Chalcogeno Morita-Baylis-Hillman Reaction of 2-(Methylchalcogeno)phenyl Vinyl Ketones with Aldehydes, Ketones, and α-Dicarbonyl Compounds

Article abstract of DOI:10.1002/ejoc.200300546

Reactions of 2-(methylchalcogeno)phenyl vinyl ketones 1 and 4 with aldehydes 5 were conducted in the presence of BF₃·Et ₂O. The reaction was quenched by addition of Et₃N and gave the Morita-Baylis-Hillman adducts 6-7 in good yields. When the reaction mixture of 1 with 5a was worked up with saturated aqueous NaHCO₃, the sulfonium salt 8a was obtained together with 6. Ketones 10, α-diketones, and α-oxo esters 13, which hardly react in the traditional Morita-Baylis-Hillman reaction, similarly reacted with 2-(methylchalcogeno)phenyl vinyl ketones 1 and 4 to give the Morita-Baylis-Hillman adducts 11-12 and 14-15. Selenochromanones 9 and 16 were obtained together with 7 and 15 from reactions of seleno derivative 4, with 5 and 13 as by-products. The formation mechanism for the sulfonium salt syn-trans-8a is discussed. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200300546

FULL PAPER
Chalcogeno Morita؊Baylis؊Hillman Reaction of 2-(Methylchalcogeno)phenyl
Vinyl Ketones with Aldehydes, Ketones, and α-Dicarbonyl Compounds
Hironori Kinoshita,[a] Sayaka Kinoshita,[a] Yukari Munechika,[a] Tatsunori Iwamura,[a]
Shin-ichi Watanabe,[a] and Tadashi Kataoka*[a]
Keywords: Aldol reactions / C-C coupling / Chalcogens / Michael addition
Reactions of 2-(methylchalcogeno)phenyl vinyl ketones 1
and 4 with aldehydes 5 were conducted in the presence of
BF3·Et2O. The reaction was quenched by addition of Et3N
and gave the Morita−Baylis−Hillman adducts 6−7 in good
yields. When the reaction mixture of 1 with 5a was worked
up with saturated aqueous NaHCO3, the sulfonium salt 8a
was obtained together with 6. Ketones 10, α-diketones, and
(methylchalcogeno)phenyl vinyl ketones 1 and 4 to give the
Morita−Baylis−Hillman adducts 11−12 and 14−15. Seleno-
chromanones 9 and 16 were obtained together with 7 and
15 from reactions of seleno derivative 4, with 5 and 13 as
by-products. The formation mechanism for the sulfonium salt
syn-trans-8a is discussed.
α-oxo esters 13, which hardly react in the traditional ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Morita−Baylis−Hillman reaction, similarly reacted with 2-
Germany, 2003)
phenyl vinyl ketones with carbonyl compounds is described
in detail in this paper.
Introduction
The MoritaϪBaylisϪHillman reaction is well known as
a coupling reaction of aldehydes and activated alkenes cata-
lyzed by tertiary amines or phosphanes to produce α-
hydroxyalkylated alkenes and is widely used because it pro-
vides densely functionalized alkenes.[1] However, this reac-
tion traditionally suffers from a low reaction rate and lim-
ited substrate scope. Therefore, we devised a tandem
Michael aldol reaction using chalcogenide/TiCl4.[2] This re-
action is much faster than the original reaction and has a
wide application to the reactions of acrylthioesters[3a][3b]
and electron-deficient alkynes,[3c][3d] which cannot undergo
the traditional MoritaϪBaylisϪHillman reaction, with al-
dehydes. However, this reaction starts with the Michael ad-
dition of a chloride ion of the TiCl4 to an activated alkene
and not with the Michael addition of a chalcogeno
ether.[2d,3b] Balenkova et al. have shown that thio derivatives
undergo cyclization in the presence of a Lewis acid.[4] This
implies that the intramolecular Michael addition is more
efficient than the intermolecular one. On the basis of these
data, we have developed a tandem intramolecular Michael
aldol reaction which starts with the Michael addition of a
chalcogeno ether to the activated alkene (the chalcogeno
MoritaϪBaylisϪHillman reaction).[5] The chalcogeno
MoritaϪBaylisϪHillman reaction of 2-(methylchalcogeno)-
Results and Discussion
Reaction of 2-(Methylchalcogeno)phenyl Vinyl Ketones with
Carbonyl Compounds
First of all, we investigated the chemical behavior of thio
derivative 1 with a Lewis acid by NMR spectroscopy. As
Lewis acids containing nucleophilic substituents cannot be
used in order to avoid the Michael addition of the substitu-
ent to the enone moiety, BF3·Et2O was used for the reac-
1
tion. The H NMR spectrum of the reaction mixture of 1-
[2-(methylthio)phenyl]propenone (1) and BF3·Et2O in
CD3CN (Scheme 1) exhibits signals at δH ϭ 3.90 (dd, J ϭ
5.0, 18.0 Hz, 1 H, 2-H), 4.39 (dd, J ϭ 2.0, 18.0 Hz, 1 H, 2-
H), and 5.27 (dd, J ϭ 2.0, 5.0 Hz, 1 H, 3-H) ppm. This
spectrum agrees closely with that of the corresponding
TMS enol ether 3, which was generated from the reaction
of 1 with TMSOTf, showing signals at δH ϭ 3.93 (dd, J ϭ
2.0, 17.0 Hz, 1 H, 2-H), 4.37 (dd, J ϭ 3.5, 17.0 Hz, 1 H, 2-
H), and 5.27 (dd, J ϭ 2.0, 3.5 Hz, 1 H, 3-H) ppm. From
[a]
Gifu Pharmaceutical University
6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Fax: (internat.) ϩ 81-58/237-5979
E-mail: kataoka@gifu-pu.ac.jp
Scheme 1. Formation of the boron γ-(sulfonio)enolate 2
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Chalcogeno MoritaϪBaylisϪHillman Reaction of 2-(Methylchalcogeno)phenyl Vinyl Ketones
FULL PAPER
these spectroscopic data, we confirmed the formation of bo- 75% by treatment of the reaction mixture with triethyl-
ron enolate 2 from the reaction of 1 with BF3·Et2O. amine (Entry 3). The reaction of the seleno congener 4 gave
We next examined the reaction of thio derivative 1 with the adduct 7a (75%) and selenochromanone 9a (syn/anti ϭ
p-nitrobenzaldehyde (5a) in the presence of 2 equiv. of 95:5, 16%) after treatment with triethylamine (Entry 4). The
BF3·Et2O[5] and the influence of the quenching method of product syn-9a was isomerized to the anti isomer anti-9a
this reaction (Table 1).
during separation of the raw product by preparative TLC
on silica gel.[6] The stereochemical assignment for 9a was
determined from the coupling constant between the meth-
ine proton at the 3-position and the benzylic proton in com-
parison with those of the isomers of 2-(α-hydroxy-
benzyl)cyclohexanone, showing J ϭ 2.5 Hz for the syn iso-
mer and J ϭ 8.3 Hz for the anti isomer.[7] One of the iso-
mers of 9a with J ϭ 3.2 Hz and another one with J ϭ
7.8 Hz were assigned to be the syn and the anti isomers,
respectively. We further examined the reactions of various
aldehydes with 2-(methylchalcogeno)phenyl vinyl ketones 1
and 4 under similar conditions to those in Entries 3 and 4
in Table 1 (see Table 2).
Table 1. Examination of quenching reagents
The reactions of benzaldehyde (5d) and hydrocinnamal-
dehyde (5e) were continued until the aldehydes had disap-
peared according to TLC. The reactions of thio derivative
1 with both aromatic and aliphatic aldehydes 5bϪ5e gave
the adducts 6bϪ6e in good yields (Table 2, Entries 1, 3Ϫ5).
The reaction of seleno derivative 4 with p-chlorobenzal-
dehyde (5b) gave adduct 7b (69%) and selenochromanone
9b (syn only, 20%) (Table 2, Entry 2).
Entry Chalcogeno
ether
Quenching base
Products
(yield [%])
1
2
3
4
1
1
1
4
satd. aq. NaHCO3[a] 6a (45), 8a (26)
satd. aq. NaHCO3
Et3N (2 equiv.)
Et3N (2 equiv.)
6a (52)
6a (75)
In addition to aldehydes, various carbonyl compounds,
such as highly fluorinated ketones and non-enolizable α-
dicarbonyl compounds, have been used as electrophiles in
the MoritaϪBaylisϪHillman reaction.[1] However, the
MoritaϪBaylisϪHillman reaction does not occur with ke-
tones and enolizable α-dicarbonyl compounds under nor-
mal conditions.[8] The intermediate of the chalcogeno
7a (75)/9a (16),
95:5[b]
[a]
The reaction mixture was poured into an excess of an NaHCO3
[b]
solution. Diastereoisomer ratio (syn/anti isomer).
