MnCl2·4H2O-catalyzed potential protocol for the synthesis of aryl/vinyl sulfides

Article abstract of DOI:10.1246/cl.2010.1149

MnCl₂ · 4H₂O is described as an efficient catalytic system for the cross coupling of aryl/vinyl halides with thiols using KOH as base and DMSO as solvent. By using this new catalytic system various aryl/vinyl sulfides were synthesize

Full text of DOI:10.1246/cl.2010.1149

doi:10.1246/cl.2010.1149
Published on the web October 5, 2010
1149
MnCl2¢4H2O-catalyzed Potential Protocol for the Synthesis of Aryl/Vinyl Sulfides
Madhav Bandaru, Narayana Murthy Sabbavarpu, Ramesh Katla, and Venkata Durga Nageswar Yadavalli*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 607, India
(Received August 20, 2010; CL-100721; E-mail: yvdnrao@iict.res.in)
MnCl2¢4H2O is described as an efficient catalytic system for
the cross coupling of aryl/vinyl halides with thiols using KOH
as base and DMSO as solvent. By using this new catalytic
system various aryl/vinyl sulfides were synthesized in moderate
to good yields. Retention of stereochemistry is observed in the
case of vinyl sulfides.
O
O
N
O
O
Ph
Ph
H2N
HO
NH2
L3
L1
L2
N
HN
NH
OH
L4
L5
Organosulfur compounds are valuable motifs and find many
applications in organic chemistry.1 Among these, aryl/vinyl
sulfides are important and attract much interest due to their
biological/therapeutical2 activity. We can find aryl sulfide
moieties in many drugs which are being used in the treatment
of various diseases like diabetes, Alzheimer’s, Parkinson’s,3
cancer,4 and HIV.1b In synthetic organic chemistry vinyl sulfides
have widespread utility as enolate ion equivalents,5 Michael
acceptors6 and key intermediates in the preparation of oxetanes.7
In view of their significance, many methods have been
developed for the synthesis of aryl/vinyl sulfides.8,9 Among
the existing methodologies in practical organic synthesis, cross
coupling of aryl/vinyl halides with thiols is the most commonly
used strategy for the synthesis of aryl/vinyl sulfides. Recently
Xu et al. synthesized aryl sulfides by using CuI as catalyst and
KF/Al2O3 as base.8n
Though the existing strategies are efficient in their own way,
there are some drawbacks such as the use of moisture-sensitive
catalysts/reagents which cause major problems in purification of
the products and separation of the metal catalyst. In view of this,
developing a simple, novel, and practicable catalytic system for
the cross coupling of aryl/vinyl halides with thiols is desirable.
We have undertaken studies to arrive at the present catalytic
system, which can be more useful and affordable, for the
synthesis of aryl/vinyl sulfides.
L6
Figure 1. Screening of ligands for optimized conditions.
Table 1. Screening study of bases and solventsa
Entry
Base
Solvent
Yieldb/%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
K3PO4
K3PO4
K3PO4
K2CO3
K2CO3
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
KOH
PhMe
DMF
DMSO
PhMe
DMF
DMSO
PhMe
DMF
DMSO
PhMe
DMF
0
35
42
0
trace
57
0
trace
63
trace
58
32c
82
0
KOH
KOH
KOH
KOH
DMSO
DMSO
Water
DMSO
none
0
aReaction conditions: iodobenzene (1.2 mmol), benzenethiol
(1.0 mmol), MnCl2¢4H2O (15 mol %), base (1.5 equiv), sol-
b
c
vent (2.0 mL), 110 °C, 24 h. Isolated yield. At 70 °C.
Literature survey indicates increased use of Mn as a catalyst
in many coupling reactions10 as it is economically affordable,
easily available, and environmentally benign compared to other
transition metals. Over the past, Pd,8c,11 Ni,8s,12 Cu,9f,13 Fe,14
In,8m and La15 catalysts were explored for C-S cross-coupling
reactions. However, there have been no reports on manganese-
catalyzed C-S cross-coupling reactions so far. To the best of our
knowledge we report herein for the first time C-S cross-coupling
reaction mediated by MnCl2¢4H2O, in continuation of our work
toward new catalytic systems15 for organic transformations. The
