A metal-free sulfenylation and bromosulfenylation of indoles: Controllable synthesis of 3-arylthioindoles and 2-bromo-3-arylthioindoles

Article abstract of DOI:10.1002/adsc.201200227

An efficient metal-free sulfenylation of indoles with disulfides has been developed, leading to 3-arylthioindoles in moderate to excellent yields. Furthermore, bromosulfenylation of indoles with disulfides has been realized for the first time providing a

Full text of DOI:10.1002/adsc.201200227

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DOI: 10.1002/adsc.201200227
A Metal-Free Sulfenylation and Bromosulfenylation of Indoles:
Controllable Synthesis of 3-Arylthioindoles and
2-Bromo-3-arylthioindoles
Dayun Huang,a Jiuxi Chen,a,* Weixing Dan,a Jinchang Ding,a,b Miaochang Liu,a
and Huayue Wua,*
a
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, Peopleꢀs Republic of China
Fax : (+86)-577-8836-8280; phone: (+86)-577-8836-8280; e-mail: jiuxichen@wzu.edu.cn or huayuewu@wuz.edu.cn
College of Light Industry, Wenzhou Vocational and Technical College, Wenzhou 325035, Peopleꢀs Republic of China
b
Received: March 18, 2012; Revised: May 9, 2012; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200227.
Abstract: An efficient metal-free sulfenylation of
indoles with disulfides has been developed, leading
to 3-arylthioindoles in moderate to excellent yields.
Furthermore, bromosulfenylation of indoles with di-
sulfides has been realized for the first time provid-
ing a new family of 2-bromo-3-arylthioindole deriv-
atives in good yield by the one-pot construction of
C S and C Br bonds. It is noteworthy that the
system enables the use of both the RS moieties in
RSSR and shows a broad functional group toler-
ance.
whereas the other route involves the cyclization reac-
tions of 2-alkynylanilines[9] or N,N-dialkyl-2-iodoani-
lines.[10] One of the first methods described above in-
volves the direct sulfenylation of indoles using excess
thiol.[5] However, the use of highly volatile and un-
pleasant smelling free thiols can lead to serious envi-
ronmental and safety issues and can also limit the
scalability of such processes in all of the reported
methods. Undesirable side reactions resulting from
the oxidation of thiols represent a further drawback
to these methodologies. To minimize or eliminate the
problems typically encountered, improved protocols
for the synthesis of 3-arlythioindoles from the direct
sulfenylation of indoles with disulfides using stoichio-
metric quantities of strong base[6a,b] or transition metal
catalysts[6c,d] have been developed. Furthermore, the
direct sulfenylation of indoles according to alternative
methods have been reported using sulfenylating
agents, such as N-thioarylphthalimides[7] and quinone
À
À
Keywords: 3-arylthioindoles; 2-bromo-3-arylthioin-
doles; bromosulfenylation; metal-free conditions;
sulfenylation
In synthetic organic chemistry, the impact of organo- mono-O,S-acetals.[8]
sulfur chemistry, especially in the area of heterocyclic
Recently, palladium[9a] and copper[9b] catalyzed an-
chemistry, has led to a resurgence of interest in this nulations of 2-alkynylanilines with disulfides have
field since sulfur-containing groups in heterocyclic been developed. Larock and co-workers reported that
compounds can serve as important auxiliary functions 3-arylthioindoles were synthesized by the Pd/Cu-cata-
in synthetic sequences.[1] The substituted indole nu- lyzed coupling of N,N-dialkyl-2-iodoanilines with ter-
cleus is prevalent in numerous natural products and is minal alkynes, followed by (n-Bu)4NI-induced electro-
extremely important in medicinal chemistry.[2] Among philic cyclization in the presence of arylsulfenyl chlor-
the numerous indole derivatives known, 3-arylthioin- ides.[10] However, the methods were restricted to the
dole and its derivatives have recently attracted con- use of toxic and unstable sulfenyl halides as the reac-
siderable attention due to their therapeutic value.[3] tion partners in the presence of a transition metal cat-
Most recently, Silvestri and co-workers reported that alyst. As a result, the development of direct and con-
indolylarylsulfones have been used as HIV-1 non-nu- cise methods for synthesizing 3-arylthioindoles under
cleoside reverse transcriptase inhibitors.[4] The impor- mild conditions using stable and readily available ma-
tance of 3-arylthioindoles has resulted in the develop- terials remains a challenging area for exploration.
ment of two synthetic routes for their preparation.