Treatment of the reaction mixture with saturated aqueous MoritaϪBaylisϪHillman reaction described above is a bo-
NaHCO3 gave the MoritaϪBaylisϪHillman adduct 6a ron enolate and can be expected to react with these car-
(45%) and the sulfonium salt syn-trans-8a (26%); the stereo- bonyl compounds under mild conditions.[9] These results
structure of 8a will be discussed below (Table 1, Entry 1). encouraged us to conduct the reactions of 2-(methylchalco-
When the reaction mixture was poured into an excess of geno)phenyl vinyl ketones 1 and 4 with various carbonyl
saturated aqueous NaHCO3, the adduct 6a was obtained in compounds that do not react under traditional
52% yield (Entry 2). The yield of 6a was increased up to MoritaϪBaylisϪHillman conditions.
Table 2. Reaction of 1-[2-(methylchalcogeno)phenyl]propenones 1 and 4 with aldehydes 5
Entry
Chalcogeno ether
Aldehyde 5
Conditions
Products (yield [%])
1
2
3
4
5
1
4
1
1
1
R ϭ p-ClC6H4 (5b)
R ϭ p-ClC6H4 (5b)
R ϭ p-CF3C6H4 (5c)
R ϭ Ph (5d)
0 °C, 2 h
6b (73)
0 °C, 2 h
7b (69), 9b (20), syn only
0 °C, 2 h
0 °C, 2 h then room temp., 3 h
0 °C, 2 h then room temp., 3 h
6c (75)
6d (60)
6e (70)
R ϭ PhC2H4 (5e)
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Table 3. Reaction of 1-[2-(methylchalcogeno)phenyl]propenones 1 and 4 with ketones 10
Entry
Chalcogeno ether
Ketone 10
Product (yield [%])
1[b]
2
3
4
5
1
1
4
1
4
1
4
R1 ϭ p-NO2C6H4, R2 ϭ Me (10a)
11a (47)
11a (47)
12a (50)
11b (19)
12b (26)
11c (56)
12c (53)
10a
10a
R1 ϭ Ph, R2 ϭ Me (10b)
10b
6
7
R1 ϭ R2 ϭ (CH2)5 (10c)
10c
[a]
[b]
The reaction mixture was poured into an NaHCO3 solution. Et3N (2 equiv.) was used instead of an NaHCO3 solution.
We first carried out the reaction of p-nitroacetophenone or α-oxo esters 13cϪd as electrophiles were studied. The
(10a) with thio derivative 1 in dry CH3CN at 0 °C for results are shown in Table 4.
30 min, quenched the reaction with triethylamine, and ob-
tained adduct 11a (47%; Table 3, Entry 1).
The reactions of α-diketones 13a and 13b gave the ad-
ducts 14a, 15a and 14b, 15b in low yields. However, this is
When the reaction mixture was poured into an excess of the first example of an enolizable α-diketone reacting as an
saturated aqueous NaHCO3, the adduct 11a was obtained electrophile under mild conditions in the MoritaϪ
in 47% yield (Entry 2). Since the quenching methods did BaylisϪHillman reaction.[5b] The reaction of ethyl pyruvate
not cause a difference in yield, the reaction mixtures of vari- (13c) with 3-buten-2-one did not give the expected adduct
ous ketones were worked up by pouring the mixture into an under various MoritaϪBaylisϪHillman reaction con-
excess of saturated aqueous NaHCO3. Acetophenone (10b), ditions,[10] while the reaction of 1 and 4 with 13c gave 14c
without an electron-withdrawing group on the benzene and 15c in 70 and 74% yield, respectively (Entries 5 and 6).
ring, gave 11b and 12b in low yields (Entries 4 and 5), and Reactions with methyl benzoylformate (13d) gave the prod-
cyclohexanone 10c afforded 11c and 12c in moderate yields ucts in low yields. The reaction of seleno derivative 4 with
(Entries 6 and 7). Next, the reactions of α-diketones 13aϪb oxo esters 13cϪd gave trace amounts of selenochromanones
Table 4. Reaction of 1-[2-(methylchalcogeno)phenyl]propenones 1 and 4 with α-dicarbonyl compounds 13
Entry
Chalcogeno ether
α-Dicarbonyl compound 13
Conditions
Products (yield [%])
1[a]
2[b]
3
4
5
6
7
8
1
4
1
4
1
4
1
4
R1 ϭ R2 ϭ Ph (13a)
0 °C, 2 h
14a (41)
13a
0 °C, 2 h
15a (4)
R1 ϭ R2 ϭ Me (13b)
0 °C, 1 h
0 °C, 1 h
room temp., 2 h
room temp., 2 h
room temp., 2 h
room temp., 2 h
14b (29)
13b
15b (24)
R1 ϭ Me, R2 ϭ OEt (13c)
14c (70)
13c
15c (74), 16c (2)[c]
14d (37)
R1 ϭ Ph, R2 ϭ OMe (13d)
13d
15d (29), 16d (6)[c]
[a] The reaction mixture was poured into an excess of an NaHCO3 solution. [b] BF3·Et2O (3 equiv.) was used. [c] Only one diastereoisomer
was obtained, but the stereostructure was not determined.
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Chalcogeno MoritaϪBaylisϪHillman Reaction of 2-(Methylchalcogeno)phenyl Vinyl Ketones
FULL PAPER
16cϪd as by-products. These compounds are only one iso- spectral pattern is very similar to that of the syn isomers.
mer, but their amounts were so small that their stereostruc- Therefore, an isomer showing the signals (CD3CN) at δH ϭ
tures could not be determined.
3.23 (s, 3 H, SMe) and 5.56 (d, J ϭ 2.4 Hz, 1 H, benzylic
H) ppm was assigned to be anti-trans-8a, and the other,
exhibiting the signals (CD3CN) at δH ϭ 3.29 (s, 3 H, SMe)
and 5.68 (d, J ϭ 3.9 Hz, 1 H, benzylic H) ppm, was as-
signed as anti-cis-8a. Surprisingly, the coupling constants of
the benzylic protons of the sulfonium salts 8a are small (2.4,
3.9 Hz), and are close to those of the syn isomers. The de-
methylation of a mixture of cis and trans isomers of anti-8a
with potassium iodide was carried out to confirm that no
isomerization of the anti isomer to the syn isomer had oc-
curred during the methylation of the anti isomer
(Scheme 3).
Structural Investigations
To clarify the stereochemistry of sulfonium salt 8a, we
synthesized authentic samples of the stereosiomers of 8a
(Scheme 2). 3-(α-Hydroxybenzyl)thiochromanone (17) was
prepared as a mixture of syn and anti isomers (syn/anti ϭ
4:1) from thiochroman-4-one by silylation of the enolate
and the aldol reaction with p-nitrobenzaldehyde (5a). The
syn and anti isomers were separated by recycling prepara-
tive HPLC. The stereochemistry of the isomers 17 was as-
signed by comparison of the coupling constants of syn-17
(3.2 Hz) and anti-17 (8.3 Hz) with those of the cyclohexa-
none derivatives (2.5 Hz for the syn isomer and 8.3 Hz for
the anti isomer).[7] The methylation of syn-17 with MeI and
AgBF4 gave two stereoisomers of 8a (syn-cis-8a/syn-trans-
8a ϭ 3:1).
Scheme 3. Demethylation of anti-sulfonium salt 8a
The product shows a large coupling constant for the
benzylic proton (J ϭ 8.3 Hz in CDCl3), which is consistent
1
with that of an authentic sample of anti-17. The H NMR
spectra of syn- and anti-17 in CD3CN were measured just
to be certain of the solvent effect of CD3CN. Surprisingly,
the chemical shifts and coupling constants changed: 1H
NMR (CD3Cl): syn-17: δ ϭ 5.83 (d, J ϭ 3.4 Hz, 1 H,
benzylic H); anti-17: δ ϭ 5.25 (d, J ϭ 8.3 Hz, 1 H, benzylic
H) ppm; (CD3CN): syn-17: δ ϭ 5.68 (t, J ϭ 4.0 Hz, 1 H,
benzylic H); anti-17: δ ϭ 5.3 (dd, J ϭ 4.0, 6.0 Hz, 1 H,
benzylic H) ppm.
