Efficient ring opening of epoxides with trimethylsilyl azide and cyanide catalyzed by erbium(III) triflate

Article abstract of DOI:10.1016/j.tetlet.2010.07.123

Epoxides can be opened under neutral conditions with TMSN₃ and TMSCN in the presence of catalytic amounts of Lewis acid, affording the corresponding ring-opened compounds in high yields.

Full text of DOI:10.1016/j.tetlet.2010.07.123

Tetrahedron Letters 51 (2010) 5150–5153
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Tetrahedron Letters
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Efficient ring opening of epoxides with trimethylsilyl azide and cyanide
catalyzed by erbium(III) triflate
a
b
b
b
Antonio Procopio a, , Paola Costanzo , Renato Dalpozzo , Loredana Maiuolo , Monica Nardi ,
*
Manuela Oliverio a
a Dipartimento Farmacobiologico, Università della Magna Graecia, Complesso Ninì Barbieri, 88021 Roccelletta Di Borgia (CZ), Italy
b Dipartimento di Chimica, Università della Calabria, ponte Bucci cubo 12/c, 87030 Arcavacata di Rende (Cs), Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Epoxides can be opened under neutral conditions with TMSN3 and TMSCN in the presence of catalytic
amounts of Lewis acid, affording the corresponding ring-opened compounds in high yields.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 19 May 2010
Revised 19 July 2010
Accepted 21 July 2010
Available online 29 July 2010
Keywords:
Erbium(III) triflate
Epoxide ring-opening
Cyanohydrins
Azido alcohols
Epoxides are recognized among the most versatile intermedi-
ates in organic synthesis. They can be easily prepared and due to
their ring strain they react with different nucleophiles with high
regioselectivity, leading to ring-opened products.1
In the past, we have found that erbium(III) triflate [Er(OTf)3] is a
very useful and environmentally friendly functional group, and tol-
erant catalyst for several acid-catalyzed reactions.2 Owing to its
unique qualities,3 erbium triflate has already proven to be a highly
efficient and regioselective catalyst for many reactions involving
epoxides; such as the rearrangement to carbonyl compounds,4
the synthesis of acetonides,5 the conversion into 1,2-diacetates,6
the synthesis of b-amino alcohols,7 and the preparation b-hydroxy
sulfides.8
the application of erbium triflate into organic transformations; in
this Letter, we aim to report that Er(OTf)3 can act as a mild and effi-
cient Lewis acid catalyst for another regio- and stereoselective
epoxide ring opening with trimethylsilylazide (TMSN3) and trim-
ethylsilylcyanide (TMSCN) (Scheme 1).
a-Azido alcohols are important precursors for alternative syn-
theses of b-aminoalcohols;9 some of them appeared in the struc-
tures of pharmaceutical, useful chiral auxiliaries, or intermediates
for the synthesis of amino sugars. The classical reagents for azi-
dohydrin synthesis are the combined use of NaN3,10 TMSN3,11 or
other azide sources12 in the presence of a Lewis acid or a transition
metal complex. The oldest reported epoxide ring-opening reactions
with NaN3 suffer from high temperatures, long reaction times or
side isomerization, epimerization, and rearrangement reactions.
Recently, a large variety of activators or promoters have been
As a consequence of the necessity of milder and environmentally
friendly reaction conditions, and in continuation of our interest on
OSiMe3
O
O
O
Er (OTf3)
N3
1a
3a
Scheme 1. Epoxide ring-opening with (TMSN3) and (TMSCN).
* Corresponding author. Tel.: +39 0961 3694120; fax: +39 0961 391270.
E-mail address: procopio@unicz.it (A. Procopio).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.123

