Transition metal-based lewis acid catalyzed ring opening of epoxides using amines under solvent-free conditions

Article abstract of DOI:10.1055/s-2004-817780

Transition metal-based Lewis acids, such as SnCl₄·5H ₂O, Co(OAc)₂·4H₂O, Ni(OAc) ₂·2H₂O, NiCl₂, Mn(OAc) ₂·4H₂O etc. catalyze the nucleophilic opening of epox

Full text of DOI:10.1055/s-2004-817780

846
LETTER
Transition Metal-based Lewis Acid Catalyzed Ring Opening of Epoxides
Using Amines under Solvent-Free Conditions
L
ewis Acid Ca
e
talyzed Rin
i
g Ope
-
ning of
E
Q
poxides ing Zhao, Li-Wen Xu, Chun-Gu Xia*
State key laboratory of Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences,
Lanzhou 730000, P. R. China
Fax +86(931)8277088; E-mail: cgxia@ns.lzb.ac.cn
Received 18 December 2003
rendering them more susceptible to nucleophilic attack
Abstract: Transition metal-based Lewis acids, such as
milder conditions is in high demand.
SnCl4·5H2O,
Co(OAc)2·4H2O,
Ni(OAc)2·2H2O,
NiCl2,
Mn(OAc)2·4H2O etc. catalyze the nucleophilic opening of epoxide
rings by amines leading to the efficient synthesis of b-amino alco-
hols. The reaction works well with aromatic and aliphatic amines in
high yields under solvent-free conditions.
To minimize the amount of harmful organic solvents used
in chemical processes, much attention has been devoted to
the use of alternative reaction media. Besides supercritical
fluids, water, and ionic liquids, the use of solvent-free
conditions has been receiving more attentions.15 The sol-
vent-free reaction has many advantages, such as reduced
pollution, low costs, and simplicity in process and han-
dling. These factors are especially important in industry.
Considering the widespread applications of the resultant
b-amino alcohols, and in our relation to our efforts to de-
velop useful synthetic methodologies for b-amino com-
pounds,16 we are also interested in the aminolysis of
epoxides under solvent-free conditions. However, few
reports12g are available on a transition metal salts-catalytic
approach for the ring opening reaction under solvent-free
conditions.
Key words: amino alcohols, amines, epoxides, Lewis acids, sol-
vent-free
b-Amino alcohols are an important class of organic com-
pounds and are versatile intermediates in the synthesis of
a vast range of biologically active natural and synthetic
products, unnatural amino acids, and chiral auxiliaries for
asymmetric synthesis.1 The most practical and widely
used route to the synthesis of these compounds is the di-
rect aminolysis of 1,2-epoxides.2 The classical approach,
involving heating epoxides with amines, works less well
with poorly nucleophilic amines. Moreover, the lack of
appreciable regioselectivity, the requirements for high
temperature, and the need for excess of amine in the clas-
sical methods of b-amino alcohol synthesis have led to the
necessity for activation of the epoxides so as to increase
their susceptibility to nucleophilic attack by amines.3
Therefore, there is significant current interest in the ring-
open reactions of epoxides using amines as nucleophile.
Since very high temperatures and other shortcomings may
be inappropriate for certain functional groups, a variety of
air-sensitive; expensive or specific catalysts have been de-
scribed in the literature to perform epoxide opening at
room temperature or low temperatures.4 However, it has
been reported that aliphatic amines failed to react with
epoxides in the presence of cobalt,5 rhodium,6 or copper7
catalyst. The improved methodologies developed for this
purpose include the use of alumina,8 metal amides,9 metal
alkoxides,10 metal triflates,11 metal halides,12 silica under
high pressure,13 and montmorillonite clay under micro-
wave irradiation.14 And these methodologies suffer from
one or more disadvantages such as high temperatures,
moderate yields, use of air and/or moisture sensitive cata-
lysts, costly reagents/catalysts. Therefore, the develop-
ment of a better catalyst for the activation of epoxides
Catalysts based on transition metals instead of conven-
tional Lewis acids and bases might be useful, because the
neutralization of reagents would not be necessary, and
salts would not form. We found that such transition metal-
based Lewis acids that have low redox potentials are en-
vironmentally benign and useful for organic synthesis.
We try to explore the catalytic activities of cheaper transi-
tion metal-salts based Lewis acids in the ring opening re-
action of epoxides. In the present letter, we reported that
several very cheap transition metal salts other than previ-
ous catalyst effective for the aminolysis of epoxides under
solvent-free conditions (Scheme 1). Advantages of the
protocol include high yielding reaction that can be con-
ducted at low temperature, these catalysts make possible
both acid- and base-promoted aminolysis reactions in a
single container without the mutual destruction of
reagents by neutralization; moderate to high regio- and
stereoselective ring opened products were obtained under
environmental benign conditions.
R3
R3
O
R4
HO
N
catalytic metal salt
solvent-free
HN
R1
R2
R4
R1
R2
2a–g
1a–f
3
Scheme 1 Transition metal salts-catalyzed aminolysis of epoxides
SYNLETT 2004, No. 5, pp 0846–0850
0
2.
0
4.
2
0
0
4
Advanced online publication: 17.02.2004
DOI: 10.1055/s-2004-817780; Art ID: U28303ST.pdf
© Georg Thieme Verlag Stuttgart · New York