Scheme 2. Synthesis of sulfonium salts 8a
Their stereostructures were determined from the NOEs
between the methyl group and the 3-proton. syn-trans-8a
shows a 6% NOE enhancement each between the methyl
Reaction Mechanism
In order to elucidate the reaction mechanism, we conduc-
group and the 3-proton and between the methyl group and ted several experiments on sulfonium salt 8a. The workup
one of the 2-protons, while syn-cis-8a shows no NOE en- of the reaction mixture of 1 and 5a with saturated aqueous
hancement between the methyl group and the 3-proton, al- NaHCO3 gave 6a (45%) and syn-trans-8a (26%), while the
though it does show a 5% NOE enhancement between the workup with saturated aqueous NaCl (without base) pro-
methyl group and one of the 2-protons. The 1H NMR spec- duced 6a and a mixture of syn-trans-8a and anti-trans-8a in
trum (CD3CN) of syn-trans-8a exhibits the signals at δH
ϭ
a ratio of 1:1 (Scheme 4).
3.10 (s, 3 H, SMe) and 5.79 (dd, J ϭ 3.0, 4.0 Hz, 1 H,
We next conducted the reactions of 8a with saturated
benzylic H) ppm, and that of syn-cis-8a shows signals at aqueous NaHCO3 in order to investigate this difference
δH ϭ 3.29 (s, 3 H, SMe) and 5.95 (d, J ϭ 2.0 Hz, 1 H, further (Scheme 5). Treatment of the syn-sulfonium salt 8a
1
benzylic H) ppm. According to the H NMR spectroscopic (syn-cis-8a/syn-trans-8a ϭ 3:1) with saturated aqueous
data, the methyl group of syn-trans-8a occupies the axial NaHCO3 gave the MoritaϪBaylisϪHillman adduct 6a, sul-
position and that of syn-cis-8a the equatorial position. This fonium salts 8a, p-nitrobenzaldehyde (5a), and thio deriva-
stereochemistry agrees with the conformation of the tive 1. On the other hand, treatment of the anti-sulfonium
syn,anti isomer of 3-(α-methoxybenzyl)-1-(methylseleno)- salts 8a (anti-cis-8a/anti-trans-8a ϭ 1:1) with saturated
chromanium salt, which was determined by X-ray analy- aqueous NaHCO3 gave the MoritaϪBaylisϪHillman ad-
sis.[6] The methylation of anti-17 similarly gave two kinds of duct 6a, p-nitrobenzaldehyde (5a), and thio derivative 1; the
sulfonium salts, anti-cis-8a and anti-trans-8a, in a ratio of 1:1 starting material 8a was not recovered. These results indi-
(Scheme 2). Neither isomers showed an NOE enhancement cate that anti-8a undergoes β-elimination more easily than
between the methyl group and the 3-proton, although the the syn isomer and that the retro-aldol reaction of 8a also
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T. Kataoka et al.
FULL PAPER
Scheme 4. Isomer ratio of sulfonium salts 8a by different quenching methods
posite position to the aldehyde, i.e. the trans configuration.
The difference of reactivity between syn- and anti-8 and a
base is shown in Scheme 7. In both isomers, the gauche con-
formation 21, in which the hydroxybenzyl group is in the
equatorial position, is more stable than the antiperiplanar
conformation 20 with an axial hydroxybenzyl group. β-
Elimination occurs via the antiperiplanar conformation 20.
Steric repulsion between the lone pair of electrons and the
benzylic hydrogen atom in anti-20 is much less than that
between the lone pair of electrons and the R group in syn-
20. Therefore, anti-20 undergoes β-elimination easier than
syn-20, which is why anti-8a was not obtained from the re-
action of 1 and 5a after working up the reaction mixture
with a base.
Scheme 5. Reaction of sulfonium salts 8a with saturated aqueous
NaHCO3
occurs in competition with β-elimination upon treatment
with a base.
On the basis of these results, a possible mechanism for
the chalcogeno MoritaϪBaylisϪHillman reaction is shown
in Scheme 6. The activation of the enone by BF3·Et2O al-
lows a chalcogeno ether to add to the β-carbon atom of an
enone moiety.
Diastereoselectivity would be induced in the reaction step
of boron enolate 2 with aldehyde 5. The transition state 19
with an equatorial R group is favored over the other tran-
sition state 18 with an axial R group, and the anti isomer 8
is preferably formed. When aldehyde 5 approaches enolate
2, the methyl group on the chalcogen atom takes the op-
Scheme 7. Structure and reactivity of sulfonium salts 8a
Conclusion
The chalcogeno MoritaϪBaylisϪHillman reaction of 2-
(methylchalcogeno)phenyl vinyl ketones with carbonyl com-
pounds has been discussed in detail. The reaction could be
applied to non-activated ketones, such as acetophenone and
cyclohexanone, and enolizable α-dicarbonyl compounds,
such as diacetyl and ethyl pyruvate, under mild conditions.
Further development of the tandem intramolecular Michael
aldol reaction is now in progress.
Scheme 6. Mechanism for the formation of α-hydroxyalkylated
compounds
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Chalcogeno MoritaϪBaylisϪHillman Reaction of 2-(Methylchalcogeno)phenyl Vinyl Ketones
FULL PAPER
H, ArH) ppm. 13C NMR (100 MHz, CD3CN): δ ϭ 24.2 (q), 33.1
(t), 33.3 (t), 127.9 (s), 131.4 (d), 132.9 (d), 134.36 (d), 134.42 (s),
136.4 (d), 191.6 (s) ppm. IR (KBr): ν˜ ϭ 1690 (CϭO), 1064 cmϪ1
Experimental Section
General: Melting points were obtained with a Yanagimoto micro-
melting-point apparatus and are uncorrected. IR spectra of solids
(KBr) and liquids (NaCl) were recorded with a JASCO FT/IR-230
(BF4Ϫ). MS (EI or FAB): no [Mϩ] or [Mϩ
ϩ H] peak.
C10H11BF4OSe (312.96): calcd. C 38.38, H 3.54; found C 38.49,
H 3.58.
1
spectrophotometer. H NMR spectra were recorded with a JEOL
EX-400 (400 MHz) spectrometer with tetramethylsilane as an in-
ternal standard. 13C NMR spectra were obtained with a JEOL EX-
400 (100 MHz) spectrometer with CDCl3 (δ ϭ 77.0 ppm) or
CD3CN (δ ϭ 1.3 ppm) as an internal standard. The degree of sub-
stitution of the carbon atoms was determined by DEPT. Mass spec-
tra were recorded with a JEOL JMS-SX102A spectrometer with a
direct-insertion probe at 70 eV. Elemental analyses of new com-
pounds were performed with a Yanaco CHN Corder MT-5. All
chromatographic isolations were accomplished with BW-350 (Fuji
Silysia) for column chromatography or with Kieselgel 60 PF254 con-
taining gypsum (Merck) for preparative TLC. CH2Cl2, MeCN,
ethanol, and THF were purified and dried by standard procedures
and freshly distilled prior to use. The recycling preparative HPLC
was performed with an LC-918 liquid chromatography (Japan Ana-
lytical Industry Co., Ltd.) equipped with JAIGEL-1H and -2H col-
umns (polystyrene gels).
1-Methyl-4-oxothiochromanium Tetrafluoroborate: This compound
was similarly prepared according to the procedure for 1-methyl-4-
oxoselenochromanium tetrafluoroborate. The physicochemical
data and spectroscopic data are identical with those of an auth-
entic sample.[14]
1-[2-(Methylseleno)phenyl]propenone (4): A solution of NaOH
(6.75 g, 169 mmol) in H2O (135 mL) was slowly added to a solution
of 1-methyl-4-oxoselenochromanium tetrafluoroborate (25.8 g,
82.4 mmol) in a mixture of CH2Cl2 (300 mL) and H2O (600 mL).
The mixture was stirred at room temperature for 20 min and then
extracted with CH2Cl2 (200 mL, three times). The combined ex-
tracts were dried with MgSO4, filtered, and concentrated to dry-
ness. The residue was purified by column chromatography (hexane/
CH2Cl2, 3:1) to yield 4 (17.4 g, 94%). Yellow oil. 1H NMR
(400 MHz, CDCl3): δ ϭ 2.25 (s, 3 H, SeCH3), 5.94 (dd, J ϭ 1.5,
10.5 Hz, 1 H, 3-H), 6.42 (dd, J ϭ 1.5, 17.0 Hz, 1 H, 3-H), 7.14 (dd,
J ϭ 10.5, 17.0 Hz, 1 H, 2-H), 7.26 (dt, J ϭ 1.5, 7.8 Hz, 1 H, ArH),
7.45 (dt, J ϭ 1.5, 7.8 Hz, 1 H, ArH), 7.50 (dd, J ϭ 1.5, 7.8 Hz, 1
H, ArH), 7.87 (dd, J ϭ 1.5, 7.8 Hz, 1 H, ArH) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 6.6 (q), 124.2 (d), 128.3 (d), 130.2 (t), 130.9
(d), 132.2 (d), 132.8 (d), 135.4 (s), 138.8 (s), 191.3 (s) ppm. IR
(NaCl): ν˜ ϭ 1651 cmϪ1 (CϭO). MS (EI): m/z (%) ϭ 226 (45) [Mϩ],
211 (100). C10H10OSe (225.15): calcd. C 53.35, H 4.48; found C
53.18, H 4.52.
