An efficient method for the ring opening of epoxides with aromatic amines catalyzed by bismuth trichloride

Article abstract of DOI:10.1016/S0040-4039(02)01896-8

We describe here the nucleophilic opening of epoxides with aromatic amines in the presence of a catalytic amount of BiCl₃. The mild reaction conditions and the low toxicity of bismuth salts make this procedure particularly attractive for the sy

Full text of DOI:10.1016/S0040-4039(02)01896-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7891–7893
An efficient method for the ring opening of epoxides with
aromatic amines catalyzed by bismuth trichloride
Thierry Ollevier* and Guillaume Lavie-Compin
De´partement de chimie, Universite´ Laval, Que´bec (Que´bec), Canada G1K 7P4
Received 26 August 2002; accepted 5 September 2002
Abstract—We describe here the nucleophilic opening of epoxides with aromatic amines in the presence of a catalytic amount of
BiCl3. The mild reaction conditions and the low toxicity of bismuth salts make this procedure particularly attractive for the
synthesis of b-amino alcohols. © 2002 Elsevier Science Ltd. All rights reserved.
Due to their ease of formation and wide reactivity with
nucleophiles, epoxides are used as starting materials
and intermediates in organic synthesis. The nucleophilic
opening of these epoxides has been studied extensively
since it provides a suitable route to the formation of
CꢀC, CꢀN, CꢀO or CꢀS s-bonds. There are several
references to the opening of epoxides with alcohols,
thiols and amines, but aromatic amines have received
less attention, perhaps because of their high affinity to
Lewis acids. Therefore, we planned to develop an
efficient catalytic ring opening reaction of meso-epox-
ides with aniline derivatives.
limitations, we report herein a mild and efficient
method for the nucleophilic opening of meso-epoxides
with anilines catalyzed by bismuth(III). The corre-
sponding trans-b-amino alcohols are obtained in good
yields using bismuth chloride as a catalyst.
Due to the interest in the use of bismuth compounds as
environmentally friendly reagents for organic synthe-
sis,18,19 we undertook a study of the utility of bismuth
chloride as a catalyst for the opening of epoxides with
aromatic amines. Bismuth compounds have attracted
recent attention due to their low toxicity,20 low cost,
and good stability. Bismuth salts have been recently
reported as catalysts for rearrangement of epoxides to
aldehydes and ketones,21 opening of epoxysilanes,22
cleavage of epoxides with alcohols,23 acylation of alco-
hols,24,25 formation of acetals,26,27 deprotection of
acetals,28,29 Friedel–Crafts acylations and sulfonyla-
tions,30–33 Diels–Alder reactions,34 aza-Diels–Alder
b-Amino alcohols are an important class of organic
compounds, which have found much use in medicinal
chemistry and organic synthesis.1,2 The classical synthe-
sis of b-amino alcohols consists of heating an epoxide
with an excess of amine at elevated temperatures.3 Since
some functional groups may be susceptible to high
temperatures, a variety of catalysts have been intro-
duced for the cleavage of epoxides at room tempera-
ture.4–17 However, there are still some limitations with
the literature methods; for example, deactivated amines
fail to open up these epoxides or still require high
temperatures. Furthermore, many of the catalysts used
are either corrosive or expensive. To overcome these
reactions,34–37
and
intramolecular
Sakurai
cyclizations.38,39
The reaction was carried out by adding bismuth trichlo-
ride to a mixture of epoxide and amine in a suitable
solvent at room temperature (Scheme 1). The optimum
Scheme 1.
Keywords: bismuth; bismuth(III) chloride; epoxide; aromatic amine; beta-amino alcohol; catalysis.
* Corresponding author. Tel.: +1-418-656-5034; fax: +1-418-656-7916; e-mail: thierry.ollevier@chm.ulaval.ca
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01896-8

