438, 1411, 748; MS (EI) m/z 95, 139,
+
1
66, 211, 243; HRMSꢀESI (m/z): calcd for C H FNS, [M+H] : 244.0591, found
14 11
2
44.0586.
12
6-Methoxy-3-(phenylthio)-1H-indole (3ai): Yield: 82% (41.8 mg) as a yellow
1
solid; mp = 111.6 ꢀ 113.2 °C; R
CDCl
d, J = 7.6 Hz, 2H), 7.05 (d, J = 6.8 Hz, 1H), 6.89 (s, 1H), 6.82 (d, J = 8.8 Hz, 1H),
f
0.28 (hexanes/ethyl acetate 4/1); H NMR (400 MHz,
3
) δ 8.25 (s, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.34 (s, 1H), 7.17 ꢀ 7.13 (m, 2H), 7.10
(
13
3.83 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 157.2, 139.3, 137.3, 129.4, 128.7, 125.8,
ꢀ1
1
24.7, 123.3, 120.3, 110.8, 102.8, 95.1, 55.7 ppm; νmax(KBr)/cm 3408, 3026, 2934,
1627, 1524, 1457, 1286, 756; MS (EI) m/z 135, 184, 212, 240, 255; HRMSꢀESI (m/z):
+
calcd for C15
H
13NNaOS, [M+Na] : 278.0610, found 278.0608.
3-(Phenylthio)-6-(trifluoromethoxy)-1H-indole (3aj): Yield: 70% (43.3 mg) as a
1
yellow solid; mp = 125.6 ꢀ 127.4 °C; R
(400 MHz, CDCl
.28 (s, 1H), 7.17 (t, J = 7.6 Hz, 2H), 7.13 ꢀ 7.06 (m, 3H), 7.03 (d, J = 8.8 Hz, 1H);
f
0.31 (hexanes/ethyl acetate 4/1); H NMR
3
) δ 8.43 (s, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 1.6 Hz, 1H),
7
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5
5
5
5
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3
3
C NMR (100 MHz, CDCl ) δ 145.8, 138.6, 136.1, 131.9, 128.9, 126.1, 125.1, 122.0,
ꢀ1
1
1
20.7 (q, J = 256.2 Hz), 120.5, 115.1, 104.7, 103.5 ppm; νmax(KBr)/cm 3386, 3028,
633, 1536, 1457, 1409, 752; MS (EI) m/z 135, 184, 223, 277, 309; HRMSꢀESI (m/z):
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
calcd for C H F NOS, [M+H] : 310.0508, found 310.0509.
15
11 3
1
5d
6
-Chloro-3-(phenylthio)-1H-indole (3ak): Yield: 82% (42.5 mg) as a white solid;
1
mp = 103.3 ꢀ 104.7 °C; R
f
0.38 (hexanes/ethyl acetate 10/1); H NMR (400 MHz,
CDCl
3
) δ 8.55 (s, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 7.6 Hz, 1H), 7.15 (t, J =
13
7
3
.2 Hz, 2H), 7.07 (dd, J = 13.6, 7.0 Hz, 4H); C NMR (100 MHz, CDCl ) δ 138.7,
1
33.8, 131.2, 130.6, 128.8, 126.1, 125.1, 122.5, 121.7, 118.4, 117.0, 104.5 ppm;
ꢀ1
ν
max(KBr)/cm 3398, 3056, 1722, 1635, 1538, 1453, 746; MS (EI) m/z 111, 146, 182,
+
224, 259; HRMSꢀESI (m/z): calcd for C14
82.0113.
H
10ClNNaS, [M+Na] : 282.0115, found
2
6
e
6-Bromo-3-(phenylthio)-1H-indole (3al): Yield: 77% (46.7 mg) as a white solid;
1
mp = 144.8 ꢀ 146.5 °C; R 0.38 (hexanes/ethyl acetate 10/1); H NMR (400 MHz,
f
CDCl
3
) δ 8.39 (s, 1H), 7.57 (d, J = 1.6 Hz, 1H), 7.44 (t, J = 5.2 Hz, 2H), 7.30 ꢀ 7.21
13
(m, 1H), 7.19 ꢀ 7.12 (m, 2H), 7.10 ꢀ 7.01 (m, 3H); C NMR (100 MHz, CDCl
3
) δ
138.7, 137.3, 131.1, 128.8, 128.0, 126.0, 125.1, 124.3, 121.0, 116.7, 114.6, 103.6 ppm;
ꢀ1
ν
max(KBr)/cm 3402, 3036, 1637, 1542, 1456, 1405, 755; MS (EI) m/z 112, 152, 191,
+
224, 271, 303; HRMSꢀESI (m/z): calcd for C H BrNNaS, [M+Na] : 325.9610,
1
4
10
found 325.9604.
