Unexpected highly efficient ring-opening of aziridines or epoxides with iodine promoted by thiophenol

Article abstract of DOI:10.1055/s-2006-950417

Ring-opening of aziridines or epoxides with iodine promoted by thiophenol afforded β-iodo amines or β-iodo alcohols in good to excellent yields under mild reaction conditions with extremely high efficiency. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950417

LETTER
2489
Unexpected Highly Efficient Ring-Opening of Aziridines or Epoxides with
Iodine Promoted by Thiophenol
H
ighly Ef
ficient
e
W
A
ziridine
s
or Epoxides u,*a,b Xiaoyu Sun,a Wei Sun,a Shengqing Yea
a
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, P. R. of China
Fax +86(21)65102412; E-mail: jie_wu@fudan.edu.cn
b
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, P. R. of China
Received 11 May 2006
thesis of b-iodo amines from aziridines have appeared in
the literature.4 However, these methods are complicated
by prolonged reaction time, heavy and/or expensive metal
employed, and reflux conditions. For example, a large ex-
cess of metal salts, such as ZnI2,4a InI3,4e or CeCl3,4f have
to be utilized as reagents in order to obtain respectable
yields. Ring-opening of aziridines with HI in the presence
of b-cyclodextrin was also reported to afford the corre-
sponding b-iodo amines.4d However, prolonged reaction
time (24 h) was needed for reaction completion. The un-
expected reaction, shown in Equation 1, is extremely
efficient and thus opens a new avenue for the synthesis of
b-iodo amines.
Abstract: Ring-opening of aziridines or epoxides with iodine
promoted by thiophenol afforded b-iodo amines or b-iodo alcohols
in good to excellent yields under mild reaction conditions with
extremely high efficiency.
Key words: aziridine, epoxide, iodine, thiophenol, ring-opening
Ring-opening reactions of aziridines with nucleophiles
provide a useful protocol in organic synthesis, and many
reagents have recently been developed to realize the open-
ing of the aziridine ring.1 On the other hand, in recent
years, iodine has emerged as an effective Lewis acid
catalyst for various organic transformations,2 since it is
relatively inexpensive compared to other Lewis acids, its
handling does not require special precautions and it is
readily reduced to relatively nontoxic iodide during work-
up procedures. In the course of our ongoing studies on
novel methods for the aziridine transformations,3 we envi-
sioned that iodine may act as a Lewis acid catalyst in the
ring-opening of aziridines with nucleophiles. Our studies
commenced with the ring-opening reaction of aziridine 1a
with thiophenol in the presence of iodine (50 mol%) in
CH2Cl2 at room temperature (Equation 1). To our delight,
the reaction was highly efficient and went to completion
in one minute (95% yield). In addition, this reaction could
be run under the air without loss of efficiency. However,
from spectral characterization, the product found was not
Table 1 Ring-Opening of Aziridine 1a with Iodine in the Presence
of Additives
I2 (0.5 equiv)
additive (1.0 equiv)
NHTs
NTs
air, r.t.
I
2a
1a
Entry
1
Additive
PhSH
Solvent
CH2Cl2
THF
Yield (%)a
95
2
PhSH
66
3
PhSH
Acetone
MeCN
Toluene
CHCl3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
32
4
PhSH
62
1
the expected thioether 4. Structure elucidation by H
NMR, 13C NMR spectroscopy and mass spectrometry
revealed the product was actually trans-N-(2-iodocyclo-
hexyl)-4-methylbenzenesulfonamide (2a). No reaction
occurred in the absence of thiophenol.
5
PhSH
79
6
PhSH
67
7
PhOH
TsOH
NR
95b
NR
NR
NR
NR
NR
76
To our surprise, there are no reports of the ring-opening of
aziridines with iodine, although several methods for syn-
8
9
HOAc
HCOOH
In(OTf)3
LiClO4
Zn(OTf)2
EtSH
I2 (0.5 equiv)
PhSH (1.0 equiv)
10
11c
12c
13c
14
NHTs
NHTs
I
NTs
air, r.t.
95%
SPh
2a
4 (not observed)
1a
Equation 1 Reaction of aziridine 1a with thiophenol in the
presence of iodine (50 mol%)
a Isolated yield based on aziridine 1a.
SYNLETT 2006, No. 15, pp 2489–2491
Advanced online publication: 08.09.2006
DOI: 10.1055/s-2006-950417; Art ID: W09906ST
© Georg Thieme Verlag Stuttgart · New York
1
8
.0
9
.2
0
0
6
b Product, from ring-opening reaction of aziridine 1a with TsOH, was
obtained.
c 10 mol% of additive were used in the reaction.

