Indium tribromide: A novel and highly efficient reagent for the conversion of oxiranes to thiiranes

Article abstract of DOI:10.1055/s-2003-37103

Epoxides react smoothly with potassium thiocyanate in the presence of 5 mol% of indium tribromide under mild and convenient reaction conditions to afford the corresponding thiiranes in high yields. This method is compatible with a wide range of protecting groups and functional groups such as alkenes, alkynes, esters, THP, TBDMS, and PMB ethers present in the molecule.

Full text of DOI:10.1055/s-2003-37103

396
LETTER
Indium Tribromide: A Novel and Highly Efficient Reagent for the Conversion
of Oxiranes to Thiiranes
I
ndium Tr
.
ibromide S. Yadav,* B. V. S. Reddy, Gakul Baishya
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax +91(40)27160512; E-mail: yadav@iict.ap.nic.in
Received 19 December 2002
Compared to conventional Lewis acids, indium halides
Abstract: Epoxides react smoothly with potassium thiocyanate in
the presence of 5 mol% of indium tribromide under mild and con-
venient reaction conditions to afford the corresponding thiiranes in
high yields. This method is compatible with a wide range of protect-
have advantages of water stability, recyclability and oper-
ational simplicity. In particular, indium tribromide is
found to be a more effective catalyst than conventional
ing groups and functional groups such as alkenes, alkynes, esters, Lewis acids in promoting various transformations such as
THP, TBDMS, and PMB ethers present in the molecule.
glycosidation, thioacetalization, cyanation of ketones, and
conjugate addition reactions.9,10 However, there are no ex-
Key words: indium reagents, oxiranes, thiocyanate, thiiranes
amples on the use of indium halides for the conversion of
oxiranes to episulfides.
Epoxides are well known carbon electrophiles capable of
reacting with various nucleophiles and their ability to un-
dergo regioselective ring opening reactions contributes
largely to their synthetic value.1 The epoxide ring opening
with certain nucleophiles is generally carried out using ei-
ther acid or base catalysis to produce ring opened prod-
ucts. A variety of methods has been developed for the
preparation of thiiranes.2 One of the most straightforward
synthetic procedures for the preparation of thiiranes is the
condensation of oxiranes with inorganic thiocyanates
such as potassium and ammonium thiocyanates3 or
thiourea in water or in aqueous alcohols.4 Potassium
thiocyanate has been the most widely used reagent for
this transformation. Other reagents such as phosphine sul-
fide,5 3-methylbenzothiazol-2-thione,6 dimethylthioform-
amide7 in the presence of trifluoroacetic acid have been
reported to produce thiiranes from oxiranes. However,
many of these methods often involve the use of stoichio-
metric amounts of the reagents, extended reaction times
and strongly acidic or oxidizing conditions and also entail
undesirable side reactions due to the rearrangement or po-
lymerization of oxiranes resulting in low yields of thi-
iranes especially in case of cyclohexene episulfide,
styrene episulfide and other higher thiiranes. Further-
more, most of these methods are of limited synthetic
scope when applied to multifunctional compounds. Since
organic sulfur compounds have become increasingly use-
ful and important in organic synthesis, the development of
convenient and practical methods for the preparation of
thiiranes especially those, which carry acid labile func-
tional groups, are desirable.
We herein report that indium tribromide is a remarkable
Lewis acid catalyst for the synthesis of thiiranes from ox-
iranes and potassium thiocyanate under mild conditions.
Thus treatment of 2-phenoxymethyloxirane with potassi-
um thiocyanate in the presence of 5 mol% InBr3 in aceto-
nitrile afforded the corresponding 2-phenoxymethyl-
thiirane in 95% yield (Scheme 1).
Scheme 1
A variety of epoxides were converted to their correspond-
ing thiiranes using this procedure. The reactions proceed-
ed smoothly in acetonitrile at 60 °C to afford the thiiranes
in excellent yields with high selectivity. The reaction con-
ditions are mild enough not to induce isomerization of C-
C multiple bonds during the preparation of thiiranes bear-
ing allylic and propagylic functionalities and are selective
enough to convert oxiranes to thiiranes in the presence of
acid sensitive protecting groups which are difficult to
achieve under conventional conditions where protic acids
i.e. trifluoroacetic acid as well as strong Lewis acids are
employed. Furthermore, the reactions are clean and high
yielding and no side products are observed. We have stud-
ied the catalytic efficiency of various Lewis acids such as
InBr3, InCl3, CeCl3, Ce(OTf)3, In(OTf)3, Sc(OTf)3 and
Yb(OTf)3 for this transformation. Among these catalysts,
indium tribromide (5 mol%) was found to be effective in
terms of conversion and functional group selectivity. Al-
though, the reactions proceeded smoothly at ambient tem-
perature with a catalytic amount of indium triflate or
scandium triflate, protecting groups such as silyl ethers,
tetrahydropyranyl ethers and p-methoxybenzyl ethers are
deprotected by these metal triflates; whereas, with 5
In recent years, indium halides have evolved as mild and
water-tolerant Lewis acids imparting high regio-, stereo-
and chemoselectivity in various organic transformations.8
Synlett 2003, No. 3, Print: 19 02 2003.
Art Id.1437-2096,E;2002,0,02,0396,0398,ftx,en;D19302ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Indium Tribromide: A Reagent for the Conversion of Oxiranes to Thiiranes
397
Table Indium Halides-Catalyzed Conversion of Epoxides to Thioranes Using KSCN11
Entry
Epoxide
Producta
5% InBr3
10% InCl3
CH3CNc
1
2
Time (h)
3.0
Yield (%)b
90
Time (h)
4.5
Yield (%)b
89
Time (h)
10.5
Yield (%)b
a
48
b
3.5
92
4.0
87
10.5
55
c
3.0
4.0
89
87
3.5
5.0
84
85
11.5
9.5
45
38
d
e
f
3.0
3.5
4.5
3.0
4.5
5.0
4.0
93
95
90
92
94
91
92
4.0
4.5
5.5
4.5
5.5
6.0
5.0
90
92
88
90
91
89
90
12.0
11.0
13.0
15.0
12.5
11.0
15.0
51
57
33
55
42
49
35
g
h
i
j
k
l
3.5
3.5
3.0
4.5
89
80
82
95
4.5
4.0
3.0
5.5
87
83
85
91
14.0
12.0
11.0
16.5
41
39
45
51
m
n
o
a All products were characterized by 1H NMR, IR and mass spectroscopy.
b Isolated and unoptimized yields.
c Reactions were carried out in refluxing acetonitrile.
mol% of indium tribromide, the acid sensitive protecting Acknowledgement
groups such as THP, TBDMS, PMB ethers and esters sur-
B. V. S thanks CSIR New Delhi for the award of fellowship.
vived (Table). Thus, the indium halide catalyzed proce-
dure is mild enough to tolerate a variety of functional
groups. The scope and generality of this process is illus-
trated with respect to various epoxides and potassium
thiocyanate and the results are presented in the Table.
References
(1) (a) Bonini, C.; Righi, G. Synthesis 1994, 225. (b) Shimizu,
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In summary, this paper describes a simple, convenient and
highly efficient method for the conversion of epoxides to
thiiranes using indium tribromide as novel catalyst. The
notable features of this procedure are mild reaction condi-
tions, greater selectivity and functional group compatibil-
ity, cleaner reaction profiles, high yields of products, short
reaction periods and operational simplicity, which make it
a useful and attractive alternative to the existing processes
for the synthesis of thiiranes of synthetic and biological
importance.
(4) Doyle, F. P.; Holland, D. O.; Hunter, W. H.; Mayer, J. H. C.;
Queen, A. J. J. Chem. Soc. 1960, 2665.
Synlett 2003, No. 3, 396–398 ISSN 0936-5214 © Thieme Stuttgart · New York

