Selectfluor: A novel and efficient reagent for the synthesis of β-hydroxy thiocyanates

Article abstract of DOI:10.1016/j.tetlet.2003.11.102

A variety of epoxides undergo rapid ring opening with ammonium thiocyanate in the presence of 10mol% Selectfluor in acetonitrile at room temperature to afford the corresponding β-hydroxy thiocyanates in excellent yields with high regioselectivity.

Full text of DOI:10.1016/j.tetlet.2003.11.102

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1291–1293
Selectfluore: a novel and efficient reagent for the synthesis of
b-hydroxy thiocyanates
J. S. Yadav,* B. V. S. Reddy and Ch. Srinivas Reddy
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500-007, India
Received 13 August 2003; revised 10 November 2003; accepted 21 November 2003
Abstract—A variety of epoxides undergo rapid ring opening with ammonium thiocyanate in the presence of 10 mol % Selectfluore
in acetonitrile at room temperature to afford the corresponding b-hydroxy thiocyanates in excellent yields with high regioselec-
tivity.
Ó 2003 Elsevier Ltd. All rights reserved.
Oxiranes are well-known carbon electrophiles capable of
reacting with various nucleophiles and their ability to
undergo regioselective ring opening reactions contrib-
low cost and is easy to handle and also retains its
activity even in the presence of amines.8 More recently,
Selectfluore has been employed as an efficient Lewis
acid catalyst for the one-pot allylation reactions of
imines and for the hydrolysis of acetals, dithia-acetals
and tetrahydropyranyl ethers.9 However, there are no
examples of the use of Selectfluore as a catalyst for the
cleavage of epoxides with thiocyanates.
1
utes largely totheir synthetic value.
Consequently,
several methods have been developed for the regiose-
lective ring opening of epoxides with various nucleo-
philes to produce ring-opened products.2 The ring
opening of epoxides with thiocyanates is a widely used
method for the preparation of thiiranes.3 The formation
of thiiranes from oxiranes and thiocyanates has been
explained by the intermediacy of the corresponding b-
hydroxy thiocyanate. However, b-hydroxy thiocyanates
have not been isolated due to rapid conversion into the
corresponding thiiranes.4 Thus, very few methods are
reported for the preparation of b-hydroxy thiocyan-
ates.5;6 Most of these methods involve high temperature
reaction conditions to obtain ring-opened products,
which are not only detrimental to certain functional
groups, but also to the control of regioselectivity.
Polymeric phase-transfer catalysts have been reported to
perform the epoxide ring opening with thiocyanates
under mild conditions.7 Since organo-sulfur compounds
are useful and important in organic synthesis, the
development of simple, convenient and efficient catalytic
systems for the preparation of b-hydroxy thiocyanates
especially those which carry acid labile functional
groups, are desirable. Recently, Selectfluore has been
introduced commercially as a user-friendly electrophilic
fluorinating agent. Selectfluore is readily available at
Herein we report the use of Selectfluore as a novel and
efficient catalyst for the preparation of b-hydroxy thio-
cyanates by a regioselective ring opening of epoxides
with ammonium thiocyanate under mild conditions10
(Scheme 1).
Treatment of styrene oxide with ammonium thiocyanate
in the presence of 10 mol % Selectfluore in acetonitrile
afforded b-hydroxy thiocyanates 2 and 3 as a mixture in
80% and 15% yields, respectively. Aryl substituted
epoxides underwent cleavage by thiocyanate in a regio-
selective manner with preferential attack at the less
hindered position (Table 1, entries a, c and d). Glycidyl
aryl ethers and esters also gave the corresponding
b-hydroxy thiocyanate 2 in high yields (Table 1, entries
h–o) with high regioselectivity. No trace of the other
regioisomers of 3 were observed during the cleavage
of glycidyl aryl ethers with ammonium thiocyanate
under the reaction conditions. Similarly, hexene oxide
OH
SelectfluorTM
CH3CN, r.t.
SCN
O
NH4SCN
+
SCN
OH
+
R
R
R
Keywords: Selectfluore; Epoxides; b-Hydroxy thiocyanates.
* Corresponding author. Tel.: +91-402-7193434; fax: +91-402-7160-
512; e-mail: yadav@iict.ap.nic.in
2
3
1
Scheme 1.
0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.11.102

