A new 3-(phenylseleno)allylic cation: Its regioselective C-C bond formation reaction with nucleophiles

Article abstract of DOI:10.1021/jo010331+

Highly useful C-C bond formation using 2-ethoxy-3-(phenylseleno)prop-2-enal acetal 2 was examined with various Lewis acids. The reaction of 2 with the silyl enol ether in the presence of BF₃·Et₂O, ZnBr₂, or SnBr₄ regioselectively provided (Z)-3,4-diethoxy-5-(phenylseleno)pent-4-enophenone 5a in high yields. On the other hand, the reaction with other Lewis acids such as EtAlCl₂ or SnCl₄ gave 5-(phenylseleno)- 6 or non-selenopentane-1,4-dione 7, respectively. Novel prop-2-enal acetals 2-4 and 13-15 reacted with various nucleophiles to give pent-4-enophenones 5a,b, 10a, 12, and 16-18, S-ethyl pent-4-enoate 5b, alkylated vinylic sulfide 10b, 3-pentenenitrile 5d, and 10c. A versatile pent-4-enophenone 5a could be converted to tetrahydrofuran 20 and penta-2,4-dienophenone 19, the Diels-Alder reactions of which with dienophiles gave the adducts 24 and 25.

Full text of DOI:10.1021/jo010331+

1078
J . Org. Chem. 2002, 67, 1078-1083
A New 3-(P h en ylselen o)a llylic Ca tion : Its Regioselective C-C
Bon d F or m a tion Rea ction w ith Nu cleop h iles
Masaru Hibino, Tomoko Koike, and Mitsuhiro Yoshimatsu*
Department of Chemistry, Faculty of Education, Gifu University, Yanagido, Gifu 501-1193, J apan
yoshimae@cc.gifu-u.ac.jp
Received March 28, 2001
Highly useful C-C bond formation using 2-ethoxy-3-(phenylseleno)prop-2-enal acetal 2 was
examined with various Lewis acids. The reaction of 2 with the silyl enol ether in the presence of
BF3·Et2O, ZnBr2, or SnBr4 regioselectively provided (Z)-3,4-diethoxy-5-(phenylseleno)pent-4-enophe-
none 5a in high yields. On the other hand, the reaction with other Lewis acids such as EtAlCl2 or
SnCl4 gave 5-(phenylseleno)- 6 or non-selenopentane-1,4-dione 7, respectively. Novel prop-2-enal
acetals 2-4 and 13-15 reacted with various nucleophiles to give pent-4-enophenones 5a ,b, 10a ,
12, and 16-18, S-ethyl pent-4-enoate 5b, alkylated vinylic sulfide 10b, 3-pentenenitrile 5d , and
10c. A versatile pent-4-enophenone 5a could be converted to tetrahydrofuran 20 and penta-2,4-
dienophenone 19, the Diels-Alder reactions of which with dienophiles gave the adducts 24 and
25.
In tr od u ction
electrophiles. We preliminarily performed the addition
reaction of nucleophiles to the 3-(phenylseleno)prop-2-
ynal acetal to introduce a chalcogene functional group
at the 2-position.6 Thus, the 3-(phenylseleno)prop-2-enal
acetals bearing a 2-ethoxy, 2-(phenylthio), or 2-(phenylse-
leno) group would easily react with Lewis acid to afford
the 3-(phenylseleno)allylic cations, R-oxy carbenium ion
Ia stabilized by the alkylidene cation Ib, and R-seleno
carbenium ions Ic stabilized by a bridged cation Id . Here
we report a new highly regioselective alkylation of
3-seleno-allylating electrophiles functionalized by the
other heteroatom at the 2-position of prop-2-enal acetals.
Sulfur-stabilized allylic cations have attracted much
attention as good electrophiles for C-C bond formation
with soft nucleophiles and are utilized to construct
cyclopentenones, which are versatile intermediates for
the synthesis of biologically active compounds, by [3 +
2] cycloaddition.1 In the cationic species, the sulfur atom
plays an important role in controlling the regio- and
stereoselectivities of the products.2 On the other hand,
the selenium-substituted allylic cations have not been
much investigated because their precursors are difficult
to prepare. A few methods exist for the generation of the
1-alkylseleno-3 and 2-selenoallylic cations4 from 1,3-bis-
(methylseleno)prop-2-ene, 3-(methylseleno)prop-2-en-1-
ol, or 1-bromo-2-(phenylseleno)prop-2-ene and their elec-
trophilic reactions with the pyrrole and the silyl enol
ethers. However, their allylic cations are quite limited
because of the low regioselectivities of the products and
the formation of dialkylated products. Recently, we have
reported that the 2-(phenylseleno)prop-2-enal diethyl
acetals are good precursors for the 2-phenylselenenyl
allylic cations and the reactions with the nucleophiles are
found to be regioselective, giving high yields of the
products, and can be applied to the penta-2,4-dienylation
or hepta-2,4,6-trienylation of the nucleophiles.5 Continu-
ing studies in this field prompted us to investigate this
type of 3-(phenylseleno)allylic cation to find more useful
Resu lts a n d Discu ssion
The 3-(phenylseleno)-2-chalcogenoprop-2-enal diethyl
acetals 2-4 (Y ) OEt, SPh, SePh) were prepared by our
original methods. The reaction of 3-selenoprop-2-ynal
diethyl acetal (1) with NaOEt in EtOH under reflux
condition provided 2-ethoxyprop-2-enal acetal 2 in 75%
yield (Scheme 1).6 The â-(phenylthio)- or â-(phenylsele-
no)prop-2-enal acetals 3 and 4 were also obtained by the
almost same method in high yields. First, we performed
the reaction of â-ethoxyprop-2-enal acetal 2 with the silyl
enol ether in the presence of BF3·Et2O to give (Z)-3,4-
diethoxy-5-(phenylseleno)pent-4-enonophenone ((Z)-5a )
in 71% yield. The structure of 5a was determined by the
1
following data. The H NMR spectrum shows a singlet
at δ 5.98 ppm due to the characteristic olefinic proton
and a dd at δ 4.52 (J 4 and 7 Hz) due to the R-proton of
the ethoxy group. The 13C NMR spectrum shows a
doublet at δ 101.02 due to the R-olefinic carbon of the
phenylseleno group. The mass and elemental analysis
exhibits the molecular formula (C21H24O3Se). Other Lewis
acids were examined, and the results are shown in Table
1. Yb(OTf)3 afforded the alkylated products (E)- and (Z)-
(1) Masuya, K.; Domon, K.; Tanino, K.; Kuwajima, I. J . Am. Chem.
