Bismuth triflate-catalyzed mild and efficient epoxide opening by aromatic amines under aqueous conditions

Article abstract of DOI:10.1016/j.tetlet.2003.10.129

Bismuth triflate catalyzes the ring opening of epoxides with aromatic amines under aqueous conditions. The reaction proceeds rapidly and affords the corresponding β-amino alcohols in excellent yields.

Full text of DOI:10.1016/j.tetlet.2003.10.129

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 49–52
Bismuth triflate-catalyzed mild and efficient epoxide opening
by aromatic amines under aqueous conditions
Thierry Ollevier* and Guillaume Lavie-Compin
Deꢀpartement de chimie, Universiteꢀ Laval, Queꢀbec (Queꢀbec), Canada G1K 7P4
Received 7 October 2003; revised 20 October 2003; accepted 22 October 2003
Abstract—Bismuth triflate catalyzes the ring opening of epoxides with aromatic amines under aqueous conditions. The reaction
proceeds rapidly and affords the corresponding b-amino alcohols in excellent yields.
Ó 2003 Elsevier Ltd. All rights reserved.
Due to their ease of formation and wide reactivity with
nucleophiles, epoxides are often used as starting mate-
rials and intermediates in organic synthesis. The nucleo-
philic opening of these epoxides has been studied
extensively and there are several references to the
opening of epoxides with alcohols, thiols, and amines,1–3
but aromatic amines have received less attention, per-
haps because of their high affinity to Lewis acids.
Therefore, we planned to develop an efficient catalytic
ring opening reaction of meso-epoxides with anilines in
water.
with anilines. This method provides good yields of the
corresponding trans-b-amino alcohols.18
Bismuth compounds have attracted recent attention due
to their low toxicity,19 low cost, and good stability.20–22
Bismuth salts have been reported as catalysts for allyla-
tion of imines,23 rearrangement of epoxides to aldehydes
and ketones,24 opening of epoxides,18;25;26 formation and
deprotection of acetals,27–30 Friedel–Crafts reactions,31–34
Diels–Alder reactions,35;36 and intramolecular Sakurai
cyclizations.37;38
b-Amino alcohols are an important class of organic
compounds, which have found much use in medicinal
chemistry and organic synthesis.4;5 The classical syn-
thesis of b-amino alcohols consists of heating an epoxide
with an excess of amine at elevated temperatures.6 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.1;3;7–17 However, there are still some limitations with
the existing methods; for example, deactivated amines
fail to open these epoxides or still require high temper-
atures. Furthermore, many of the catalysts used are
either corrosive or expensive. To overcome these limi-
tations, we previously reported the use of BiCl3 as an
efficient catalyst for the nucleophilic opening of epoxides
In this context, we have examined bismuth triflate as a
Lewis acid for the opening of epoxides. Recently, great
attention has been paid to the development of organic
reactions in water. We wish to report our new method
for epoxide opening using Bi(OTf)3 under aqueous
conditions instead of BiCl3 in an organic solvent.
Bi(OTf)3 can be easily prepared from commercially
available starting materials.39;40 We have already studied
the use of BiCl3 (10%) as an efficient catalyst for the
nucleophilic opening of cyclohexene oxide with aniline
in cyclohexane. Compared to BiCl3, Bi(OTf)3 is partic-
ularly attractive because it can be used in water.41;42 As it
has been demonstrated that a water solution of Bi(OTf)3
is acidic,43 it may be possible that the true catalyst is
TfOH released from hydrolysis of Bi(OTf)3. However,
the observation that TfOH is not as effective as Bi(OTf)3
to catalyze the epoxide opening (1 equiv aniline, 1 equiv
cyclohexene epoxide, 10% TfOH, 25 °C, 7 h, 28%) sug-
gests that a Lewis acid is likely involved in activating the
epoxide. The corresponding trans-b-amino alcohol 3a
was obtained in good yield with BiCl3 (Table 1, entry
1).18 When the reaction was run with Bi(OTf)3 (10%)
Keywords: bismuth; bismuth(III) triflate; epoxide; aromatic amine;
beta-amino alcohol; aqueous conditions.
* Corresponding author. Tel.: +1-418-656-5034; fax: +1-418-656-7916;
e-mail: thierry.ollevier@chm.ulaval.ca
0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.129