In contrast, bromosulfenylation by the one-pot for-
À
À
One route involves the introduction of substituents by mation of C S and C Br bonds has been scarcely ex-
direct sulfenylation of a preexisting indole ring,[5–8] plored.[11] To the best of our knowledge, there are no
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Scheme 1. Sulfenylation and bromosulfenylation of indoles with disulfides.
known reports of the bromosulfenylation of indoles in (Table 1). Our investigation began with a model reac-
the literature. tion run in the absence of NBS and no target product
As part of the continuing efforts in our laboratory was detected (Table 1, entry 1). Next, the solvent
towards the development of new methodologies using effect was tested in the presence of NBS. Among all
disulfides as sulfur sources,[12] we herein report a new the solvents screened, traces or low yields of product
route to 3-arylthioindoles (3) by regioselective sulfen- were observed in CH2Cl2, 1,4-dioxane, acetone,
ACHTUNGTRENNUNGylation of indoles (1) with disulfides (2) in the pres- CH3CN, EtOH and DMSO (Table 1, entries 2–7).
ence of N-bromosuccinimide (NBS) under metal-free However, we were encouraged to find that the yield
conditions (Scheme 1, a). Furthermore, a new family of the desired product 3-phenylthioindole (3a) was
of 2-bromo-3-arylthioindole (4) compounds has been improved to 67% when DMF was employed as the
À
synthesized by the one-pot construction of C S and solvent at room temperature (Table 1, entry 8). En-
À
C Br bonds (Scheme 1, b).
couraged by these promising results, we further ad-
Initially, the reaction between indole (1a) and di- justed the reaction parameters including reaction tem-
phenyl disulfide (2a) was chosen as a model reaction perature and the loading amount of NBS. At the ele-
to screen for the optimal reaction conditions vated temperatures, upon completion of the reaction,
significant levels of side products were found in the
product mixture, as indicated by TLC or GC-MS
Table 1. Screening for optimal reaction conditions.[a]
analysis. As a result, a decrease in the yield of 3a was
observed when the reaction was carried out at elevat-
ed temperatures (Table 1, entries 9 and 10). In con-
trast, we were pleased to discover that the yield of 3a
was dramatically improved at lower temperatures
(Table 1, entries 11–15). The results indicated that the
reaction could be conducted successfully to afford
a 93% yield of 3a in the presence of 3 equiv. of NBS
at À158C (Table 1, entries 15–18).
Entry Temp. [8C] Time [h] Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
25
25
25
25
25
25
25
25
50
80
0
À5
À10
À20
À15
À15
À15
À15
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
1.5
2.0
2.5
2.0
2.0
2.0
2.0
DMF
CH2Cl2
1,4-dioxane trace
NR[c]
trace
With the optimized reaction conditions in hand, the
scope and generality of the sulfenylation reaction was
investigated using several structurally diverse indoles
and disulfides. As shown in Table 2, a range of func-
tional groups, including methyl, methoxy, fluoro,
chloro, nitro and phenyl groups, was tolerated in this
procedure.
acetone
CH3CN
EtOH
DMSO
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
trace
14
17
39
67
52
43
72
78
9
10
11
12
13
14
15
16
17
18
First, we examined the reactions of indole (1a) with
different disulfides and the results are summarized in
Table 2. The electronic properties of the groups on
the phenyl ring of indoles had little effect on the reac-
tion. Generally, disulfides possessing electron-with-
drawing groups gave the corresponding 3-arylthioin-
doles with higher yields than their electron-donating
analogues (Table 2, entries 1–5). However, the steric
hindrance had an obvious impact on the yields of the
reaction. For example, the sulfenylation reactions of
indole (1a) with the para-, meta- and ortho-fluoro-
phenyl disulfides 2d, 2e and 2f, respectively, were ex-
amined. Isolated yields of 96 and 91% were obtained
for 3d and 3e were respectively, whereas the yield of
3f was much lower at 62% (Table 2, entries 4-6).