6-Nitro-3-(phenylthio)-1H-indole (3am): Yield: 61% (32.9 mg) as a yellow solid;
1
mp = 147.5 ꢀ 148.7 °C; R
f
0.26 (hexanes/ethyl acetate 1/4); H NMR (400 MHz,
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CDCl
3
) δ 9.00 (s, 1H), 8.43 (d, J = 1.6 Hz, 1H), 8.05 (dd, J = 8.8, 2.0 Hz, 1H), 7.77 (d,
J = 2.4 Hz, 1H), 7.67 (d, J = 8.8 Hz, 1H), 7.22 ꢀ 7.14 (m, 2H), 7.10 (dd, J = 7.2, 5.2
1
3
3
Hz, 3H); C NMR (100 MHz, CDCl ) δ 144.3, 137.9, 135.7, 135.1, 134.0, 128.9,
10
11
12
13
14
15
16
17
18
19
20
21
22
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52
53
54
55
56
57
58
59
60
ꢀ
1
1
1
26.3, 125.5, 119.9, 116.4, 108.6, 105.1 ppm; νmax(KBr)/cm 3394, 3026, 1646, 1578,
436, 1404, 746; MS (EI) m/z 120, 191, 224, 240, 270; HRMSꢀESI (m/z): calcd for
+
C
14
H
10
N
2
NaO
2
S, [M+Na] : 293.0355, found 293.0358.
7
-Fluoro-3-(phenylthio)-1H-indole (3an): Yield: 80% (38.8 mg) as a yellow solid;
1
mp = 114.4 ꢀ 115.2 °C; R
f
0.35 (hexanes/ethyl acetate 10/1); H NMR (400 MHz,
CDCl ) δ 8.51 (s, 1H), 7.44 (d, J = 2.4 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.15 (t, J =
3
7
.6 Hz, 2H), 7.09 (d, J = 7.6 Hz, 2H), 7.04 (ddd, J = 12.8, 7.2, 5.6 Hz, 2H), 6.95 (dd,
1
3
J = 10.8, 8.0 Hz, 1H); C NMR (100 MHz, CDCl
3
) δ 149.6 (d, J = 243.6 Hz), 138.7,
1
32.6 (d, J = 4.4 Hz), 131.2, 128.8, 126.1, 125.0, 124.9 (d, J = 13.6 Hz), 121.2 (d, J =
6.1 Hz), 115.4 (d, J = 3.5 Hz), 107.9 (d, J = 15.8 Hz), 104.1 (d, J = 2.9 Hz) ppm;
ꢀ1
νmax(KBr)/cm 3408, 3046, 1644, 1618, 1543, 1425, 750; MS (EI) m/z 95, 122, 166,
+
183, 211, 243; HRMSꢀESI (m/z): calcd for C14
44.0587.
H
11FNS, [M+H] : 244.0591, found
2
5,6-Difluoro-3-(phenylthio)-1H-indole (3ao): Yield: 76% (39.7 mg) as a white solid;
1
mp = 157.0 ꢀ 158.6 °C; R
f
0.32 (hexanes/ethyl acetate 8/1); H NMR (400 MHz,
CDCl ) δ 8.38 (s, 1H), 7.48 (d, J = 2.4 Hz, 1H), 7.31 (dd, J = 10.2, 7.6 Hz, 1H), 7.23 ꢀ
3
13
7
.14 (m, 3H), 7.08 (dd, J = 5.2, 3.0 Hz, 3H); C NMR (100 MHz, CDCl
3
) δ 148.7 (dd,
J = 242.9, 16.0 Hz), 147.4 (dd, J = 240.6, 14.9 Hz), 138.4, 131.9 (d, J = 3.3 Hz),
1
31.3 (d, J = 10.6 Hz), 128.9, 126.0, 125.2, 124.8 (dd, J = 8.1, 1.3 Hz), 106.5 (dd, J =
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6
9.8, 1.0 Hz), 103.6 (dd, J = 4.3, 1.3 Hz), 99.7 (d, J = 22.2 Hz) ppm; νmax(KBr)/cm
402, 3034, 1653, 1616, 1568, 1524, 1419, 748; MS (EI) m/z 77, 113, 184, 201, 229,
+
61; HRMSꢀESI (m/z): calcd for C14
84.0311.
