Michael-type addition of hydroxide to alkynylselenonium salt: Practical use as a ketoselenonium ylide precursor

Article abstract of DOI:10.1016/j.tetlet.2004.08.036

A novel synthetic method of ketodiphenylselenonium ylide from alkynylselenonium salt is described. A reaction of alkynylselenonium salt, hydroxide ion, and aldehyde in the presence of silver triflate and triethylamine gave oxiranylketones just as a trans-

Full text of DOI:10.1016/j.tetlet.2004.08.036

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 7459–7463
Michael-type addition of hydroxide to alkynylselenonium
salt: practical use as a ketoselenonium ylide precursor
Shin-ichi Watanabe,* Shinsuke Asaka and Tadashi Kataoka*
Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Received 17 June 2004; revised 9 August 2004; accepted 9 August 2004
Abstract—A novel synthetic method of ketodiphenylselenonium ylide from alkynylselenonium salt is described. A reaction of alkyn-
ylselenonium salt, hydroxide ion, and aldehyde in the presence of silver triflate and triethylamine gave oxiranylketones just as a
trans-isomer in moderate to good yields, whereas benzoyl aziridine derivatives were obtained from the reaction with sodium p-tolu-
enesulfonamide instead of a hydroxide ion.
Ó 2004 Elsevier Ltd. All rights reserved.
Selenonium ylide, a versatile synthetic species in the
field of organic synthesis, induces several types of C–C
bond formation reactions.1 While the properties of
selenonium and sulfonium ylides show remarkable
resemblance, selenonium ylides stabilized by an elec-
tron-withdrawing group are more reactive than the cor-
responding sulfonium ylides toward electrophiles.2
Some stable selenonium ylides stabilized by two elec-
tron-withdrawing substituents on the carbanionic center
were generated by the reactions of the corresponding
selenuranes and the active methylene compounds,3 the
treatment of stable selenoxides with active methylene
compounds,4 or electron-deficient alkynes,5 and the dis-
placement of an aryliodonium group from the iodonium
ylide with the selenide.6 On the other hand, selenonium
ylides bearing an electron-withdrawing group were
formed only by the deprotonation of the corresponding
selenonium salts.2a,7 These stabilized ylides have dialkyl
groups on the selenium atom, which are inconvenient
for the reactions with nucleophiles because of the occur-
rence of a side reaction, dealkylation.8 There is only one
report on the synthesis of the b-ketodiarylselenonium
salt, but its reactivities are unknown.9 Thus, we are
interested in developing a new synthetic method of keto-
diarylselenonium ylide. Through our research on the
reactivities of diarylalkynylselenonium salts, we found
that diarylalkynylselenonium salts act as a good
Michael acceptor toward certain nucleophiles.10 If the
Michael-type addition of the hydroxide ion occurs
toward an alkynylselenonium salt, a ketodiarylseleno-
nium ylide would be formed after enol–keto tautomeri-
zation (Scheme 1). On the basis of this hypothesis, we
investigated the reactions of the alkynylselenonium salts
with hydroxide to form the ketodiphenylselenonium
ylides and the capture of the ylide with aldehydes to
produce oxiranylketones.
We first examined the reactions of phenylethynyldiphen-
ylselenonium triflate 1a and lithium hydroxide with
aromatic aldehydes (Table 1). The reaction of p-nitro-
benzaldehyde with 2equiv of alkynylselenonium salt 1a
in the presence of 3equiv of lithium hydroxide at room
temperature proceeded slowly, and trans-oxiranylketone
2a and diphenyl selenoxide 3 were obtained in 17%
yields (entry 1). The formation of the selenoxide proba-
bly arose from the attack of hydroxide to the seleno-
nium cation directly.11 In order to activate the triple
R
+
R
SeAr2
TfO
OH
HO
SeAr2
R
O
Keywords: Michael reactions; Oxiranes; Selenonium ions; Ylides;
Aziridines.
