An efficient catalytic ylide route to vinyl epoxides

Article abstract of DOI:10.1016/S0040-4039(03)00822-0

The ylide epoxidation catalyzed by telluronium salts provides a simple and extremely efficient route to vinyl epoxides in excellent yields. Both aromatic and aliphatic aldehydes work well. The best results were obtained by using 2 mol% of telluronium salts with Cs₂CO₃ in t-BuOH.

Full text of DOI:10.1016/S0040-4039(03)00822-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4137–4140
An efficient catalytic ylide route to vinyl epoxides
Kai Li, Zheng-Zheng Huang and Yong Tang*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, 354 Fenglin Lu, Shanghai 200032,
China
Received 6 January 2003; revised 14 March 2003; accepted 20 March 2003
Abstract—The ylide epoxidation catalyzed by telluronium salts provides a simple and extremely efficient route to vinyl epoxides
in excellent yields. Both aromatic and aliphatic aldehydes work well. The best results were obtained by using 2 mol% of
telluronium salts with Cs2CO3 in t-BuOH. © 2003 Elsevier Science Ltd. All rights reserved.
1)12 is a good catalyst for Wittig-type reactions, in
which the catalyst loading could be reduced to 2 mol%.
In this communication, we wish to report a highly
efficient catalytic ylide reaction of aldehydes with b-
silylated allyl bromide and allyl bromide to form vinyl
epoxides, in which the catalyst loading was as low as 2
mol%.
Vinyl epoxides have proven utility as building blocks
for the preparation of pharmaceutical targets1 and nat-
ural products.2 Of the methods available for their syn-
thesis,3 ylide epoxidation4 is especially attractive as it
involves the regioselective construction of the vinyl
epoxide unit with concomitant formation of a car-
bonꢀcarbon bond. However, in contrast to the reac-
tions of benzylide5 with aldehydes in which
considerable progress has been made, the addition6 of
allylides to aldehydes to form vinyl epoxides is still less
developed. This is probably due to the difficulties asso-
ciated with [2,3]-Wittig rearrangement7 and stereoselec-
tivity.6a,8 Reports from both the Osuka and Huang
groups demonstrated that allylic telluronium ylides6a–c
could react with aldehydes to afford desired com-
pounds. Dai described that the stereoselectivity of ylide
epoxidation could be tuned in some cases by changing
both the reaction conditions and the ligands of the
sulfur ylides.9 To the best of our knowledge, only one
catalytic version was documented, in which Huang et
al. found that aldehydes could react with allyl bromide
in the presence of diisobutyl telluride to give vinyl
epoxides.8 However, the amount of diisobutyl telluride
used was 20 mol% and reduction of catalyst loading
resulted in low yields even if the reaction times were
prolonged. In addition, this reaction could not be
extended to b-substituted allylic bromides, such as b-
trimethylsilylallyl bromide. In this case, no product was
The initial attempt to employ PEG-telluride 1 as the
catalyst to conduct the epoxidation under Huang’s
reaction conditions failed (entry 1 in Table 1). Consid-
ering that salts of PEG-telluride are more efficient than
PEG-telluride itself in catalytic Wittig-type olefination,
we tried 20 mol% of telluronium salt 2, an analogue of
PEG-telluronium salt, as the catalyst. We were pleased
to find that the desired epoxide was isolated in 66%
yield (entry 2). This suggested that the scope of cata-
lytic ylide reaction to prepare vinyl epoxides could be
extended by employing a suitable catalyst and this
result encouraged us to optimize the reaction conditions
to improve both the yield and catalytic efficiency. As
shown in Table 1, although K2CO3 was good as the
formed even when
a stoichiometric amount of
diisobutyl telluride was used.10 In our studies of ylide
chemistry,11 we focused on the catalytic efficiency of
ylide reactions and found that PEG-telluride 1 (Scheme
Keywords: catalytic ylide epoxidation; solvent effect.
* Corresponding author. E-mail: tangy@pub.sioc.ac.cn
Scheme 1. Catalysts.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00822-0

