The first isolation of allenylselenonium salts: their synthesis and properties as electrophiles

Article abstract of DOI:10.1016/j.tetlet.2006.11.150

The first synthesis of allenylselenonium salts and their reactivities are described. The corresponding allenyl methyl selenides were alkylated with methyl trifluoromethanesulfonate to afford the desired compounds. Their reactions with active methylene car

Full text of DOI:10.1016/j.tetlet.2006.11.150

Tetrahedron Letters 48 (2007) 813–816
The first isolation of allenylselenonium salts:
their synthesis and properties as electrophiles
Shin-ichi Watanabe,a,* Yukio Miura,b Tatsunori Iwamura,b
Hideko Nagasawab and Tadashi Kataokac
aCollege of Pharmacy, Kinjo Gakuin University, 1723 Omori 2 chome, Moriyama-ku, Nagoya 463-8521, Japan
bGifu Pharmaceutical University, 6-1 Mitahora-higashi 5 chome, Gifu 502-8585, Japan
cYokohama College of Pharmacy, 601 Matanocho, Totsuka-ku, Yokohama 245-0066, Japan
Received 2 November 2006; revised 24 November 2006; accepted 27 November 2006
Available online 18 December 2006
Abstract—The first synthesis of allenylselenonium salts and their reactivities are described. The corresponding allenyl methyl sele-
nides were alkylated with methyl trifluoromethanesulfonate to afford the desired compounds. Their reactions with active methylene
carbanions produced furan, dihydrofuran or methylene cyclopropane derivatives via the Michael addition of nucleophiles to the
selenonium salts.
Ó 2006 Elsevier Ltd. All rights reserved.
The addition of nucleophiles to electron deficient allene
compounds is one of the most widely used construction
methods in organic synthesis.1 In particular, stabilized
carbon nucleophiles undergo the Michael-type addition
toward allenes to afford highly functionalized materials2
as well as heteronucleophiles.3 Although the study on
the reactivity of allenes bearing electron withdrawing
groups has been fairly often reported, there are few
examples of their reaction as Michael acceptors of allen-
ylchalcogenonium salts.4 For the reported reactions of
allenylsulfonium salts with active methylene carbanions,
the salts were generated in situ from the corresponding
propargylic salts. Thus, the isolation of allenylchalco-
genonium salts has not yet been achieved.
esting features, allenylselenonium salts, which have still
not been synthesized, should be targeted to determine
their properties. We now report the first synthesis of
the allenylselenonium salts and the study of their reac-
tions with active methylene carbanions.
We planned the synthesis of the dimethylallenylseleno-
nium salts by alkylation of the allenyl methyl selenide
precursors. The racemic allenylselenonium salt 1a was
prepared as shown in Scheme 1. The reaction of (3-bro-
mo-1-propynyl)benzene, which was produced from phe-
nyl acetylene in high yield and in two steps,6 with
lithium methaneselenolate that had been generated from
methyllithium and elemental selenium, gave methyl 3-
phenyl-2-propynyl selenide 2 in a good yield. Although
the isomerization of 2 to an allene did not proceed in
good yield with various bases at room temperature,
the desired allenyl selenide 3 could be obtained in 69%
by the treatment with potassium tert-butoxide at 60 °C
for 4 h. The methylation of the selenium atom in 3 with
methyl triflate in ether at ꢀ40 °C for 72 h formed the
allenylselenonium salt 1a in 61% yield.7 This salt 1a
was isolated as an oil, however, it was too hygroscopic
to be isolated as stable crystals. Next, the preparation
of an achiral one was examined in order to obtain a sta-
ble allenylselenonium salt. The reaction of 1-propynese-
lenolate with methyl iodide afforded methyl 1-propynyl
selenide 4 in high yield. Allenyl selenide 5 was formed
by the reaction of 4 with LDA followed by a treatment
During the course of our work to investigate selenonium
salts bearing unsaturated carbon–carbon bond groups,
we developed alkynyl and alkenylselenonium salts as
versatile synthons for organic synthesis.5 Notably, their
reactions with active methylene carbanions produced
highly functionalized furan and cyclopropane deriva-
tives, respectively, through the tandem Michael addi-
tion–cyclization routes.5b,j Therefore, these selenonium
salts act as useful Michael acceptors. Due to their inter-
Keywords: Allenylselenonium salt; Michael addition; Furan; Dihydro-
furan; Methylene cyclopropane.
*
Corresponding author. Tel.: +81 52 798 0180; fax: +81 52 798
0754; e-mail: swatana@kinjo-u.ac.jp
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.11.150