LETTER
Lewis Acid Catalyzed Ring Opening of Epoxides
847
Table 1 Ring Opening of Various Epoxides with Amines Catalyzed by SnCl4·5H2O under Solvent-Free Conditions
Entrya
1
Epoxides
Products
Temperature (°C) Time (h)
Yields (%)b
O
HO
89
(77:23)
50
50
12
12
n-Bu
n-Bu
HN
HN
HO
O
80
(73:27)
2
3
4
5
HO
HO
HO
O
O
O
O
r.t. (CH2Cl2)
12
12
12
trace
HN
HN
HN
46
(64:36)
r.t.
20
(92:8)
50 (DMF)
HO
O
91
(96:4)
O
O
6
50
10
HN
O
HO
O
83
(97:3)
7
8
9
50
50
50
10
6
HN
OH
Bu
57
O
N
H
O
O
87
(90:10)
N
6
OH
OH
78
(86:14)
N
10
11
50
50
6
HO
O
O
O
24
0
N
H
N
a All reactions were carried out using 2 mmol of epoxide, 2.2 mmol of amine, and 5 mmol% of SnCl4·5H2O under solvent-free conditions.
b Yields refer to isolated yield.
Synlett 2004, No. 5, 846–850 © Thieme Stuttgart · New York

848
P.-Q. Zhao et al.
LETTER
Considering the widespread applications of resultant b- for example, Mn(OAc)2·4H2O, CuI, and NiCl2. It was
amino alcohols, we felt that a catalyst of choice should be easy to prove that the transition metal-based Lewis acids
one that is easily available and less costly, less toxic, and catalysts showed high catalytic activity at 50 °C under
operable under environmentally friendly conditions so as solvent-free conditions.
to fulfill the reaction. We reasoned that the high abun-
Table 2 b-Amino Alcohol Produced via Scheme 2
dance of tin in the earth’s crust should make tin com-
pounds less costly. Therefore, we planned to employ
cheaper SnCl4·5H2O to evaluate the catalytic efficiency in
carrying out the ring-opening reaction of epoxides with
amines and found that SnCl4·5H2O acts as an efficient
catalyst for the desired transformation under solvent-free
conditions. The aminolysis reactions of various epoxides
with amines under solvent-free conditions at 50 °C were
investigated (Table 1).17 As expected, the reaction oc-
curred comparatively efficient and went to completion in
almost each case under solvent-free conditions. From the
results (Table 1) it is evident that aminolysis of epoxides
gave the corresponding amino alcohols in good yields
under above conditions. In all cases, the reactions were
complete with 6–12 hours, except in the case of phenyl
glycidyl ether with 2-aminopyridine (entry 11). Moderate
yields were achieved for cyclohexene oxide (entry 8),
taking into account that aliphatic epoxides are less reac-
tive than the aromatic ones. And we found the result
obtained with 2-aminopyridine was surprising where no
conversion of the epoxide could be detected after 24
hours. This may be due to co-ordination of transition
metal salt by the pyridine. However, it is possible that
pyridine-containing ligands may be used in order to fine-
tune the properties of transition metal catalyst. We believe
the utilization of chiral pyridine-based ligands may allow
the enantioselective opening of the epoxides. We next
planned to evaluate the aminolysis reaction in CH2Cl2 or
solvent-free condition at room temperature, but with very
low reactivities (entries 3–5).
Entrya
MXn Catalyst
NiCl2
Yield (%)
1
2
89
0
b
NiCl2
3
CuCl2·2H2O
Mn(OAc)2·4H2Ob
Mn(OAc)2·4H2O
FeCl3·6H2O
80
0
4
5
84
88
90
80
86
72
70
88
6
7
CrCl3·6H2O
8
AuCl3·4H2O
Co(OAc)2·4H2O
CuI
9
10
11
12
FeSO4·7H2O
Ni(OAc)2·2H2O
a All reactions were carried out using 2 mmol of epoxide, 2.2 mmol of
amine, and 5 mmol% of transition metal salts catalysts under solvent-
free conditions for 12 h. Yields of 3a refer to isolated yield.
b The reaction performed was at r.t.
We next planned to evaluate the outcome of selective
transition metal salts-catalyzed epoxides opening reaction
with various amines under the same conditions and the
results are summarized in Table 3. In all case the corre-
sponding amino alcohols were obtained in good yields un-
der solvent-free conditions at 50 °C for 12 hours. These
transition-metal-based Lewis acids catalysts have similar
catalytic activities compared with SnCl4·5H2O and few
products were obtained at room temperature.
O
HO
O
NH2
O
HN
catalytic metal salt
solvent-free
In summary, we have developed a novel, efficient, and
general ring-opening reaction of various amines and cata-
lysts that proceed with a wide range of transition metal
salts under solvent-free conditions. Simple and cheaper
transition metal salts catalyzed aminolysis of aromatic or
aliphatic epoxides performed under air and solvent-free
conditions are reported with good to excellent yields. And
the specific advantages are that the reactions are carried
out under mild conditions for aromatic amines or aliphatic
amines. The solvent-free reaction conditions employed in
the present method will make it environmentally friendly
and potentially useful for industrial applications.
1a
2a
3a
Scheme 2 Transition metal salts-catalyzed aminolysis of phenyl
glycidyl ether
With several cheaper transition metal-based Lewis acids
catalysts in hand, we surveyed catalytic activity of various
cheap transition metal salts in the ring-opening reaction
with phenyl glycidyl ether and aniline at 50 °C under sol-
vent-free conditions (Table 2). Among the metal salts
tested, almost all the transition metal salts, such as NiCl2,
Mn(OAc)2·4H2O,
Zn(OAc)2·2H2O,
CrCl3·6H2O,
Co(OAc)2·4H2O, Ni(OAc)2·2H2O, and AuCl3·4H2O were
found to be effective as ZnCl2 under solvent-free condi-
tions. On the other hand, in the ring opening reaction of
Acknowledgment
This study was supported in part by the Natural Science Founder of
phenyl glycidyl ether with aniline, no products were ob- National for financial support of the works (29933050 and
20373082).
tained with these metal salts catalyst at room temperature,
Synlett 2004, No. 5, 846–850 © Thieme Stuttgart · New York