H
R
SeAr2
*
SeAr2
Corresponding authors. Tel.: +81 58 237 3931; fax: +81 58 237
5979; e-mail addresses: watanabe@gifu-pu.ac.jp; kataoka@gifu-pu.
ac.jp
O
Scheme 1. Michael addition of hydroxide to alkynylselenonium salt.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.08.036

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S. Watanabe et al. / Tetrahedron Letters 45 (2004) 7459–7463
Table 1. Reactions of alkynylselenonium salt 1a and ArCHO with
LiOH
In view of the results above, the conditions for the reac-
tion with p-chlorobenzaldehyde were optimized, and the
best yield was obtained by the use of 4equiv of alkynyl-
selenonium salt 1a, silver triflate, and triethylamine and
2equiv of lithium hydroxide toward the aldehyde after
12h (Table 3, entry 1).13 Under the same conditions,
several aromatic aldehydes underwent the reactions,
and good yields of the desired oxiranylketones were
obtained. The drop in the electron density of the aro-
matic ring accelerated the reaction rate. Furthermore,
the reactions of p-nitrobenzaldehyde with other alkynyl-
selenonium salts bearing p-chlorophenylethynyl or
p-methylphenylethynyl groups also afforded the corre-
sponding oxirane derivatives in high yields.14 NMR
analysis showed that these oxirane compounds obtained
from the above reactions were just trans-isomers.
LiOH
Additive
H
Ar
H
Ph
SePh2
TfO
Ph2Se(O)
Ph
CH2Cl2-MeCN
r.t., 24 h
O
O
1a
2
3
+
ArCHO
Entry Ar
Additive
Products (yield, %)
1
2
3
4
p-NO2C6H4
2a (17) 3 (17)
2a (78)
2b (67)
p-NO2C6H4
p-CNC6H4
p-ClC6H4
AgOTf (4equiv)
AgOTf (4equiv)
AgOTf (4equiv)
2c (25)
Second, to broaden the scope of this reaction, we exam-
ined the reactions with a variety of aliphatic aldehydes
(Table 4). The reactions with linear aliphatic aldehydes
were carried out under the same reaction conditions that
were used for aromatic aldehydes. While the reaction
with 1-propanal gave the oxirane derivative 2l in 18%
yield, the chain lengthening of an aldehyde improved
the yield of the product, and the desired compound 2n
was obtained in 54% yield from the reaction with hydro-
cinnamaldehyde (entries 1–3). Additionally, isobutyl-
aldehyde as a chain-branching aldehyde, reacted with
the ketoselenonium ylide to produce the oxiranyl ketone
2o in 37% yield, and the reaction with valeraldehyde
showed a better result, giving a 63% yield of oxirane
2p (entries 4 and 5). Probably, the cause of the lower
yields of oxiranyl ketones in the reactions with aliphatic
aldehydes than with aromatic aldehydes is attributable
to side reactions, such as the self aldol reaction. In prac-
tice, when the more sterically hindered aldehyde was
used, the yields of desired products were increased by
preventing the side reactions. On the other hand, isobut-
ylaldehyde is too bulky to react with the ylide ade-
quately. The compounds obtained from the reactions
were single trans-isomers, and their structures were
bond toward the Michael-type addition of a nucleophile,
a silver salt was added as a soft metal to the reaction
mixtures. Thus, the reaction with 4equiv of silver triflate
gave the product 2a in 78% yield (entry 2). While p-
cyanobenzaldehyde reacted with the alkynylselenonium
salt and lithium hydroxide to afford the desired epoxide
2b in good yield (entry 3), the reactivity of p-chlorobenz-
aldehyde was low to give the product 2c only in 25%
yield (entry 4). The compounds obtained from the reac-
tions were single trans-isomers, and their structures were
1
determined by comparing their H and 13C NMR data
with those of authentic samples.12
Next, in order to boost the formation of ketoselenonium
ylide by catalyzing the enol–keto tautomerization, the
effect of amine was examined in the reaction of p-chloro-
benzaldehyde (Table 2). The reaction of alkynylseleno-
nium salt 1a (2equiv) with the aldehyde and 3equiv of
lithium hydroxide in the presence of 4equiv of silver tri-
flate and 2equiv of triethylamine in a mixed solvent of
CH2Cl2–MeCN was carried out at room temperature
for 1day, and the yield of the desired compound 2c
was improved up to 61% (entry 1). While the reflux con-
dition reduced the reaction time, the yield of 2c was
decreased (entry 2). Although the increase of the
amount of triethylamine to 4equiv afforded the product
2c in 63% yield, the use of 10equiv of triethylamine
decreased the yield (entries 3 and 4).