4138
K. Li et al. / Tetrahedron Letters 44 (2003) 4137–4140
Table 1. Effects of reaction conditions on the catalytic ylide epoxidationa
Entry
Catalyst
Loadingb
Solvent
Basec
cis/trans
Yieldd (%)
1
2
3
4
5
6
7
8
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
3
3
3
3
4
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
10
10
10
10
10
2
THF
THF
THF–H2O
THF
THF
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
Na2CO3
NaOH
/
0
66
12
62
0
0
0
0
60
0
49
32
55g
89g
84
69g
0
47:53
42:58
44:56
/
/
/
THF
THF
KOH
Toluene
DME
CH3CN
Dioxane
DMF
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
/
9
42:58
/
10
11
12
13
14
15
16
17
18
19
20
21
22
49:51
37:63
49:51
48:52
48:52
49:51
/
49:51
49:51
49:51
49:51
49:51
EtOH
i-PrOH
t-BuOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
t-BuOH
t-BuOH
t-BuOH
e
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
e
e
f
77g
83g
92
82
86
f
f
f
2
a All reactions were carried out under reflux for 10 h.
b Mol% according to telluronium salt.
c 2 equiv. of base used.
d Isolated yield.
e 1.5 equiv. of base used.
f 1.1 equiv. of base used.
g Etherification of alcohol with the allylic bromide was observed and this side reaction lowered the yield.
base, Cs2CO3 was better. In the presence of a trace of
water, the yield decreased greatly (entry 3). This reac-
tion was found to be solvent-dependant. In toluene, no
epoxide was detected at all. In ethereal solvents, this
reaction gave the desired product in only moderate
yields (entries 2, 9 and 11 in Table 1). Alcoholic sol-
vents proved to be better than THF (entries 14–16 and
18–21), probably due to the formation of hydrogen
bonds between the solvent and aldehydes, which acti-
vated the aldehydes.13 The best solvent of those
screened was t-BuOH (entries 20, 21). The amount of
base also influenced the yield of this reaction. The best
results were achieved when 1.1 equiv. of Cs2CO3 was
used (entry 20). Increasing the amount of base led to
lower yield. Finally, we found that both dibutyl telluro-
nium salt 3 and diiso-butyl telluronium salt 4 were
better than salt 2. The catalyst loading could be low-
ered from 20 to 2 mol% (entries 21, 22 in Table 1) when
compound 3 or 4 was used as a catalyst. Noticeably,
although the stereoselectivity was not good, the isomers
could be separated easily by flash-chromatography.
turally different aldehydes. The results are summarized
in Table 2. As shown in Table 2, both electron-rich and
electron-deficient aromatic aldehydes gave vinyl-type
epoxides in excellent yields (entries 1–8). Compared
with aromatic aldehydes, aliphatic aldehydes such as
cyclohexanecarboxaldehyde and nonyl aldehyde are
usually less active in catalytic ylide reactions, but they
worked well (entries 9, 10) in our conditions in the
presence of 20 mol% of salt 4. It is worth noting that
allyl bromide also participated in this reaction to give
the desired epoxide in excellent yield (entry 11).
In the past decades, highly efficient catalysis has
become one of the most important frontiers in
exploratory organic synthesis research.14 Compared
with diisobutyl telluride and dibutyl telluride, we have
found that the corresponding salts 3, 4 and 5 are much
better in catalytic ylide epoxidation reactions. The mild
reaction conditions, in particular the high catalytic
efficiency, provides a possibility for the regioselective
synthesis of vinyl-type epoxides. Improvement of the
stereoselectivity in this epoxidation is currently being
studied in our laboratory.
Using the optimized conditions, we studied the general-
ity of this reaction by investigating a variety of struc-

K. Li et al. / Tetrahedron Letters 44 (2003) 4137–4140
Table 2. Reactions of different aldehydes with allylic bromides15
4139
Entry
Catalyst
Loadinga
R
R1
cis/trans
Yieldb (%)
1
2
3
4
5
6
7
8
3
4
3
3
4
3
3
3
4
4
5
2
2
2
2
2
2
2
2
4-ClC6H4
4-ClC6H4
C6H5
4-CH3C6H4
4-CH3C6H4
4-NO2C6H4
2-ClC6H4
2-Naphthyl
n-C9H19
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
H
49:51
49:51
51:49
50:50
49:51
51:49
45:55
52:48
54:46
58:42
55:45
82
86
88
83
88
78
82
92
83
73
92
9
10
11
20
20
2
Cyclohexyl
4-ClC6H4
a Mol% according to telluronium salt.
b Isolated yield.
Acknowledgements
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We are grateful for the financial support from the
National Natural Sciences Foundation of China, and
the ‘Talented Scientist Program’ from the Chinese
Academy of Sciences.
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mg, 3.75 mmol), dry Cs2CO3 (907 mg, 2.7 mmol), and
dry tert-butyl alcohol (5 ml). The resulting mixture was
refluxed for 4 h. After the reaction was complete (moni-
tored by GC), the reaction mixture was filtered through
a silica gel pad. The filtrate was concentrated under
vacuum. The residue was purified by flash-chromato-
graphic (hexane/ethyl acetate, 200:1) to afford the
product: Yield: 86%, 270 mg (trans-product, white
solid,) and 269 mg (cis-product, colorless oil).
15. Typical procedure. To a Schlenk tube was added materi-
als under nitrogen in the following sequence: p-
chlorobenzyl aldehyde (350 mg, 2.5 mmol), catalyst 4