3-(Phenylseleno)propionic Acid: NaBH4 (about 16 g) was slowly ad-
ded to a solution of diphenyl diselenide (36.7 g, 0.117 mol) in dry
ethanol (600 mL) until the solution became colorless. An aqueous
solution of sodium 3-chloropropionate, prepared from Na2CO3
(15.3 g, 0.144 mol) and 3-chloropropionic acid (31.4 g, 0.289 mol)
in H2O (60 mL), was added to the resulting solution. The mixture
was heated at reflux for 2.5 h and was then allowed to cool to room
temperature. H2O (600 mL) was added and extracted with benzene
(200 mL, twice). The aqueous layer was acidified with concentrated
hydrochloric acid and extracted with benzene (300 mL, three
times). The extracts were washed with water, dried with MgSO4,
and filtered. The solvent was removed in vacuo to give the crude
product as a white powder (52 g, 96%), which was used without
further purification. The spectroscopic data are identical to those
cited in the literature.[11]
1-[2-(Methylthio)phenyl]propenone (1): Yellow oil. 1H NMR
(400 MHz, CDCl3): δ ϭ 2.45 (s, 3 H, SCH3), 5.96 (dd, J ϭ 1.4,
10.8 Hz, 1 H, 3-H), 6.31 (dd, J ϭ 1.4, 17.6 Hz, 1 H, 3-H), 6.98 (dd,
J ϭ 10.8, 17.6 Hz, 1 H, 2-H), 7.21 (dt, J ϭ 1.0, 7.3 Hz, 1 H, ArH),
7.37 (dd, J ϭ 1.0, 7.3 Hz, 1 H, ArH), 7.47 (dt, J ϭ 1.0, 7.3 Hz, 1
H, ArH), 7.66 (dd, J ϭ 1.0, 7.3 Hz, 1 H, ArH) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 16.2 (q), 123.8 (d), 125.9 (d), 129.9 (d),
130.5 (t), 131.8 (d), 134.4 (d), 135.5 (s), 141.3 (s), 192.7 (s) ppm.
IR (NaCl): ν˜ ϭ 1653 cmϪ1 (CϭO). MS (EI): m/z (%) ϭ 178 (55)
[Mϩ], 150 (100). C10H10OS (178.25): calcd. C 67.38, H 5.66; found
C 67.16, H 5.74.
Selenochroman-4-one: 3-(Phenylseleno)propionic acid (20 g, 0.087
mol) was heated in polyphosphoric acid (160 g) at 100 °C for 1 h
and was then allowed to cool to room temperature. The mixture
was poured into ice-cold water (500 mL), stirred for 1 h, and ex-
tracted with CH2Cl2 (150 mL, four times). The combined extracts
were washed with brine (150 mL, twice) and then with saturated
aqueous NaHCO3, dried with MgSO4, and filtered. After evapor-
ation of the solvent, the product was purified by distillation (150
°C, 8 Torr) to yield an orange solid (15.6 g, 80%). The spectro-
scopic data are identical to those cited in the literature.[11] Thioch-
roman-4-one was similarly synthesized from 3-(phenylthio)pro-
pionic acid.[12]
Generation of Boron Enolate 2: BF3·Et2O (32 µL, 0.25 mmol) was
added to a solution of thio derivative 1 (45 mg, 0.25 mmol) in
CD3CN (1 mL) at 0 °C. The solution was stirred at the same tem-
1
perature for 15 min and then submitted to H NMR spectroscopy.
Generation of Boron Enolate 3: The reaction was similarly conduc-
ted on the same scale using TMSOTf (56 mg, 0.25 mmol) instead
of BF3·Et2O.
1-Methyl-4-oxoselenochromanium Tetrafluoroborate: A solution of
BF3·Et2O (38 mL, 0.3 mol) in dry CH2Cl2 (60 mL) was slowly ad-
General Procedure for Reactions of 2-(Methylchalcogeno)phenyl Vi-
ded to trimethyl orthoformate (32 g, 0.3 mol) at Ϫ30 °C.[13] The nyl Ketone 1 or 4 with Aldehyde 5: BF3·Et2O (127 mL, 1.0 mmol)
solution was stirred at that temperature for 1 h and then at 0 °C for
15 min. The solution was cooled to Ϫ30 °C again, and a solution of
selenochroman-4-one (32 g, 0.15 mol) in dry CH2Cl2 (200 mL) was
slowly added. The resulting mixture was stirred at 0 °C for 12 h,
and the precipitate was collected and washed with diethyl ether to
yield the product (38 g, 80%). Brown crystals (from acetone/diethyl
ether), m.p. 133Ϫ136 °C (dec.). 1H NMR (400 MHz, CD3CN): δ ϭ
was added dropwise at 0 °C to a stirred solution of 1-[2-(methylthio)-
phenyl]propenone (1; 178 mg, 1.0 mmol) and p-nitrobenzal-
dehyde (5a; 76 mg, 0.5 mmol) in dry CH3CN (1.5 mL). The mixture
was stirred at the same temperature for 2 h and then quenched by
addition of Et3N (140 mL, 1.0 mmol). After stirring the mixture at
the same temperature for 10 min, it was poured into saturated
aqueous NaCl (10 mL) and extracted with CH2Cl2 (5 mL, three
3.04 (s, 3 H, SeCH3), 3.19Ϫ3.33 (m, 2 H, 2-CH2), 3.79 (ddd, J ϭ times). The combined extracts were dried with MgSO4 and concen-
4.5, 6.4, 11.2 Hz, 1 H, 3-CH2), 4.06 (ddd, J ϭ 2.0, 4.5, 11.2 Hz, 1 trated under reduced pressure. The residue was purified by prepara-
H, 3-CH2), 7.78Ϫ7.88 (m, 3 H, ArH), 8.28 (dd, J ϭ 2.4, 6.4 Hz, 1 tive TLC eluting with hexane/EtOAc (3:1) to give 6a.
Eur. J. Org. Chem. 2003, 4852Ϫ4861
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4857

T. Kataoka et al.
FULL PAPER
2-[1-Hydroxy-1-(4-nitrophenyl)methyl]-1-[2-(methylthio)phenyl]-
propenone (6a): Yellow oil. H NMR (400 MHz, CDCl3): δ ϭ 2.39
(s, 3 H, SCH3), 3.55 (d, J ϭ 5.4 Hz, 1 H, OH), 5.79 (s, 1 H, olefinic
(s, 3 H, SeCH3), 3.48 (d, J ϭ 5.4 Hz, 1 H, OH), 5.77 (s, 1 H, olefinic
H), 5.91 (d, J ϭ 5.4 Hz, 1 H, benzylic H), 6.05 (s, 1 H, olefinic H),
7.21 (t, J ϭ 7.3 Hz, 1 H, ArH), 7.41 (t, J ϭ 7.3 Hz, 1 H, ArH),
1
H), 6.09 (s, 1 H, olefinic H), 5.91 (d, J ϭ 5.4 Hz, 1 H, benzylic H), 7.42 (d, J ϭ 7.3 Hz, 1 H, ArH), 7.49 (d, J ϭ 7.3 Hz, 1 H, ArH),
7.17 (dt, J ϭ 1.3, 7.5 Hz, 1 H, ArH), 7.43 (dt, J ϭ 1.3, 7.5 Hz, 1 7.66 (d, J ϭ 8.3 Hz, 2 H, ArH), 8.21 (d, J ϭ 8.3 Hz, 2 H, ArH)
H, ArH), 7.26 (dd, J ϭ 1.3, 7.5 Hz, 1 H, ArH), 7.35 (dd, J ϭ 1.3, ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 7.6 (q), 72.9 (d), 123.7
7.5 Hz, 1 H, ArH), 7.66 (d J ϭ 8.8 Hz, 2 H, ArH), 8.21 (d J ϭ
(d), 124.8 (d), 127.4 (d), 128.7 (t), 129.9 (d), 130.9 (d), 132.1 (d),
8.8 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 17.0 135.8 (s), 137.1 (s), 147.5 (s), 148.5 (s), 148.6 (s), 198.0 (s) ppm. IR
(q), 72.4 (d), 123.8 (d), 124.6 (d), 127.4 (d), 127.7 (d), 129.7 (d),
130.1 (t), 131.7 (d), 136.9 (s), 139.3 (s), 147.5 (s), 149.1 (s), 149.2
(NaCl): ν˜ ϭ 3440 (OH), 1640 (CϭO), 1520 (NO2), 1350 cmϪ1
(NO2). MS (EI): m/z (%) ϭ 377 (25) [Mϩ], 282 (100). C17H15NO4Se
(s), 198.2 (s) ppm. IR (NaCl): ν˜ ϭ 3423 (OH), 1651 (CϭO), 1517 (376.27): calcd. C 54.27, H 4.02, N 3.72; found C 54.09, H 4.19,
(NO2), 1343 cmϪ1 (NO2). MS (EI): m/z (%) ϭ 329 (10) [Mϩ], 177 N 3.64.
