A mild and efficient procedure for the oxidation of epoxides and aziridines using cerium(IV) ammonium nitrate and NBS

Article abstract of DOI:10.1016/j.tetlet.2005.04.008

The CAN and NBS combination has been used for the first time for the synthesis of versatile α-hydroxy ketones and α-amino ketones from oxiranes/aziridines, respectively, in excellent yields. This method is a direct, one-pot, synthesis under mild conditions using acetonitrile-water (9:1) as solvent.

Full text of DOI:10.1016/j.tetlet.2005.04.008

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 4111–4113
A mild and efficient procedure for the oxidation of epoxides and
aziridines using cerium(IV) ammonium nitrate and NBSI
K. Surendra, N. Srilakshmi Krishnaveni and K. Rama Rao*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 20 September 2004; revised 30 March 2005; accepted 4 April 2005
Available online 20 April 2005
Abstract—The CAN and NBS combination has been used for the first time for the synthesis of versatile a-hydroxy ketones and
a-amino ketones from oxiranes/aziridines, respectively, in excellent yields. This method is a direct, one-pot, synthesis under mild
conditions using acetonitrile–water (9:1) as solvent.
ꢀ 2005 Elsevier Ltd. All rights reserved.
O
Cerium(IV) ammonium nitrate (CAN) is a powerful
one-electron oxidant useful for a variety of synthetic
transformations.1,2 CAN has become attractive in or-
ganic synthesis due to its ease of handling, non-toxicity
and solubility in organic solvents such as MeOH,
MeCN, etc. We have studied the use of CAN for the
direct synthesis of a-hydroxy ketones and a-amino
ketones from easily accessible epoxides and aziridines,
respectively. However, these reactions resulted in the
formation of diols and hydroxy amines only. Therefore,
to access keto alcohols and amino ketones, we studied
the combination of CAN with NBS, another oxidizing
agent.3 This yielded excellent results. A number of meth-
ods are reported for the synthesis of a-hydroxy
ketones,4–7 but only few methods are available for the
preparation of a-amino arylketones although they are
important in providing an alternative route to biologi-
cally active b-aminoalcohols.8
X
XH
CAN/NBS
CH3CN:H2O
R
R
R=H,Br, Cl, Me, OMe, NO2, COMe
1. X=O
3. X=O
2. X=NTs
4. X=NTS
Scheme 1.
R2
R2
R1
R1
NHTs
CAN/NBS
CH3CN:H2O
NTs
O
R3
R3
a: R1, R3 = -(CH2)n- ; R2 = H
n=3, 4
b: R1 = -(CH2)3 CH3 ; R2, R3 =H
We report the oxidation of oxiranes/aziridines using
ceric ammonium nitrate and NBS to give the corres-
ponding a-hydroxy ketones and a-amino ketones,
respectively, in good yields9 (Schemes 1 and 2).
Scheme 2.
a-hydroxy ketone after simple workup in 94% yield.
However, with phenoxy epoxide the desired keto alcohol
was obtained in very poor yields (ꢀ15%) along with the
corresponding 3-phenoxy-1,2-propanediol (ꢀ45%) and
1-bromo-3-phenoxy-2-propanol (ꢀ30%), whereas with
cycloalkyl epoxides and alkyl epoxides a complex
mixture of products was obtained, which could not be
analyzed. To explore further the utility of this transfor-
mation, phenyl-N-tosylaziridine (Table 3, entry 1) was
treated with a CAN and NBS combination to yield the
a-amino ketones in 92% yield. Encouraged by this
Initially, our efforts began with styrene oxide (Table 2,
entry 1), which was treated with CAN (0.2 equiv) and
NBS (1.0 equiv) in acetonitrile–water (9:1) to give the
Keywords: Oxiranes; Aziridines; a-Hydroxy ketones; a-Amino ketones;
CAN; NBS; Oxidation.
q IICT Communication no. 050321.
*
Corresponding author. Tel.: +91 40 271 93164; fax: +91 40 271
60757; e-mail: ramaraok@iict.res.in
0040-4039/$ - see front matter ꢀ 2005Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.04.008