814
S. Watanabe et al. / Tetrahedron Letters 48 (2007) 813–816
MeOTf
Se, MeLi
Ph
Ph
t-BuOK
Ph
Ph
Br
t-BuOH
60 °C, 4 h
Et2O
-40 °C, 72 h
THF
rt, 2 h
SeMe
2 (79%)
SeMe
3 (69%)
SeMe2
TfO
1a (61%)
Se, MeI
Bn
MeOTf
Bn
BnBr, LDA
Me
MgBr
Me
SeMe
4 (80%)
Et2O
0 °C, 72 h
THF
-40 °C, 4 h
THF
80 °C, 4 h
SeMe
SeMe2
TfO
1b (52%)
5 (36%)
Scheme 1. Synthesis of allenylselenonium salts.
with benzyl bromide.8 Selenide 5 reacted with methyl tri-
flate to give the desired selenonium salt 1b in 52% yield.9
The structures of 1 were determined from its spectral
data. The 13C NMR spectrum indicated the presence
of the quaternary carbons in the allenic moieties at d
203.8 of 1a and 202.5 of 1b, respectively. In particular,
two singlet peaks (d 2.87 and 2.86) of diastereotopic
methyl protons on the selenium atom in 1a showed the
existence of a chiral allenyl group.
tive 9 in 33% yield and this transformation also sup-
ported the fact that 7 had a dihydrofuran skeleton
(Scheme 2).11 The stereochemistry of the exo double
bond in compound 7 was determined to be the
(Z)-geometry by the NOE enhancement between the
methylene protons of the dihydrofuran ring and
the ortho-protons of the cis-phenyl group (23%). On
the other hand, the (E)-configuration of the methylene
cyclopropane derivatives 8 was determined by the
NOE experiment of 8b showing the enhancement
of the ortho-protons of the cis-phenyl group (5%)
upon the irradiation of the cyclopropane’s methylene
protons.
Table 1 shows the reactions of the allenylselenonium salt
1a with active methylene carbanions.10 We first con-
ducted the reaction of 1a with acetylacetone (6a) in
DMF (entry 1) and t-BuOH (entry 2) at room tempera-
ture for 3 h to afford the dihydrofuran derivative 7a in
32% and 42%, respectively, together with allenyl selenide
3 formed by the demethylation of the selenonium salt 1a
with a nucleophile. The benzoylacetone (6b) reacted with
1a in t-BuOH to form the 4-benzylidene-3-benzoyl-
2-methyl-4,5-dihydrofuran 7b in moderate yield as a
major product accompanied by a small amount of iso-
mer 7b0 (entry 3). The reaction with ketoester 6c in the
mixture of t-BuOH and DMF gave 7c in a better yield
(entry 4). On the other hand, the methylene cyclopro-
pane derivatives 8 were obtained from the reaction with
the dibenzyl and diethyl malonates (entries 5 and 6). The
structures of 7 and 8 were determined on the basis of
their spectral data. The isomerization of compound 7c
under basic conditions produced a known furan deriva-
Next, the reactions of the allenylselenonium salt 1b with
active methylene carbanions were carried out (Table
2).10 Interestingly, the reactions of 1b gave different
products from those of 1a. The tetra substituted furan
derivative 10a was produced in 60% yield by the reaction
O
O
DBU
Me
Me
Ph
Ph
DMF
r.t., 24 h
O
O
EtO
7c
EtO
33%
9
Scheme 2. Isomerization of 7c into 9.
Table 1. Reactions of 1a with active methylene carbanions
O
O
O
NaH (1.25 equiv.)
Ph
R1
Ph
R1
R2
R1
Ph
Ph
+
Ph
Solvent
r.t., Time
SeMe2
TfO
O
O
O
O
O
R2
R2
Me
7b'
6 (1.0 equiv.)
1a (1.5 equiv.)
8
7
Entry
6
Solvent
Time (h)
Products
Yield (%)
1a
2
3
4
5
6
6a: R1 = R2 = Me
6a
6b: R1 = Me, R2 = Ph
6c: R1 = Me, R2 = OEt
6d: R1 = R2 = OBn
6e: R1 = R2 = OEt
DMF
t-BuOH
t-BuOH
t-BuOH–DMF (3:1)
t-BuOH
t-BuOH
3
3
24
24
12
24
7a
7a
7b, 7b0
7c
8a
8b
32
42
41, 7
42
50
b
29
a NaH (1.0 equiv) was used.
b Determined by 1H NMR.