(100). C17H15NO4S (329.37): calcd. C 61.99, H 4.59, N 4.25; found
C 61.93, H 4.94, N 3.99.
2-[1-(4-Chlorophenyl)-1-hydroxymethyl]-1-[2-(methylseleno)-
phenyl]propenone (7b): Yellow plates (CH2Cl2/hexane), m.p. 97Ϫ98
2-[1-(4-Chlorophenyl)-1-hydroxymethyl]-1-[2-(methylthio)phenyl]-
1
°C. H NMR (400 MHz, CDCl3): δ ϭ 2.25 (s, 3 H, SeCH3), 3.29
propenone (6b): Light yellow oil. 1H NMR (400 MHz, CDCl3): δ ϭ
(br. s, 1 H, OH), 5.69 (s, 1 H, olefinic H), 5.81 (s, 1 H, benzylic H),
6.00 (s, 1 H, olefinic H), 7.19 (t, J ϭ 7.3 Hz, 1 H, ArH), 7.32 (d,
2.40 (s, 3 H, SCH3), 3.28 (d, J ϭ 4.9 Hz, 1 H, OH), 5.72 (s, 1 H,
olefinic H), 5.80 (d, J ϭ 4.9 Hz, 1 H, benzylic H), 6.03 (s, 1 H,
J ϭ 8.3 Hz, 2 H, ArH), 7.39Ϫ7.48 (m, 5 H, ArH) ppm. 13C NMR
olefinic H), 7.14Ϫ7.18 (m, 1 H, ArH), 7.27Ϫ7.44 (m, 7 H, ArH)
(100 MHz, CDCl3): δ ϭ 7.7 (q), 73.3 (d), 125.0 (d), 127.9 (t), 128.3
(d), 128.9 (d), 129.9 (d), 131.4 (d), 132.2 (d), 133.9 (s), 136.2 (s),
ppm. 13C NMR (400 MHz, CDCl3): δ ϭ 16.8 (q), 72.5 (d), 124.4
(d), 127.2 (d), 128.1 (d), 128.6 (d), 129.1 (t), 129.6 (d), 131.3 (d),
137.6 (s), 140.0 (s), 149.6 (s), 198.5 (s) ppm. IR (KBr): ν˜ ϭ 3444
133.5 (s), 137.1 (s), 139.1 (s), 139.8 (s). 149.7 (s), 198.3 (s) ppm. IR
(OH), 1644 cmϪ1 (CϭO). MS (EI): m/z (%) ϭ 366 (20) [Mϩ], 271
(NaCl): ν˜ ϭ 3453 (OH), 1651 cmϪ1 (CϭO). MS (FAB, NBA): m/z
(100). C17H15ClO2Se (365.71): calcd. C 55.83, H 4.13; found C
55.70, H 4.16.
(%) ϭ 319 (25) [Mϩ ϩ H], 154 (100). C17H15ClO2S (318.82): calcd.
C 64.04, H 4.74; found C 64.07, H 4.97.
(1R*,1ЈS*,3S*)-3-[1-Hydroxy-1-(4-nitrophenyl)methyl]-1-methyl-4-
2-{1-Hydroxy-1-[4-(trifluoromethyl)phenyl]methyl}-1-[2-(methyl-
oxothiochromanium Tetrafluoroborate (8a): Colorless needles (ace-
thio)phenyl]propenone (6c): Yellow oil. 1H NMR (400 MHz,
tone/CH2Cl2), m.p. 199Ϫ201 °C (dec.). 1H NMR (400 MHz,
CDCl3): δ ϭ 2.39 (s, 3 H, SCH3), 3.46 (d, J ϭ 5.0 Hz, 1 H, OH),
CDCl3): δ ϭ 3.10 (s, 3 H, SCH3), 3.60 (dd, J ϭ 4.9, 15.1 Hz, 1 H, -
5.75 (s, 1 H, olefinic H), 5.87 (d, J ϭ 5.0 Hz, 1 H, benzylic H), 6.05
CH2S), 3.61 (ddd, J ϭ 2.9, 4.9, 10.3 Hz, 1 H, CHCO), 4.02 (dd,
(s, 1 H, olefinic H), 7.16 (t, J ϭ 7.5 Hz, 1 H, ArH), 7.28 (d, J ϭ
J ϭ 10.3, 15.1 Hz, 1 H, -CH2S), 4.36 (d, J ϭ 4.4 Hz, 1 H, OH),
7.5 Hz, 1 H, ArH), 7.34 (d, J ϭ 7.5 Hz, 1 H, ArH), 7.42 (t, J ϭ
5.79 (dd, J ϭ 2.9, 4.4 Hz, 1 H, benzylic H), 7.71 (d, J ϭ 8.8 Hz, 2
7.5 Hz, 1 H, ArH), 7.57Ϫ7.62 (m, 4 H, ArH) ppm. 13C NMR
H, ArH), 7.93 (m, 3 H, ArH), 8.28 (d, J ϭ 8.8 Hz, 2 H, ArH), 8.38
(100 MHz, CDCl3): δ ϭ 16.8 (q), 72.6 (d), 122.8 (s), 124.5 (d), 125.3
(d), 125.4 (d), 127.0 (d), 129.4 (t), 129.6 (d), 129.7 (s), 131.4 (d),
(dd, J ϭ 2.2, 7.1 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 29.6 (q), 38.0 (t), 51.3 (d), 70.1 (d), 124.5 (d), 128.2
(d), 128.8 (s), 129.1 (d), 131.4 (d), 131.7 (s), 134.1 (d), 136.6 (d),
137.1 (s), 139.1 (s), 145.3 (s), 149.4 (s), 198.3 (s) ppm. IR (NaCl):
ν˜ ϭ 3452 (OH), 1651 (CϭO), 1121 cmϪ1 (CF3). MS (EI): m/z (%) ϭ
148.6 (s), 149.7 (s), 189.8 (s) ppm. IR (KBr): ν˜ ϭ 3414 (OH), 1618
352 (7) [Mϩ], 177 (100). C18H15F3O2S (352.37): calcd. C 61.35, H
(CϭO), 1521 (NO2), 1306 (NO2), 1084 cmϪ1 (BF4Ϫ). MS (EI or
4.29; found C 61.13, H 4.28.
FAB): no [Mϩ] or [Mϩ ϩ1] peak. C17H16BF4NO4S (417.18): calcd.
2-(1-Hydroxy-1-phenylmethyl)-1-[2-(methylthio)phenyl]propenone
C 48.94, H 3.87, N 3.36; found C 49.06, H 3.90, N 3.18.
(6d): Yellow prisms (from CH2Cl2/hexane), m.p. 88Ϫ89 °C. 1H
NMR (400 MHz, CDCl3): δ ϭ 2.40 (s, 3 H, SCH3), 3.23 (d, J ϭ
4.5 Hz, 1 H, OH), 5.71 (s, 1 H, olefinic H), 5.84 (d, J ϭ 4.5 Hz, 1
H, benzylic H), 6.02 (s, 1 H, olefinic H), 7.13 Ϫ7.17 (m, 1 H, ArH),
7.27Ϫ7.47 (m, 8 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ
17.1 (q), 73.4 (d), 124.6 (d), 127.0 (d), 127.5 (d), 128.0 (d), 128.7
(d), 129.0 (t), 129.9 (d), 131.5 (d), 137.7 (s), 139.4 (s), 141.5 (s),
150.4 (s), 198.7 (s) ppm. IR (KBr): ν˜ ϭ 3503 (OH), 1631 cmϪ1 (Cϭ
O). MS (EI): m/z (%) ϭ 284 (6) [Mϩ], 237 (100). C17H16O2S
(284.37): calcd. C 71.80, H 5.67; found C 71.59, H 5.72.
(1ЈR*,3R*)-3-[1-Hydroxy-1-(4-nitrophenyl)methyl]selenochroman-4-
one (syn-9a): Yellow needles (CH2Cl2/hexane), m.p. 129Ϫ130 °C.
