Highly regioselective ring opening of epoxides and aziridines using (bromodimethyl)sulfonium bromide

Article abstract of DOI:10.1016/j.tetlet.2006.04.059

Epoxides and aziridines undergo ring opening efficiently with (bromodimethyl)sulfonium bromide at room temperature to form the corresponding β-bromohydrins and β-bromoamines, respectively. The conversions are highly regioselective and afford the products in excellent yields within a short period of time.

Full text of DOI:10.1016/j.tetlet.2006.04.059

Tetrahedron Letters 47 (2006) 4457–4460
Highly regioselective ring opening of epoxides and aziridines
I
using (bromodimethyl)sulfonium bromide
*
Biswanath Das, Maddeboina Krishnaiah and Katta Venkateswarlu
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, Andhra Pradesh, India
Received 3 March 2006; revised 3 April 2006; accepted 10 April 2006
Available online 11 May 2006
Abstract—Epoxides and aziridines undergo ring opening efficiently with (bromodimethyl)sulfonium bromide at room temperature
to form the corresponding b-bromohydrins and b-bromoamines, respectively. The conversions are highly regioselective and afford
the products in excellent yields within a short period of time.
ꢀ
2006 Elsevier Ltd. All rights reserved.
1
2
Epoxides and aziridines are versatile intermediates in
organic synthesis. They can be easily prepared and
cleaved with different nucleophiles, leading to the forma-
tion of regio- and stereoselective ring opened products.
Vicinal halohydrins and haloamines are useful precur-
sors in the synthesis of halogenated marine natural
OH
O
+
Me S BrBr
O
2
O
Br
MeCN
r. t., 20 min
98%
3
products and other bioactive molecules. The ring open-
ing of epoxides to form halohydrins can generally be
carried out with halogens,
metal halides.
with metal halides.
methods suffer from drawbacks, such as unavailability
of the reagents, long reaction times, unsatisfactory
yields, formation of side products and harsh reaction
conditions. Thus, a mild and effective method suitable
for opening of both epoxides and aziridines is highly
desirable.
+
Me S BrBr
NHTs
NTs
2
4
a,b
4c
hydrogen halides and
MeCN
Br
4
d,e
Aziridine rings can also be opened
3
b,4e
r. t., 30 min
However, many of the reported
9
6%
Scheme 1.
Various epoxides and N-tosylaziridines underwent ring
cleavage easily with Me S BrBr in MeCN at room
temperature (Table 1). The desired products were
+
À
2
7
5
In continuation of our work on the development of
useful synthetic methodologies, we have observed that
bromodimethyl)sulfonium bromide (Me S BrBr )
can be utilized efficiently for the cleavage of epoxides
and aziridines to produce b-halohydrins and b-haloam-
ines, respectively (Scheme 1).
formed in excellent yields and no side products were
observed. The reaction times were short—for opening
of epoxides it took only 20 min, while opening of aziri-
dines only 30 min was required. The cleavage of both
epoxides and aziridines took place with high regioselec-
tivity. 2-Arylepoxides and N-tosyl-2-arylaziridines affor-
ded the products of opening at the benzylic position,
while 2-alkylepoxides and N-tosyl-2-alkylaziridines gave
the products formed by cleavage at the terminal posi-
tion. These observations demonstrated that in the for-
mer case, the products are generated through the
formation of a stabilized benzylic cation during the reac-
tion and in the second case, they are formed by predom-
inant attack of the halide ion on the less hindered
carbon of the epoxide or aziridine. The structures of
+
À 6
(
2
Keywords: Epoxide; Aziridine; (Bromodimethyl)sulfonium bromide;
Regioselectivity.
q
Part 89 in the series, ‘Studies on novel synthetic methodologies’;
IICT Communication No. 060332.
Corresponding author. Tel./fax: +91 40 7160512; e-mail:
biswanathdas@yahoo.com
*
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.04.059