4112
K. Surendra et al. / Tetrahedron Letters 46 (2005) 4111–4113
Table 1. Oxidation of oxirane/aziridine under various conditionsa
Table 3. Oxidation of aziridines with CAN/NBS
Entry Substrate
Producta
Entry Substrate
CAN
(equiv) (equiv) (h)
NBS
Time Yield
(%)b
Time Yieldb
(h)
(%)
c
1
2
3
4
Styrene oxide
Styrene oxide
Styrene oxide
0.2
—
—
10
10
4
—
1
15d
94
Ts
O
1.0
1.0
—
8
92
N
0.2
NHTs
e
Phenyl-N-tosylaziridine 0.2
N-tosylaziridine
Phenyl-N-tosylaziridine 0.2
12
12
8
—
f
5Phenyl-
—
1.0
1.0
—
92
6
Ts
N
O
a All reactions were carried out at rt.
NHTs
NHTs
b All reactions were analyzed by HPLC and compared with authentic
samples.
2
3
8
8
90
90
Br
Cl
c Only 1-phenyl-1,2-ethanediol was formed.
Br
Cl
Ts
N
O
d Yielded 2-bromo-1-phenyl-1-ethanol, 2-bromo-2-phenyl-1-ethanol
(50% 1:1) and 1-phenyl-1,2-ethanediol (30%) along with keto alcohol.
e Only N-(2-hydroxy-2-phenylethyl)-4-methyl-1-benzene sulfonamide
was formed.2d
f Yielded N-(2-bromo-2-phenylethyl)-4-methyl-1-benzene (35%) and
Ts
N
N-(2-hydroxy-2-phenylethyl)-4-methyl-1-benzene sulfonamide (65%).
O
NHTs
4
5
6
10
10
10
86
89
88
Table 2. Oxidation of epoxides with CAN/NBS
Cl
Producta
Time Yield
(%)b
Cl
Ts
N
O
Entry Epoxide
(h)
NHTs
O
O
1
4
94
Me
Me
OH
Ts
O
N
NHTs
O
O
O
MeO
MeO
OH
OH
2
4
4
92
92
Ts
N
O
Br
Br
NHTs
7
10
90
O
3
O
O
Cl
NHTs
Cl
8
12
12
12
86
88
84
O
O
NTs
NTs
O
OH
4
588
NHTs
O
Cl
Cl
9
O
O
OH
OH
5
8
90
86
CHO
NHTs
Me
Me
10
NTs
O
O
a All the products were characterized by IR, 1H NMR and mass
spectroscopy.
b Isolated yields.
6
8
O2N
O2N
a All the compounds were characterized by 1H NMR, IR and mass
spectroscopy.
b Isolated yields.
Some of the functionalities, which were stable to CAN
and NBS included the bromo, methoxy, methyl, chloro
and acetoxy groups. The a-hydroxy ketones and a-ami-
no ketones synthesized are being explored as building
blocks for new chemical entities. The compounds were
finding cyclopentyl/cyclohexyl-N-tosylaziridines were
oxidized to yield 1-(N-(p-tolylsulfonyl)amino-2-cylco-
pentanone (Table 3, entry 8) and 1-(N-(p-tolylsulfon-
yl)amino-2-cylcohexanone (Table 3, entry 9), respec-
tively. In the case of an acyclic terminal aziridine
(Table 3, entry 10), the reaction was highly regioselective
with the formation of only one product oxidized at the
less hindered terminal carbon.
1
characterized by H NMR, mass spectra, IR and com-
pared with known compounds.5,8
Phenyl oxirane and phenyl-N-tosylaziridine were chosen
for several control experiments to determine the role of
each reagent (Table 1). CAN and NBS are both impor-

K. Surendra et al. / Tetrahedron Letters 46 (2005) 4111–4113
4113
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tant since no reaction occurs or oxidation takes place
if either is omitted.
The oxidation mechanism may be postulated as follows:
CAN first hydrolyses the substrate, which is further oxi-
dized with NBS to give the corresponding keto
products.10
Thus, we have demonstrated that a-hydroxy ketones
and a-amino ketones can be generated directly from
epoxides/aziridines in the presence of CAN and NBS.
6. (a) Filler, R. Chem. Rev. 1963, 63, 21; (b) Macrouchi, F.;
Namy, J. L.; Kagan, H. B. Tetrahedron Lett. 1997, 38,
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Acknowledgements
7. Ho, T. L.; Olah, G. A. Synthesis 1976, 815.
K.S. and N.S.K. thank CSIR, New Delhi, India, for the
award of research fellowships.
8. (a) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Am.
Chem. Soc. 1994, 116, 2742; (b) Du Bois, J.; Hong, J.;
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References and notes
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9. General procedure: To epoxide 1/aziridine 2 (1 equiv) in
5ml of acetonitrile: water (9:1) was added CAN
(0.2 equiv) followed by NBS (1 equiv) and the mixture
was left stirring at room temperature (Table 1 and 2).
After completion of the reaction, the solvent was removed,
the reaction mixture was diluted with water and extracted
with ether (3 · 10 ml). The combined organic extract was
dried over Na2SO4 and concentrated under vacuum. The
crude product was purified by column chroma-
tography on silica gel using n-hexane/ethyl acetate as
eluent.
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