NaHSO3-Promoted ring openings of n-tosylaziridines and epoxides with H2O

Article abstract of DOI:10.3987/COM-13-12885

NaHSO₃-oriented ring openings of a wide variety of N-tosylaziridines and epoxides with H₂O under mild conditions in acetone was found to be a convenient and effective method, which provided the desired ss-aminoalcohols and ss-diols in good to excellent yields and with uniformly high regioselectivity.

Full text of DOI:10.3987/COM-13-12885

HETEROCYCLES, Vol. 89, No. 4, 2014
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HETEROCYCLES, Vol. 89, No. 4, 2014, pp. 1009 - 1015. © 2014 The Japan Institute of Heterocyclic Chemistry
Received, 14th November, 2013, Accepted, 24th February, 2014, Published online, 6th March, 2014
DOI: 10.3987/COM-13-12885
NaHSO3-PROMOTED RING OPENINGS OF N-TOSYLAZIRIDINES AND
EPOXIDES WITH H2O
Xing Li, Bin Ni, Hong-Hong Chang, and Wen-Long Wei*
Department of Chemistry and Chemical Engineering, Taiyuan University of
Technology, 79 West Yingze Street, Taiyuan 030024, P. R. of China. Fax: (+86)
0351-6111165. E-mail: weiwenlong@tyut.edu.cn
Abstract – NaHSO3-oriented ring openings of a wide variety of N-tosylaziridines
and epoxides with H2O under mild conditions in acetone was found to be a
convenient and effective method, which provided the desired β-aminoalcohols and
β-diols in good to excellent yields and with uniformly high regioselectivity.
β-Aminoalcohols are very useful building blocks for the preparation of drugs, natural products and
relevant compounds.1,2 Due to their synthetic value and pharmacological properties, considerable interest
and effort have been focused on the construction of β-aminoalcohols and their derivatives.3 In recent
years, some attractive methods for the synthesis of them have been developed.4-9 Among these methods,
the ring openings of N-tosylaziridines with H2O provides direct access to them, and several catalysts and
activators have been employed and identified for this transformation, respectively.10 Despite these
creative efforts and significant progress, the discovery of new catalysts or activators which are cheaper
and more efficient and the development of new methods which are more effective remain urgent.
NaHSO3 has been applied to the ring-opening reactions of nonactivated aziridines as a nucleophilic
reagent.11 Herein, we will describe another new and successful application of NaHSO3 as a promoting
reagent in the ring opening.
We began with our studies by selecting the ring opening of N-tosylcyclohexylaziridine12 1a with H2O as
the model reaction and NaHSO3 as a promoting reagent. Initially, the survey of solvents clearly
highlighted the beneficial effect of mixture solvents (Table 1, entries 2-4 vs. 1). It was observed that the
mixture solvent of acetone and H2O (1:1) was the most suitable for this transformation (Table 1, entry
4).13 No ring-opening product was detected when H2O was used as a kind of solvent at 25 C (Table 1,
entry 1).

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HETEROCYCLES, Vol. 89, No. 4, 2014
Table 1. Screening of reaction conditions for ring opening of N-tosylcyclohexylaziridine 1a with H2Oa
OH
NaHSO3
N-Ts
H2O
solvent
NHTs
1a
3a
2
Entry
Solvent
H2O
Yieldb (%)
T (C)
25
1
trace
trace
22
2
DMSO/H2O=1:1
MeCN/H2O=1:1
25
3
25
4
5c
acetone/H2O=1:1
acetone/H2O=1:1
25
33
55
99
a
Unless otherwise noted, all reactions were carried out with N-tosylcyclohexylaziridine 1a
(50 mg, 0.2 mmol) and 1.1 equiv. of NaHSO3 in 1.0 mL solvent under identified conditions
for 24 h. b Isolated yield. c 2.0 equiv. of NaHSO3 and 3.0 mL solvent were used.14
Under these optimized reaction conditions,14 a wide variety of N-tosylaziridines such as aromatic,
aliphatic (cyclic and acyclic), and condensed-ring ones could be smoothly transformed into the desired
ring-opening products in good to excellent yields with high regioselectivity and the results are listed in
Table 2. Except for the N-tosylaziridine 1q which afforded the two corresponding isomers (3q:4q = 9:2)
(Table 2, entry 16), all other N-tosylaziridines showed the remarkable regioselectivity and provided only
single regioisomers 3 (Table 2, entries 2-13). In addition, it was observed that steric hindrance of the
substituent groups at the aromatic ring of N-tosylaziridines played an important role on the reactivity of
this reaction. The para-substituted N-tosylaziridines indicated higher reactivity than those substituted in
ortho- and meta-position (Table 2, entry 5 vs. 3, 4 and entry 8 vs. 6, 7). Excitedly, the N-tosylaziridines
1n could give the desired ring-opening product with the moderate yield (Table 2, entry 14).
Table 2. Ring-opening reactions of various N-tosylaziridines 1 with H2Oa
R1
R2
R1
R2
NH-Ts R1
OH
NaHSO3
N-Ts
H2O
acetone, 55 oC
R2
OH
NH-Ts
1
4
2
3
Entry
1
N-Tosylaziridine 1
Product
t (h)
Yieldb (%)
99
OH
24
N-Ts
1a
NHTs
3a