4458
B. Das et al. / Tetrahedron Letters 47 (2006) 4457–4460
+
À a
Table 1. Ring opening of epoxides and aziridines with Me
2
S BrBr
Entry
a
Epoxide/aziridine 1
Product 2
Isolated yield (%)
O
Br
OH
O
9
8
O
O
Br
b
84
OH
OH
O
O
O
Br
c
98
98
O
OH
O
O
Br
d
F
F
O
OH
O
O
Br
e
f
98
98
Cl
Cl
O
OH
O
O
Br
MeO
MeO
O
Br
OH
g
h
i
O
O
78
95
98
98
OH
O
Br
O
OH
Cl
Cl
Br
OH
Br
O
j
OH
k
O
98
84
84
Br
Br
NTs
NHTs
Br
l
NTs
NHTs
m
H C
H C
3
3
O
O

B. Das et al. / Tetrahedron Letters 47 (2006) 4457–4460
4459
Table 1 (continued)
Entry
Epoxide/aziridine 1
Product 2
Isolated yield (%)
96
NHTs
Br
NTs
n
o
NHTs
Br
NTs
95
98
NHTs
Br
NTS
NTS
p
NHTS
Br
q
98
a
1
13
The structures of the products were established from their spectral ( H and C NMR and MS) data.
1
the products were established from their spectral ( H
In conclusion, we have described a simple and efficient
procedure for ring-opening of epoxides and aziridines
using (bromodimethyl)sulfonium bromide at room tem-
perature for the preparation of b-bromohydrins and
b-bromoamines, respectively. The present method is
associated with several advantages, such as application
of an inexpensive reagent, operational simplicity, short
reaction times, high yields and excellent regioselectivity.
A novel useful utilization of the reagent is also disclosed.
1
3
7
and C NMR and MS) data.
The data for known products were compared with those
4
reported in the literature. In the EIMS, 2b showed sig-
nificant peaks at m/z 171 and 169 (each 7%) (resulting
from benzylic cleavage), while 2g demonstrated a peak
at m/z 165 (5%) (resulting from b-cleavage with respect
to the hydroxyl group) which suggested the regiochem-
istry of these two compounds. The regiostructures of
other products were also similarly determined from their
1
mass fragmentation patterns along with H NMR spec-
Acknowledgements
tral values. The regiochemistries of 2b and 2g were fur-
ther confirmed from 2D-NMR and chemical evidence.
Thus, the HMBC spectrum of 2b showed that the pro-
ton of the hydroxyl group (d 3.56, 1H, d, J = 6.0 Hz)
was correlated with the carbonyl group (d 196.8) and
also with the benzylic carbon (d 53.2). Similarly, the
HMBC spectrum of 2g revealed that the hydroxyl group
proton (d 2.56, 1H, br s) correlated with the carbons of a
methyl group (d 18.5), C(OH)CH , a –CH O– group
The authors thank CSIR, New Delhi, for financial
assistance.
References and notes
1. Parker, R. E.; Isaacs, N. S. Chem. Rev. 1959, 59, 737–799.
2. Kemp, J. E. G. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergomon: Oxford, 1991; Vol. 7,
pp 469–513.
3
2
(
non-benzylic) (d 74.9) and a –CHBr– group (d 56.3).
1 1
The H– H COSY spectrum of 2g indicated the absence
of a proton at the adjacent carbon atom with respect to
this hydroxyl group. Compound 2g did not afford an
3
. (a) Moore, R. E. In Marine Natural Products; Scheuer, P.
J., Ed.; Academic Press: New York, 1978; Vol. 1, Chapter
2
1
; (b) Righi, G.; Franchini, T.; Bonini, C. Tetrahedron Lett.
998, 39, 2385–2388; (c) Babudri, F.; Fiandanese, V.;
acetylation product on overnight treatment with Ac O
2
and pyridine at room temperature, suggesting it to be
a tertiary alcohol.
Marchese, G.; Punzi, A. Tetrahedron 2001, 57, 549–554; (d)
Boukhris, S.; Souizi, A. Tetrahedron Lett. 2003, 44, 3259–
3
261.
Ring-opening of bicyclic epoxides and aziridines with
4. (a) Konnaklieva, M. L.; Dahi, M. L.; Turos, E. Tetrahedron
Lett. 1992, 33, 7093–7096; (b) Sharghi, H.; Eskandari, M.
M. Tetrahedron 2003, 59, 8509–8514; (c) Stewart, C. A.;
Vander Werf, C. A. J. Am. Chem. Soc. 1954, 76, 1259–1264;
(
bromodimethyl)sulfonium bromide afforded products
1
whose stereochemistry was found to be trans ( H
NMR spectra).
7
(
d) Kotsuki, H.; Shimanouchi, T. Tetrahedron Lett. 1996,
6
37, 1845–1848; (e) Sabitha, G.; Babu, R. S.; Rajkumar, M.;
Reddy, C. S.; Yadav, J. S. Tetrahedron Lett. 2001, 42,
(
Bromodimethyl)sulfonium bromide is an inexpensive
reagent. It works under mild reaction conditions and
was employed earlier to carry out some synthetic trans-
formations, mainly as a catalyst. In the present case, it
has been applied efficiently for cleavage of both epoxides
and aziridines with equal ease. No additional catalyst
was required.
3
955–3958.
5
. (a) Das, B.; Ramu, R.; Reddy, M. R.; Mahendar, G.
Synthesis 2005, 250–254; (b) Das, B.; Venkateswarlu, K.;
Mahendar, G.; Mahendar, I. Tetrahedron Lett. 2005, 46,
3041–3044; (c) Das, B.; Majhi, A.; Banerjee, J.; Chow-
dhury, N.; Venkateswarlu, K. Tetrahedron Lett. 2005, 46,