89
92
93
63[d]
81[e]
89[f]
[a]
Reaction conditions: 1a (0.42 mmol), 2a (0.2 mmol) and
NBS (3 equiv., loading amount based on 2a) in solvent
(3 mL).
Isolated yield.
Without NBS (NR=no reaction).
2 equiv. of NBS.
2.5 equiv. of NBS.
3.5 equiv. of NBS.
[b]
[c]
[d]
[e]
[f]
2
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A Metal-Free Sulfenylation and Bromosulfenylation of Indoles
Table 2. Sulfenylation of indoles with disulfides.[a]
Entry
Indole (1)
Disulfide (2)
R
Yield [%][b] (Product)
R1
R2
R3
1
H
H
H (1a)
Ph (2a)
93 (3a)
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
H
H
H
H
H
H
H
H
H
H
H
CH3
CH3
CH3
CH3
CH3
CH3
Ph
H
H
H
H
H
H (1a)
H (1a)
H (1a)
H (1a)
H (1a)
H (1b)
H (1b)
H (1b)
H (1c)
H (1c)
H (1c)
H (1c)
H (1c)
H (1d)
5-CH3 (1e)
6-CH3 (1f)
7-CH3 (1g)
5-MeO (1h)
6-F (1i)
p-MeC6H4 (2b)
p-ClC6H4 (2c)
p-FC6H4 (2d)
m-FC6H4 (2e)
o-FC6H4 (2f)
Ph (2a)
p-MeC6H4 (2b)
p-FC6H4 (2d)
Ph (2a)
p-MeC6H4 (2b)
p-ClC6H4 (2c)
p-FC6H4 (2d)
p-NO2C6H4 (2g)
Ph (2a)
84 (3b)
91 (3c)
96 (3d)
91 (3e)
62 (3f)
92 (3g)
81 (3h)
90 (3i)
H
CH3
CH3
CH3
H
H
H
H
H
H
H
97[c] (3j)
90[c] (3k)
85[c] (3l)
93[c] (3m)
98[c] (3n)
81[c] (3o)
92[d] (3p)
81[d] (3q)
93[d] (3r)
80[d] (3s)
68[d] (3t)
Ph (2a)
Ph (2a)
Ph (2a)
Ph (2a)
H
H
H
H
Ph (2a)
[a]
Reaction conditions: 1 (0.42 mmol), 2 (0.2 mmol) and NBS (0.6 mmol) in DMF (3 mL) for 2 h at À158C.
[b]
[c]
[d]
Isolated yield.
At room temperature.
At À108C.
Next, the sulfenylation reactions of disulfides with
several substituted indoles were explored. Pleasingly,
it was observed that N-containing heterocycle-substi-
tuted indoles, such as N-methylindole (1b) (Table 2,
entries 7–9), 2-methylindole (1c) and 2-phenylindole
(1d) (Table 2, entries 10–15) did not cause any diffi-
culties for this transformation.
Benzo-substituted indoles (1e–1h) possessing elec-
tron-donating groups on the phenyl ring provided the
corresponding 3-arylthioindoles (3p–3s) in good yields
(Table 2, entries 16–19). However, benzo-substituted
indoles containing an electron-withdrawing group on
the benzene ring, such as 6-fluoroindole (1i), afforded
the corresponding desired product 3t in 68% yield
(Table 2, entry 20), indicating a preference of the
Figure 1. X-ray structure of 3t.