Soc. 1998, 120, 1724 and references therein.
(2) Hunter, R.; Simon, C. D. Tetrahedron Lett. 1986, 27, 1385.
Hunter, R.; Michael, J . P.; Walter, D. S. Tetrahedron Lett. 1992, 33,
5413. Hunter, R.; Michael, J . P.; Walter, D. S. Tetrahedron Lett. 1994,
35, 5481.
(3) 1-Selenoallylic cation: Hevesi, L.; Renard, M.; Process, G. J .
Chem. Soc., Chem. Commun. 1986, 1725. Renard, M.; Hevesi, L. J .
Chem. Soc., Chem. Commun. 1986, 688. Hevesi, L.; Lavoix, A.
Tetrahedron Lett. 1989, 30, 4433. Hevesi, L. Phosphorous, Sulfur,
Silicon 1992, 67, 155.
(4) 2-Selenoallylic cation: Halazy, S.; Hevesi, L. J . Org. Chem. 1983,
48, 5242.
(5) Yoshimatsu, M.; Gotoh, S.; Ikeda, K.; Komori, M. J . Org. Chem.
1998, 63, 6619.
(6) Yoshimatsu, M.; Shimizu, H.; Kataoka, T. J . Chem. Soc, Chem.
Commun. 1995, 149. Yoshimatsu, M.; Naito, M.; Shimizu, H.; Muraoka,
O.; Tanabe, G.; Kataoka, T. J . Org. Chem. 1996, 61, 8201.
10.1021/jo010331+ CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/18/2002

A New 3-(Phenylseleno)allylic Cation
J . Org. Chem., Vol. 67, No. 4, 2002 1079
Sch em e 1a
Sch em e 2a
a
Reagent: i, HCl/EtOH-H2O; ii, SnCl4/CH2Cl2/0 °C; iii, TiCl4/
CH2Cl2/0 °C.
ingly, the cyclized product 9 was obtained in low yield
(entry 5).
In some cases tried with commonly used Lewis acids
such as BF3·Et2O and ZnBr2, the nearly exclusive forma-
tion of the 4-pentenone 5a was observed, whereas strong
Lewis acids promote successive side reactions. The use
of TiCl4 and SnCl4 led to the formation of byproducts such
as 1,4-diketones 6 and 7, which were considered to be
obtained from the acid-promoted hydrolysis of the adduct
5a . The mechanism of the hydrolysis of vinylic selenides
has been thoroughly investigated by Hevesi et al.;7
however, that of the â-alkoxy vinylic selenides has not
been reported, to our knowledge. The results, the forma-
tion of the 1,4-diketones 6 and 7, shown in Table 1
(entries 4, 5, 7, and 11-13), are rationalized as follows.
We speculated that the diketones would be obtained from
the hydrolysis of 5a with HCl, formed from the reaction
mixture. Therefore, we conducted the hydrolysis of (Z)-
and (E)-5a with HCl/EtOH/H2O and obtained the 5-
(phenylseleno)pentan-1,4-dione 6 (Scheme 2). As seen for
entry 5 in Table 1, the use of SnCl4 led to a high yield of
the deselenylated 1,4-diketone 7, which would be due to
the strong affinity between SnCl4 and the selenenyl
functional groups. The activated C-Se bond was easily
cleaved with Lewis acids to form the Lewis acid-SeR
complex.8 To confirm the mechanism for formation of 7,
we performed the reaction of 5a with SnCl4 or TiCl4 as
shown in Scheme 2. The hydrolysis of 5a easily proceeded
to give the deselenylated ketone 7, accompanied with the
â-keto selenide 6. This result shows that the C-Se bond
of the 1,4-diketone 6 is cleaved in the reaction media by
the effect of SnCl4 or TiCl4. On the other hand, most
reactions proceeded with retention of their stereochem-
istries; however, the use of Yb(OTf)3 led to the isomer-
ization of (E)-5a as shown in Table 1, entries 8 and 9.
We consider that this isomerization results from the slow
rate of the reaction with Yb(OTf)3.
a
Reagents: i, NaOEt/EtOH/reflux or PhSH/NaOEt/EtOH/reflux
or (PhSe)2/NaH/THF-EtOH/reflux; ii, Lewis Acid.
Ta ble 1. Rea ction of
2-Eth oxy-3-(p h en ylselen o)p r op -2-en a l Aceta l 2 w ith Silyl
En ol Eth er
entry
Lewis acid
product (% yield)
(Z)-5a (71)
(Z)-5a (82)
(Z)-5a (66)
6 (33), 7 (8)
7 (36), (Z)-5a (20), 9 (4)
(Z)-5a (83)
1
2
3
4
5
BF3·Et2O/-78 °C
ZnBr2/-78 °C
Al(OBut)3/-78 °C
TiCl4/-78 °C
SnCl4/-78 °C
SnBr4
6
7
8
9
10
11
12
13
EtAlCl2/-78 °C
Yb(OTf)3/0 °C
Yb(OTf)3/-10 °C
La(OTf)3/0 °C
HfCl4
(Z)-5a (28), 6 (52)
(Z)-5a (40), (E)-5a (34)
(Z)-5a (6), (E)-5a (52)
(Z)-5a (34), 8 (47)
6 (46), 7 (5)
TaCl5
WCl6
(Z)-5a (18), 6 (17), 7 (4)
6 (21), 7 (9)
Next, we examined the reactions of 2 with other soft
nucleophiles, and the results are shown in Table 2
(entries 1-6). Almost the same products were obtained
in good yields except for entries 3 and 6. Furthermore,
the nucleophilic addition of 3 (Y ) SPh) with silyl enol
ether, Et3Al, and (TMS)CN gave the products in good
yields (entries 7-11). The 3-(phenylsulfenyl)propenal
acetal 3 exclusively and stereoselectively formed the
alkylated products, without the formation of byproducts
(entries 7-9), for two main reasons. One is that the
2-(phenylsulfenyl)prop-2-enylated products are more stable
5a . The stereostructures of the products were determined
by the NOE experiments. Irradiation of the olefinic
proton of (Z)-5a at δ 5.98 ppm increased the intensity of
the R-proton of the ethoxy group (4%). On the other hand,
irradiation of the olefinic proton of (E)-5a at δ 5.57 ppm
increased the intensities of both the methylene protons
of the 4-ethoxy group (5%) and the methylene protons of
the 3-ethoxy group (5%) and not the R-proton of the
phenylseleno group. We also examined other Lewis acids
such as those in entries 5-7. EtAlCl2 gave the 1,4-
diketone 6 in 52% yield, accompanied with the normal
adduct 5a . The reaction with La(OTf)3 was very slow and
afforded the R-ethoxy aldehyde 8 (entry 10). Interest-
(7) Hevesi, L.; Piquard, J .-L.; Wautier, H. J . Am. Chem. Soc. 1981,
103, 870.