4460
B. Das et al. / Tetrahedron Letters 47 (2006) 4457–4460
1
7
913–7915; (d) Das, B.; Majhi, A.; Banerjee, J.; Chowdhury,
Product 2g: H NMR (200 MHz): d 7.41–7.23 (5H, m),
4.59 (1H, d, J = 12.8 Hz), 4.52 (1H, d, J = 12.8 Hz), 3.96
(1H, dd, J = 12.0, 2.0 Hz), 3.77 (1H, d, J = 9.0 Hz), 3.35
(1H, d, J = 9.0 Hz), 2.56 (1H, br s), 2.19 (1H, m), 1.62 (1H,
N.; Venkateswarlu, K. Chem. Lett. 2005, 34, 1492–1493.
. (a) Furukawa, N.; Inoue, T.; Aida, T.; Oae, S. J. Chem.
Soc., Chem. Commun. 1973, 212; (b) Olah, G. A.; Vankar,
Y. D.; Arvanaghi, M.; Prakash, G. K. S. Synthesis 1979,
6
1
3
m), 1.21 (3H, s), 1.04 (3H, t, J = 7.0 Hz); C NMR
7
20–721; (c) Khan, A. T.; Mondal, E.; Ghosh, S.; Islam, S.
Eur. J. Org. Chem. 2004, 2002–2009, and references therein;
d) Kudrimoti, S.; Bommena, V. R. Tetrahedron Lett. 2005,
6, 1209–1210.
(50 MHz): d 137.8, 128.4, 128.0, 127.8, 127.4, 75.2, 74.9,
73.6, 56.3, 25.1, 18.5, 12.2; FABMS: m/z 289, 287 [M+H] ;
EIMS: m/z (%) 165 (5), 121 (9), 107 (6); Anal. Calcd for
+
(
4
C
13
H19BrO
2
: C, 54.36; H, 6.62%. Found: C, 54.44; H,
7
. General procedure for ring opening of epoxides and
6.68%.
1
aziridines: To a solution of an epoxide or N-tosylaziridine
Product 2j: H NMR (200 MHz): d 4.31 (1H, ddd, J = 10.0,
9.0, 4.0 Hz), 3.99 (1H, ddd, J = 10.5, 9.0,4.0 Hz), 3.27 (1H,
br s), 2.32 (1H, m), 2.23 (1H, m), 1.98 (1H, m), 1.92–1.74
(2H, m), 1.55 (1H, m); EIMS: m/z (%) 166 (46), 164 (46),
+
À
(
1 mmol) in MeCN (5 mL), Me S BrBr (1 mmol) (pre-
2
6
b
pared by the reported method ) was added. The mixture
was stirred at room temperature for 20 or 30 min. The
reaction was quenched with water (10 mL) and the mixture
was extracted with EtOAc (3 · 5 mL). The combined
organic portion was dried and concentrated. The residue
was purified by column chromatography over silica gel
+
Å
5 9
(M ) 137 (12), 135 (12), 86 (71); Anal. Calcd for C H BrO:
C, 36.36; H, 5.45%. Found: C, 36.42; H, 5.49%.
Product 2l:
J = 8.0 Hz), 7.36–7.19 (7H, m), 4.90 (1H, dd, J = 8.0,
1
H NMR (200 MHz): d 7.72 (2H, d,
(