H
9
F
2
NNaS, [M+Na] : 284.0316, found
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9
0
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7
8
9
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4
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6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
-Chloro-5-fluoro-3-(phenylthio)-1H-indole (3ap): Yield: 81% (44.9 mg) as a
1
yellow solid; mp = 165.4 ꢀ 167.2 °C; R
f
0.34 (hexanes/ethyl acetate 8/1); H NMR
(400 MHz, CDCl
3
) δ 8.39 (s, 1H), 7.50 (d, J = 2.4 Hz, 1H), 7.44 (d, J = 6.0 Hz, 1H),
13
7
.31 (d, J = 9.2 Hz, 1H), 7.21 ꢀ 7.13 (m, 2H), 7.08 (dd, J = 7.2, 5.4 Hz, 3H); C NMR
(
100 MHz, CDCl ) δ 153.9 (d, J = 239.1 Hz), 138.3, 132.6, 128.9, 128.6, 128.4 (d, J =
3
8
.8 Hz), 126.1, 125.2, 117.3 (d, J = 21.5 Hz), 112.9, 105.9 (d, J = 24.1 Hz), 103.8 (d,
ꢀ1
J = 4.5 Hz) ppm; νmax(KBr)/cm 3384, 3026, 1646, 1628, 1544, 1411, 1400, 753; MS
(
9
EI) m/z 77, 121, 173, 242, 277; HRMSꢀESI (m/z): calcd for C14H ClFNNaS,
+
[M+Na] : 300.0020, found 300.0027.
6
-Bromo-5-fluoro-3-(phenylthio)-1H-indole (3aq): Yield: 74% (47.5 mg) as a white
1
solid; mp = 153.1 ꢀ 154.3 °C; R
CDCl
7.17 (t, J = 7.2 Hz, 2H), 7.08 (t, J = 6.8 Hz, 3H); C NMR (100 MHz, CDCl
54.6 (d, J = 238.8 Hz), 138.3, 133.2, 132.6, 129.3 (d, J = 8.8 Hz), 128.9, 126.1,
f
0.34 (hexanes/ethyl acetate 8/1); H NMR (400 MHz,
3
) δ 8.41 (s, 1H), 7.59 (d, J = 5.2 Hz, 1H), 7.49 (s, 1H), 7.30 (d, J = 8.8 Hz, 1H),
1
3
3
) δ
1
125.2, 115.8, 105.7 (d, J = 25.4 Hz), 104.8 (d, J = 25.0 Hz), 103.8 (d, J = 4.8 Hz) ppm;
ꢀ1
ν
max(KBr)/cm 3392, 3031, 1647, 1623, 1554, 1447, 1408, 748; MS (EI) m/z 77, 121,
+
183, 242, 289, 321; HRMSꢀESI (m/z): calcd for C14
found 343.9513.
H
9
BrFNNaS, [M+Na] : 343.9515,
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,6-Dichloro-3-(phenylthio)-1H-indole (3ar): Yield: 70% (41.0 mg) as a yellow
1
solid; mp = 148.6 ꢀ 150.2 °C; R
f
0.35 (hexanes/ethyl acetate 10/1); H NMR (400
MHz, CDCl
3
) δ 8.42 (s, 1H), 7.66 (s, 1H), 7.52 (s, 1H), 7.48 (d, J = 2.0 Hz, 1H), 7.18
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
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50
51
52
53
54
55
56
57
58
59
60
1
3
(
t, J = 7.6 Hz, 2H), 7.08 (t, J = 8.2 Hz, 3H); C NMR (100 MHz, CDCl ) δ 138.3,
3
1
35.1, 132.5, 128.9, 128.8, 127.2, 126.0, 125.4, 125.3, 120.7, 113.2, 103.3 ppm;
ꢀ1
ν
max(KBr)/cm 3402, 3025, 1648, 1615, 1536, 1443, 1400, 746; MS (EI) m/z 112, 223,
+
2
3
5
58, 293; HRMSꢀESI (m/z): calcd for C14
H
9
Cl
2
NNaS, [M+Na] : 315.9725, found
15.9730.