HETEROCYCLES, Vol. 89, No. 4, 2014
1011
OH
N-Ts
N-Ts
NHTs
2
12
99
1b
3b
OH
Me
NHTs
3
4
5
10
4
99
96
92
Me
1c
3c
OH
OH
N-Ts
Me
Me
NHTs
3d
1d
N-Ts
NHTs
2
Me
Me
3e
1e
OH
Cl
N-Ts
NHTs
6
7
8
36
24
9
97
92
81
Cl
3f
1f
OH
OH
N-Ts
Cl
Cl
NHTs
NHTs
3g
1g
N-Ts
Cl
Cl
3h
1h
OH
N-Ts
NHTs
9
4
93
OMe
OMe
3i
3j
1i
OH
N-Ts
MeO
MeO
NHTs
10
11
8
97
83
1j
OH
N-Ts
NHTs
21
3k
3l
1k
OH
N-Ts
NHTs
12
13
3
96
97
1l
OH
N-Ts
NHTs
12
Br
Br
3m
1m

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Ts
NHTs
HO
N
14
15
48
48
53
91
(±)-3n
3o
1n
OH
N-Ts
1o
NHTs
OH
NHTs
12
3q
4q
16
36
62c
N-Ts
12
(3q:4q = 82:18)
1q
OH
12
NHTs
a Unless otherwise noted, all reactions were performed at 0.2 mmol scale of N-tosylaziridines 1 and 2.0 equiv.
of NaHSO3 (41.9 mg) in 3 mL of mixture solvent of acetone/water (1:1) under air atmosphere at 55C within
specified time. b Isolated yield. c Combined yield of isolated 3q and 4q.
Moreover, from a practical point of view, epoxides as substrates were also tested to obtain β-diols for
examining the scope of application of the reaction system under the optimal conditions. It can be seen
from Table 3 that various epoxides could be hydrolyzed to give the desired 1,2-diols in good to excellent
yields using NaHSO3 as a catalyst. The ring-opening reaction of chiral epoxide 1u also proceeded
smoothly and provided product 3u in 87 yield (Table 3, entry 4).
a
Table 3. The hydrolysis of epoxides in the presence of NaHSO3
R3
R3
OH
OH
NaHSO3
O
H2O
acetone, 55 oC
R4
R4
1
2
3
Entry
1
Epoxide 1
Product
t (h)
Yieldb (%)
82
OH
36
O
1r
OH
HO
3r
O
2
3
36
40
86
83
4
OH
4
1s
1t
3s
3t
HO
O
OH

HETEROCYCLES, Vol. 89, No. 4, 2014
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HO
O
O
O
4
5
36
28
87
91
1u
OH
3u
3v
OH
O
OH
1v
O
O
O
O
6
40
68
OH
O
OH
1w
3w
a
Unless otherwise noted, all reactions were performed at 0.2 mmol scale of epoxides 1 and 2.0 equiv. of
o
NaHSO3 (41.9 mg) in 3 mL of mixture solvent of acetone/water (1:1) under air atmosphere at 55 C within
specified time. b Isolated yield.
In summary, we have developed a single, practical and efficient method for the synthesis of
β-aminoalcohols through the ring-opening reactions of N-tosylaziridines with H2O using NaHSO3 as a
promoting reagent. All substrates gave high regioselectivity and good to excellent yields. In addition, the
same experimental conditions can be successfully applied in the ring openings of epoxides with H2O to
afford the desired β-diols with good yields.
ACKNOWLEDGEMENTS
We appreciate gratefully the Natural Science Foundation of Shanxi Province (No. 2012021007-2 and No.
2011011010-2) for financial support. The project is also supported by Scientific and Technological
Innovation Programs of Higher Education Institutions in Shanxi (No. 20120006).
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13. The results that some other ratio of acetone to H2O provided were relatively wore.
14. These are the optimal reaction conditions. The screening about experimental parameters can be seen
in the Supporting Information.