À
À
methodology for electron-donating groups on benzo- actions via the one-pot construction of C S and C Br
substituted indoles. To further confirm the structure bonds in the presence of NBS. In the following stud-
of the product, an X-ray diffraction analysis was per- ies, the bromosulfenylation of 7-methylindole (1g)
formed. The crystal structure of compound 3t as a rep- with diphenyl disulfide (2a) was conducted as a model
resentative example is shown in Figure 1.[13a]
reaction to screen for optimal reaction conditions. As
NBS is well known as a highly useful and easy to expected, the product 2-bromo-7-methyl-3-phenyl-
handle brominating reagent.[14] Thus, we assumed that thioindole (4f) was observed by increasing the loading
a new family of 2-bromo-3-arylthioindoles (4) could amount of NBS at elevated temperature. We found
be generated by the sulfenylation and bromination re- that the yield increased dramatically to 87% only
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Figure 2. X-ray structure of 4f.
Scheme 2. Applications in organic synthesis. Reaction condi-
tions: (a) or (d) p-MeOC6H4B(OH)2 (1.3 equiv.), LiCl
(2 equiv.), Na2CO3 (2.5 equiv.), PdACHTNUTRGNEUGN(PPh3)4 (0.04 equiv.), tolu-
when 5 equiv. of NBS were added at room tempera-
ture. It is noteworthy that the structure of 4f was un-
ambiguously confirmed by an X-ray single-crystal dif-
fraction analysis (Figure 2).[13b]
ene/EtOH/H2O=1:1:1, 1108C, 24 h; (b) or (d) m-CPBA
(3 equiv.), CHCl3, À108C, 30 min.
Similarly, we explored the synthesis of several
structurally diverse 2-bromo-3-arylthioindoles (4). As action. The bromosulfenylation of indoles (1) with di-
shown in Table 3, the electronic properties of the sulfides (2) proceeded smoothly to afford the corre-
groups on the phenyl ring had little impact on the re- sponding desired 2-bromo-3-arylthioindoles (4a–4j) in
good yields. It is noteworthy that N-substituted in-
doles, such as N-methylindole, also gave the corre-
sponding desired products 4k and 4l in 78% and 81%
Table 3. Bromosulfenylation of indoles with disulfides.[a]
yields, respectively.
It is worthy of special mention that the above bro-
mosulfenylation products are a new family of 2-
bromo-3-arylthioindoles compounds 4 which leave the
À
C Br bond intact as an attractive handle for further
synthetic elaboration. Similarly, the organosulfide
compounds readily suffer oxidation. As shown in
Scheme 2, the coupling and oxidation reactions of the
product 4f, as a representative example, were exam-
ined under the previously reported reaction condi-
tions.[15,16] Pleasingly, 2-bromo-3-arylthioindole (4f)
smoothly underwent Suzuki coupling with p-methoxy-
phenylboronic acid[15] and oxidation reaction of sul-
fide,[16] affording the corresponding products 5 and 6
in 86 and 82% yields, respectively. As a result, the
two different methods have achieved their ultimate
purpose in the synthesis of the potentially pharmaco-
logically active[17] 2-aryl-3-phenylsulfonylindoles (7)
from the 2-bromo-3-arylthioindoles 4 starting materi-
al.
Furthermore, the present synthetic route to 3-ar-
ylthioindoles and 2-bromo-3-arylthioindoles was suc-
cessfully applied to the multigram-scale operations.
For instance, the sulfenylation and bromosulfenyla-
tion of indole (21 mmol, 2.475 g) with diphenyl disul-
fide (10 mmol, 2.18 g) provided the desired products
3a and 4a in 85% and 76% yields, respectively.
To elucidate the mechanism of the formation of 3-
arylthioindoles and 2-bromo-3-arylthioindoles, the fol-
lowing control experiments were performed
(Scheme 3). We found that 3-phenylthioindole was
not detected by TLC or GC-MS analysis from the re-
action of N-phenylthiosuccinimide[18] with 1g [Eq.
[a]
Reaction conditions: 1 (0.45 mmol), 2 (0.2 mmol) and
NBS (1.0 mmol) in DMF (3 mL) for 4 h at room temper-
ature. Isolated yields in parentheses.
For 6 h.