-Bromo-6-chloro-3-(phenylthio)-1H-indole (3as): Yield: 73% (49.2 mg) as a white
1
solid; mp = 154.7 ꢀ 156.0 °C; R
f
0.35 (hexanes/ethyl acetate 10/1); H NMR (400
MHz, CDCl
3
) δ 8.45 (s, 1H), 7.84 (s, 1H), 7.54 (s, 1H), 7.46 (s, 1H), 7.18 (t, J = 7.2
13
Hz, 2H), 7.08 (t, J = 8.0 Hz, 3H); C NMR (100 MHz, CDCl
3
) δ 138.3, 135.8, 132.4,
ꢀ1
129.5, 128.9, 128.8, 126.0, 125.3, 124.1, 114.7, 113.1, 103.1 ppm; νmax(KBr)/cm
3
402, 3032, 1654, 1623, 1546, 1510, 1436, 1405, 748; MS (EI) m/z 111, 223, 258,
+
307, 337; HRMSꢀESI (m/z): calcd for C14
59.9223.
H
9
BrClNNaS, [M+Na] : 359.9220, found
3
6-Bromo-4-chloro-3-(phenylthio)-1H-indole (3at): Yield: 76% (51.2 mg) as a green
1
solid; mp = 133.5 ꢀ 134.8 °C; R
f
0.35 (hexanes/ethyl acetate 10/1); H NMR (400
MHz, CDCl ) δ 8.46 (s, 1H), 7.42 (d, J = 13.6 Hz, 2H), 7.24 (s, 1H), 7.18 (d, J = 7.6
3
13
Hz, 2H), 7.11 ꢀ 7.04 (m, 3H); C NMR (100 MHz, CDCl
3
) δ 140.3, 138.4, 133.0,
ꢀ1
128.8, 127.8, 126.0, 125.1, 125.0, 124.3, 115.9, 113.5, 103.7 ppm; νmax(KBr)/cm
3
396, 3025, 1662, 1635, 1547, 1523, 1448, 1410, 744; MS (EI) m/z 111, 154, 223,
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5
5
5
5
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6
+
2
58, 304, 337; HRMSꢀESI (m/z): calcd for C14
9
H BrClNNaS, [M+Na] : 359.9220,
found 359.9217.
1
5d
2
-Methyl-3-(phenylthio)-1H-indole (3au): Yield: 90% (43.0 mg) as a white solid;
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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1
2
3
4
5
6
7
8
9
0
1
mp = 112.3 ꢀ 113.9 °C; R 0.34 (hexanes/ethyl acetate 10/1); H NMR (400 MHz,
f
3
CDCl ) δ 8.11 (s, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.19 ꢀ 7.17
13
(
m, 1H), 7.16 ꢀ 7.08 (m, 3H), 7.02 (dd, J = 11.6, 5.6 Hz, 3H), 2.45 (s, 3H); C NMR
(100 MHz, CDCl
3
) δ 141.2, 139.4, 135.5, 130.3, 128.7, 125.6, 124.6, 122.2, 120.7,
ꢀ1
1
19.0, 110.7, 99.4, 12.2 ppm; νmax(KBr)/cm 3398, 2924, 1722, 1583, 1524, 1445,
1
411, 747; MS (EI) m/z 77, 118, 162, 206, 239; HRMSꢀESI (m/z): calcd for
+
C
15
H
13NNaS, [M+Na] : 262.0661, found 262.0665.
1
5a
5-Methoxy-2-methyl-3-(phenylthio)-1H-indole (3av): Yield: 87% (46.8 mg) as a
1
colorless solid; mp = 130.2 ꢀ 131.5 °C; R
f
0.25 (hexanes/ethyl acetate 5/1); H NMR
(400 MHz, CDCl
3
) δ 8.13 (s, 1H), 7.20 ꢀ 7.10 (m, 3H), 7.06 ꢀ 6.98 (m, 4H), 6.82 (d, J
13
=
8.8 Hz, 1H), 3.77 (s, 3H), 2.44 (s, 3H); C NMR (100 MHz, CDCl ) δ 155.0, 141.8,
3
139.4, 131.2, 130.3, 128.7, 125.4, 124.5, 112.2, 111.5, 100.9, 98.9, 55.8, 12.2 ppm;
ꢀ1
ν
max(KBr)/cm 3386, 3048, 2961, 1592, 1456, 1419, 1356, 752; MS (EI) m/z 118, 148,
+
192, 239, 269; HRMSꢀESI (m/z): calcd for C16
H
16NOS, [M+H] : 270.0947, found
2
70.0946.
