Hydrothiolation of unactivated alkynes catalyzed by indium(III) bromide

Article abstract of DOI:10.1246/cl.2007.1474

Indium(III) bromide is found to catalyze efficiently the hydrothiolation of unactivated alkynes with various thiols under mild conditions to produce the corresponding dithioacetals in excellent yields. However, addition of aromatic thiols on aromatic alky

Full text of DOI:10.1246/cl.2007.1474

1474
Chemistry Letters Vol.36, No.12 (2007)
Hydrothiolation of Unactivated Alkynes Catalyzed by Indium(III) Bromide
J. S. Yadav,Ã B. V. Subba Reddy, A. Raju, K. Ravindar, and Gakul Baishya
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
(Received August 20, 2007; CL-070881; E-mail: yadavpub@iict.res.in)
Indium(III) bromide is found to catalyze efficiently the hy-
drothiolation of unactivated alkynes with various thiols under
mild conditions to produce the corresponding dithioacetals in ex-
cellent yields. However, addition of aromatic thiols on aromatic
alkynes gave the ꢀ-vinyl sulfides in high yields. This new proce-
dure offers significant advantages such as high conversions,
short reaction times, and simplicity in operation.
reactions of thiols with various alkynes. Interestingly, aromatic
thiols such as benzenethiol, p-thiocresol, and naphthalene-2-
thiol reacted readily with 1-octyne to produce the corresponding
dithioacetals (Entries A–E, Table 1). Like aromatic thiols, ali-
phatic thiols such as n-butanethiol and ethanethiol also under-
Table 1. Hydrothiolation of alkynes with thiols using 10 mol %
of indium(III) bromide in dichloromethane
Entry
Thiol
Alkyne
Producta
Time/min
Yield/%b
1
2
3
The sulfur-containing natural products and synthetic materi-
als coupled with the utility of sulfur-based reagents in synthetic
organic chemistry illustrates the need for efficient and versatile
strategies for the construction of sulfur-containing molecules.1
Consequently, various synthetic methods have been developed
for the conversion of alkynes into a variety of sulfur-containing
compounds by hydrothiolation.2 The hydrothiolation is one of
the most attractive methods for the formation of disulfides and
ꢀ-vinyl sulfides, which are valuable as synthetic intermediates
in total synthesis and as precursors to a wide range of function-
alized molecules. As a result, several methods such as radical,
nucleophilic, and metal-catalyzed hydrothiolation using aryl-
and alkyl-thiols have been reported under various reaction
conditions.3–6 In addition, hydrothiolation of activated alkynes
by thiols has also been reported to furnish 1,1-disulfides (di-
thianes).7 However, there have been no reports on hydrothiola-
tion of unactivated alkynes with aryl- and alkylthiols.
Recently, indium tribromide has received increasing atten-
tion as a water-tolerant green Lewis acid catalyst for various or-
ganic transformations demonstrating highly chemo-, regio-, and
stereoselective results.8 Compared to conventional Lewis acids,
it has advantages of water stability, recyclability, operational
simplicity, strong tolerance to oxygen- and nitrogen-containing
substrates and functional groups, and it can often be used in cat-
alytic amounts.