1H NMR (400 MHz, CDCl3): δ ϭ 2.63 (dd, J ϭ 3.2, 12.2 Hz, 1 H,
CH2Se), 3.15 (br. s, 1 H, OH), 3.32 (dt, J ϭ 3.2, 13.2 Hz, 1 H, -
CHCO), 3.48 (dd, J ϭ 12.2, 13.2 Hz, 1 H, CH2Se), 5.78 (d, J ϭ
3.2 Hz, 1 H, benzylic H), 7.24 (dd, J ϭ 3.4, 7.8 Hz, 1 H, ArH),
7.36 (d, J ϭ 3.4 Hz, 2 H, ArH), 7.57 (d, J ϭ 8.8 Hz, 2 H, ArH),
8.11 (d, J ϭ 7.8 Hz, 1 H, ArH), 8.25 (d, J ϭ 8.8 Hz, 2 H, ArH)
ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 16.9 (t), 54.7 (d), 70.8 (d),
123.7 (d), 125.7 (d), 126.8 (d), 129.9 (d), 130.4 (d), 133.2 (s), 133.7
(d), 136.4 (s), 147.3 (s), 148.5 (s), 196.8 (s) ppm. IR (KBr): ν˜ ϭ
3503 (OH), 1668 (CϭO), 1518 (NO2), 1346 cmϪ1 (NO2). MS (EI):
m/z (%) ϭ 363 (8) [Mϩ], 184 (100). C16H13NO4Se (362.24): calcd.
C 53.05, H 3.62, N 3.87; found C 53.17, H 3.60, N 3.90.
2-(1-Hydroxy-3-phenylpropyl)-1-[2-(methylthio)phenyl]propenone
(6e): Light yellow oil. 1H NMR (400 MHz, CDCl3): δ ϭ 2.03Ϫ2.11
(m, 2 H, 2Ј-H), 2.43 (s, 3 H, SCH3), 2.74Ϫ2.81 (m, 2 H, 3Ј-H and
OH), 2.86Ϫ2.94 (m, 1 H, 3Ј-H), 4.67 (dd, J ϭ 4.9, 7.8 Hz, 1 H, 1Ј-
H), 5.67 (s, 1 H, olefinic H), 6.12 (s, 1 H, olefinic H), 7.17Ϫ7.45
(m, 9 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 16.8 (q),
32.0 (t), 37.7 (t), 70.9 (d), 124.4 (d), 125.8 (d), 127.3 (d), 128.3 (t),
128.4 (d), 128.5 (d), 129.3 (d), 131.0 (d), 137.8 (s), 138.5 (s), 141.7
(s), 150.2 (s), 198.8 (s) ppm. IR (NaCl): ν˜ ϭ 3451 (OH), 1651 cmϪ1
(CϭO). MS (EI): m/z (%) ϭ 312 (7) [Mϩ], 91 (100). C19H20O2S
(312.43): calcd. C 73.04, H 6.45; found C 72.76, H 6.55.
(1ЈR*,3S*)-3-[1-Hydroxy-1-(4-nitrophenyl)methyl]selenochroman-4-
one (anti-9a): Yellow oil. 1H NMR (400 MHz, CDCl3): δ ϭ 2.67
(dd, J ϭ 3.4, 12.2 Hz, 1 H, CH2Se), 2.98 (t, J ϭ 12.2 Hz, 1 H,
CH2Se), 3.27 (ddd, J ϭ 3.4, 7.8, 12.2 Hz, 1 H, -CHCO), 4.01 (br.
s, 1 H, OH), 5.25 (d, J ϭ 7.8 Hz, 1 H, benzylic H), 7.26 (dd, J ϭ
3.4, 7.8 Hz, 1 H, ArH), 7.36Ϫ7.39 (m, 2 H, ArH), 7.65 (d, J ϭ
8.8 Hz, 2 H, ArH), 8.14 (d, J ϭ 7.8 Hz, 1 H, ArH), 8.25 (d, J ϭ
8.8 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 19.4
2-[1-Hydroxy-1-(4-nitrophenyl)methyl]-1-[2-(methylseleno)phenyl]-
1
propenone (7a): Yellow oil. H NMR (400 MHz, CDCl3): δ ϭ 2.25
4858
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4852Ϫ4861

Chalcogeno MoritaϪBaylisϪHillman Reaction of 2-(Methylchalcogeno)phenyl Vinyl Ketones
FULL PAPER
(t), 54.2 (d), 73.9 (d), 123.8 (d), 125.9 (d), 128.1 (d), 129.9 (d), 130.7
(d), 132.9 (s), 133.8 (d), 136.3 (s), 147.7 (s), 147.8 (s), 197.9 (s) ppm.
J ϭ 1.3, 7.3 Hz, 1 H, ArH), 7.42Ϫ7.46 (m, 2 H, ArH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 16.5 (q), 21.6 (t), 25.6 (t), 36.3 (t),
IR (NaCl): ν˜ ϭ 3503 (OH), 1669 (CϭO), 1518 (NO2), 1345 cmϪ1 72.9 (s), 124.0 (d), 126.1 (t), 126.6 (d), 130.5 (d), 131.3 (d), 137.4
(NO2). MS (FAB, Gly): m/z (%) ϭ 364 (2) [Mϩ ϩ H], 185 (100). (s), 139.8 (s), 153.7 (s), 200.8 (s) ppm. IR (NaCl): ν˜ ϭ 3484 (OH),
HRMS (FAB, Gly): calcd. for C16H14NO4Se [Mϩ ϩ H]: 364.0010,
1651 cmϪ1 (CϭO). MS (EI): m/z (%) ϭ 276 (20) [Mϩ], 261 (100).
found 364.0085.
C16H20O2S (276.39): calcd. C 69.53, H 7.29; found C 69.25, H 7.31.
3-Hydroxy-2-methylene-1-[2-(methylseleno)phenyl]-3-(4-nitro-
phenyl)butan-1-one (12a): Yellow needles (from CHCl3), m.p.
170Ϫ171.5 °C. 1H NMR (400 MHz, CDCl3): δ ϭ 1.77 (s, 3 H,
CH3), 2.24 (s, 3 H, SeCH3), 5.06 (br. s, 1 H, OH), 5.84 (s, 1 H,
olefinic H), 6.26 (s, 1 H, olefinic H), 7.22 (dt, J ϭ 1.5, 7.8 Hz, 1
H, ArH), 7.41 (dt, J ϭ 1.5, 7.8 Hz, 1 H, ArH), 7.46 (dd, J ϭ 1.5,
7.8 Hz, 1 H, ArH), 7.49 (dd, J ϭ 1.5, 7.8 Hz, 1 H, ArH), 7.70 (d,
J ϭ 8.8 Hz, 2 H, ArH), 8.18 (d, J ϭ 8.8 Hz, 2 H, ArH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 7.3 (q), 28.9 (q), 76.2 (s), 123.6 (d),
124.6 (d), 126.0 (d), 128.4 (t), 129.6 (d), 131.4 (d), 132.2 (d), 136.7
(s), 136.8 (s), 147.0 (s), 150.0 (s), 153.9 (s), 199.8 (s) ppm. IR (KBr):
ν˜ ϭ 3446 (OH), 1604 (CϭO), 1519 (NO2), 1347 cmϪ1 (NO2). MS
(EI): m/z (%) ϭ 391 (15) [Mϩ], 225 (100). C18H17NO4Se (390.29):
calcd. C 55.39, H 4.39, N 3.59; found C 55.13, H 4.44, N 3.52.
(1ЈR*,3R*)-3-[1-Hydroxy-1-(4-chlorophenyl)methyl]selenochroman-
4-one (syn-9b): Light yellow powder, m.p. 90Ϫ90.5 °C. 1H NMR
(400 MHz, CDCl3): δ ϭ 2.73 (dd, J ϭ 2.9, 12.5 Hz, 1 H, CH2Se),
2.99 (br. s, 1 H, OH), 3.24 (dt, J ϭ 2.9, 12.5 Hz, 1 H, -CHCO),
3.45 (t, J ϭ 12.5 Hz, 1 H, CH2Se), 5.65 (t, J ϭ 2.9 Hz, 1 H, benzylic
H), 7.21Ϫ7.37 (m, 7 H, ArH), 8.10 (d, J ϭ 7.8 Hz, 1 H, ArH) ppm.
13C NMR (100 MHz, CDCl3): δ ϭ 17.2 (t), 54.8 (d), 70.9 (d), 125.6
(d), 127.3 (d), 128.7 (d), 129.9 (d), 130.3 (d), 133.3 (s), 133.5 (d),
136.5 (s), 139.4 (s), 197.3 (s) ppm. One quaternary carbon is over-
lapped. IR (KBr): ν˜ ϭ 3745 (OH), 1665 cmϪ1 (CϭO). MS (EI):
m/z (%) ϭ 352 (3) [Mϩ], 184 (100). C16H13ClO2Se (351.69): calcd.
C 54.64, H 3.73; found C 54.86, H 3.77.