LETTER
Lewis Acid Catalyzed Ring Opening of Epoxides
849
Table 3 Ring Opening of Various Epoxides with Amines Catalyzed by Other Selective Transition Metal Salt Catalyst under Solvent-Free
Conditions
Entrya
1
Catalysts
Epoxides
Products
Yield (%)
88
PhHN
OH
O
Mn(OAc)2·4H2O
Et
O
Et
N
97
(65:35)
2
Mn(OAc)2·4H2O
OH
O
3
4
Mn(OAc)2·4H2O
Ni(OAc)2·2H2O
0
N
N
H
OH
O
HO
92
(95:5)
O
O
N
N
H
O
O
99
(96:4)
5
6
Ni(OAc)2·2H2O
OH
OH
Et
Et
N
30b
(74:26)
NiCl2
HO
n-Bu
O
7
8
NiCl2
0
n-Bu
HN
N
O
PhHN
83
(93:8)
CrCl3·6H2O
OH
O
HO
45
(88:12)
9
CuI
N
H
a All reactions were carried out using 2 mmol of epoxide, 2.2 mmol of amine, and 5 mmol% of transition metal salts catalysts under solvent-
free conditions for 12 h. Yields refer to isolated yield.
b The reaction performed was at r.t.
(2) (a) Hodgson, D. M.; Gibbs, A. R.; Lee, G. P. Tetrahedron
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(17) Typical Experimental Procedure: A mixture of the phenyl
glycidyl ether (2 mmol), the aniline (2.2 mmol), and
SnCl4·5H2O (0.1 mmol, 5%mol) was stirred at 50 ° for 12 h.
After completion of the reaction, as indicated by TLC, the
reaction mixture was directly purified by column
chromatography on silica gel (100–200mesh, EtOAc–
petroleum ether) to afford corresponding b-amino alcohols.
Selected spectra data: 1H NMR (400 MHz, CDCl3): d = 3.24
(m, 1 H), 3.40 (m, 1 H), 3.61 (m, 2 H), 4.02 (m, 2 H), 4.22
(br s, 1 H), 6.65 (m, 2 H), 6.72 (m, 2 H), 6.90 (m, 2 H), 7.15
(m, 2 H), 7.26 (m, 2 H). 13C NMR (100 MHz, CDCl3): d =
158.4, 148.0, 121.2, 118.4, 117.9, 115.0, 114.5, 113.2, 69.9,
60.3, 46.5. GC–MS: m/z = 243, 106, 94, 77, 65, 51. All other
known compounds were fully characterized by GC–MS
(Agilent 6890N GC/5973N MS, HP-5MS) and usual
spectral methods.
Synlett 2004, No. 5, 846–850 © Thieme Stuttgart · New York