A new and efficient epoxide ring opening via poor nucleophiles: Indole, p-nitroaniline, borane and O-trimethylsilylhydroxylamine in lithium perchlorate

Article abstract of DOI:10.1055/s-2004-822406

Highly regioselective ring opening of 2,3-dimethyloxirane, 2-epoxyphenylether and allyl(2-epoxymethyl) ether are observed through reactions with poor nucleophiles such as indole, borane, O-trimethylsilylhydroxylamine, p-nitroaniline and sterically hindered tert-butylamine in the presence of 5.0 M lithium perchlorate-Et₂O solution. These reactions are fast, convenient, with rather high yields and are carried out at ambient temperatures.

Full text of DOI:10.1055/s-2004-822406

SHORT PAPER
1563
A New and Efficient Epoxide Ring Opening via Poor Nucleophiles: Indole,
p-Nitroaniline, Borane and O-Trimethylsilylhydroxylamine in Lithium
Perchlorate
New
a
ndEfficient
k
E
poxide
R
in
b
g
O
pening
v
a
ia Poor
N
uc
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leophiles Heydari,*a Morteza Mehrdad,b Aziz Maleki,a Nafiseh Ahmadia
a
Chemistry Department, Tarbiat Modarres University, P. O. Box 14155-4838, Tehran, Iran
Fax +98(21)8006544; E-mail: akbar.heydari@gmx.de
b
Department of Phytochemistry, Shahid Beheshti University, Evin 1983963113, Tehran, Iran
Received 23 February 2004; revised 29 March 2004
and primary amines show no regioselectivity). Good re-
gioselectivity of ring opening by nucleophiles has been
observed with LiClO4.12 However, with this catalyst, de-
activated aromatic amines and some sterically hindered
Abstract: Highly regioselective ring opening of 2,3-dimethylox-
irane, 2-epoxyphenylether and allyl(2-epoxymethyl) ether are ob-
served through reactions with poor nucleophiles such as indole,
borane, O-trimethylsilylhydroxylamine, p-nitroaniline and sterical-
ly hindered tert-butylamine in the presence of 5.0 M lithium per- amines fail to open up epoxides or require high tempera-
chlorate–Et2O solution. These reactions are fast, convenient, with
ture or pressure. Although a wide choice of promoters is
rather high yields and are carried out at ambient temperatures.
available many are associated with one or other drawback.
Key words: lithium perchlorate, epoxide, b-amino alcohols
Hence, there is a need for new versatile methods.
In the course of our investigations toward the develop-
ment of new reactions promoted by lithium perchlorate in
Et2O (LPDE) solution, we have found that 5.0 M LPDE
solutions promote the addition of deactivated p-nitro-
aniline and secondary amines to epoxides under mild ex-
perimental conditions (r.t., 30 min).13 The reaction was
highly regioselective as 3 was the only detectable product.
The results are summarized in Scheme 1.
Oxiranes (epoxides) are widely distributed in nature and
are of industrial and biochemical interest. In addition, they
are becoming a powerful tool in the field of synthetic or-
ganic chemistry.1 Epoxides are efficiently converted into
functionalized alcohols by employing nucleophilic ring-
opening reactions. However, this reaction, which is usual-
ly carried out with a large excess of nucleophiles at elevat-
ed temperature with long reaction times and drastic
conditions, often fails when poor nucleophiles and/or ster-
ically bulky nucleophiles or epoxides are used.2 There-
fore, there is a significant current interest in the ring
opening of epoxides.
b-Amino alcohols constitute an important class of well-
known organic compounds that have importance in natu-
ral products, medicinal chemistry and other chemical
fields.3 The most practical and widely used method for
preparing these compounds is the direct aminolysis of ep-
oxides with an excess of amines or their synthetic equiva-
lents at elevated temperatures.4 Due to the elevated
temperature, these reactions often fail when poorly nu-
cleophilic or sterically bulky amines and in some case low
boiling points amines are concerned. These are some sig-
nificant limitations on the general utility of epoxide ami-
nolysis.5 To obviate these problems, several useful
modifications activator/promoters have been reported:
COCl2,6 fluoro-alcohols as reaction media7 (benzylic and
aliphatic amines do not react under these conditions),
Ti(O-i-Pr)4,8 SmI2 and SmCl3,9 metal triflates,10 metal
amides,11 Mg, Li, Pb, Sn, Si (an important drawback of
these methods is that epoxides bearing a-hydrogens, fre-
quently undergo rearrangement to produce allyl alcohols
Scheme 1
This encouraging result prompts us to further investigate
the use of LPDE solution (5.0 M) as catalyst. We have
been investigating the use of hydroxylamine in the synthe-
sis of a range of functionalized b-hydroxyhydroxyl-
amines. In order to prepare the desired compounds, we
proposed to ring open functionalized epoxides with O-tri-
methylsilylhydroxylamine. We were surprised to note,
that to our knowledge, there are very few examples of the
ring opening of epoxides with hydroxylamines, and the
SYNTHESIS 2004, No. 10, pp 1563–1565
x
x.
x
x
.
2
0
0
4
Advanced online publication: 16.06.2004
DOI: 10.1055/s-2004-822406; Art ID: Z03804SS
© Georg Thieme Verlag Stuttgart · New York