2490
J. Wu et al.
LETTER
Further investigations are shown in Table 1. Dichloro- reaction and disulfide was isolated as another product. Re-
methane was the best choice of solvent among solvents action of iodine with thiol has been reported to generate
screening. Other additives, including PhOH, AcOH and disulfide.5 However, prolonged reaction time (overnight,
Lewis acids, were inert in this transformation. Aliphatic r.t.)5b,5c or high temperature (96 °C)5a was necessary to
thiol, such as EtSH, was also effective in this reaction effect the transformation, which could not explain the
although lower yield was obtained (Table 1, entry 14). A extremely high efficiency of the reaction we have ob-
quantitative amount of thiol was essential to effect this served. Combination of iodine with thiol for other organic
transformations was also reported previously.6
Table 2 Ring-Opening of Aziridine 1 with Iodine Promoted by
Thiophenol9
A variety of aziridines have thus been examined for the
ring-opening reactions, and the results are summarized in
Table 2. As shown in Table 2, this condition has proved to
be general and useful for regioselective ring-openings of
a range of aziridines 1. All reactions were very clean and
highly efficient (finished in 1 min), and the desired prod-
Yield ucts were afforded in good to excellent yields. It is note-
I2 (0.5 equiv)
PhSH (1.0 equiv)
R1
NTs
R2
1
R1
R2
NHTs
I
R1
R2
I
+
air, r.t., <1 min
NHTs
2
3
Entry Aziridine 1
Product
(%)b
worthy that aziridine 1d, which has been previously
reported to be unreactive under nucleophilic attack,1 is
1
95
NHTs
I
also a suitable substrate in this reaction (90% yield,
Table 2, entry 4). Furthermore, the conditions were also
suitable for the ring-opening reactions of epoxides (results
NTs
1a
2a
2b
2c
2d
shown in Table 3), which afforded to the highly versatile
2
96
NHTs
I
intermediates vicinal iodohydrins.7 The mild method
presented in Table 3 showed high efficiency compared to
previous synthesis of iodohydrins from epoxide.8 For
NTs
1b
example, reaction of iodine with epoxide 5b or 5c pro-
moted by thiophenol afforded the corresponding product
regioselectively in 90% and 99% yield in 1 minute, re-
spectively. (Table 3, entries 2 and 3)
3
95
90
NHTs
NTs
I
1c
4
NHTs
I
In conclusion, we have developed a highly efficient and
convenient method for the ring-opening reactions of
aziridines or epoxides with iodine promoted by thio-
phenol. These reactions go to completion in one minute
under mild conditions to afford the desired products in
good to excellent yields. The advantages of this novel
method include: (1) avoiding using heavy and/or ex-
pensive metal salts as reagents, (2) experimentally opera-
tional ease, and (3) mild conditions with extremely high
efficiency.
NTs
1d
5
6
90
99
NTs
I
Ph
NHTs
I
Ph
1e
2e
NTs
p-ClC6H4
NHTs
NHTs
p-ClC6H4
1f
2f
7
8
75
98
98
93
NTs
I
Table 3 Ring-Opening of Epoxide 5 with Iodine Promoted by
p-MeC6H4
Thiophenol9
p-MeC6H4
1g
2g
I2 (0.5 equiv)
PhSH (1.0 equiv)
R1
R2
OH
I
R1
R2
NHTs
NTs
I
O
I
NHTs
NHTs
n-C4H9
air, r.t., <1 min
+
n-C4H9
n-C4H9
1h
6
5
2h/3h (10:1)
9
Entry
1
Epoxide 5
Product
Yield (%)a
84
NTs
NHTs
I
n-C8H17
I
+
n-C8H17
n-C8H17
OH
1i
2i/3i (12:1)
O
I
10
NHTs
I
NTs
5a
I
NHTs
6a
+
15
15
15
2
3
90
99
I
O
1j
2j/3j (10:1)
OH
Ph
Ph
11
98
Ts
I
5b
6b
N
NHTs
Me
O
OH
Ph
Ph
Cl
Cl
I
1k
5c
2k (syn/anti = 1:7)
6c
a Isolated yields based on aziridine 1.
Synlett 2006, No. 15, 2489–2491 © Thieme Stuttgart · New York
a Isolated yields based on epoxide 4.