A. Procopio et al. / Tetrahedron Letters 51 (2010) 5150–5153
5151
Table 1
reported to promote epoxide ring-opening reactions with azides
under milder reaction conditions.10–12
Reaction of 3-phenyloxy-1,2-epoxypropane (a) with TMSN3 catalyzed by Er(OTf3)
Entry
Er (OTf3)
(mol %)
TMSN3
(equiv)
T
Conversion
(%)
Yieldb
(%)
Moreover, b-hydroxynitriles are useful synthetic intermediates
in organic synthesis owing to their versatile hydroxy and cyano
moieties. The reaction of epoxides with different cyanide sources;
such as hydrogen cyanide,13 cyanids,14 TMSCN,15 or cyanide
formed upon treatment of acetone cyanohydrins with bases;16are
among the most direct methods for the preparation of these com-
pounds. However, some of them usually require long reaction
times and harmful solvents.
(°C)a
1
2
3
4
5
6
5
5
5
5
3
1
2
25
100
100
95
95
64
9
83 (5)c
67 (21)
81 (4)
69 (16)
30 (26)
14 (9)
1.1
1.5
1.5
1.5
1.5
0?25
0?25
25
0?25
0?25
a
b
c
Reaction was monitored up to 400 min.
Determined by GC/MS.
% of hydrolyzed product determined by GC/MS.
In order to find the best experimental conditions, we tested the
catalytic activity of Er(OTf)3 in the epoxide ring opening of the sub-
Table 2
Reaction of epoxides with TMSN3 (1.5 equiv) and TMSCN (2.0 equiv) in the presence of Er(OTf3) (5 mol %)
Entry
Epoxide
Productb
Time (min)
30
Yield (%)
86
Ratio
O
N3
Ph
1
0:100
OTMS
1a
Ph
3a
O
OTMS
PhO
2
3
400
86
100:0
51:49
PhO
N3
1b
2b
O
OTMS
N3
OTMS
N3
30
100
1c
3c
2c
O
OTMS
N3
4
5
30
30
74
—
2d
1d
O
OTMS
N3
N3
OTMS
93a
83:17
3e
2e
1e
O
N3
OTMS
C10H21
6
7
8
9
400
120
300
240
83
81
80
89
65:35
100:0
100:0
100:0
OTMS
N3
1f
C
10H21
C10H21
3f
2f
OTMS
O
Cl
1g
1h
Cl
N3
2g
OTMS
O
Br
Br
N3
2h
OTMS
1a
1b
PhO
CN
4a
OTMS
10
CN
30
57
0:100
Ph
4b
(continued on next page)

5152
A. Procopio et al. / Tetrahedron Letters 51 (2010) 5150–5153
Table 2 (continued)
Entry
Epoxide
Productb
Time (min)
Yield (%)
Ratio
OTMS
CN
CN
OTMS
11
1c
10
95
47:53
4c
5c
OTMS
CN
12
13
1d
1e
20
10
91
—
4d
OTMS
CN
CN
OTMS
96a
82:18
5e
4e
OTMS
14
15
16
1f
CN
60
94
100:0
100:0
100:0
C10H21
4f
OTMS
1g
1h
10
100
82
Cl
CN
4g
OTMS
240
Br
CN
4h
OTMS
O
O
O
CN
1i
4i
O
O
17
60
97
62:38
CN
OTMS
O
5i
O
a
All four diastereomers were detected.
b
Compounds 2a, 3b, 2d,10h 2c, 3c,18 2g,19 2h,11d 4a, 4b, 4d, 4g, and 4h15c are known products and were characterized by the comparison of their spectra with the literature
data. Spectroscopic data for unknown products supplied in Supplementary data. The minor isomers 3e and 3f were detected by the EI-MS spectra only.
TMSN3
strate model 3-phenyloxy-1,2-epoxypropane (a) with TMSN3
TMSO
R
N3
R1
N3
R
OTMS
R1
(1.5 equiv)
(Scheme 1). After a series of preliminary experiments, the best con-
version was observed when a slightly defective silyl derivative was
added to the epoxide at 0 °C in the presence of 5 mol % of the cat-
alyst and then allowed to warm to room temperature (Table 1).16
This is surprising, since in all the reported procedures the limiting
reagent is always the epoxide.
All the reactions proceeded smoothly under these conditions
and, after the appropriate reaction time (Table 2), afforded the de-
sired products in excellent yields and high purity. The product can
be separated with simple and mild work-up and only a partial
desilylation was observed in some cases, but without rearrange-
ments to isonitriles (see Scheme 2).15d
+
+
O
Er(OTf) 3
(5 mol %)
2 a,c-h
3 b,c,e,f
R
R1
1 a-i
TMSCN
(2 equiv)
NC
R
OTMS
R1
TMSO
R
CN
R1
5 c,e,i
4 a-i
Scheme 2.
Experiments conducted with both cis and trans-stilbene lead to
the complex mixtures of products, both with TMSN3 and TMSCN.17
A GC/MS analysis of the reaction-product distribution allowed sig-
nificant amounts of elimination products; namely, non-hydrolyzed
(1,2-diphenylvinyloxy)trimethylsilane and hydrolyzed 1,2-diphe-
nylethanone; to be recognized together with some additional
products. TMSCN was more reactive than TMSN3, as its reaction