(8) Hermans, B.; Colard, N.; Hevesi, L. Tetrahedron Lett. 1992, 33,
4629. Yoshimatsu, M.; Asahi, T.; Shimizu, H.; Kataoka, T. Heteroat.
Chem. 1995, 6, 259.

1080 J . Org. Chem., Vol. 67, No. 4, 2002
Hibino et al.
Sch em e 3a
Ta ble 2. Rea ction of
2-Eth oxy-3-(p h en ylselen o)p r op -2-en a l Aceta ls 2-4 w ith
Soft Nu cleop h iles
a
Reagents: i, LDA/THF/-78 °C or NaOEt/THF-EtOH; ii,
LiAlH4/Et2O/t-BuOK/t-BuOH (75%).
F igu r e 1.
Sch em e 4a
a
Reagent: i, TiCl4/-78 °C.
Ta ble 3. Rea ction of 2-Eth oxy-3-(p h en ylth io)p r op -2-en a l
Aceta ls w ith Soft Nu cleop h iles
Sch em e 5a
entry
acetal (Y)
Lewis acid
product (% yield)
1
2
3
4
13 (OEt)
13
14 (SPh)
15 (SePh)
BF3·Et2O
Yb(OTf)3
BF3·Et2O
BF3·Et2O
16 (74)
16 (70)
17 (80)
18 (80)
than the 2-ethoxyprop-2-enylated products, which contain
the structure of the enol ether. The other is the stabilizing
effect of the 2-phenylsulfenyl group of the propenyl
cation. The 2-phenylsulfenyl group would more effectively
stabilize the transient allylic cation Ia ,b (Y ) SPh) than
the 2-alkoxyallylic cation Ia ,b (Y ) OEt). The 2-selenium-
substituted prop-2-enal acetal 4 with the silyl enol ether
afforded the adduct 12 (entries 12 and 13). Furthermore,
the reaction of 3-(phenylthio)-substituted derivatives 13-
15 gave satisfactory results (Table 3).
The method reported here appears to be one choice for
the efficient preparation of the 4-pentenones. We next
tried to apply the conversion of the new types of 4-pen-
tenones to other useful compounds. First, we examined
the transformation of the 4-ethoxy-4-pentenone 5a , and
the results are shown in Scheme 3. The treatment of 5a
with LDA gave the 2,4-pentadienophenone 19 in 45%
yield. A better result was obtained from the reaction
using NaOEt in THF-EtOH (E:Z ) 90:10). Previously,
we reported the transformation of the 4-pentenones to
furanosides.6 The reduction of 5a and the successive
treatment with t-BuOK/t-BuOH afforded the intermedi-
ate alkoxide 21 (Figure 1). We thought that the 5-exo-
mode cyclization gives the carbanion stabilized by the
selenium functional group. The procedure provided two
a
Reagents: i, dimethyl acetylenedicarboxylate/benzene/reflux/
52 h; ii, benzoquinone/toluene/reflux/8 h.
kinds of the furanoside 20 in 75% yield. The two furan-
osides were found to be the stereoisomers by determining
their structures. The stereochemistries of the isomers
were assigned by the NOE experiments and Williams’s
chemical shift method9 of the 3,5-disubstituted tetrahy-
drofurans. Furthermore, we conducted the transforma-
tion of the 4-(phenylthio)-4-pentenophenone 10a with
Lewis acid to afford the 2,4-pentadienophenone 23 in 71%
yield (Scheme 4).
Dichalcogene-substituted 1,3-butadienes have been
easily applied to the Diels-Alder reactions with the
activated dienophiles.10 We further performed the Diels-
Alder reactions of the 4,5-bis(chalcogeno)penta-2,4-di-
enophenone 19 with the dienophiles. The reaction with
dimethyl acetylenedicarboxylate in benzene afforded the
dimethyl phthalate 24 in 65% yield (Scheme 5). The
reaction with benzoquinone also underwent the desele-
(9) Williams, D. R.; Harigaya, Y.; Moore, J . L.; D’sa, A. J . Am. Chem.
Soc. 1984, 106, 2641. Mihelich, E. D.; Hite, G. A. J . Am. Chem. Soc.
1992, 114, 7318.

A New 3-(Phenylseleno)allylic Cation
J . Org. Chem., Vol. 67, No. 4, 2002 1081
P r ep a r a tion of (Z)-2-(P h en ylth io)-3-(p h en ylselen o)-
p r op -2-en a l Dieth yl Aceta l (3). A THF (3.00 mL) solution
of 1 (0.28 g, 1.00 mmol) was added dropwise to a EtOH solution
of PhSNa (prepared from PhSH (1.10 mmol) and NaOEt (5.5
mmol)). The mixture was refluxed for 30 min and poured into
water (50 mL), and the organic layer was separated. The
aqueous layer was extracted with ether. The workup procedure
afforded a titled compound 3 (0.33 g, 84%) as a yellow oil: 1H
NMR (400 MHz, CDCl3) δ 1.15 (6H, t, J ) 7 Hz), 3.41-3.49
(2H, m), 3.53-3.61 (2H, m), 4.78 (1H, d, J ) 1 Hz), 7.18-7.32
(5H, m), 7.41-7.44 (2H, m), 7.55-7.59 (3H, m); 13C NMR (100
MHz, CDCl3) δ 15.24 (q × 2), 62.01 (t × 2), 101.67 (d), 126.78
(d), 127.95 (d), 129.11 (dx2), 129.49 (dx2), 129.75 (s), 129.81
(dx2), 130.49 (s), 133.29 (d × 2), 133.95 (s), 138.21 (d); high-
resolution mass calcd for C19H22O2SSe 394.0505, found m/z
394.0502.