LETTER
Highly Efficient Ring-Opening of Aziridines or Epoxides
2491
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Acknowledgment
We thank Professor Pengyuan Yang for his invaluable advice du-
ring the course of this research. We also thank Dr. Jason Wong for
English polishing. Financial support from National Natural Science
Foundation of China (20502004), Ministry of Education of China,
the Science and Technology Commission of Shanghai Municipality
(05ZR14013), and Fudan University is gratefully acknowledged.
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(9) General Procedure for the Reactions of Aziridines 1 or
Epoxide 4 with Iodine Promoted by Benzenethiol
Benzenethiol (1.0 equiv) was added to a solution of aziri-
dines 1 or epoxide 4 (0.30 mmol) and iodine (0.15 mmol) in
CH2Cl2 (2.0 mL). The reaction mixture was stirred at r.t.
(open to air). After the reaction was completed in 1 min, the
mixture was purified directly by flash column chromatog-
raphy on silica gel afforded the corresponding product.
Data of New Compounds
N-(2-Iodocycloheptyl)-4-methylbenzenesulfonamide (2c):
1H NMR (400 MHz, CDCl3): d = 1.41–1.69 (m, 7 H), 1.95–
2.10 (m, 3 H), 2.43 (s, 3 H), 3.63–3.64 (m, 1 H), 4.25–4.27
(m, 1 H), 5.35 (d, J = 6.8 Hz, 1 H), 7.31 (d, J = 7.8 Hz, 2 H),
7.80 (d, J = 8.3 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
d = 21.6, 22.4, 26.0, 27.2, 31.6, 36.0, 38.6, 63.0, 127.5,
129.7, 137.0, 143.6 ppm. MS: m/z = 393 [M+]. HRMS:
m/z calcd for C14H20INO2S: 393.0259; found: 393.0264.
N-(1-Iodooctadecan-2-yl)-4-methylbenzenesulfonamide-
(2j): 1H NMR (400 MHz, CDCl3): d = 0.87 (t, J = 6.4 Hz, 3
H), 1.12–1.42 (m, 30 H), 2.43 (s, 3 H), 2.92–3.01 (m, 1 H),
3.14–3.25 (m, 2 H), 4.89 (d, J = 8.3 Hz, 1 H), 7.30 (d, J = 8.3
Hz, 2 H), 7.79 (d, J = 8.3 Hz, 2 H) ppm. 13C NMR (100
MHz, CDCl3): d = 14.1, 14.7, 21.5, 22.7, 25.2, 28.7, 29.0,
29.2, 29.4, 29.5, 29.7, 31.9, 35.5, 52.6, 127.1, 129.8, 137.9,
143.6 ppm. MS: m/z = 549 [M+]. HRMS: m/z calcd for
C25H44INO2S: 549.2137; found: 549.2132.
N-(2-Iodooctadecyl)-4-methylbenzenesulfonamide (3j): 1H
NMR (400 MHz, CDCl3): d = 0.87 (t, J = 6.4 Hz, 3 H), 1.20–
1.42 (m, 30 H), 2.43 (s, 3 H), 3.20–3.24 (m, 2 H), 3.98–4.01
(m, 1 H), 5.12 (t, J = 6.4 Hz, 1 H), 7.30 (d, J = 8.3 Hz, 2 H),
7.79 (d, J = 8.3 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
d = 14.1, 14.7, 21.5, 22.7, 25.2, 28.7, 29.0, 29.2, 29.4, 29.5,
29.7, 31.9, 35.5, 52.6, 127.1, 129.8, 137.9, 143.6 ppm. MS:
m/z = 549 [M+]. HRMS: m/z calcd for C25H44INO2S:
549.2137; found: 549.2132.
N-(1-Iodo-1-phenylpropan-2-yl)-4-methylbenzenesulfona-
mide (anti-2k): 1H NMR (400 MHz, CDCl3): d = 1.16 (d,
J = 6.4 Hz, 3 H), 2.42 (s, 3 H), 3.06–3.10 (m, 1 H), 4.92 (d,
J = 8.8 Hz, 1 H), 5.15 (d, J = 4.4 Hz, 1 H), 7.21–7.35 (m, 7
H), 7.73 (d, J = 8.3 Hz, 2 H) ppm.
N-(1-Iodo-1-phenylpropan-2-yl)-4-methylbenzenesulfona-
mide (syn-2k): 1H NMR (400 MHz, CDCl3): d = 1.14 (d,
J = 6.4 Hz, 3 H), 2.38 (s, 3 H), 3.59–3.60 (m, 1 H), 4.80 (d,
J = 8.3 Hz, 1 H), 5.05 (d, J = 5.8 Hz, 1 H), 7.21–7.35 (m, 7
H), 7.73 (d, J = 8.3 Hz, 2 H) ppm. MS: m/z = 415 [M+].
HRMS: m/z calcd for C16H18INO2S: 415.0103; found:
415.0106.
(6) (a) Capaccio, C. A. I.; Varela, O. Carbohydrate Res. 2005,
340, 2104. (b) Blazejewski, J. C.; Dorme, R.; Wakselman,
C. Synthesis 1985, 1120.
Synlett 2006, No. 15, 2489–2491 © Thieme Stuttgart · New York