1
5a
5-Chloro-2-methyl-3-(phenylthio)-1H-indole (3aw): Yield: 73% (39.8 mg) as a
1
pink solid; mp = 140.8 ꢀ 141.9 °C; R
f
0.36 (hexanes/ethyl acetate 10/1); H NMR (400
MHz, CDCl
3
) δ 8.21 (s, 1H), 7.51 (s, 1H), 7.21 (d, J = 8.4 Hz, 1H), 7.17 ꢀ 7.10 (m,
13
3
H), 7.05 (d, J = 7.2 Hz, 1H), 7.01 (d, J = 8.0 Hz, 2H), 2.47 (s, 3H); C NMR (100
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8
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) δ 142.7, 138.8, 133.8, 131.6, 128.8, 126.7, 125.6, 124.8, 122.5, 118.5,
ꢀ1
111.7, 99.5, 12.2 ppm; νmax(KBr)/cm 3394, 3056, 1708, 1583, 1448, 1360, 744; MS
(EI) m/z 119, 152, 196, 238, 273; HRMSꢀESI (m/z): calcd for C15H12ClNNaS,
10
11
12
13
14
15
16
17
18
19
20
21
22
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49
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52
53
54
55
56
57
58
59
60
+
[
M+Na] : 296.0271, found 296.0274.
1
5e
Ethyl 3-(Phenylthio)-1H-indole-2-carboxylate (3ax): Yield: 67% (39.8 mg) as a
1
white solid; mp = 106.3 ꢀ 107.5 °C; R
f
0.26 (hexanes/ethyl acetate 2/1); H NMR (400
MHz, CDCl
3
) δ 9.20 (s, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.40 ꢀ
7
2
1
.31 (m, 1H), 7.21 ꢀ 7.12 (m, 5H), 7.09 (dq, J = 8.8, 4.4 Hz, 1H), 4.38 (q, J = 7.2 Hz,
1
3
H), 1.31 (t, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl ) δ 161.2, 137.9, 135.7,
3
30.1, 128.7, 127.3, 126.1, 125.3, 121.8, 121.5, 112.0, 110.6, 61.4, 14.2 ppm;
ꢀ1
ν
max(KBr)/cm 3368, 3054, 2928, 1684, 1505, 1444, 1368, 744; MS (EI) m/z 105,
+
1
46, 223, 297; HRMSꢀESI (m/z): calcd for C17
H
15NNaO
2
S, [M+Na] : 320.0716,
found 320.0723.
15a
2
-(4-Fluorophenyl)-3-(phenylthio)-1H-indole (3ay): Yield: 84% (53.6 mg) as a
1
yellow oil; R
f
0.32 (hexanes/ethyl acetate 10/1); H NMR (400 MHz, CDCl
3
) δ 8.47 (s,
1
H), 7.76 ꢀ 7.65 (m, 2H), 7.62 (d, J = 7.6 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.26 (t, J
1
3
= 7.6 Hz, 1H), 7.20 ꢀ 7.00 (m, 8H); C NMR (100 MHz, CDCl
3
) δ 162.9 (d, J =
2
49.5 Hz), 141.1, 139.1, 135.8, 131.1, 130.2 (d, J = 8.1 Hz), 128.9, 127.6 (d, J = 3.4
Hz), 125.6, 124.8, 123.5, 121.3, 120.0, 115.9 (d, J = 21.7 Hz), 111.2, 99.5 ppm;
ꢀ1
ν
max(KBr)/cm 3396, 3058, 1648, 1583, 1504, 1452, 748; MS (EI) m/z 77, 121, 183,
+
242, 287, 319; HRMSꢀESI (m/z): calcd for C20
42.0725.