present approach will be a promising protocol as it avoids the
use of co-metals and additives as well as complicated work-up
procedures.
Iodobenzene and benzenethiol were reacted as model
substrates in the study toward the development of MnCl2¢
4H2O-catalyzed cross-coupling reactions. Initially, the ligand
screening was taken up (Figure 1) and among different ligands
L5 gave desired product in 35% yield after 24 h in the presence
of K3PO4 and DMF. L1 and L2 did not influence the reaction
Ph-SH
I
SPh
·
MnCl2 4H2O(15 mol%)
TMEDA, DMSO, KOH
110 °C, 24h
Scheme 1. Cross coupling of aryl halides with thiols.
whereas the rest of the ligands had little impact. Encouraged by
this result, the efficiency of different bases such as K2CO3,
Cs2CO3, and KOH in the presence of various solvents like
toluene, water, DMSO, and DMF (Table 1), was evaluated.
DMSO proved to be the best among different solvents
studied. KOH played a significant role in taking forward the
reaction whereas the remaining bases were comparatively less
effective. The combination of KOH/TMEDA and DMSO
evolved out as promising, resulting in high yields (Scheme 1
and Table 1, Entry 13). In the absence of MnCl2¢4H2O or KOH,
Chem. Lett. 2010, 39, 1149-1151
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1150
Table 2. Coupling of aryl halides with thiolsa
Table 3. Coupling of vinyl halides with thiolsa
Entry Vinyl iodide
Thiol
SH
Product
S
Yieldb/%
Entry
Aryl iodide
X
Thiol
HS
Product
S
Yieldb/%
X
76
25 (Br)
82
1
1
2
3
X= I, Br
X = I, Br
25 (Br)
I
S
SH
HS
HS
HS
I
S
2
3
72
71
74
75
F
F
SH
S
I
S
S
I
MeO
Cl
OMe
Cl
SH
S
I
I
I
I
4
5
72
71
77
4
5
6
7
8
73
74
72
OMe
OMe
S
S
SH
SH
S
HS
HS
MeO
F
MeO
F
I
S
I
6
7
Ph
Ph
X
S
64
I
HS
HS
S
S
S
SH
SH
SH
76
75
24 (Br)
X= I, Br
I
S
I
60
0
8
9
O
O
O
O
X
70
9
C4H9
C4H9SH
I
SPh
25 (Br)
X = I, Br
I
S
C5H11
aReaction conditions: trans-¢-iodostyrene (1.2 mmol), thiol
(1.0 mmol), catalyst (15 mol %), KOH (1.5 equiv), L5
(1 mol %), DMSO (2.0 mL) at 110 °C, 15 h. Isolated yield.
10
C5H11SH
68
65
62
I
S
SH
SH
b
11
12
I
S
conditions (Tables 2 and 3). However, lower yields were
observed in the coupling reaction of aryl bromide or trans-¢-
bromo-styrenes and different thiols compared to aryl/vinyl
iodides respectively. Furthermore, retention of stereochemistry
is observed in the case of vinyl halides.
aReaction conditions: aryl halides (1.2 mmol), thiol (1.0
mmol), MnCl2¢4H2O (15 mol %), KOH (1.5 equiv), L5
(1 mol %), DMSO (2.0 mL) at 110 °C, 24 h. Isolated yield.
b
In conclusion, we have developed an active, moisture-
stable, inexpensive, and nontoxic catalytic system for the
synthesis of aryl/vinyl sulfides in good yields. The catalytic
system consists of catalytic amount of MnCl2¢4H2O, KOH as
base, and TMEDA as a ligand in DMSO solvent.
Ph-SH
·
MnCl2 4H2O(15 mol%)
I
SPh
R
R
TMEDA,DMSO, KOH
110 °C, 15h
References and Notes
Scheme 2. Cross coupling of vinyl halides with thiols.
1
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no reaction took place even at elevated temperatures and longer
reaction times.
In general, all the reactions were clean, and the aryl sulfides
were obtained in high yields under the optimized conditions.16
The scope of the catalytic system was evaluated by carrying out
the study of various aryl halides and benzenethiols. Electron-
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2
Encouraged by these results, we extended the MnCl2¢
4H2O-catalyzed cross-coupling reaction to vinyl halides also
(Scheme 2). It was observed that the reaction time was reduced
to 15 h. The catalytic system worked well for both electron-rich
and electron-poor vinyl iodides with various benzenethiols.
There was no significant effect of substituents when present on
vinyl halides. Coupling of vinyl halides with aliphatic/cyclic
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9
Chem. Lett. 2010, 39, 1149-1151
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www.csj.jp/journals/chem-lett/