Antimony(III) chloride-catalyzed ring opening of epoxides with anilines

Article abstract of DOI:10.1016/j.tetlet.2007.08.023

A mild and convenient ring opening of epoxides with aniline and its derivatives takes place at room temperature in the presence of antimony trichloride as catalyst to afford the corresponding β-amino alcohols in good yields.

Full text of DOI:10.1016/j.tetlet.2007.08.023

Tetrahedron Letters 48 (2007) 7354–7357
Antimony(III) chloride-catalyzed ring opening
of epoxides with anilines
Mahesh Chander Singh and Rama Krishna Peddinti*
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India
Received 5 July 2007; revised 3 August 2007; accepted 6 August 2007
Available online 10 August 2007
Abstract—A mild and convenient ring opening of epoxides with aniline and its derivatives takes place at room temperature in the
presence of antimony trichloride as catalyst to afford the corresponding b-amino alcohols in good yields.
Ó 2007 Published by Elsevier Ltd.
b-Amino alcohols are versatile intermediates for the
preparation of natural products and pharmacologically
important targets and are used extensively as chiral aux-
iliaries and ligands.1–4 The most practical and widely
employed strategy for the synthesis of b-amino alcohols
is the direct aminolysis of epoxides with an excess of
amine at elevated temperature.5 However, high temper-
ature is detrimental to some functional groups and is
also not ideal for control of regioselectivity. To circum-
vent these problems, a variety of activators such as
Lewis acids and metal salts have been introduced for
the ring opening of epoxides with amines. These include
Sn(OTf)2,6a Cu(OTf)2,6a Bi(OTf)3,6b,c Al(OTf)3,6d
TaCl5,7a InCl3,7b BiCl3,7c VCl3,7d ZnCl4,7e InBr3,7f
CoCl2,7g Cu(BF4)2,8 Zn(ClO4)2,9 heteropoly acids,10
ionic liquids,11 and fluoro alcohols.12 Limitations such
as low yields, failure of deactivated amines and sterically
demanding aromatic amines are associated with most of
the literature methods. Therefore, the introduction of
new and efficient methods are still in demand.
SbCl3 in solvents such as cyclohexane and dichloro-
methane at room temperature. The reaction in dichloro-
methane produced trans-2-phenylaminocyclohexanol (1)
in better yield. To optimize the catalyst loading, the
reactions were carried out with 2 mol %, 5 mol %,
10 mol %, and 15 mol % catalyst in dichloromethane
and the efficiency of the catalyst loading was determined
from the time needed for the complete conversion of the
starting materials to products by monitoring the reac-
tion by TLC at regular intervals. It was found that at
lower catalyst loadings the reaction proceeded slowly
(15–20 h for 2 and 5 mol %), whereas the reaction
reached completion in 7 h with 10 mol % of catalyst
and the product was isolated in 85% yield. There was
not much improvement on the rate of reaction with
15 mol % SbCl3.
Encouraged by this result, several structurally diverse
aniline derivatives were investigated for the ring-opening
reaction with cyclohexene oxide (Scheme 1, Table 1).
Thus cyclohexene oxide was treated with 4-bromoani-
line, 4-chloroaniline, and p-anisidine under catalytic
influence of SbCl3 to furnish the corresponding b-amino
alcohols 2–4 in high yields13 (entries 2–4). Likewise,
4-trifluoromethylaniline and 3,5-dimethylaniline also
In the course of our investigations on catalytic asymmet-
ric synthesis, we required racemic b-amino alcohols. For
this purpose we chose antimony trichloride as a new
activator for the aminolysis of epoxides. Herein we dis-
close our results on the SbCl3-mediated mild and conve-
nient ring opening of meso-epoxides with aromatic
amines.
OH
SbCl3
H2N
O
+
n
n
At the outset of this work, we studied cyclohexene oxide
ring-opening with aniline in the presence of 10 mol %
CH2Cl2, RT
4-20 h
R
N
H
R
n = 1, 2
1-16
*
Corresponding author. Tel.: +91 133 228 5438; fax: +91 133 227
3560; e-mail: rkpedfcy@iitr.ernet.in
Scheme 1.
0040-4039/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2007.08.023