P r ep a r a t ion of (Z)-2,3-Bis(p h en ylselen o)p r op -2-en a l
Dieth yl Aceta l (4). A mixture of diphenyl diselenide (0.33 g,
1.06 mmol) and NaH (0.14 g, 3.54 mmol) was refluxed for 1 h
under an Ar atmosphere. To the cooling mixture of PhSeNa,
a EtOH (5.00 mL) solution of 1 (0.50 g, 1.77 mmol) was added
dropwise. The whole was refluxed for 30 min and poured into
water (50.0 mL). The workup procedure afforded the titled 4
(0.65 g, 83%) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ
1.14 (3H, t, J ) 7 Hz), 3.40-3.48 (2H, m), 3.53-3.61 (2H, m),
4.81 (1H, d, J ) 1 Hz), 7.23-7.35 (6H, m), 7.54-7.59 (4H, m),
7.70 (1H, d, J ) 1 Hz); 13C NMR (100 MHz, CDCl3) δ 15.19 (q
× 2), 62.13 (t × 2), 103.19 (d), 127.23 (d), 128.89 (d), 128.87
(s), 129.22 (d × 2), 129.44 (d × 2), 129.64 (s), 130.68 (s), 132.40
(d × 2), 133.24 (d × 2), 138.38 (d); MS m/z 442 (M+). Anal.
Calcd for C19H22O2Se2: C, 51.83; H, 5.04. Found: C, 51.57; H,
4.97.
nylation to give the aromatic compound 25 in good yield.
Now, we are investigating the Diels-Alder reactions of
the 4-ethoxy-5-(phenylseleno)penta-2,4-dienophenone with
other dienophiles and the Diels-Alder reactions of other
chalcogene-substituted penta-2,4-dienophenones. The full
details of the Diels-Alder reactions will be reported
elsewhere.
Con clu sion
We have shown novel allylating reactions using the
new 2- and 3-chalcogene-substituted allylic cations with
soft nucleophiles. The reactions of the 2-ethoxy-3-(phen-
ylseleno)prop-2-enal acetal 2 with the soft nucleophiles
afforded the adducts using BF3·Et2O and ZnBr2. The use
of a strong Lewis acid such as SnCl4 or TiCl4 afforded
the 1,4-diketones, exclusively. The 2-(phenylsulfenyl)-3-
(phenylseleno)-prop-2-enal acetal 3 underwent various
C-C bond formations to give the products using BF3·
Et2O, Yb(OTf)3, and SnCl4. The 4-ethoxy-5-(phenylsele-
no)pent-4-enophenone 5a , formed from the reaction of the
2-ethoxy-3-(phenylseleno)prop-2-enal acetal 2 with the
silyl enol ether, was found to be a versatile precursor for
the synthesis of useful compounds such as 1,4-diketones,
2,4-pentadienophenones, tetrahydrofurans, and Diels-
Alder adducts.
Exp er im en ta l Section
P r ep a r a tion of (Z)-2-Eth oxy-3-(p h en ylth io)p r op -2-en a l
Dieth yl Aceta l (13). An EtOH (3.00 mL) solution of 3-(phen-
ylthio)prop-2-enal diethyl acetal (0.47 g, 2.00 mmol) was added
dropwise to a EtONa (prepared from EtOH (10.0 mL) and Na
(0.23 g, 10.0 mmol)). The mixture was refluxed for 30 min.
The workup procedure gave the titled compound 13 (0.23 g,
42%) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 1.23 (6H,
t, J ) 7 Hz), 1.32 (3H, t, J ) 7 Hz), 3.51-3.60 (2H, m), 3.62-
3.71 (2H, m), 4.09-4.17 (2H, m), 4.92 (1H, s), 5.94 (1H, d, J )
1 Hz), 7.16-7.21 (1H, m), 7.26-7.33 (2H, m), 7.33-7.43 (2H,
m); 13C NMR (100 MHz, CDCl3) δ 15.33 (q × 2), 15.81 (q), 61.95
(t × 2), 66.58 (t), 99.46 (d), 106.14 (d), 126.29 (d), 128.63 (d ×
2), 128.93 (d × 2), 136.59 (s), 151.08 (s); MS m/z 282 (M+).
Anal. Calcd for C15H22O3S: C, 63.80; H, 7.85. Found: C, 63.65;
H, 7.73.
Melting points were determined on a Yanagimoto micro
melting point apparatus and are uncorrected. Elemental
analyses were performed at the Center of Instrumentation of
Gifu University. 1H and 13C NMR spectra were determined
with a Varian Inova 400 (400 MHz) spectrometer at Gifu
University. Chemical shifts are expressed in parts per million
(ppm) with respect to tetramethylsilane as an internal stan-
dard. Splitting patterns are designated as follows: s, singlet;
d, doublet; t, triplet; q, quartet. IR spectra were determined
on a J ASCO IRA-100 infrared spectrometer and are expressed
in reciprocal centimeters. EI mass spectra (MS) were obtained
using a J EOL GCmate spectrometer with direct-insertion
probe at 70 eV. All exact mass determinations were obtained
on the J MA 2000 on-line system.
P r ep a r a tion s of (Z)-2-Eth oxy-3-(p h en ylselen o)-2-p r o-
p en a l Dieth yl Aceta ls (2). A EtOH (5.0 mL) solution of 1
(1.85 g, 6.53 mmol) was added dropwise to a EtOH solution of
NaOEt (prepared from Na (0.75 g, 32.7 mmol) and EtOH (20
mL)). The mixture was refluxed for 30 min. The solvent was
removed under reduced pressure. The mixture was poured into
water (100 mL), and the organic layer was separated. The
aqueous layer was extracted with ether. The combined organic
layer was dried over MgSO4. The solvent was removed under
reduced pressure. The residue was purified by column chro-
matography on silica gel eluting with AcOEt-hexane (1:10).