hexane–EtOAc, 9:1) to afford pure b-bromohydrin (or N-
6.0 Hz), 4.69 (1H, br s), 3.59–3.47 (2H, m), 2.42 (3H, s);
EIMS: m/z (%) 355 (6), 353 (6) (M ), 234 (22), 171 (88),
+
Å
tosyl-b-bromoamine).
The spectral and analytical data of some representative
169 (88); Anal. Calcd for C H BrNO S: C, 50.85; H, 4.50;
1
5
16
2
compounds are given below.
N, 3.96%. Found: C, 50.81; H, 4.58; N, 3.92%.
Product 2n: H NMR (200 MHz): d 7.62 (2H, d, J =
1
1
Product 2b:
H
NMR (200 MHz):
d
7.85 (2H, d,
J = 8.0 Hz), 7.62 (1H, t, J = 8.0 Hz) 7.50 (2H, t,
J = 8.0 Hz), 7.29–7.10 (5H, m), 5.52 (1H, dd, J = 6.0,
8.0 Hz), 7.30 (2H, d, J = 8.0 Hz), 5.09 (1H, d, J = 6.0 Hz),
3.42–3.29 (3H, m), 2.45 (3H, s), 1.57–1.40 (2H, m), 1.32–
1.05 (4H, m), 0.82 (3H, t, J = 7.0 Hz); EIMS: m/z (%) 335
2
.0 Hz), 5.28 (1H, d, J = 2.0 Hz), 3.56 (1H, d, J = 6.0 Hz);
C NMR (50 MHz): d 196.8, 135.5, 134.0, 132.2, 128.9,
28.6, 128.2, 128.0, 127.4, 77.0, 53.2; EIMS: m/z (%) 306 (2)
1
3
+Å
(5) 333 (5) (M ), 278 (11), 276 (11), 240 (16), 214 (9), 163
1
3
(27); Anal. Calcd for C13
2
H20BrNO S: C, 40.71; H, 5.99; N,
+
Å
04 (2) (M ), 225 (5), 171 (7), 169 (7), 135 (4), 105 (100);
4.19%. Found: C, 40.76; H, 5.92; N, 4.23%.
1
Anal. Calcd for C15
2
H13BrO : C, 59.02; H, 4.26%. Found:
Product 2q:
H NMR (200 MHz): d 7.80 (2H, d,
C, 59.18; H, 4.34%.
J = 8.0 Hz), 7.32 (2H, d, J = 8.0 Hz), 5.71 (1H, d,
J = 6.0 Hz), 4.10 (1H, ddd, J = 10.0, 9.0, 4.0 Hz), 3.67
(1H, m) 2.45 (3H, s), 2.22 (1H, m), 2.13 (1H, m), 1.95 (1H,
m), 1.84–1.62 (2H, m), 1.42 (1H, m); EIMS: m/z (%) 333
1
Product 2f:
H
NMR (200 MHz): d
7.08 (2H, d,
J = 8.0 Hz), 6.75 (2H, d, J = 8.0 Hz), 4.07 (1H, m), 4.02–
.92 (2H, m), 3.57–3.42 (4H, m), 3.31 (3H, s), 2.76 (2H, t,
3
+
Å
+Å
J = 7.0 Hz); EIMS: m/z (%) 290 (7), 288 (7) (M ), 245 (22),
43 (22), 195 (14) 108 (100); Anal. Calcd for C H BrO :
(42), 331 (42) (M ), 252 (18), 186 (78), 167 (16); Anal.
2
Calcd for C H BrNO S: C, 46.99; H, 5.42; N, 4.22%.
1
2
17
3
13 18
2
C, 49.83; H, 5.88%. Found: C, 49.79; H, 5.92%.
Found: C, 47.02; H, 5.46; N, 4.28%.