H
14FNNaS, [M+Na] : 342.0723, found
3
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6
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-(4-Chlorophenyl)-3-(phenylthio)-1H-indole (3az): Yield: 82% (54.9 mg) as a
1
yellow oil; R
f
0.33 (hexanes/ethyl acetate 10/1); H NMR (400 MHz, CDCl
3
) δ 8.45 (s,
1
H), 7.62 (t, J = 6.8 Hz, 3H), 7.44 ꢀ 7.32 (m, 3H), 7.26 (t, J = 7.6 Hz, 1H), 7.14 (dd, J
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
=
14.4, 7.6 Hz, 3H), 7.04 (dd, J = 16.0, 7.6 Hz, 3H); C NMR (100 MHz, CDCl ) δ
3
1
1
1
40.8, 138.9, 135.9, 134.7, 131.2, 129.8, 129.4, 129.0, 128.9, 125.6, 124.9, 123.7,
ꢀ1
21.4, 120.1, 111.3, 100.1 ppm; νmax(KBr)/cm 3384, 3048, 1652, 1560, 1512, 1437,
410, 746; MS (EI) m/z 121, 190, 267, 303, 335; HRMSꢀESI (m/z): calcd for
+
C
20
H
14ClNNaS, [M+Na] : 358.0428, found 358.0431.
2
-(3-(Phenylthio)-1H-indol-2-yl)aniline (3ba): Yield: 58% (36.7 mg) as a yellow oil;
1
R
f
0.21 (hexanes/ethyl acetate 5/1); H NMR (400 MHz, CDCl
3
) δ 8.71 (s, 1H), 7.59
(d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.26 (d, J = 7.2 Hz, 2H), 7.20 ꢀ 7.10 (m,
H), 7.07 (d, J = 7.2 Hz, 2H), 7.02 (t, J = 7.0 Hz, 1H), 6.81 ꢀ 6.72 (m, 2H), 3.54 (s,
4
13
2H); C NMR (100 MHz, CDCl
3
) δ 144.7, 140.4, 138.9, 136.0, 131.5, 130.3, 130.2,
1
28.8, 125.8, 124.7, 123.2, 121.0, 119.8, 118.9, 117.4, 116.5, 111.3, 101.0 ppm;
ꢀ1
ν
max(KBr)/cm 3408, 3026, 1658, 1503, 1437, 1411, 756; MS (EI) m/z 104, 152, 180,
+
2
83, 316; HRMSꢀESI (m/z): calcd for C20
H
17
N
2
S, [M+H] : 317.1107, found
317.1103.
15e
2
-(Naphthalen-2-yl)-3-(phenylthio)-1H-indole (3bb): Yield: 87% (61.1 mg) as a
1
white solid; mp = 96.5 ꢀ 97.8 °C; R 0.30 (hexanes/ethyl acetate 8/1); H NMR (400
f
MHz, CDCl
3
) δ 8.55 (s, 1H), 8.14 (s, 1H), 7.90 ꢀ 7.83 (m, 2H), 7.79 (ddd, J = 9.0, 6.0,
3.2 Hz, 2H), 7.66 (d, J = 8.0 Hz, 1H), 7.50 ꢀ 7.44 (m, 2H), 7.42 (d, J = 8.0 Hz, 1H),
7
.27 (t, J = 7.2 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 7.16 ꢀ 7.11 (m, 4H), 7.03 (ddd, J =
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1
.4, 6.0, 2.8 Hz, 1H); C NMR (100 MHz, CDCl
3
) δ 141.9, 139.3, 136.0, 133.2,
33.2, 131.4, 128.9, 128.4, 128.4, 127.8, 127.5, 126.7, 126.6, 125.8, 125.7, 124.8,
ꢀ1
23.5, 121.3, 120.0, 111.2, 100.1 ppm; νmax(KBr)/cm 3386, 3035, 1649, 1594, 1526,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
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43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
502, 1437, 745; MS (EI) m/z 120, 175, 215, 273, 318, 351; HRMSꢀESI (m/z): calcd
+
for C24
H
18NS, [M+H] : 352.1154, found 352.1159.