S. Watanabe et al. / Tetrahedron Letters 48 (2007) 813–816
Table 2. Reactions of 1b with active methylene carbanions
815
Bn
O
NaH (1.25 equiv.)
Bn
R1
R1
R2
+
DMF
r.t., 24 h
SeMe2
TfO
1b (1.5 equiv.)
O
O
O
R2
10
6 (1.0 equiv.)
Entry
6
Products
Yield (%)
1
6a: R1 = R2 = Me
10a
10b
10c
10d
60
56
47
39
2a
3
6c: R1 = Me, R2 = OEt
6d: R1 = R2 = OBn
6e: R1 = R2 = OEt
4
a 1b (1.1 equiv) and NaH were used.
of 1b with acetylacetone in the presence of sodium
hydride in DMF for 24 h (entry 1). Ketoester 6c also
reacted with 1b to afford the corresponding furan 10b
in 56% yield (entry 2). Furthermore, the reactions with
the dialkyl malonates produced the furan derivatives
10c and 10d (entries 3 and 4) different from the reaction
forming methylenecyclopropanes 8 from 1a. Selenide 5
generated through the pathway similar to the reaction
with 1a was detected by TLC as a by-product in all
the reactions.
(R2 = H) of the selenonio group to give methylene
cyclopropane derivatives 8, in spite of the ring strain
of them (path b). Since carbanions 6 attack the center
carbon of the allenyl moiety in 1 from the backside of
the R1 (phenyl) group, the geometry of R1 and the
nucleophiles is the Z (7) or E (8) configuration, respec-
tively. Meanwhile, the reactions of 1b with 6 proceed
through path a regardless of the structure of the active
methylene compounds. Due to the steric hindrance of
the secondary a-carbon (R2 = Bn) of the selenonio
group, path b is inhibited and the enolization predomi-
nantly proceeds (path a) to produce the unstable
dihydrofurans, which are easily transformed into the
more stable furan derivatives 10 under the given reac-
tion conditions.
A plausible reaction mechanism of the allenylseleno-
nium salts 1 with the carbanions is shown in Scheme
3. The selenonium ylides 11 are formed from the Mi-
chael addition of carbanion 6 to the allenylselenonium
salt 1 followed by the deprotonation of an active meth-
yne proton to generate betaine 12. In the case of seleno-
nium salt 1a, the intramolecular nucleophilic attack of
the enolate occurs to afford dihydrofuran derivatives 7
(path a) when the active methylene compound possesses
not less than one acyl group. On the other hand, an
active methyne carbanion of the ester derivatives 12
(R3 = R4 = alkoxy) which has the greater electron den-
sity on the carbon attacks the primary a-carbon
In conclusion, the first synthesis and isolation of allen-
ylselenonium salts 1 have been achieved by the alkyl-
ation of the corresponding allenyl methyl selenides
with methyl triflate. The reactions of 1 and active meth-
ylene carbanions produced highly functionalized furan
or dihydrofuran derivatives via the tandem Michael-
intramolecular cyclization reaction. In particular, we
developed a novel synthetic method of methylene cyclo-
R1
R2
R1
R1
R1
R2
SeMe
Me
R2
R2
R1 = H
TfO
1
O
R2 = Bn
O
O
H SeMe2
R3
O
O
R4
R4
R3
R4
R4
R3
7
R3
O
11
O
O
1
0
6
3 or 5
R3 = alkyl or aryl
path a
R1
R1 = Ph
R2 = H
R1
Ph
R2
SeMe2
R2
b
O
R3 = R4 = alkoxy
path b
O
O
SeMe2
R4
O
R4
R4
R3
R3
a
R3
8
O
O
13
12
Scheme 3. Plausible mechanism for the reactions of 1 with 6.

816
S. Watanabe et al. / Tetrahedron Letters 48 (2007) 813–816
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currently under investigation.
Acknowledgments
This research was partially supported by Grants-in-Aid
(Nos. 16659007 and 17790015) from the Ministry of
Education, Culture, Sports, Science and Technology
(Japan).
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