(Z)-2-Ethoxy-3-(phenylseleno)prop-2-enal diethyl acetal (2)
(1.60 g, 75%) was obtained as a yellow oil: 1H NMR (400 MHz,
CDCl3) δ 1.22 (3H, t, J ) 7 Hz), 1.23 (3H, t, J ) 7 Hz), 1.31
(3H, t, J ) 7 Hz), 3.50-3.58 (2H, m), 3.62-3.69 (2H, m), 4.07
(2H, q, J ) 7 Hz), 4.93 (1H, s), 6.09 (1H, d, J ) 1 Hz), 7.21-
7.36 (3H, m), 7.50-7.70 (2H, m); 13C NMR (100 MHz, CDCl3)
δ 15.31 (q × 2), 15.83 (q), 61.84 (t × 2), 66.11 (t), 99.29 (d),
103.47 (d), 127.04 (d), 129.27 (d × 2), 131.08 (s), 132.14 (d ×
2), 150.91 (s); MS m/z 330 (M+). Anal. Calcd for C15H22O3Se:
C, 54.88; H, 6.73. Found: C, 54.72; H, 6.54.
Rea ction of 2-Eth oxy-3-(p h en ylselen o)p r op -2-en a l Di-
eth yl Aceta l 2 w ith Nu cleop h iles: Typ ica l P r oced u r e.
BF3·Et2O (0.14 g, 1.00 mmol) was added dropwise to a CH2Cl2
(1.00 mL) solution of 2 (0.16 g, 0.50 mmol) and 1-phenyl
O-(trimethylsilyl)enol ether (0.28 g, 1.50 mmol) at -78 °C
under an Ar atmosphere. The mixture was stirred for 10 min
and poured into a NaHCO3 (50 mL) solution. The organic layer
was separated, and the aqueous layer was extracted with
CHCl3. The combined organic layer was dried over MgSO4. The
solvent was removed under reduced pressure. The residue was
purified by preparative TLC on silica gel eluting with AcOEt-
hexane (1:20) to give (Z)-3,4-diethoxy-5-(phenylseleno)pent-4-
1
enophenone (5a ) (0.14 g, 71%) as a yellow oil: H NMR (400
MHz, CDCl3) δ 1.14 (3H, t, J ) 7 Hz), 1.33 (3H, t, J ) 7 Hz),
3.18 (1H, dd, J ) 4 and 16 Hz), 3.39-3.53 (1H, m), 3.50 (1H,
dd, J ) 7 and 16 Hz), 3.64-3.71 (1H, m), 4.06-4.17 (2H, m),
4.52 (1H, dd, J ) 4 and 7 Hz), 5.98 (1H, s), 7.21-7.32 (3H, m),
7.43-7.50 (4H, m), 7.53-7.61 (1H, m), 7.95-7.99 (2H, m); 13
C
NMR (100 MHz, CDCl3) δ 15.40 (q), 15.93 (q), 43.19 (t), 65.24
(t), 67.09 (t), 101.02 (d), 127.03 (d), 128.40 (d × 2), 128.63 (d ×
2), 129.39 (d × 2), 131.41 (s), 131.64 (d × 2), 133.31 (d), 137.35
(s), 155.39 (s), 197.87 (s); MS m/z 404 (M+). Anal. Calcd for
C21H24O3Se: C, 62.53; H, 6.00. Found: C, 62.37; H, 5.89.
(10) 1-Phenylthio-1,3-butadiene: Maddaluno, J .; Gaonac’h, O.; Mar-
cual, A.; Toupet, L.; Giessner-Prettre, C. J . Org. Chem. 1996, 61, 5290.
4-Alkoxy-1-(phenylseleno)-1,3- butadiene: Fryzuk, M. D.; Bates, G. S.;
Stone, C. J . Org. Chem. 1987, 52, 2234. 2-Thio- or 2-Seleno-1,3-
butadiene: Liotta, C. L.; Verbicky, J . W. Tetrahedron Lett. 1985, 26,
1395.
(E )-3,4-D ie t h o x y -5-(p h e n y ls e le n o )p e n t -4-e n o p h e -
n on e (5a ): a yellow oil; 1H NMR (400 MHz, CDCl3) δ 1.15 (3H,
t, J ) 7 Hz), 1.33 (3H, t, J ) 7 Hz), 3.27 (1H, dd, J ) 6 and 16
Hz), 3.52 (1H, dd, J ) 7 and 16 Hz), 3.43-3.60 (2H, m), 3.81-

1082 J . Org. Chem., Vol. 67, No. 4, 2002
Hibino et al.
3.90 (2H, m), 5.29 (1H, dd, J ) 6 and 7 Hz), 5.57 (1H, s), 7.16-
7.26 (3H, m), 7.41-7.56 (4H, m), 7.94-7.96 (2H, m); 13C NMR
(100 MHz, CDCl3) δ 14.55 (q), 15.45 (q), 41.95 (t), 63.65 (t),
64.65 (t), 73.78 (d), 87.96 (d), 126.35 (d), 128.42 (d × 2), 128.65
(d × 2), 129.26 (d × 2), 129.97 (d × 2), 133.18 (d), 133.51 (s),
137.31 (s), 159.89 (s), 197.65 (s); high-resolution mass calcd
for C21H24O3Se 404.0889, found m/z 404.0881.
5.78 (1H, s), 7.16-7.20 (1H, m), 7.23-7.35 (4H, m), 7.43-7.47
(2H, m), 7.51-7.57 (1H, m), 7.96-7.99 (2H, m); 13C NMR (100
MHz, CDCl3) δ 15.39 (q), 15.88 (q), 43.18 (t), 65.24 (t), 67.49
(t), 76.82 (d), 102.96 (d), 126.16 (d), 128.28 (d × 2), 128.40 (d
× 2), 128.73 (d × 2), 129.18 (d × 2), 133.29 (d), 136.97 (s),
137.38 (s), 155.96 (s), 197.85 (s); MS m/z 356 (M+). Anal. Calcd
for C21H24O3S: C, 70.76; H, 6.79. Found: C, 70.50; H, 6.65.
Hyd r olysis of 5a w ith HCl/EtOH-H2O. A 3% HCl solu-
tion (2.00 mL) was added to a EtOH (3.00 mL) solution of 5a
(0.12 g, 0.293 mmol). The mixture was refluxed for 10 min and
then poured into a NaHCO3 solution (50.0 mL). The organic
layer was separated, and the aqueous layer was extracted with
ether. The workup procedure afforded 3-ethoxy-1-phenyl-5-
(phenylseleno)-1,4-pentanedione (6) (57 mg, 52%).