M. C. Singh, R. K. Peddinti / Tetrahedron Letters 48 (2007) 7354–7357
7355
Table 1. Ring opening of epoxides with various anilines at room temperature using antimony trichloridea
Entry
Epoxide
Nucleophile
Time (h)
Product
Yieldb (%)
OH
O
H2N
1
7
1
2
3
4
5
85
80
85
83
85
N
H
OH
2
3
4
5
4
4
8
6
H2N
H2N
H2N
H2N
Br
N
H
Br
Cl
OH
Cl
N
H
OH
OMe
CF3
N
H
OMe
OH
N
H
CF3
OH
6
7
8
8
6
7
75
72
H2N
H2N
N
H
OH
N
H
OH
8
9
20
12
8
8
9
46
82
86
85
H2N
H2N
H2N
H2N
NO2
N
H
NO2
OH
O
N
H
OH
10
11
10
11
Br
Cl
N
H
Br
Cl
OH
7
N
H
OH
12
13
10
15
12
13
83
80
H2N
H2N
OMe
CF3
N
H
OMe
CF3
OH
N
H
OH
14
15
14
83
H2N
N
H
(continued on next page)

7356
M. C. Singh, R. K. Peddinti / Tetrahedron Letters 48 (2007) 7354–7357
Table 1 (continued)
Entry
Epoxide
Nucleophile
Time (h)
15
Product
Yieldb (%)
72
OH
15
16
15
16
H2N
N
H
OH
20
54
H2N
NO2
N
H
NO2
a The reactions were carried out with 5 mM epoxide, 5 mM of aromatic amine in the presence of 0.5 mM of SbCl3 in 5 mL of dichloromethane.13
b Yield of pure and isolated products.
underwent facile ring-opening with cyclohexene oxide
to afford the desired products 5 and 6 in high yields after
6–8 h (entries 5 and 6). The structurally demanding 2,6-
dimethylaniline reacted smoothly offering amino alcohol
7 in good yield (entry 7). The reaction of 4-nitroaniline
did not reach completion and therefore, this reaction
was stopped at 20 h to produce b-amino alcohol 8 in
acceptable yield (entry 8). The decreased reactivity of
4-nitroaniline may be due to the fact that the deactivat-
ing nitro functionality diminishes the nucleophilicity of
this aniline.
Acknowledgements
We thank the Department of Science and Technol-
ogy, New Delhi, for providing financial assistance.
M.C.S. thanks MHRD, New Delhi, for the award of
fellowship.
References and notes
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ogy are summarized in Table 1. Again, a very clean reac-
tion was observed in each case studied, albeit with
slightly longer reaction times. The nucleophilic opening
of cyclopentene oxide with various substituted aniline
derivatives proceeded smoothly to provide the corre-
sponding b-amino alcohols 9–16 in yields comparable
to those of cyclohexene oxide-derived b-amino alcohols
1–8, respectively.
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The structures of b-amino alcohols 1–16 were
1
assigned on the basis of their IR, H and 13C NMR,
and GC–MS spectral analysis. The trans stereochemis-
try of the amino alcohols was deduced from the
coupling constants of the protons on carbons 1 and 2.
1
For example, in the H NMR (500 MHz) spectrum of
2-(phenylamino)cyclohexan-1-ol (1) two 1H signals
appeared at d 3.15 (ddd, J = 13.0, 9.5, 4.0 Hz) and
d 3.36 (ddd, J = 13.5, 9.5, 4.0 Hz) for the CHNH
and CHOH protons, respectively, which are indicative
of trans stereochemistry. Furthermore, the 1H NMR
data of the b-amino alcohols were in accordance
with those of the compounds reported in the
literature.6a,7c,12,14
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In conclusion, we have demonstrated a mild and efficient
method for the preparation of b-amino alcohols using
SbCl3 as a catalyst. To the best of our knowledge, anti-
mony trichloride is not known to catalyze aminolysis of
epoxides with aniline and its derivatives. The worthy
feature of this transformation is that highly deactivated
and sterically demanding anilines also served as nucleo-
philes for the ring opening of epoxides.
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´
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13. General procedure: To a mixture of epoxide (5 mM) and
amine (5 mM) in dichloromethane (5.0 mL) was added
anhydrous SbCl3 (0.5 mM) at room temperature and the

M. C. Singh, R. K. Peddinti / Tetrahedron Letters 48 (2007) 7354–7357
7357
reaction contents were stirred for a period of time as
indicated in Table 1. Then the reaction mixture was
quenched by the addition of aqueous NaHCO3, and
extracted with dichloromethane. The organic layer was
dried over anhydrous Na2SO4 and concentrated. The
residue was purified by column chromatography (silica
gel, hexanes/ethyl acetate) to furnish pure trans-2-
arylaminocycloalkanol.
14. Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.
Eur. J. Org. Chem. 2001, 4149.