50
T. Ollevier, G. Lavie-Compin / Tetrahedron Letters 45 (2004) 49–52
Table 1. Bismuth(III) catalyzed epoxide opening with aromatic amines
produced via Scheme 1
good yields (Table 2). The procedure worked well with
anilines bearing a variety of substituents (Scheme 2,
Table 2). Cyclohexene oxide was treated with amines
such as p-methylaniline (entry 3) to isolate the corre-
sponding b-amino alcohols in good yields. Sterically
more hindered anilines such as o-methylaniline also led
to the alcohols in good yield (entry 2). The corre-
sponding b-amino alcohol was also produced efficiently
when less nucleophilic amines like p-trifluoromethyl-
aniline were used in the same conditions (entry 4).
Electron rich amines like p-methoxyaniline afforded the
product in good yield as well (entry 5). In some cases
where the starting materials precipitated out of the re-
action mixture, the ring opening reaction was studied in
a micellar solution of sodium dodecyl sulfate (SDS)44
and the product could be obtained with a substantially
improved yield. The use of p-trifluoromethylaniline and
p-bromoaniline as nucleophiles led to good yields of the
amino alcohols using 40% SDS in water (Table 2, entries
4 and 6). However, it should be pointed out that the
addition of 40% SDS did not afford the b-amino alcohol
with a better yield for cases where SDS was not neces-
sary.
Entry
X
Solventa
Yield (%)b
1
2
3
4
Cl
Cyclohexane
Cyclohexane
Et2O
78
76
84
83
OTf
OTf
OTf
H2O
a Substrates 1 and 2 were mixed in 1:1 ratio with 10% BiX3 at 25 °C.
b Refers to yield of isolated product.
either in cyclohexane or diethyl ether, the b-amino
alcohol was obtained in very similar yields (Table 1,
entries 2 and 3). The ring opening reaction was finally
studied in water (Table 1, entry 4) and the b-amino
alcohol 3a was isolated in a good yield (83%).
Encouraged by our results in the nucleophilic opening
reaction catalyzed by 10% Bi(OTf)3 in water, we studied
the scope and limitations of this reaction with respect
to the aniline and meso-epoxide employed in the process.
The results are summarized in Table 2.
The reaction was carried out by adding Bi(OTf)3 to a
mixture of epoxide and amine in an aqueous solution at
room temperature (Scheme 1). The optimum amount of
Bi(OTf)3 was found to be 10 mol %. The biphasic reac-
tion mixture was stirred at room temperature for 7–24 h
to give the corresponding trans-b-amino alcohols in
The same method was also effective for the opening re-
action of cyclopentene oxide affording the correspond-
ing b-amino alcohols (entries 7–10) albeit with lower
yields (62–69%) after longer reaction times (21–24 h).
Aliphatic amines have also been employed using these
Table 2. Bismuth triflate catalyzed epoxide opening with aromatic amines produced via Scheme 2
Entry
t (h)
Additive
Amino alcohol
Yield (%)a;b
OH
NHAr
1
2
3
4
5
6
3a
3b
3c
3d
3e
3f
7
9
9
8
9
8
––
––
Ar ¼ Ph
83
86
84
79
77
84
Ar ¼ o-CH3C6H4
Ar ¼ p-CH3C6H4
Ar ¼ p-CF3C6H4
Ar ¼ p-CH3OC6H4
Ar ¼ p-BrC6H4
––
40% SDS
––
40% SDS
OH
NHAr
7
3g
3h
3i
24
24
21
23
40% SDS
40% SDS
––
Ar ¼ Ph
68
62
63
69
8
Ar ¼ o-CH3C6H4
Ar ¼ p-CH3C6H4
Ar ¼ p-CF3C6H4
9
10
3j
––
a Substrates 1 and 2 were mixed in 1:1 ratio with 10% Bi(OTf)3 at 25 °C.
b Refers to yield of isolated product. All products have been previously reported in the literature.
OH
10% BiX3
+
O
H2N
Solvent, 25 °C, 7-9 h
N
H
1
2
3a
Scheme 1.

T. Ollevier, G. Lavie-Compin / Tetrahedron Letters 45 (2004) 49–52
51
OH
R
10% Bi(OTf)3•nH2O
+
O
H2N
H2C
H2C
R
n
n
H2O, SDS (0-40%), 25 °C
N
H
1
2
n = 1, 2
3
Scheme 2.
7. Chandrasekhar, S.; Ramachandar, T.; Prakash, S. J.
Synthesis 2000, 1817–1818.
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yields (1 equiv piperidine, 1 equiv cyclohexene epoxide,
10% Bi(OTf)3, 25 °C, 24 h, 74%; 1 equiv cyclohexyl-
amine, 1 equiv cyclohexene epoxide, 10% Bi(OTf)3, 40%
SDS, 25 °C, 18 h, 78%).
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The general procedure for the Bi(OTf)3-catalyzed
epoxide opening can be described as follows. To a mix-
ture of epoxide 1 (1 mmol) and amine 2 (1 mmol) in
water (1 mL) was added Bi(OTf)3 (0.10 mmol) at 25 °C
for 7–9 h (21–24 h for the opening of cyclopentene
oxide). The resulting biphasic mixture of liquids was
magnetically stirred. In the case where the reagents were
precipitated, SDS (40%) was added. The reaction mix-
ture was quenched by the addition of aqueous sodium
hydrogen carbonate, extracted with ether, dried over
anhydrous sodium sulfate, filtered, and concentrated
under vacuum (rotary evaporator). The residue was
purified by column chromatography on silica gel using
hexanes/ethyl acetate as eluent. All the compounds were
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1
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This method offers several advantages including aque-
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Acknowledgements
This work was financially supported by NSERC
ꢀ ꢀ
(Canada), FQRNT (Quebec, Canada) and Universite
Laval.
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