[b]
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A Metal-Free Sulfenylation and Bromosulfenylation of Indoles
the synthesis of 3-arylthioindoles (3). Finally, bromi-
nation of 3-arylthioindoles (3) gave the corresponding
2-bromo-3-arylthioindoles (4).
In summary, we have developed a metal-free
sulfenACHTNUTRGNEyUNG lation and bromosulfenylation of indoles with
disulfides, namely a controllable synthesis of the cor-
responding 3-arylthioindoles and 2-bromo-3-arylth-
ioindoles in moderate to excellent yields. The first re-
action (sulfenylation) is a useful complement to the
known literature protocols for preparing 3-arylthioin-
doles. The latter protocol (bromosulfenylation) gave
a new family of 2-bromo-3-arylthioindoles and pro-
vides a simple method for the one-pot construction of
Scheme 3. Control experiments.
À
À
C S and C Br bonds. Moreover, this technique also
avoids the formation of 1 equiv. of RS waste that
occurs when using a disulfide as the electrophilic
(1)]. Benzenesulfenyl bromide was not isolated but sulfur source. Efforts to explore the detailed mecha-
prepared in situ, predominantly because benzenesul- nism and further applications of the present system in
fenyl bromide is too reactive and unstable to be other transformations using disulfide as a reaction
stored.[19] These results showed that the reaction of partner are ongoing in our group.
benzenesulfenyl bromide with 1g proceeded smoothly
to afford the corresponding desired 3-arylthioindole
3r in 76% yield [Eq. (2)].[20] In contrast, 2-bromo-3- Experimental Section
phenylthioindole (4f) was obtained in 84% yield by
the bromination of 7-methyl-3-phenylthioindole (3r) General Experimental Procedure for the Synthesis of
[Eq. (3)].
3-Arylthioindoles (3)
On the basis of the above experimental results and
relevant reports in the literature,[19,20] a possible mech-
anism for the formation of 3-arylthioindoles (3) and
2-bromo-3-arylthioindoles (4) was established as out-
lined in Scheme 4. First, the role of NBS as a promoter
for the cleavage of disulfides 2 affords the reactive ar-
ylsulfenyl bromide (A) and N-(arylthio)succinimide
(B). The arylsulfenyl bromide (A) species subsequent-
ly undergoes facile sulfenylation with indoles 1, giving
the desired product 3-arylthioindoles (3) along with
a bromide anion. In the presence of NBS, the N-(ar-
ylthio)succinimide (B) can also be converted into the
reactive arylsulfenyl bromide (A) by reaction with
a bromide anion. As a result, the present process ena-
bles the use of both of the RS moieties in RSSR,
which represents an atom-economical procedure for
A mixture of indole 1 (0.42 mmol), disulfide 2 (0.2 mmol),
and NBS (0.6 mmol) in DMF (3 mL) was stirred for 2 h at
the respective temperature given in Table 2. After the com-
pletion of the reaction, as monitored by TLC and GC-MS
analysis, the reaction mixture washed with water and ex-
tracted with ethyl acetate. The organic phase was separated
and dried over anhydrous magnesium sulfate and filtered.
The filtrate was concentrated and the resulting residue was
purified by flash column chromatography on silica gel (300–
400 mesh) with petroleum ether-EtOAc as eluent to provide
the products 3.
General Experimental Procedure for the Synthesis of
2-Bromo-3-arylthioindoles (4)
A mixture of indole 1 (0.45 mmol), disulfide 2 (0.2 mmol),
and NBS (1.0 mmol) in DMF (3 mL) was stirred for 4 h at
room temperature as stated in Table 3. After the completion
of the reaction, as monitored by TLC and GC-MS analysis,
the reaction mixture washed with water and extracted with
ethyl acetate. The organic phase was separated and dried
over anhydrous magnesium sulfate and filtered. The filtrate
was concentrated and the resulting residue was purified by
flash column chromatography on silica gel (300–400 mesh)
with petroleum ether-EtOAc as eluent to provide the prod-
ucts 4.
Acknowledgements
We thank the National Natural Science Foundation of China
(Nos. 21102105 and 21172175) for financial support.
Scheme 4. Plausible mechanism.