1292
J. S. Yadav et al. / Tetrahedron Letters 45 (2004) 1291–1293
Table 1. Selectfluore promoted synthesis of b-hydroxy thiocyanates from epoxides
Entry
Epoxide
b-Hydroxy thiocyanatea
Reaction time (h)
2.5
Yield (%)b
80(15)c
O
OH
SCN
a
Ph
Ph
SCN
O
Ph
O
Ph
b
c
3.5
4.0
92
Ph
Ph
OH
OH
SCN
75(20)c
OH
O
70(15)c
89
SCN
d
e
f
3.0
4.5
OH
O
SCN
OH
6.0
4.5
85
O
SCN
OH
O
75(10)c
90
g
SCN
OH
O
SCN
PhO
h
i
PhO
Ph
3.5
5.0
OH
O
SCN
O
Ph
86
O
O
O
OH
OH
O
O
SCN
SCN
O
O
O
j
4.0
91
O
k
l
3.0
3.5
95
89
Me
Me
OH
OH
O
O
SCN
O
O
O
O
Me
Me
SCN
SCN
m
n
4.0
3.5
94
92
Me
Me
OH
O
O
O
BnO
BnO
OH
O
O
SCN
O
o
5.0
90
a All products were characterized by 1H NMR, IR and mass spectroscopy.
b Isolated and unoptimized yields.
c Yield in parenthesis refers to the other regioisomer.