1
determined by comparing their H and 13C NMR data
with those of authentic samples.15
On the basis of these results, we propose a plausible
mechanism for the reactions of an alkynylselenonium
salt with aldehydes and a hydroxide in the presence of
a silver salt and triethylamine (Scheme 2). The triple
bond of the alkynylselenonium salt is activated by a sil-
ver cation, and a hydroxide ion attacks the b-carbon of
the alkynylselenonium salt, similarly to the Michael-
type addition, to form the vinyl ylide 4, which is
transformed to the ketodiphenylselenonium ylide by
enol–keto tautomerization accelerated by triethylamine.
The ylide reacts with aldehydes to give oxiranylketones
together with diphenyl selenide (route A). On the other
hand, diphenyl selenoxide is formed by the attack of
hydroxide to a selenonium cation without activation of
a triple bond by a silver ion (route B). Since these reac-
tions were examined at room temperature, the diastereo-
selectivity on the betaine 5 would not be observed. The
reason that only trans-oxiranes are formed can be
explained by the assumption that an active methine
Table 2. The effect of triethylamine
LiOH, Et3N, AgOTf
H
C6H4 -p-Cl
H
Ph
SePh2
TfO
Ph
CH2Cl2 -MeC N
O
O
1a
2c
+
p-ClC6 H4CHO
Entry
Et3N
Conditions
rt, 1d
2c
1
2
3
4
2equiv
2equiv
4equiv
10equiv
61%
53%
63%
56%
Reflux, 8.5h
rt, 1.5d
rt, 1.5d

S. Watanabe et al. / Tetrahedron Letters 45 (2004) 7459–7463
7461
Table 3. Preparation of oxiranylketones
LiOH (6 eq), Et3 N (4 eq),
AgOTf (4 eq)
H
Ar2
Ar1
SePh2
TfO
Ar1
H
CH2Cl2-MeCN
O
O
1 (4 eq)
2
+
Ar2CHO
Entry
1
Ar2
Time (h)
Products (yield, %)
1
2
1a (Ar1 = Ph)
p-ClC6H4
p-NO2C6H4
o-NO2C6H4
m-NO2C6H4
p-BrC6H4
o-BrC6H4
m-BrC6H4
Ph
12
3.5
1.5
2
2c (78)
2a (84)
2d (71)
2e (58)
2f (55)
2g (92)
2h (90)
2i (40)
2j (89)
2k (71)
1a
1a
1a
1a
1a
1a
1a
3
4
5
9
6
2
7
5
8
6.5
3
9
10
1b (Ar1 = p-ClC6H4)
1c (Ar1 = p-MeC6H4)
p-NO2C6H4
p-NO2C6H4
3
Table 4. Reactions of ketoselenonium ylide with RCHO
Table 5. Reactions of alkynylselenonium salt with ArCHO and
TsNHNa
LiOH (6 eq), Et3N (4 eq),
AgOTf (4 eq)
TsNHNa (6 eq), Et3 N (4 eq),
H
R
Ph
SePh2
TfO
Ph
AgOTf (4 eq)
H
H
H
CH2Cl2-MeCN
Ph
SePh2
TfO
O
Ph
Ar
O
Solvent, r.t., 3 d
N
Ts
O
1a (4 eq)
2
1a (4 eq)
6
+
+
RCHO
ArCHO
Entry
R
Time
Products (yield, %)
(1 e q)
1
2
3
4
5
CH3CH2
CH3(CH2)2
Ph(CH2)2
Overnight
24h
2l (18)
2m (34)
2n (54)
2o (37)
2p (63)
Entry
Ar
Solvent
Products (yield, %)
1
2
3
4
p-ClC6H4
CH2Cl2–MeCN
MeCN
MeCN
6a (44)
6b (44)
6c (48)
6d (30)
Overnight
Overnight
24h
p-NO2C6H4
o-BrC6H4
o-MeOC6H4
(CH3)2CH
(CH3)CHCH2
CH2Cl2–MeCN
A
thermodynamically stable conformer cyclizes to produce
the trans-epoxides 2.2a
B
OH
Et3N
Ph
Ph
Ph
SePh2
TfO
SePh2
One reaction feature of the alkynylselenonium salt is
that other nucleophiles are available as Michael donor
in place of hydroxide ion. In anticipation of the produc-
tion of oxiranyl imines, a p-toluenesulfonamide was
selected as a nucleophile (Table 5). The reaction of