A. Procopio et al. / Tetrahedron Letters 51 (2010) 5150–5153
5153
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The higher reactivity of the TMSCN also affected regioselectivity.
In fact, addition to 1-dodecene oxide (1f) was completely selective
in the case of TMSCN, but not when using TMSN3 where significant
amounts of the isomer 3f were recovered (Table 2, entry 6). Con-
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a-selective with
TMSN3 and b-selective TMSCN. Other addition of azides10–12 al-
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whereas nitrile was already reported to give prevalence of 4b.15 Fi-
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always observed.
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anism,8 where Er(OTf)3 serves as Lewis acid by coordination to the
oxygen atom; we envisaged that in an asymmetrical epoxide, the
higher nucleophilic CNÀ added at an early transition state in which
epoxide was still intact and crowded, the positions highly influ-
À
enced the attack. On the other hand, the less nucleophilic N3
added at a late transition state where ring opening proceeded in
a manner that C–O bond cleavage gave the best stabilization of
the developing positive charge. Thus, the b- and benzylic positions
were the favored sites for the nucleophilic attack for CNÀ and N3
,
À
respectively. However, highly encumbered substrates such as 1e
led to mixtures, since crowding inhibits to charge-stabilization (Ta-
**
ble 2 , entries 5 and 13). In summary, we have developed an eco-
nomical and green method for the synthesis of a wide range of b-
hydroxynitriles and a-azido alcohols by using readily available re-
agents under neutral conditions. This method is yield- and selectiv-
ity-competitive with the previously reported methods, even the
most recent ones. Moreover, these results have allowed better clar-
ification of the mechanisms involved in the erbium(III) triflate-cat-
alyzed epoxide ring opening, by expanding the perspective of its
interaction with other nucleophiles. Further studies in this direc-
tion are in progress in our laboratory.
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Supplementary data
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17. General procedure: TMSN3 (1.5 equiv) or TMSCN (2.0 equiv) was added to a
mixture of 2.5 mmol of epoxide and Er(OTf)3 (5 mol %) in a test tube. The
mixture was stirred at 0 °C for a few minutes, and then at room temperature
for 30–400 (TMSN3) or 10–240 min (TMSCN). The reaction was monitored by
TLC or GC/MS. The mixture was subsequently diluted with ether, and three
samples were extracted using water. The catalyst was recovered from the
aqueous phases by evaporation under vacuum. The collected organic phases
were dried on Na2SO4, filtered, and then evaporated under vacuum. The
desired pure product was separated from tars by flash chromatography on a
short silica gel column. Samples containing the products were collected,
whereby the yields and the diastereoisomeric ratios are calculated on the
entire set. A more careful chromatographic separation was performed in order
to obtain pure samples of unknown products to be characterized (see
Supplementary data).
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.07.123.
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