Rea ction of 5a w ith TiCl4. TiCl4 (94 mg, 0.50 mmol) was
added dropwise to a CH2Cl2 (1.00 mL) solution of 5a (0.10 g,
0.25 mmol) at 0 °C under an Ar atmosphere. The mixture was
stirred for 10 min and poured into a saturated NaHCO3
solution (50 mL). The workup procedure afforded 7 (30.0 mg,
56%) and 6 (23.0 mg, 25%).
3-E t h oxy-1-p h e n yl-5-(p h e n ylse le n o)-1,4-p e n t a n e d i-
1
on e (6): a yellow oil; H NMR (400 MHz, CDCl3) δ 1.17 (3H,
t, J ) 7 Hz), 3.44 (2H, dd, J ) 5 and 6 Hz), 3.56-3.65 (2H,
m), 3.80 (1H, d, J ) 12 Hz), 4.02 (1H, d, J ) 12 Hz), 4.62 (1H,
dd, J ) 5 and 6 Hz), 7.26-7.30 (3H, m), 7.44-7.48 (2H, m),
7.55-7.59 (3H, m), 7.92-7.94 (2H, m); 13C NMR (100 MHz,
CDCl3) δ 15.59 (q), 32.43 (t), 41.79 (t), 67.20 (t), 79.50 (d),
127.98 (d), 128.25 (s), 128.38 (d × 2), 128.81 (d × 2), 129.43 (d
× 2), 129.53 (s), 133.39 (d × 2), 133.55 (d), 197.00 (s), 206.98
(s); MS m/z 376 (M+). Anal. Calcd for C19H20O3Se: C, 60.80;
H, 5.37. Found: C, 60.89; H, 5.41.
3-Eth oxy-1-p h en yl-1,4-p en ta n ed ion e (7): 1H NMR (400
MHz, CDCl3) δ 1.21 (3H, t, J ) 7 Hz), 2.32 (3H, s), 3.35 (2H,
d, J ) 6 Hz), 3.62 (2H, q, J ) 7 Hz), 4.37 (1H, t, J ) 6 Hz),
Rea ction of 5a w ith Sn Cl4. SnCl4 (0.04 mL, 0.40 mmol)
was added dropwise to a CH2Cl2 (1.00 mL) solution of 5a (0.10
g, 0.25 mmol) at 0 °C under an Ar atmosphere. The reaction
mixture was stirred for 2 h, and the workup procedure afforded
7 (30 mg, 55%).
7.45-7.49 (2H, m), 7.55-7.59 (1H, m), 7.94-7.96 (2H, m); 13
C
NMR (100 MHz, CDCl3) δ 15.58 (q), 26.62 (q), 40.98 (t), 67.12
(t), 81.36 (d), 128.43 (d × 2), 128.87 (d × 2), 133.56 (d), 136.98
(s), 197.12 (s), 206.37 (s); MS m/z 220 (M+). Anal. Calcd for
C
13H16O3: C, 70.89; H, 7.32. Found: C, 70.52; H, 7.29.
Rea ction of 4-P en ten op h en on e 5a w ith LDA. A THF
(0.50 mL) solution of 5a (0.10 g, 0.248 mmol) was added
dropwise to a THF (0.50 mL) solution of LDA (prepared from
diisopropylamine (0.15 g, 1.49 mmol) and n-BuLi (0.66 mL,
0.99 mmol)) at -45 °C. The mixture was stirred for 10 min
and poured into water (50 mL). The workup procedure afforded
(2E,4Z)- and (2Z,4Z)-4-ethoxy-5-(phenylseleno)penta-2,4-di-
enophenone (19) as a yellow oil: 2E:2Z ) 81:19; 1H NMR (400
MHz, CDCl3) δ 1.44 (t, J ) 7 Hz), 1.45 (t, J ) 7 Hz), 4.04 (2H,
q, J ) 7 Hz), 6.03 (s), 6.72 (s), 7.07 (d, J ) 15 Hz), 7.21 (d, J
) 15 Hz), 7.30-7.59 (m), 7.90-7.99 (m); 13C NMR (100 MHz,
CDCl3) δ 6.05 (q), 67.29 (t), 99.23 (s), 119.47 (d), 124.53 (d),
128.59 (d × 2), 128.82 (d × 2), 129.73 (d × 2), 132.93 (d), 132.96
(dx2), 136.28 (s), 138.40 (d), 152.77 (s), 190.67 (s); high-
resolution mass calcd for C19H18O2Se 358.0471, found m/z
358.0477.
Red u ction a n d Cycliza tion of 5a w ith LiBH 4/Su cces-
sive Tr ea tm en t w ith t-Bu OK/t-Bu OH. A THF (1.00 mL)
solution of 5a (0.10 g, 0.248 mmol) was added dropwise to a
dry Et2O (3.00 mL) suspension of LiBH4 (11 mg, 0.50 mmol)
at -78 °C. The mixture was stirred for 10 min and poured
into water (50 mL). The organic layer was separated, and the
aqueous layer was extracted with ether. The combined organic
layer was dried over MgSO4. The solvent was removed under
reduced pressure. The residue was dissolved in t-BuOH (2.00
mL). t-BuOK (0.24 g, 2.12 mmol) was added to the mixture.
The whole was refluxed for 2.5 h and poured into water (50
mL). The workup procedure afforded (2R*,3S*,5R*)-20 (47 mg,
40%) and (2S*,3S*,5S*)-2,3-diethoxy-5- phenyl-2-(phenylsele-
nomethyl)tetrahydrofuran ((2S*,3S*,5S*)-20) (40 mg, 35%) as
a yellow oil.
(Z)-2-Eth oxy-3-(p h en ylselen o)p r op -2-en a l (8): a yellow
1
oil; H NMR (400 MHz, CDCl3) δ 1.35 (3H, t, J ) 7 Hz), 4.22
(2H, q, J ) 7 Hz), 7.27 (1H, s), 7.35-7.38 (3H, m), 7.59-7.62
(2H, m), 9.17 (1H, s); 13C NMR (100 MHz, CDCl3) δ 15.97 (q),
67.21 (t), 128.77 (d), 128.99 (s), 129.85 (d × 2), 133.48 (d × 2),
138.76 (d), 153.05 (s), 183.91 (d); MS m/z 256 (M+). Anal. Calcd
for C11H12O2Se: C, 52.10; H, 4.74. Found: C, 52.07; H, 4.98.