alkynylselenonium salt 1a with p-chlorobenzaldehyde
and sodium p-toluenesulfonamide16 in the presence of
triethylamine and silver trifluoromethanesulfonate was
undertaken under similar conditions to Table 3. Unex-
pectedly, 2-benzoyl-3-(p-chlorophenyl)-1-tosylaziridine
6a was obtained in 44% yield as a single cis-isomer after
3days (entry 1). The structure of 6a was determined by
comparing its spectral data with that of an authentic
sample.17 Other aldehydes also reacted to give tosylazir-
idine derivatives in moderate yields (entries 2–4). The
coupling constants of the methine protons on the azir-
idine ring of 6 (7–8Hz) indicate that these isomers are
cis geometry.17
HO
SePh2
O
Ag
route A
4
5
route B
RCHO
Ph
H
R
O
H
R
Ph
H
+
Ph2Se(O)
Ph
H
O
O
SePh2
O
2
Scheme 2. Plausible mechanism of the reactions of an alkynylseleno-
nium salt with an aldehyde and a hydroxide in the presence of a silver
cation and triethylamine.
hydrogen in the betaine intermediate is easily deproto-
nated by excess bases in this system and the resulting

7462
S. Watanabe et al. / Tetrahedron Letters 45 (2004) 7459–7463
Voloshchuk, S. A. Zh. Org. Khim. 1978, 14, 958–962; (f)
Shevelev, S. A.; Semenov, V. V.; FainzilÕberg, A. A. Izv.
Akad. Nauk SSSR, Ser. Khim. 1978, 1091–1098.
4. (a) Magdesieva, N. N.; Kyandzhetsian, R. A. Zh. Org.
Khim. 1973, 9, 1755–1756; (b) Magdesieva, N. N.;
Kyandzhetsian, R. A. Zh. Org. Khim. 1974, 10, 1708–
1711; (c) Magdesieva, N. N.; Kyandzhetsian, R. A.;
Astafurov, V. M. Zh. Org. Khim. 1975, 11, 508–511; (d)
Tamagaki, S.; Akatsuka, R.; Kozuka, S. Bull. Chem. Soc.
Jpn. 1980, 53, 817–818.
5. (a) Magdesieva, N. N.; Kyandzhetsian, R. A.; Gordeev,
M. F. Zh. Org. Khim. 1982, 18, 2514–2523; (b) Kataoka,
T.; Tomimatsu, K.; Shimizu, H.; Hori, M. Tetrahedron
Lett. 1983, 24, 75–78.
6. Semenov, V. V.; MelÕnikova, L. G.; Shevelev, S. A.;
FainzilÕberg, A. A. Izv. Akad. Nauk SSSR, Ser. Khim.
1980, 138–144.
The initial step of the above reaction is presumed to be a
formation of an N-sulfonylaldimine and a hydroxide ion
from a p-toluenesulfonamide monosodium salt and an
aromatic aldehyde. The subsequent reaction of the N-
sulfonylaldimine with b-ketoselenonium ylide, which is
generated by an alkynylselenonium salt and a hydroxide
ion would lead to producing an aziridine derivative.
However, the reaction of alkynylselenonium salt 1a with
N-tosyl-4-nitrobenzaldimine and lithium hydroxide in
the presence of triethylamine and silver trifluoromethan-
sulfonate at room temperature for 10h gave oxiranyl-
ketone 2a in 42% yield and the desired aziridine
derivative was not obtained. The reason for the cis selec-
tivity on the aziridine formation is attributable to the
stability of the cis-isomer.18 While so far reports on
the preparation of aziridines starting from ylides and
imines are limited,17,19 we have been able to achieve a
novel type of aziridine formation reaction using alkynyl-
selenonium salt, aldehyde, and sodium p-toluene-
sulfonamide.