2
-Methyl-3-(phenylthio)-6,7-dihydro-1H-indol-4(5H)-one (3bc): Yield: 46% (23.6
1
f
mg) as a white solid; mp = 248.7 ꢀ 250.4 °C; R 0.18 (hexanes/ethyl acetate 1/1); H
NMR (400 MHz, CDCl
.76 (t, J = 6.4 Hz, 2H), 2.47 ꢀ 2.39 (m, 2H), 2.23 (s, 3H), 2.16 ꢀ 2.06 (m, 2H); C
NMR (100 MHz, CDCl ) δ 193.2, 143.7, 139.4, 135.1, 128.5, 126.2, 124.6, 120.2,
104.4, 38.6, 23.7, 23.2, 11.0 ppm; νmax(KBr)/cm 3384, 2928, 2850, 1650, 1555, 1508,
3
) δ 8.94 (s, 1H), 7.14 (t, J = 7.6 Hz, 2H), 7.10 ꢀ 6.96 (m, 3H),
13
2
3
ꢀ1
1
452, 1407, 749; MS (EI) m/z 115, 180, 202, 228, 257; HRMSꢀESI (m/z): calcd for
+
C
15
H
16NOS, [M+H] : 258.0947, found 258.0940.
15d
1
-Methyl-3-(phenylthio)-1H-indole (5a): Yield: 90% (43.0 mg) as a white solid;
1
mp = 84.7 ꢀ 86.4 °C; R
f
0.46 (hexanes/ethyl acetate 50/1); H NMR (400 MHz, CDCl
3
)
δ 7.60 (d, J = 7.6 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.24 (d, J = 10.0 Hz, 2H), 7.17 ꢀ
13
7.07 (m, 5H), 7.01 (dd, J = 9.6, 4.4 Hz, 1H), 3.77 (s, 3H); C NMR (100 MHz,
CDCl ) δ 139.7, 137.6, 135.1, 129.9, 128.7, 125.8, 124.7, 122.6, 120.6, 119.8, 109.8,
3
ꢀ1
100.6, 33.1 ppm; νmax(KBr)/cm 3032, 1612, 1506, 1450, 1378, 746; MS (EI) m/z
+
1
18, 162, 207, 239; HRMSꢀESI (m/z): calcd for C15
H
13NNaS, [M+Na] : 262.0661,
found 262.0661.
7b
1
-Methyl-2-phenyl-3-(phenylthio)-1H-indole (5b): Yield: 85% (53.6 mg) as a
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6
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yellow solid; mp = 95.7 ꢀ 97.5 °C; R
MHz, CDCl ) δ 7.63 (d, J = 8.0 Hz, 1H), 7.42 ꢀ 7.34 (m, 6H), 7.29 (t, J = 7.6 Hz, 1H),
.20 ꢀ 7.14 (m, 1H), 7.09 (t, J = 7.6 Hz, 2H), 7.03 (d, J = 7.6 Hz, 2H), 6.98 (t, J = 7.2
f
0.44 (hexanes/ethyl acetate 50/1); H NMR (400
3
7
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
Hz, 1H), 3.67 (s, 3H); C NMR (100 MHz, CDCl ) δ 145.9, 140.1, 137.7, 130.7,
3
1
30.6, 129.9, 128.8, 128.7, 128.4, 125.7, 124.5, 122.9, 121.1, 119.9, 109.9, 99.8, 31.8
ꢀ1
ppm; νmax(KBr)/cm 3044, 1630, 1504, 1400, 1381, 748; MS (EI) m/z 118, 165, 204,
+
2
3
1
83, 315; HRMSꢀESI (m/z): calcd for C21
H
17NNaS, [M+Na] : 338.0974, found
38.0979.
-Methyl-5-nitro-3-(phenylthio)-1H-indole (5c): Yield: 65% (36.9 mg) as a yellow
1
solid; mp = 183.4 ꢀ 185.2 °C; R
f
0.32 (hexanes/ethyl acetate 10/1); H NMR (400
MHz, CDCl
3
) δ 8.54 (d, J = 2.0 Hz, 1H), 8.16 (dd, J = 9.0, 2.0 Hz, 1H), 7.48 (s, 1H),
13
7
.40 (d, J = 8.8 Hz, 1H), 7.21 ꢀ 7.14 (m, 2H), 7.14 ꢀ 7.05 (m, 3H), 3.90 (s, 3H); C
NMR (100 MHz, CDCl
3
) δ 142.6, 140.3, 138.2, 137.9, 129.4, 128.9, 126.4, 125.5,
ꢀ1
1
18.3, 116.9, 109.9, 104.9, 33.6 ppm; νmax(KBr)/cm 3038, 1626, 1456, 1410, 1376,
757; MS (EI) m/z 118, 165, 207, 238, 284; HRMSꢀESI (m/z): calcd for
+
C
15
H
12
N
2
NaO
2
S, [M+Na] : 307.0512, found 307.0517.