5-E t h oxy-3-h yd r oxy-3-p h en yl-2-(p h en ylselen o)cyclo-
p en ta n on e (9): 1H NMR (400 MHz, CDCl3) δ 1.34 (3H, t, J )
7 Hz), 3.18-3.23 (2H, m), 5.50 (1H, s), 7.16-7.27 (3H, m),
7.41-7.59 (6H, m), 7.93 (2H, dd, J ) 8 and 1 Hz); MS m/z 376
(small M+).
(Z)-S-Eth yl 3,4-Dieth oxy-5-(ph en ylselen o)pen t-4-en oate
(5b): a yellow oil; 1H NMR (400 MHz, CDCl3) δ 1.16 (3H, t, J
) 7 Hz), 1.25 (3H, t, J ) 7 Hz), 1.32 (3H, t, J ) 7 Hz), 2.82-
2.94 (4H, m), 3.39-3.47 (1H, m), 3.60-3.68 (1H, m), 4.04-
4.11 (2H, m), 4.29 (1H, dd, J ) 4 and 7 Hz), 5.90 (1H, s), 7.22-
7.32 (3H, m), 7.46-7.56 (2H, m); 13C NMR (100 MHz, CDCl3)
δ 14.90 (q), 15.30 (q), 15.90 (q), 23.63 (t), 48.51 (t), 65.24 (t),
67.10 (t), 77.18 (d), 101.06 (d), 127.09 (d), 129.40 (d × 2), 131.38
(s), 131.70 (d × 2), 154.65 (s), 197.11 (s); MS m/z 388 (M+).
Anal. Calcd for C17H24O3SSe: C, 52.71; H, 6.24. Found: C,
52.19; H, 5.97.
(E)-S-Eth yl 3,4-Dieth oxy-5-(ph en ylselen o)pen t-4-en oate
(5b): a yellow oil; 1H NMR (400 MHz, CDCl3) δ 1.16 (3H, t, J
) 7 Hz), 1.23 (3H, t, J ) 7 Hz), 1.37 (3H, t, J ) 7 Hz), 2.81
(1H, dd, J ) 6 and 15 Hz), 2.86 (2H, dd, J ) 1 and 7 Hz), 3.04
(1H, dd, J ) 8 and 15 Hz), 3.38-3.46 (1H, m), 3.50-3.58 (1H,
m), 3.85-3.93 (2H, m), 5.13 (1H, dd, J ) 6 and 8 Hz), 5.57
(1H, s), 7.17-7.28 (3H, m), 7.38-7.42 (2H, m); 13C NMR (100
MHz, CDCl3) δ 14.56 (q), 14.93 (q), 15.38 (q), 23.57 (t), 47.31
(t), 63.77 (t), 64.76 (t), 73.87 (d), 87.89 (d), 126.40 (d), 129.29
(d × 2), 129.90 (d × 2), 133.35 (s), 159.60 (s), 196.55 (s); MS
m/z 388 (M+). Anal. Calcd for C17H24O3SSe: C, 52.71; H, 6.24.
Found: C, 52.47; H, 6.12.
(Z)-3-Cya n o-2,3-d ieth oxy-1-(p h en ylselen o)-1-p r op en e
(5d ): 1H NMR (400 MHz, CDCl3) δ 1.27 (3H, t, J ) 7 Hz), 1.35
(3H, t, J ) 7 Hz), 3.56-3.64 (1H, m), 3.73-3.80 (1H, m), 4.07-
4.23 (2H, m), 4.74 (1H, d, J ) 1 Hz), 6.26 (1H, s), 7.25-7.40
(3H, m), 7.50-7.58 (2H, m); 13C NMR (100 MHz, CDCl3) δ
14.92 (q), 15.65 (q), 65.73 (t), 67.38 (t), 69.08 (d), 107.79 (d),
116.14 (s), 127.76 (d), 129.55 (d × 2), 130.54 (s), 132.58 (d ×
2), 146.40 (s); MS m/z 311 (M+). Anal. Calcd for C14H17NO2Se:
C, 54.20; H, 5.52; N, 4.51. Found: C, 54.09; H, 5.49; N, 4.28.
(Z)-3,4-Dieth oxy-5-(ph en ylth io)pen t-4-en oph en on e (16):
(2R*,3S*,5R*)-20: 1H NMR (400 MHz, CDCl3) δ 1.10 (3H,
t, J ) 7 Hz), 1.16 (3H, t, J ) 7 Hz), 2.24-2.37 (2H, m), 3.43
(1H, d, J ) 12 Hz), 3.36-3.52 (2H, m), 3.56 (1H, d, J ) 12
Hz), 3.63-3.70 (2H, m), 4.09 (1H, d, J ) 4 Hz), 5.30 (1H, dd,
J ) 6 and 10 Hz), 7.22-7.30 (4H, m), 7.34-7.35 (4H, m), 7.56-
7.59 (2H, m); 13C NMR (100 MHz, CDCl3) δ 15.24 (q), 15.68
(q), 28.70 (t), 37.96 (t), 56.63 (t), 65.73 (t), 82.61 (d), 110.98
(s), 126.83 (d × 2), 126.93 (d), 127.88 (d), 128.63 (d × 2), 129.13
(d × 2), 131.29 (s), 132.92 (s), 142.22 (s); high-resolution mass
calcd for C21H26O3Se 406.1046, found m/z 406.1055.