General Procedure for Reactions of 2-(Methylchalcogeno)phenyl Vi-
nyl Ketone 1 or 4 with Ketone 10 or α-Dicarbonyl Compound 13:
BF3·Et2O (127 mL, 1.0 mmol) was added dropwise at 0 °C to a
stirred solution of 1-[2-(methylthio)phenyl]propenone (1; 178 mg,
1.0 mmol) and p-nitroacetophenone (10a; 83 mg, 0.5 mmol) in dry
CH3CN (1.5 mL). The mixture was stirred at the same temperature
for 30 min, then poured into an NaHCO3 solution (10 mL), and
extracted with CH2Cl2 (5 mL, three times). The combined extracts
were dried with MgSO4 and concentrated under reduced pressure.
The residue was purified by preparative TLC eluting with hexane/
EtOAc (3:1) to give 11a.
3-Hydroxy-2-methylene-1-[2-(methylseleno)phenyl]-3-phenylbutan-1-
one (12b): Yellow plates (from CH2Cl2/hexane), m.p. 94Ϫ94.5 °C.
1H NMR (400 MHz, CDCl3): δ ϭ 1.77 (s, 3 H, CH3), 2.22 (s, 3 H,
SeMe), 5.02 (s, 1 H, OH), 5.70 (s, 1 H, olefinic H), 6.15 (s, 1 H,
olefinic H), 7.16Ϫ7.22 (m, 2 H, ArH), 7.31 (t, J ϭ 7.8 Hz, 2 H,
ArH), 7.38 (dt, J ϭ 1.4, 7.3 Hz, 1 H, ArH), 7.44 (dd, J ϭ 1.4,
7.3 Hz, 1 H, ArH), 7.52Ϫ7.53 (m, 3 H, ArH) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 7.2 (q), 29.1 (q), 76.4 (s), 124.3 (d), 125.0
(d), 126.96 (d), 127.04 (t), 128.2(d), 129.2 (d), 131.7 (d), 132.0 (d),
136.8 (s), 137.2 (s), 146.2 (s), 151.2 (s), 200.3 (s) ppm. IR (KBr):
ν˜ ϭ 3451 (OH), 1638 cmϪ1 (CϭO). MS (EI): m/z (%) ϭ 346 (15)
[Mϩ], 225 (100). C18H18O2Se (345.29): calcd. C 62.61, H 5.25;
found C 62.41, H 5.28.
3-Hydroxy-2-methylene-1-[2-(methylthio)phenyl]-3-(4-nitrophenyl)-
butan-1-one (11a): Yellow needles (EtOAc/hexane), m.p. 100Ϫ101
1
°C. H NMR (400 MHz, CDCl3): δ ϭ 1.76 (s, 3 H, CH3), 2.40 (s,
3 H, SCH3), 4.98 (s, 1 H, OH), 5.90 (s, 1 H, olefinic H), 6.31 (s, 1
H, olefinic H), 7.19 (dt, J ϭ 1.3, 7.5 Hz, 1 H, ArH), 7.31 (dd, J ϭ
1.3, 7.5 Hz, 1 H, ArH), 7.33 (d, J ϭ 7.5 Hz, 1 H, ArH), 7.44 (dt,
J ϭ 1.3, 7.5 Hz, 1 H, ArH), 7.71 (d, J ϭ 8.8 Hz, 2 H, ArH), 8.19
(d, J ϭ 8.8 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3):
δ ϭ 16.8 (q), 29.0 (q), 76.1 (s), 123.5 (d), 124.4 (d), 126.0 (d), 127.2
(d), 129.7 (d), 130.1 (t), 131.6 (d), 136.8 (s), 139.6 (s), 147.0 (s),
150.5 (s), 154.1 (s), 200.0 (s) ppm. IR (KBr): ν˜ ϭ 3448 (OH), 1631
(CϭO), 1509 (NO2), 1347 cmϪ1 (NO2). MS (EI): m/z (%) ϭ 343
(2) [Mϩ], 177 (100). C18H17NO4S (343.40): calcd. C 62.96, H 4.99,
N 4.08; found C 63.08, H 5.10, N 3.98.
2-(1-Hydroxycyclohexyl)-1-[2-(methylseleno)phenyl]propenone (12c):
Yellow oil. H NMR (400 MHz, CDCl3): δ ϭ 1.24Ϫ1.32 (m, 1 H,
1
cyclohexy H), 1.53Ϫ1.60 (m, 2 H, cyclohexyl H), 1.63Ϫ1.91 (m, 7
H, cyclohexyl H), 2.27 (s, 3 H, SeMe), 3.60 (s, 1 H, OH), 5.46 (s,
1 H, olefinic H), 5.99 (s, 1 H, olefinic H), 7.21 (dt, J ϭ 1.3, 7.5 Hz,
1 H, ArH), 7.42 (dt, J ϭ 1.3, 7.5 Hz, 1 H, ArH), 7.48 (dd, J ϭ 1.3,
7.5 Hz, 1 H, ArH), 7.65 (dd, J ϭ 1.3, 7.5 Hz, 1 H, ArH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 7.0 (q), 21.8 (t), 26.0 (t), 36.5 (t),
73.1 (s), 123.7 (t), 124.3 (d), 128.8 (d), 132.1 (d), 132.6 (d), 137.1
(s), 137.3 (s), 153.4 (s), 200.8 (s) ppm. IR (NaCl): ν˜ ϭ 3472 (OH),
1641 cmϪ1 (CϭO). MS (EI): m/z (%) ϭ 324 (45) [Mϩ], 309 (100).
C16H12O2Se (323.29): calcd. C 59.44, H 6.24; found C 59.16, H
6.38.
3-Hydroxy-2-methylene-1-[2-(methylthio)phenyl]-3-phenylbutan-1-
one (11b): Yellow powder (EtOAc/hexane), m.p. 82Ϫ85 °C. 1H
NMR (400 MHz, CDCl3): δ ϭ 1.77 (s, 3 H, CH3), 2.40 (s, 3 H,
SCH3), 5.00 (s, 1 H, OH), 5.76 (s, 1 H, olefinic H), 6.19 (s, 1 H,
olefinic H), 7.15 (t, J ϭ 7.8 Hz, 1 H, ArH), 7.22 (dt, J ϭ 1.3,
7.8 Hz, 1 H, ArH), 7.31Ϫ7.35 (m, 4 H, ArH), 7.41 (t, J ϭ 7.8 Hz,
1 H, ArH), 7.53 (d, J ϭ 7.8 Hz, 2 H, ArH) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 16.7 (q), 29.2 (q), 76.3 (s), 124.1 (d), 124.9
(d), 126.90 (d), 126.95 (d), 128.2 (d), 128.7 (t), 130.0 (d), 131.4 (d),
137.1 (s), 139.8 (s), 146.3 (s), 151.6 (s), 200.3 (s) ppm. IR (KBr):
ν˜ ϭ 3445 (OH), 1626 cmϪ1 (CϭO). MS (EI): m/z (%) ϭ 298 (2)
[Mϩ], 177 (100). HRMS (EI): calcd. for C18H18O2S [Mϩ]: 298.1027;
found 298.1041.
2-Hydroxy-3-methylene-4-[2-(methylthio)phenyl]-1,2-diphenyl-
butane-1,4-dione (14a): Yellow powder (from EtOAc/hexane), m.p.
130Ϫ133 °C. 1H NMR (400 MHz, CDCl3): δ ϭ 2.46 (s, 3 H,
SCH3), 5.39 (s, 1 H, olefinic H), 5.70 (s, 1 H, olefinic H), 5.90 (s,
1 H, OH), 7.23Ϫ7.31 (m, 3 H, ArH), 7.36 (dt, J ϭ 1.3, 7.5 Hz, 2
H, ArH), 7.40Ϫ7.51 (m, 4 H, ArH), 7.68 (dd, J ϭ 1.3, 7.5 Hz, 2
H, ArH), 7.94 (dd, J ϭ 1.3, 7.5 Hz, 1 H, ArH), 7.95 (dt, J ϭ 1.3,
7.5 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 16.2
(q), 86.5 (s), 123.7 (d), 125.9 (d), 126.6 (d), 127.8 (d), 128.3 (d),
128.7 (d), 130.8 (d), 130.9 (t), 132.0 (d), 132.4 (d), 132.7 (d), 134.8
(s), 135.5 (s), 137.7 (s), 141.1 (s), 152.2 (s), 201.2 (s), 201.3 (s) ppm.
IR (KBr): ν˜ ϭ 3412 (OH), 1669 (CϭO), 1613 cmϪ1 (CϭO). MS
(EI): m/z (%) ϭ 388 (1) [Mϩ], 105 (100). HRMS (EI): calcd. for
C24H20O3S [Mϩ]: 388.1133; found 388.1126.