7892
T. Olle6ier, G. La6ie-Compin / Tetrahedron Letters 43 (2002) 7891–7893
insoluble in common organic solvents and is used in
cyclohexane as a suspension.
ratio of bismuth trichloride was found to be 10%. The
reaction mixture was stirred at room temperature for
6–24 h to give the corresponding trans-b-amino alco-
hols in good yields (Table 1).
The trans stereochemistry of the b-amino alcohols was
determined from the coupling constants of the C–H
1
protons a to the heteroatoms in the H NMR spectra.
The best results were obtained using 0.1 equiv. of BiCl3
and 1.1 equiv. of the aniline. The procedure works well
with differently substituted anilines (Scheme 1, Table
1). In the first place, we examined the reaction of
cyclohexene oxide with aniline and 0.1 equiv. BiCl3 at
20°C to give the corresponding b-amino alcohol 3a in
84% yield (entry 4). This success encouraged us to
exploit the generality of this reaction by opening that
epoxide with various amines. For example, cyclohexene
oxide was treated with amines such as o-methylaniline
(entry 5), p-methylaniline (entry 6), o-methoxyaniline
(entry 8), p-methoxyaniline (entry 9) to isolate the
corresponding alcohols in good yields. Sterically more
hindered anilines such as o-methylaniline or o-
methoxyaniline led to the alcohols still in good yields.
Electron deficient amines like p-trifluoromethylaniline
led also to the corresponding b-amino alcohol in good
yield (entry 7). Cyclopentene oxide also afforded the
b-amino alcohols in good yield (entries 11–14). The
isolated yields for the amino alcohols were in the range
For example, the trans stereochemistry of the com-
pound 3c was assigned from the coupling constants of
the peaks at 3.31 ppm (ddd, J=10.5, 9.2, 4.1 Hz,
CH
6
-NHAr) and 3.31 ppm (ddd, J=10.5, 9.7, 4.4 Hz,
1
CH
6
-OH) in the H NMR spectrum.12
The general procedure for the b-amino alcohol synthe-
sis can be described as follow. To a mixture of epoxide
1 (1 mmol) and amine 2 (1.1 mmol) in the solvent (0.5
mL) was added anhydrous BiCl3 (0.10 mmol) at 20°C
for 7–11 h (20–24 h for the opening of cyclopentene
oxide).
It was quenched by the addition of aqueous sodium
hydrogen carbonate, extracted with dichloromethane,
dried over anhydrous sodium sulfate, filtered, and con-
centrated under vacuum (rotary evaporator). The
residue was purified by column chromatography on
silica gel using chloroform as eluent. All the com-
1
pounds were fully characterized by IR, H NMR, and
of 65–85%. Except for entries
1 and 3 where
13C NMR by comparison with the known
compounds.40
dichloromethane or diethyl ether were chosen, cyclo-
hexane was usually the solvent of choice. Among vari-
ous solvents tested, it was indeed found to be the best
solvent for the epoxide opening. Bismuth chloride is
In summary, we have demonstrated a novel, mild and
efficient method for the ring opening of meso-epoxides
with aromatic amines using bismuth trichloride as a
catalyst. To the best of our knowledge, the above
catalyst is not known to catalyze epoxide opening
reaction with aromatic amines. This method is compat-
ible with deactivated and sterically hindered aromatic
amines. Advantages of this method include low toxicity
and low cost of the Lewis acid catalyst, and insensitiv-
ity of the Lewis acid to air and moisture.
Table 1. Bismuth trichloride catalyzed epoxide opening
with aromatic amines produced via Scheme 1
Entry
Solventa
Amino alcohol
Yield (%)b
1
2
3
4
5
6
7
8
9
3a
3a
3a
3a
3b
3c
3d
3e
3f
CH2Cl2 (1 M)
C6H12 (1 M)
Et2O (1 M)
C6H12
C6H12
C6H12
C6H12
C6H12
C6H12
Ar=Ph
Ar=Ph
Ar=Ph
Ar=Ph
Ar=o-CH3Ph
Ar=p-CH3Ph
Ar=p-CF3Ph
Ar=o-OCH3Ph 70
Ar=p-OCH3Ph 65
78
78
72
84
68
69
85
Acknowledgements
This research was supported by NSERC (Canada) and
Universite´ Laval.
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;
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