1564
A. Heydari et al.
SHORT PAPER
few cases that have been reported are simple O-protected
glycidol ethers14 and N-alkylhydroxylamines.15 Accord-
ingly, we have examined the ring opening of epoxides
with O-tri-methylsilylhydroxylamine and found that the
reaction is high yielding and regioselective (Scheme 2).
Scheme 4
hols, b-hydroxyhydroxylamines, tryptophol and alcohols
derivatives, respectively). Further synthetic applications
of the reaction are now in progress in our laboratory.
Scheme 2
All reactions were carried out under Ar. 1H and 13C NMR spectra
were recorded at 90 Mhz and 22.5 MHz on JEOL EX-90A spec-
trometers, respectively. The chemical shifts are reported in ppm (d)
relative to Me4Si in CDCl3. IR spectra were recorded on a Perkin
Elmer Model 1600 spectrophotometer. Mass spectra were recorded
on a Shimadzu IR-460 spectrometer or on a FINNIGAN-MATT
8430 mass spectrometer operating at an ionization potential of 70
eV. Elemental analyses for C, H, and N were performed using a
Heraus CHN-O-Rapid analyzer. The experimental data were in
agreement with the calculated values.
In order to extend the scope of effectiveness of the above-
mentioned new ring opening, reactions between indole
and epoxides were studied and it was found that the corre-
sponding indolyl derivatives were obtained. It is interest-
ing to note that the procedures for the indole ring-opening
reaction can be catalyzed by high pressure (10 kbar) or by
the use of SiO2 and InBr3.16 Several examples of Friedel–
Crafts (F–C) reactions between indole and epoxides using
the novel 5.0 M LPDE catalyst are shown in Scheme 3. In
all cases, the desired tryptophol derivatives (which are of
interest as synthetic intermediates toward antibiotics such
as indolmycin)17 were obtained in good yields.
Typical Experimental Procedure
To a mixture of epoxide (2 mmol) in 5 M LPDE (4 mL) was added
nucleophile (2.2 mmol) at r.t. The mixture was stirred for 30 min
and then water was added and the product was extracted with
CH2Cl2. The organic phase was collected, dried (Na2SO4) and evap-
orated to afford the crude product. The product was purified by flash
chromatography (hexane–EtOAc). 1H NMR, 13C NMR, IR and MS
spectra were entirely consistent with the assigned structures.
3b
1H NMR (90 MHz, CDCl3): d = 7.2 (m, 2 H), 6.6 (m, 3 H), 3.2 (br
s, 2 H), 3.0 (s 2 H), 1.2 (s, 6 H).
13C NMR (22.5 MHz, CDCl3): d = 146.66 (C), 129.16 (CH), 118.49
(CH), 117.47 (CH), 115.07 (CH), 113.07 (CH), 70.64 (C), 54.88
(CH2), 27.40 (CH3).
3e
1H NMR (90 MHz, CDCl3): d = 8 (m, 2 H), 6.5 (m, 2 H), 3.6 (br s,
2 H), 3.2 (s, 2 H), 1.3 (s, 6 H).
13C NMR (22.5 MHz, CDCl3): d = 154.04 (C), 137.42 (C), 116.39
(CH), 112.16 (CH), 70.32 (C), 50.66 (CH2), 27.44 (CH3).
Scheme 3
To explore the generality and scope of the LPDE cata-
lyzed ring opening of epoxides, the reaction was exam-
ined with a borane–Et3N complex (Scheme 4). In all 2 H), 1.2 (s, 6 H), 1.0 (t, 6 H).
3h
1H NMR (90 MHz, CDCl3): d = 3.4 (br s, 1 H), 2.7 (q, 4 H), 2.4 (s,
13C NMR (22.5 MHz, CDCl3): d = 68.69 (C), 64.62 (CH2), 49.02
(CH2), 28.01 (CH3), 12.21 (CH3).
cases, the reactions proceeded cleanly, and the desirable
secondary alcohols were obtained in good yields.
In conclusion, the discovery of the LPDE (5.0 M) solution
catalyzed method for the ring opening of epoxides with
amines, O-silylatedhydroxylamine, indole and BH3·Et3N
complex to give, under mild conditions and in fair yields,
the corresponding ring opening products (b-amino alco-
3k
1H NMR (90 MHz, CDCl3): d = 3.7 (br s, 1 H), 3.3 (br s, 1 H), 2.4
(s, 2 H), 1.1 (s, 6 H), 1.0 (s, 9 H).
13C NMR (22.5 MHz, CDCl3): d = 68.20 (C), 52.60 (CH2), 50.24
(C), 29.03 (CH3), 27.19 (CH3).
Synthesis 2004, No. 10, 1563–1565 © Thieme Stuttgart · New York

SHORT PAPER
New and Efficient Epoxide Ring Opening via Poor Nucleophiles
1565
5b
(11) (a) Carre, M. C.; Houmounou, J. P.; Caubere, P. Tetrahedron
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been used in epoxide ring opening only with silylated
nucleophiles: Ipaktschi, J.; Heydari, A. Chem. Ber. 1993,
126, 1905. (k) For the sake of comparison we first
1H NMR (90 MHz, CDCl3): d = 5.5 (br s, 1 H), 3.8 (br s, 1 H), 2.8
(s, 2 H), 1.2 (s, 6 H), 0.2 (s, 9 H).
13C NMR (22.5 MHz, CDCl3): d = 71.05 (C), 63.44 (CH2), 27.44
(CH3), –0.1 (CH3).
7a
Comparison of the spectroscopic data to those reported in ref.17
9a
1H NMR (90 MHz, CDCl3): d = 7.4 (m, 2 H), 7.0 (m, 3 H), 4.2 (m,
1 H), 3.9 (d, 2 H), 2.5 (br s, 1 H), 1.3 (d, 3 H).
13C NMR (22.5 MHz, CDCl3): d = 159.53 (C), 130.31 (CH), 121.89
(CH), 115.28 (CH), 73.76 (CH2), 66.76 (CH), 19.01 (CH3).
Acknowledgment
Research supported by the National Research Council of I. R. Iran
as a National Research project under the number 984.
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Synthesis 2004, No. 10, 1563–1565 © Thieme Stuttgart · New York