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References
[9] a) Y. J. Guo, R. Y. Tang, J. H. Li, P. Zhong, X. G.
Zhang, Adv. Synth. Catal. 2009, 351, 2615; b) Z. Li, L.
Hong, R. Liu, J. Shen, X. Zhou, Tetrahedron Lett. 2011,
52, 1343.
[10] a) Y. Chen, C.-H. Cho, R. C. Larock, Org. Lett. 2009,
11,173; b) Y. Chen, C.-H. Cho, F. Shi, R. C. Larock, J.
Org. Chem. 2009, 74, 6802.
[11] Only one example has described the copper-catalyzed
bromosulfenylation of alkynes for the synthesis of bro-
moalkenyl sulfides. See: N. Taniguchi, Synlett 2008, 849.
[12] a) W. Guo, J. Chen, D. Wu, J. Ding, F. Chen, H. Wu,
Tetrahedron 2009, 65, 5240; b) W. Dan, H. Deng, J.
Chen, M. Liu, J. Ding, H. Wu, Tetrahedron 2010, 66,
7384.
[13] CCDC 851461 and CCDC 851462 contain the supple-
mentary crystallographic data for 3t and 4f, respective-
ly.These data can be obtained free of charge from The
[1] a) P. Kielbasinski, Phosphorus, Phosphorus Sulfur Sili-
con Relat. Elem. 2011, 186, 1104; b) J. J. Voss, Sulfur
Chem. 2009, 30, 167; c) M. Nawaz, M. Sher, P. Langer,
Synlett 2010, 2383; d) T. Toru, C. Bolm, Angew. Chem.
2009, 121, 2112; Angew. Chem. Int. Ed. 2009, 48, 2078;
e) P. Page, Organosulfur Chemistry: Synthetic Aspects,
Academic Press, London, 1995.
[2] a) R. J. Sundberg, Indoles, Academic Press, New York,
1996; b) R. Ragno, A. Coluccia, G. La Regina, G. De
Martino, F. Piscitelli, A. Lavecchia, E. Novellino, A.
Bergamini, C. Ciaprini, A. Sinistro, G. Maga, E. Cre-
span, M. Artico, R. Silvestri, J. Med. Chem. 2006, 49,
3172; c) A. J. Kochanowska-Karamyan, M. T. Hamann,
Chem. Rev. 2010, 110, 4489; d) D. Crich, A. Banerjee,
Acc. Chem. Res. 2007, 40, 151.
[3] a) G. De Martino, M. C. Edler, G. La Regina, A. Co-
luccia, M. C. Barbera, D. Barrow, R. I. Nicholson, G.
Chiosis, A. Brancale, E. Hamel, M. Artico, R. Silvestri,
J. Med. Chem. 2006, 49, 947; b) G. De Martino, G. La
Regina, A. Coluccia, M. C. Edler, M. C. Barbera, A.
Brancale, E. Wilcox, E. Hamel, M. Artico, R. Silvestri,
J. Med. Chem. 2004, 47, 6120.
[4] G. La Regina, A. Coluccia, A. Brancale, F. Piscitelli, V.
Gatti, G. Maga, A. Samuele, C. Pannecouque, D.
Schols, J. Balzarini, E. Novellino, R. Silvestri, J. Med.
Chem. 2011, 54, 1587.
[5] a) J. A. Campbell, C. A.; Broka, L. Gong, K. A. M.
Walker, J.-H. Wang, Tetrahedron Lett. 2004, 45, 4073;
b) Y. Maeda, M. Koyabu, T. Nishimura, S. Uemura, J.
Org. Chem. 2004, 69, 7688; c) K. M. Schlosser, A. P.
Krasutsky, H. W. Hamilton, J. E. Reed, K. Sexton, Org.
Lett. 2004, 6, 819; d) J. S. Yadav, B. V. S. Reddy, Y. J.