(2S*,3S*,5S*)-20: 1H NMR (400 MHz, CDCl3) δ 1.17 (3H,
t, J ) 7 Hz), 1.27 (3H, t, J ) 7 Hz), 2.12-2.27 (1H, m), 2.44-
2.61 (1H, m), 3.33 (1H, d, J ) 13 Hz), 3.46 (1H, d, J ) 13 Hz),
3.42-3.55 (1H, m), 3.56-3.67 (1H, m), 3.67-3.85 (2H, m), 4.33
(1H, t, J ) 8 Hz), 5.17 (1H, dd, J ) 5 and 8 Hz), 7.20-7.30
(4H, m), 7.32-7.38 (4H, m), 7.55-7.57 (2H, m); 13C NMR (100
MHz, CDCl3) δ 15.65 (q), 16.22 (q), 32.68 (t), 38.87 (t), 57.00
(t), 66.58 (t), 78.24 (d), 80.91 (d), 105.94 (d), 126.03 (d × 2),
126.92 (d), 127.68 (d), 127.91 (s), 128.64 (d × 2), 129.30 (d ×
1
a yellow oil; H NMR (400 MHz, CDCl3) δ 1.16 (3H, t, J ) 7
Hz), 1.32 (3H, t, J ) 7 Hz), 3.21 (1H, dd, J ) 4 and 16 Hz),
3.42 (1H, dd, J ) 8 and 16 Hz), 3.30-3.55 (1H, m), 3.65-3.72
(1H, m), 4.10-4.23 (2H, m), 4.48 (1H, dd, J ) 4 and 8 Hz),

A New 3-(Phenylseleno)allylic Cation
J . Org. Chem., Vol. 67, No. 4, 2002 1083
2), 131.54 (s), 132.13 (d × 2), 142.95 (s); high-resolution mass
calcd for C21H26O3Se 406.1046, found m/z 406.1033.
(s), 159.88 (s), 167.12 (s), 167.42 (s), 195.63 (s); MS m/z 342
(M+). Anal. Calcd for C19H18O6: C, 66.66; H, 5.30. Found: C,
66.48; H, 5.23.
Rea ction of 19 w ith Ben zoqu in on e. A toluene (2.0 mL)
solution of 19 (0.10 g, 0.28 mmol) and benzoquinone (0.30 g,
2.80 mmol) was refluxed for 8 h. The solvent was removed
under reduced pressure. The residue was purified by prepara-
tive TLC on silica gel eluting with AcOEt-hexane (1:10) to
give 5-benzoyl-7-ethoxynaphthoquinone (25) (63 mg, 74%) as
purple prisms.
25: mp 145-150 °C; 1H NMR (400 MHz, CDCl3) δ 1.47 (3H,
t, J ) 7 Hz), 4.21 (2H, q, J ) 7 Hz), 6.80 (1H, d, J ) 9 Hz),
6.93 (1H, d, J ) 9 Hz), 7.07 (1H, d, J ) 2 Hz), 7.41-7.47 (3H,
m), 7.53-7.58 (1H, m), 7.63 (1H, dd, J ) 1 and 2 Hz), 7.76-
7.79 (2H, m); 13C NMR (100 MHz, CDCl3) δ 14.72 (q), 65.02
(t), 111.86 (d), 119.22 (d), 128.82 (d × 2), 129.24 (d × 2), 133.59
(d), 134.72 (s), 136.56 (s), 138.15 (d), 139.24 (d), 139.51 (s),
143.92 (s), 163.46 (s), 183.31 (s), 184.73 (s), 196.39 (s); MS m/z
306 (M+). Anal. Calcd for C19H14O4: C, 74.50; H, 4.61. Found:
C, 74.41; H, 4.58.
Rea ction of 4-P en ten op h en on e 10a w ith TiCl4. TiCl4
(0.05 mL, 0.40 mmol) was added dropwise to a CH2Cl2 (3.00
mL) solution of 10a (mg, mmol) at -78 °C. The reaction
mixture was poured into a saturated NaHCO3 (100 mL). The
organic layer was separated the aqueous layer was extracted
with CHCl3. The combined organic layer was dried over
MgSO4. The workup procedure afforded (2E,4Z)-5-(phenylse-
leno)-4-(phenylthio)pent-2,4-dienophenone (23) (64 mg, 71%)
as a yellow oil. 23: 1H NMR (400 MHz, CDCl3) δ 7.19 (1H, d,
J ) 14 Hz), 7.37 (1H, d, J ) 14 Hz), 7.15-7.61 (12H, m), 7.77-
7.80 (3H, m), 8.05 (1H, d, J ) 1 Hz); 13C NMR (100 MHz,
CDCl3) δ 122.4 (d), 126.6 (d), 128.1 (d × 2), 128.4 (s), 128.6 (d
× 2), 128.7 (d × 2), 128.8 (d), 129.5 (d × 2), 129.9 (d × 2),
132.9 (d), 133.5 (d × 2), 133.9 (s), 138.4 (s), 142.8 (d), 153.9
(d), 190.6 (s); MS m/z 265 (M+ - PhSe). Anal. Calcd for C23H18
OSSe: C, 65.55; H, 4.31. Found: C, 65.18; H, 4.41.
-
Diels-Ald er R ea ct ion of 4-E t h oxy-5-(p h en ylselen o)-
p en ta -2,4-d ien op h en on e (19). Rea ction of 19 w ith Di-
m eth yl Acetylen ed ica r boxyla te. A toluene (1.00 mL) so-
lution of 19 (0.10 g, 0.28 mmol) and dimethyl acetylenedicarbox-
ylate (0.40 g, 2.80 mmol) was heated under the reflux condition
for 52 h. The solvent was removed under reduced pressure.
The residue was purified by preparative TLC on silica gel
eluting with AcOEt-hexane (1:10) to give dimethyl 3-benzoyl-
5-ethoxyphthalate (24) (62 mg, 65%) as a yellow oil: 1H NMR
(400 MHz, CDCl3) δ 1.43 (3H, t, J ) 7 Hz), 3.60 (3H, s), 3.90
(3H, s), 4.10 (2H, q, J ) 7 Hz), 7.07 (1H, d, J ) 2 Hz), 7.41
(1H, d, J ) 2 Hz), 7.44-7.48 (2H, m), 7.57-7.61 (1H, m), 7.76-
7.78 (2H, m); 13C NMR (100 MHz, CDCl3) δ 14.77 (q), 52.66
(q), 53.10 (q), 64.64 (t), 116.92 (d), 117.96 (d), 125.07 (s), 128.74
(s), 128.98 (s), 130.06 (d × 2), 133.64 (d), 136.69 (s), 141.40
Ack n ow led gm en t. The support of a part of this
work by the Ministry of Education, Science, and Culture
of J apan is gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for the products 5c, 10a -c, 11, 12, 14, 15, 17, and 18,
1H and 19F NMR spectra complete peak assignments of other
products, and full lists of IR spectral data. This material data
is available free of charge via the Internet at http://pubs.acs.org.
J O010331+