1
5h
1-Phenyl-3-(phenylthio)-1H-indole (5d): Yield: 86% (51.8 mg) as a yellow oil; R
f
1
0
3
.34 (hexanes/ethyl acetate 50/1); H NMR (400 MHz, CDCl ) δ 7.65 (d, J = 7.6 Hz,
1H), 7.61 ꢀ 7.55 (m, 2H), 7.52 (d, J = 4.4 Hz, 4H), 7.43 ꢀ 7.35 (m, 1H), 7.26 (d, J =
13
7
.6 Hz, 1H), 7.22 ꢀ 7.14 (m, 5H), 7.06 (d, J = 2.8 Hz, 1H); C NMR (100 MHz,
CDCl
3
) δ 139.0, 138.9, 136.8, 133.9, 130.3, 129.8, 128.8, 127.2, 126.2, 125.0, 124.5,
ꢀ1
1
23.4, 121.4, 120.1, 111.0, 104.1 ppm; νmax(KBr)/cm 3040, 1624, 1600, 1508, 1406,
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44; MS (EI) m/z 77, 121, 165, 223, 269, 301; HRMSꢀESI (m/z): calcd for
+
C
20
H
15NNaS, [M+Na] : 324.0817, found 324.0821.
1
-Benzyl-5-bromo-3-(phenylthio)-1H-indole (5g): Yield: 80% (62.9 mg) as a yellow
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
oil; R 0.32 (hexanes/ethyl acetate 50/1); H NMR (400 MHz, CDCl ) δ 7.75 (s, 1H),
f
3
7
2
1
.34 (s, 1H), 7.27 (t, J = 7.6 Hz, 4H), 7.17 ꢀ 7.12 (m, 3H), 7.11 ꢀ 7.00 (m, 5H), 5.25 (s,
13
3
H); C NMR (100 MHz, CDCl ) δ 139.0, 136.2, 135.8, 135.7, 131.9, 129.1, 128.9,
28.8, 128.2, 126.9, 125.9, 125.1, 122.5, 114.5, 111.9, 101.3, 50.7 ppm;
ꢀ1
ν
max(KBr)/cm 3026, 1620, 1600, 1466, 1454, 1405, 748; MS (EI) m/z 91, 223, 302,
+
3
4
60, 393; HRMSꢀESI (m/z): calcd for C H BrNNaS, [M+Na] : 416.0079, found
21 16
16.0079.
1-(4-Methylbenzyl)-3-(phenylthio)-1H-indole (5h): Yield: 91% (59.8 mg) as a
1
yellow oil; R
f
0.35 (hexanes/ethyl acetate 50/1); H NMR (400 MHz, CDCl
3
) δ 7.60
(d, J = 8.0 Hz, 1H), 7.35 ꢀ 7.30 (m, 2H), 7.20 (dd, J = 11.2, 4.0 Hz, 1H), 7.15 ꢀ 7.07
13
(
m, 7H), 7.06 ꢀ 6.98 (m, 3H), 5.23 (s, 2H), 2.29 (s, 3H); C NMR (100 MHz, CDCl )
3
δ 139.7, 137.8, 137.3, 134.5, 133.6, 130.2, 129.7, 128.8, 127.2, 125.8, 124.8, 122.8,
ꢀ1
1
20.8, 119.9, 110.4, 101.3, 50.3, 21.2 ppm; νmax(KBr)/cm 3036, 1646, 1610, 1473,
1454, 1410, 780; MS (EI) m/z 77, 105, 224, 296, 329; HRMSꢀESI (m/z): calcd for
+
C
22
H
19NNaS, [M+Na] : 352.1130, found 352.1128.
1-(4-(tert-Butyl)benzyl)-3-(phenylthio)-1H-indole (5i): Yield: 87% (64.6 mg) as a
1
yellow solid; mp = 118.8 ꢀ 119.3 °C; R
f
0.35 (hexanes/ethyl acetate 50/1); H NMR
(400 MHz, CDCl
3
) δ 7.61 (d, J = 8.0 Hz, 1H), 7.34 (dd, J = 10.8, 8.0 Hz, 4H), 7.23 ꢀ
13
7
.18 (m, 1H), 7.16 ꢀ 7.06 (m, 7H), 7.05 ꢀ6.96 (m, 1H), 5.28 (s, 2H), 1.29 (s, 9H); C
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