398
J. S. Yadav et al.
LETTER
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were dried over anhydrous Na2SO4, concentrated in vacuo
and purified by column chromatography on silica gel
(Merck, 100–200 mesh, ethyl acetate–hexane 1:9) to afford
pure thiirane after removal of solvent. The aqueous layer
was concentrated in vacuo to recover the catalyst.
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(11) Experimental Procedure: A mixture of epoxide (5 mmol),
potassium thiocyanate (5 mmol) and InBr3 (5 mol%) or InCl3
(10 mol%) in acetonitrile (10 mL) was stirred at 60 °C
temperature for an appropriate time (Table). After
completion of the reaction, as indicated by TLC, the reaction
mixture was diluted with water (2 × 10 mL) and extracted
with diethyl ether (2 × 15 mL). The combined organic layers
Spectroscopic data for selected products: 2a: 2-phenyl-
thiirane: Liquid. IR (KBr): 2922, 1628, 1457, 1216, 1031,
767 cm–1. 1H NMR (CDCl3): δ 2.60 (dd, 1 H, J = 1.4 Hz, 6.0
Hz), 2.85 (d, 1 H, J = 6.0 Hz), 3.85 (t, 1 H, J = 6.0 Hz), 7.20–
7.88 (m, 5 H). EIMS (m/z): 136 (M+), 104, 91, 69, 43.
2l: 2-[2-(4-methoxybenzyloxy)ethyl]thiirane: Liquid. IR
(KBr): 2925, 1629, 1451, 1217, 1182, 1045, 760 cm–1.
1H NMR (CDCl3): δ 1.58–1.67 (m, 1 H), 2.05–2.25 (m, 2 H),
2.50 (dd, 1 H, J = 1.5, 6.0 Hz), 1.95–3.05 (m, 1 H), 3.60 (t, 2
H, J = 6.0 Hz), 3.80 (s, 3 H), 4.45 (s, 2 H), 6.80 (d, 2 H, J =
8.0 Hz), 7.25 (d, 2 H, J = 8.0 Hz). EIMS (m/z): 224 (M+),
191, 137, 121, 78, 55. 2o: 2-(2-naphthyloxymethyl)thiir-
ane: Solid, mp 74 °C. IR (KBr): 2927, 1628, 1596, 1465,
1257, 1217, 1182, 1006, 839, 742 cm–1. 1H NMR (CDCl3): δ
2.28 (dd, 1 H, J = 1.4, 5.2 Hz), 2.60 (d, 1 H, J = 5.9 Hz),
3.20–3.25 (m, 1 H), 3.90 (dd, 1 H, J = 7.0 Hz, 10.5 Hz), 4.38
(dd, 1 H, J = 5.2 Hz, 10.5 Hz), 7.0–7.18 (m, 2 H), 7.25–7.40
(m, 2 H), 7.60–7.80 (m, 4 H). EIMS (m/z): 216 (M+), 145,
116, 73, 45.
Synlett 2003, No. 3, 396–398 ISSN 0936-5214 © Thieme Stuttgart · New York