Reddy, Tetrahedron Lett. 2007, 48, 7034; e) P. Barraja,
P. Diana, A. Carbone, G. Cirrincione, Tetrahedron
2008, 64, 11625; f) J. S. Yadav, B. S. Reddy, Y. J. Reddy,
K. Praneeth, Synthesis 2009, 1520.
[6] a) J. G. Atkinson, P. Hamel, Y. Girard, Synthesis 1988,
480; b) R. Sanz, V. Guilarte, M. P. Castroviejo, Synlett
2008, 3006; c) X. L. Fang, R. Y. Tang, P. Zhong, J. H.
Li, Synthesis 2009, 4183; d) Z. Li, L. Hong, X. Zhou,
Tetrahedron 2011, 67, 3690.
Cambridge
Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[14] a) F. Mo, J. M. Yan, D. Qiu, F. Li, Y. Zhang, J. Wang,
Angew. Chem. 2010, 122, 2072; Angew. Chem. Int. Ed.
2010, 49, 2028; b) M. Jiang, Y. Wei, M. Shi, J. Org.
Chem. 2010, 75, 2528; c) R. B. Bedford, M. F. Haddow,
C. J. Mitchell, R. L. Webster, Angew. Chem. 2011, 123,
5638; Angew. Chem. Int. Ed. 2011, 50, 5524; d) P.
Zhang, R. Liu, J. M. Cook, Tetrahedron Lett. 1995, 36,
3103; e) M. Hussain, ꢂ. T. Tꢃng, P. Langer, Synlett
2009, 1822.
[15] R. Silvestri, G. De Martino, G. La Regina, M. Artico, S.
Massa, L. Vargiu, M. Mura, A. G. Loi, T. Marceddu, P.
La Colla, J. Med. Chem. 2003, 46, 2482.
[16] P. L. Beaulieu, J. Gillard, D. Bykowski, C. Brochu, N.
Dansereau, J. Duceppe, B. Hachꢄ, A. Jakalian, L.
Lagacꢄ, S. LaPlante, G. McKercher, E. Moreau, S. Per-
reault, T. Stammers, L. Thauvette, J. Warrington, G.
Kukolj, Bioorg. Med. Chem. Lett. 2006, 16, 4987.
[17] a) H. Shirani, B. Stensland, J. Bergman, T. Janosik, Syn-
lett 2006, 2459; b) R. Silvestri, M. Artico, G. De Marti-
no, G. La Regina, R. Loddo, M. La Colla, P. La Colla,
J. Med. Chem. 2004, 47, 3892; c) G. De Martino, G. L.
Regina, A. Coluccia, M. C. Edler, M. C. Barbera, A.
Brancale, E. Wilcox, E. Hamel, M. Artico, R. Silvestri,
J. Med. Chem. 2004, 47, 6120.
[7] a) M. Tudge, M. Tamiya, C. Savarin, G. R. Humphrey,
Org. Lett. 2006, 8, 565; b) C. C. Silveira, S. R. Mendes,
L. Wolf, G. M. Martins, Tetrahedron Lett. 2010, 51,
2014.
[18] N-Phenylthiosuccinimide was isolated when PhSSPh
was reacted with NBS. See: C. B. Reese, U.S. Patent
0,099,981, 2003; Chem. Abstr. 1995, 123, 2870.
[8] a) M. Matsugi, K. Gotanda, K. Murata, Y. Kita, Chem.
Commun. 1997, 1387; b) M. Matsugi, K. Murata, K.
Gotanda, H. Nambu, Y. Kita, Tetrahedron Lett. 2001,
42, 1077; c) M. Matsugi, K. Murata, K. Gotanda, H.
Nambu, G. Anilkumar, K. Matsumoto, Y. Kita, J. Org.
Chem. 2001, 66, 2434.
[19] a) A. J. Bridges, J. W. Fischer, J. Org. Chem. 1984, 49,
2954; b) P. B. Hopkins, P. L. Fuchs, J. Org. Chem. 1978,
43, 1208.
[20] a) P. Hamel, P. Prꢄville, J. Org. Chem. 1996, 61, 1573;
b) P. Hamel, J. Org. Chem. 2002, 67, 2854.
6
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A Metal-Free Sulfenylation and Bromosulfenylation of
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