In continuation of our interest on the catalytic use of
indium(III) reagents for various organic transformations,9 we
herein disclose a mild and efficient methodology for the hydro-
thiolation of unactivated alkynes using indium(III) bromide
as the novel catalyst. Initially, we attempted the nucleophilic ad-
dition of benzenethiol (1) onto 3-phenyl-1-propyne (2) in the
presence of 10 mol % of indium(III) bromide. The reaction pro-
ceeded rapidly at room temperature to produce [2,2-di(phenyl-
sulfanyl)propyl]benzene (3A) in 96% yield (Scheme 1,
Entry A, Table 1). Similarly, 4-phenyl-1-butyne was also partici-
pated well in this reaction (Entry B, Table 1). The remarkable
catalytic activity of InBr3 provided the incentive for further
SH
PhS
SPh
A
B
20
25
96
98
Ph
Ph
SH
SH
PhS
SPh
SPh
Ph
Ph
PhS
n-C6H13
C
D
25
20
98
96
n-C6H13
n-C6H13
SH
SH
S
S
S
n-C6H13
E
F
25
20
95
98
n-C6H13
S
n-C6H13
SH
SH
S
S
n-C6H13
n-C5H11
n-C6H13
PhS SPh
n-C5H11
G
H
20
25
95
98
SH
SH
S
S
n-C5H11
n-C5H11
n-C5H11
I
20
30
96
98
S
S
S
n-C5H11
S
SH
SH
J
n-C5H11
n-C5H11
n-C5H11
n-C4H9
K
L
25
30
95
96
S
S
S
n-C5H11
S
SH
SH
n-C4H9
PhS SPh
n-C4H9
n-C4H9
n-C4H9
M
N
20
25
96
98
SH
S
S
n-C4H9
S
SH
SH
O
P
25
20
20
96 (7:3)c
S
94 (6:4)c
95 (7:3)c
92 (6:4)c
S
S
SH
SH
Q
R
30
Cl
Cl
SPh
SH
SH
S
T
20
15
90
92
Ph
Ph
Ph
O
SPh
O
OEt
OEt
SPh
SPh
SPh
10 mol % InBr3
CH2Cl2, R.T.
SH
1
+
aAll the products were characterized by H NMR, IR, and mass
spectrometry. Yield refers to pure products after chromatogra-
Ph
b
1
2
3A
c
1
phy. E/Z ratio was determined by H NMR spectrum of crude
product.
Scheme 1.
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.12 (2007)
1475
In summary, we have developed a rapid and efficient proto-
col for the preparation of dithioacetals and ꢀ-vinyl sulfides from
alkynes and thiols using indium(III) bromide as a novel catalyst.
The notable features of this procedure are mild reaction condi-
tions, high to quantitative yields, operational simplicity, cleaner
reaction profile, and very short reaction times, which make
it a useful and attractive strategy for the direct conversion of
aliphatic alkynes to dithioacetals.
10 mol% InBr3
SH
S
+
CH2Cl2, R.T.
3O
E/Z = 7:3
Scheme 2.
Table 2. The effects of various indium(III) reagents for the
preparation of 3A
AR, KR, and GB thank CSIR New Delhi for the award of
fellowships.
Catalyst
(10 mol %)
Entry
Conditions
Time/min Yield/%a
1
2
3
4
5
5
5
5
InCl3
CH2Cl2, R.T.
CH2Cl2, R.T.
CH2Cl2, R.T.
H2O, R.T.
CH2Cl2, R.T.
MeOH, R.T.
CH3CN, R.T.
Et2O, R.T.
30
30
30
30
30
30
30
30
70
60
40
0
96
20
80
30
References
In(OTf)3
In(ClO4)3
InBr3
InBr3
InBr3
1
Sulfur Reagents in Organic Synthesis, Academic Press, New
York, 1994; Perspectives in Organic Chemistry of Sulfur,
Elsevier, Amsterdam, 1987; Transition Metal Sulfur Chem-
istry: Biological and Industrial Significance, ed. by E. I.
Stiefel, K. Matsumoto, ACS Symposium Series 653, Amer-
ican Chemical S, Washington, DC, 1996.
InBr3
InBr3
2
3
4
The Chemistry of the Thiol Group, ed. by S. Patai, Wiley,
London, 1974, Vol. 2.
W. E. Truce, H. E. Hill, M. M. Boudakian, J. Am. Chem. Soc.
1956, 78, 2760.
H. Kuniyasu, A. Ogawa, K. Sato, I. Ryu, N. Kambe, N.
Sonoda, J. Am. Chem. Soc. 1992, 114, 5902; J.-E. Baeckvall,
A. Ericsson, J. Org. Chem. 1994, 59, 5850; L.-B. Han, C.
Zhang, H. Yazawa, S. Shimada, J. Am. Chem. Soc. 2004,
126, 5080.
aYield refers to pure product after chromatography.
went smooth addition onto alkynes (Entries F, J, and L, Table 1).
In addition to this, aliphatic alkynes such as 1-heptyne and
1-hexyne were participated efficiently in this reaction
(Entries G–N, Table 1). Subsequently, we have investigated
the reaction of aromatic thiols with aromatic alkynes. Unlike ali-
phatic alkynes, the reaction of aromatic alkynes with aromatic
thiols in the presence of 10 mol % of indium(III) bromide gave
vinylic sulfides as a mixture of E/Z isomers favoring E isomer.