J. S. Yadav et al. / Tetrahedron Letters 45 (2004) 1291–1293
1293
References and notes
OH
SelectfluorTM
CH3CN, r.t.
O
NH4SCN
+
( )n
SCN
( )n
1. (a) Bonini, C.; Righi, G. Synthesis 1994, 225–238; (b)
Shimizu, M.; Yoshida, A.; Fujisawa, T. Synlett 1992, 204–
206; (c) Smith, J. G. Synthesis 1984, 629–656.
2. (a) Parker, R. E.; Isaacs, N. S. Chem. Rev. 1959, 59, 737–
799; (b) Rao, A. S.; Paknikar, S. K.; Kirtane, J. G.
Tetrahedron 1983, 39, 2323–2367; (c) Hirose, T.; Sun-
azuka, T.; Zhi-ming, T.; Handa, M.; Vchida, R.; Shiomi,
K.; Harigaya, Y.; Omura, S. Heterocycles 2000, 53, 777–
784.
3. (a) Jankowski, K.; Harvey, R. Synthesis 1972, 627; (b)
Iranpoor, N.; Kazemi, F. Synthesis 1996, 821–822; (c)
Tamami, B.; Kiasat, A. R. Synth. Commun. 1996, 26,
3953–3958; (d) Brimeyer, M. O.; Mehrota, A.; Quici, S.;
Nigam, A.; Regen, S. L. J. Org. Chem. 1980, 45, 4254–
4255.
4. (a) Sander, M. Chem. Rev. 1966, 66, 297–339; (b) Vedejs,
E.; Krafft, G. A. Tetrahedron 1982, 38, 2857–2881; (c)
Iranpoor, N.; Kazemi, F. Tetrahedron 1997, 53, 11377–
11382.
5. (a) Van Tamelen, E. E. J. Am. Chem. Soc. 1951, 73, 3444–
3448; (b) Kawashima, K.; Eshiguro, T. Chem. Pharm.
Bull. 1978, 26, 951–955; (c) Gao, Y.; Sharpless, K. B.
J. Am. Chem. Soc. 1988, 110, 7538–7539.
6. Sharghi, H.; Nasseri, M. A.; Niknam, K. J. Org. Chem.
2001, 66, 7287–7293.
7. Tamami, B.; Mahdavi, H. Tetrahedron Lett. 2002, 43,
6225–6228.
8. (a) Shibata, N.; Suzuki, E.; Asahi, T.; Shiro, M. J. Am.
Chem. Soc. 2001, 123, 7001–7009; (b) Burkart, M. D.;
Zhang, Z.; Hung, S.-C.; Wong, C.-H. J. Am. Chem. Soc.
1997, 119, 11743–11746.
9. (a) Liu, J.; Wong, C.-H. Tetrahedron Lett. 2002, 43, 3915–
3917; (b) Liu, J.; Wong, C.-H. Tetrahedron Lett. 2002, 43,
4037–4039.
n = 1, 2
1
n = 1, 2
4
Scheme 2.
underwent cleavage by thiocyanate in a regioselective
manner with preferential attack at the terminal position
(Table 1, entry g). The structures and the regiochemical
1
ratios of products were determined by H NMR spec-
troscopy and also by comparison with authentic com-
pounds.6;7 In all cases, the reactions proceeded rapidly at
room temperature with high efficiency. The b-hydroxy
thiocyanates were obtained in excellent yields without
the formation of corresponding thiiranes. Furthermore,
cycloalkyl epoxides such as cyclohexene oxide and
cyclopentene oxide reacted smoothly with ammonium
thiocyanate to produce the corresponding b-hydroxy
thiocyanates 4 under similar conditions (Scheme 2).
Except for the reactions of styrene oxide, hexene oxide,
indene oxide and tetrahydronaphtho[1,2-b]oxirane,
which gave minor amounts of the other regioisomer, the
reactions of other epoxides were found to be highly
regioselective affording a single product in good to
excellent yields. In the case of cyclic epoxides, the ste-
reochemistry of the ring opened products was found to
be trans from the coupling constants of the ring
hydrogens as has been observed in most the epoxide
ring-opening reactions.5–7 The direction of ring opening
is that characteristically observed for terminal epoxides
under SN2 conditions, and is probably dictated by steric
and electronic factors. The reactivity of several epoxides
with ammonium thiocyanate was examined using vari-
ous Lewis acids such as CeCl3Æ7H2O, YCl3, TaCl5, In-
Cl3, InBr3, In(OTf)3, Bi(OTf)3 and Sc(OTf)3. In most of
these cases, thiiranes were obtained exclusively and no
b-hydroxy thiocyanate was isolated. Acetonitrile ap-
pears to be the solvent of choice giving the best results.
The scope and generality of this process is illustrated
with respect to various epoxides and ammonium thio-
cyanate and the results are presented in Table 1.
10. Experimental procedure: A mixture of epoxide (1 mmol)
and ammonium thiocyanate (1 mmol) and Selectfluore
(10 mol %) in acetonitrile (10 mL) was stirred at room
temperature for the appropriate time (Table 1). After
completion of the reaction, as indicated by TLC, the
solvent was evaporated under reduced pressure. Then the
resulting product was directly charged onto a small silica
gel column and eluted with a mixture of ethyl acetate: n-
hexane (2:8) toafford pure b-hydroxy thiocyanate. Spec-
tral data for selected products: 2-Hydroxy-2-phenylethyl
thiocyanate 3a: Liquid, IR (neat): m 2165, 1600, 1453,
1319, 1270, 1165, 1105, 1025, 710 cmꢀ1
;
1H NMR
(200 MHz, CDCl3): d 2.80 (br s, OH, 1H), 3.05–3.25 (m,
2H), 4.95–5.05 (m, 1H), 7.25–7.45 (m, 5H). 13C NMR
(50 MHz, CDCl3): 42.5, 73.1, 113.0, 126.3, 128.4, 129.6,
135.7. EIMS: m=z: 179 Mþ, 153, 140, 131, 119, 105, 91, 77,
45. 3-Phenoxy-2-hydroxypropyl thiocyanate 3h: Liquid, IR
(neat): m 2160, 1605, 1450, 1316, 1271, 1160, 1109, 1027,
711 cmꢀ1; 1H NMR (200 MHz, CDCl3): d 2.95 (br s, OH,
1H), 3.05–3.15 (m, 1H), 3.20–3.29 (m, 1H), 4.05–4.10 (m,
2H), 4.25–4.30 (m, 1H), 6.80 (d, 2H, J ¼ 8:0 Hz), 6.95 (t,
1H, J ¼ 7:9 Hz), 7.20–7.30 (m, 2H). EIMS: m=z: 209 Mþ,
170, 154, 139, 133, 117, 103, 80, 69, 56, 44.
1-(4-Isopropylphenoxy)-3-thiocyanato-2-propanol 3j: Liquid,
IR (neat): m 2167, 1601, 1457, 1311, 1278, 1165, 1101,
In summary, we describe a novel and efficient protocol
for the synthesis of b-hydroxy thiocyanates by the reg-
ioselective ring opening of epoxides with ammonium
thiocyanate using Selectfluore as a novel catalyst. This
method offers several advantages including mild reac-
tion conditions, high conversions, greater regioselectiv-
ity, short reaction times, clean reaction profiles, ease of
handling and ready availability of the catalyst at low
cost, which makes it a useful and attractive process for
the synthesis of b-hydroxy thiocyanates.
1
1030, 714 cmꢀ1; H NMR (200 MHz, CDCl3): d 1.20 (d,
6H, J ¼ 6:9 Hz), 2.80–2.95 (m, 1H), 3.05–3.15 (m, 1H),
3.20–3.27 (m, 1H), 4.0–4.05 (m, 2H), 4.20–4.30 (m, 1H),
6.80 (d, 2H, J ¼ 8:1 Hz), 7.15 (d, 2H, J ¼ 8:1 Hz). EIMS:
m=z: 251 Mþ, 239, 207, 175, 161, 149, 133, 121, 107, 95,
81, 73, 55.
Acknowledgements
B.V.S., Ch.S.R. thank CSIR New Delhi for the award of
fellowships.