7. Lotz, W. W.; Gosselck, J. Tetrahedron 1973, 29, 917–919.
8. Magdesieva, N. N.; Kyandzhetsian, R. A.; Chovnikova,
N. G.; EmelÕyanova, N. N. Zh. Org. Khim. 1981, 17, 340–
342.
9. Hashimoto, T.; Kitano, H.; Fukui, K. Nippon Kagaku
Zasshi 1968, 89, 784–786.
10. (a) Kataoka, T.; Banno, Y.; Watanabe, S.; Iwamura, T.;
Shimizu, H. Tetrahedron Lett. 1997, 38, 1809–1812; (b)
Kataoka, T.; Watanabe, S.; Yamamoto, K.; Yoshimatsu,
M.; Tanabe, G.; Muraoka, O. J. Org. Chem. 1998, 63,
6382–6386; (c) Watanabe, S.; Yamamoto, K.; Itagaki, Y.;
Kataoka, T. J. Chem. Soc., Perkin Trans. 1 1999, 2053–
2055; (d) Watanabe, S.; Mori, E.; Nagai, H.; Kataoka, T.
Synlett 2000, 49–52; (e) Watanabe, S.; Mori, E.; Nagai,
H.; Iwamura, T.; Iwama, T.; Kataoka, T. J. Org. Chem.
2000, 65, 8893–8898; (f) Watanabe, S.; Yamamoto, K.;
Itagaki, Y.; Iwamura, T.; Iwama, T.; Kataoka, T.;
Tanabe, G.; Muraoka, O. J. Chem. Soc., Perkin Trans. 1
2001, 239–247.
In summary, we have developed a novel synthetic
method of ketodiphenylselenonium ylide from alkyny-
lselenonium salt, and the formation of the ylide was
indirectly confirmed by a trap of aldehydes to afford
oxiranyl-ketones. On the other hand, by the use of
sodium p-toluenesulfonamide as nucleophile instead of
lithium hydroxide, benzoyl aziridines were obtained in
moderate yields. A silver cation assists the Michael-type
addition of hydroxide to an alkynylselenonium salt.
Although the excess amount of starting materials
toward aldehyde is a disadvantage, we found interesting
reactions with alkynylselenonium salt involving the con-
trol on the addition of a hydroxide ion with a silver ion
to alkynylselenoioum salt. In addition, the preparation
of oxiranes and aziridines was successful by only chang-
ing the hydroxide to amide. This is the first example in
which an alkynylonium salt is used as an ylide precur-
sor. Further applications of this methodology are cur-
rently underway in our laboratory.
11. (a) Detty, M. R. J. Org. Chem. 1980, 45, 274–279;
Harirchian, B.; Magnus, P. D. Chem. Commun. 1977, 522–
523.
12. Shi, M.; Itoh, N.; Masaki, Y. J. Chem. Res. (S) 1995,
304–305.
13. Typical procedure: Alkynylselenonium salt 1 (0.8mmol),
an aromatic aldehyde (0.2mmol) and silver triflate
(0.8mmol) were dissolved in CH2Cl2–MeCN (4:1, 5mL).
Anhydrous lithium hydroxide (1.2mmol) and then trieth-
ylamine (0.8mmol) were added to the solution. The
mixture was stirred for 1.5–12h at room temperature.
The typical work-up with water, extraction with ethyl
acetate, and preparative TLC purification afforded 2.
14. Chlorophenylethynyldiphenylselenonium triflate 1c was
prepared by the addaption of published procedure.10b
15. (a) Enders, D.; Zhu, J.; Kramps, L. Liebigs Ann. Chem.
1997, 1101–1113; (b) Mukaiyama, T.; Iwasawa, N.;
Stevens, R. W.; Haga, T. Tetrahedron 1984, 40, 1381–1390.
16. Bottini, F.; Grazia, M. D.; Finocchiaro, P.; Fronczek
F. R.; Mamo, A.; Pappalardo, S. J. Org. Chem. 1988, 53,
3521–3529.
Acknowledgements
This research was partially supported by the Ministry of
Education, Science, Sports, and Culture, Grant-in-Aid
for the Encouragement of Young Scientists (B), 2004,
14771246.
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