For example, treatment of phenylacetylene with benzenethiol
gave (E)-phenyl(styryl)sulfane (3O) as a mixture of E/Z isomers
in 7:3 ratios (Entry O, Scheme 2, Table 1).
The (E/Z) ratio of the products was determined by the
1H NMR spectrum of the crude product. Similarly, substituted
benzenethiols reacted well to give the corresponding vinylic sul-
fides (Entries P–T, Table 1). However, treatment of diphenylace-
tylene with benzenethiol for 30 min afforded 1,2-disulfide in
90% yield (Entry S, Table 1). Furthermore, the reaction of
ethyl 1-phenylpropiolate with benzenethiol gave mono-adduct
(Entry T, Table 1). In all cases, the reactions proceeded rapidly
at room temperature with high efficiency. To compare the
selectivity, phenylacetylene was treated with benzenethiol in
the presence of various catalysts. The exomethylene products
are obtained when using transition metals such as Ni(acac)2,
Pd(OAc)2, or PdCl2(PhCN)2 arising from the Markovnikov-type
addition. By using 10 mol % of InBr3, anti-Markovnikov-type,
ꢀ-vinyl sulfides are obtained with excellent regioselectivity. In
the absence of catalyst, no reaction was observed even after long
reaction times (10–20 h). As solvent, dichloromethane gave the
best results. The scope and generality of this process is illustrat-
ed in Table 1. The effects of various indium(III) catalysts such as
InBr3, InCl3, In(OTf)3, and In(ClO4)3 were tested and the results
are presented in Table 2. Of these catalysts, InBr3 was found to
be the most effective in terms reaction time and conversion.
5
6
A. Ogawa, T. Ikeda, K. Kimura, T. Hirao, J. Am. Chem. Soc.
1999, 121, 5108; S. Burling, L. D. Field, B. A. Messerle,
K. Q. Vuong, P. Turner, Dalton Trans. 2003, 4181.
S.-I. Usugi, H. Yorimitsu, H. Shinokubo, K. Oshima, Org.
Lett. 2004, 6, 601; V. P. Ananikov, N. V. Orlov, I. P.
Beletskaya, Organometallics 2006, 25, 1970; Y. Misumi,
H. Seino, Y. Mizobe, J. Organomet. Chem. 2006, 691, 3157.
H. F. Sneddon, A. van den Heuvel, A. K. H. Hirsch, R. A.
Booth, D. M. Shaw, M. J. Gaunt, S. V. Ley, J. Org. Chem.
2006, 71, 2715.
V. Nair, S. Ros, C. N. Jayan, B. S. Pillai, Tetrahedron 2004,
60, 1959; G. Tocco, M. Begala, G. Delogu, C. Picciau,
G. Podda, Tetrahedron Lett. 2004, 45, 6909; M. Bandini,
P. G. Cozzi, P. Melchiorre, A. Umani-Ronchi, Tetrahedron
Lett. 2001, 42, 3041; M. A. Ceschi, L. A. Felix, C. Peppe,
Tetrahedron Lett. 2000, 41, 9695; M. Bandini, P. G. Cozzi,
M. Giocomini, P. Mechiorre, S. Selva, A. Umani-Ronchi,
J. Org. Chem. 2002, 67, 3700.
7
8
9
J. S. Yadav, B. V. S. Reddy, A. D. Krishna, T. Swamy,
Tetrahedron Lett. 2003, 44, 6055; J. S. Yadav, B. V. S.
Reddy, A. K. Raju, C. V. Rao, Tetrahedron Lett. 2002, 43,
5437; J. S. Yadav, B. V. S. Reddy, Synthesis 2002, 511;
J. S. Yadav, B. V. S. Reddy, G. Bhaishya, Green Chem.
2003, 5, 264; J. S. Yadav, B. V. S. Reddy, K. V. Rao,
K. S. Raj, A. R. Prasad, S. K. Kumar, A. C. Kunwar, P.
Jayaprakash, B. Jagannath, Angew. Chem., Int. Ed. 2003,
42, 5198.
Published on the web (Advance View) November 17, 2007; doi:10.1246/cl.2007.1474