2-(1-Hydroxycyclohexyl)-1-[2-(methylthio)phenyl]propenone (11c):
1
Yellow oil. H NMR (400 MHz, CDCl3): δ ϭ 1.23Ϫ1.32 (m, 1 H),
1.55Ϫ1.62 (m, 2 H), 1.65Ϫ1.83 (m, 5 H), 1.84Ϫ1.95 (m, 2 H), 2.44
(s, 3 H, SCH3), 3.81 (s, 1 H, OH), 5.54 (s, 1 H, olefinic H), 6.05 (s,
3-Hydroxy-3-methyl-2-methylene-1-[2-(methylthio)phenyl]pentane-
1 H, olefinic H), 7.18 (dt, J ϭ 1.3, 7.3 Hz, 1 H, ArH), 7.34 (dd, 1,4-dione (14b): Yellow prisms (from EtOAc/hexane), m.p. 130Ϫ131
Eur. J. Org. Chem. 2003, 4852Ϫ4861
www.eurjoc.org  2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 4859

T. Kataoka et al.
FULL PAPER
1
°C. H NMR (400 MHz, CDCl3): δ ϭ 1.55 (s, 3 H, CH3), 2.33 (s, (100). C14H10O3Se (311.24): calcd. C 54.03, H 5.18; found C 53.92,
3 H, CH3), 2.44 (s, 3 H, SCH3), 4.55 (s, 1 H, OH), 5.72 (s, 1 H,
olefinic H), 6.17 (s, 1 H, olefinic H), 7.18 (dt, J ϭ 1.3, 7.8 Hz, 1
H, ArH), 7.33 (dd, J ϭ 1.3, 7.8 Hz, 1 H, ArH), 7.45 (dt, J ϭ 1.3,
7.8 Hz, 1 H, ArH), 7.57 (dd, J ϭ 1.3, 7.8 Hz, 1 H, ArH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 16.3 (q), 22.9 (q), 23.5 (q), 79.1 (s),
123.9 (d), 126.2 (d), 126.9 (t), 131.4 (d), 131.8 (d), 135.6 (s), 140.7
(s), 150.3 (s), 198.3 (s), 209.4 (s) ppm. IR (KBr): ν˜ ϭ 3467 (OH),
1717 (CϭO), 1651 cmϪ1 (CϭO). MS (FAB, Gly): m/z (%) ϭ 265
(12) [Mϩ ϩ H], 185 (100). C14H16O3S (264.34): calcd. C 63.61, H
6.10; found C 63.40, H 5.92.
H 5.21.
Ethyl 2-Hydroxy-2-methyl-3-[2-(methylseleno)benzoyl]but-3-enoate
(15c): Pale yellow cubic (diethyl ether), m.p. 53Ϫ54.5 °C (dec.). H
1
NMR (400 MHz, CDCl3): δ ϭ 1.24 (t, J ϭ 6.8 Hz, 3 H, CH2CH3),
1.69 (s, 3 H, CH3), 2.26 (s, 3 H, SeCH3), 4.10 (br. s, 1 H, OH), 4.25
(m, 2 H, CH2CH3), 5.69 (s, 1 H, olefinic H), 6.18 (s, 1 H, olefinic
H), 7.21 (dt, J ϭ 1.3, 7.8 Hz, 1 H, ArH), 7.41 (dt, J ϭ 1.3, 7.8 Hz,
1 H, ArH), 7.47 (dd, J ϭ 1.3, 7.8 Hz, 1 H, ArH), 7.63 (dd, J ϭ
1.3, 7.8 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ
6.9 (q), 14.0 (q), 24.0 (q), 62.2 (t), 74.6 (s), 124.3 (d), 126.1 (t),
129.0 (d), 132.0 (d), 132.2 (d), 136.6 (s), 136.7 (s), 149.1 (s), 174.9
(s), 197.9 (s) ppm. IR (KBr): ν˜ ϭ 3493 (OH), 1731 (CϭO), 1651
cmϪ1 (CϭO). MS (EI): m/z (%) ϭ 342 (29) [Mϩ], 269 (100).
C15H18O4Se (341.26): calcd. C 52.79, H 5.32; found C 52.77, H
5.44.
Ethyl
2-Hydroxy-2-methyl-3-[2-(methylthio)benzoyl]but-3-enoate
1
(14c): Colorless prisms (from EtOAc/hexane), m.p. 56Ϫ59 °C. H
NMR (400 MHz, CDCl3): δ ϭ 1.27 (t, J ϭ 7.0 Hz, 3 H, CH3), 1.68
(s, 3 H, CH3), 2.44 (s, 3 H, SCH3), 4.11 (s, 1 H, OH), 4.22Ϫ4.28
(m, 2 H, CH2), 5.76 (s, 1 H, olefinic H), 6.24 (s, 1 H, olefinic H),
7.17 (dt, J ϭ 1.3, 7.5 Hz, 1 H, ArH), 7.34 (dd, J ϭ 1.3, 7.5 Hz, 1
H, ArH), 7.42 (dd, J ϭ 1.3, 7.5 Hz, 1 H, ArH), 7.43 (dt, J ϭ 1.3,
7.5 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 14.0
(q), 16.4 (q), 23.8 (q), 62.0 (t), 74.2 (s), 124.0 (d), 126.5 (d), 127.9
(t), 130.3 (d), 131.4 (d), 136.4 (s), 139.8 (s), 149.5 (s), 174.8 (s),
198.0 (s) ppm. IR (KBr): ν˜ ϭ 3464 (OH), 1722 (CϭO), 1658 cmϪ1
(CϭO). MS (EI): m/z (%) ϭ 294 (2) [Mϩ], 221 (100). C15H18O4S
(297.37): calcd. C 61.20, H 6.16; found C 61.20, H 6.20.
Methyl 2-Hydroxy-3-[2-(methylseleno)benzoyl]-2-phenylbut-3-eno-
ate (15d): Yellow prisms (EtOAc/hexane), m.p. 139.5Ϫ140.5 °C. 1H
NMR (400 MHz, CDCl3): δ ϭ 2.29 (s, 3 H, SeCH3), 3.80 (s, 3 H,
CO2CH3), 4.83 (br. s, 1 H, OH), 5.60 (s, 1 H, olefinic H), 5.75 (s,
1 H, olefinic H), 7.24 (dt, J ϭ 1.2, 7.8 Hz, 1 H, ArH), 7.35Ϫ7.45
(m, 4 H, ArH), 7.49 (d, J ϭ 7.8 Hz, 1 H, ArH), 7.69 (dd, J ϭ 1.2,
7.8 Hz, 2 H, ArH), 7.73 (dd, J ϭ 1.2, 7.8 Hz, 1 H, ArH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 7.0 (q), 53.2 (q), 80.0 (s), 124.4 (d),
126.7 (d), 128.3 (d), 128.4 (d), 129.1 (d), 130.8 (t), 132.1 (d), 136.5
(s), 136.7 (s), 137.9 (s), 150.3 (s), 174.0 (s), 198.9 (s) ppm. IR (KBr):
ν˜ ϭ 3480 (OH), 1732 (CϭO), 1651 (CϭO). MS (EI): m/z (%) ϭ
390 (17) [Mϩ], 105 (100). C19H18O4Se (389.30): calcd. C 58.62, H
4.66; found C 58.46, H 4.76.
Methyl 2-Hydroxy-3-[2-(methylthio)benzoyl]-2-phenylbut-3-enoate
(14d): Light yellow crystal (from CH2Cl2/hexane), m.p. 109Ϫ111
1
°C. H NMR (400 MHz, CDCl3): δ ϭ 2.46 (s, 3 H, SCH3), 3.81 (s,
3 H, OCH3), 4.75 (s, 1 H, OH), 5.64 (s, 1 H, olefinic H), 5.78 (s, 1
H, olefinic H), 7.20 (dt, J ϭ 1.3, 7.5 Hz, 1 H, ArH), 7.35Ϫ7.44 (m,
5 H, ArH), 7.58 (dd, J ϭ 1.3, 7.5 Hz, 1 H, ArH), 7.70 (dd, J ϭ
1.3, 7.5 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ
16.4 (q), 53.2 (q), 79.5 (s), 124.0 (d), 126.5 (d), 126.7 (d), 128.2 (d),
128.3 (d), 130.6 (d), 131.6 (d), 132.0 (t), 136.2 (s), 137.8 (s), 140.0
(s), 150.8 (s), 174.0 (s), 198.7 (s) ppm. IR (KBr): ν˜ ϭ 3448 (OH),
1728 (CϭO), 1656 cmϪ1 (CϭO). MS (EI): m/z (%) ϭ 342 (3) [Mϩ],
177 (100). HRMS (EI): calcd. for C19H18O4S [Mϩ]: 342.0926;
found 342.0934.
Ethyl 2-Hydroxy-2-(4-oxoselenochroman-3-yl)propionate (16c): Yel-
low oil. H NMR (400 MHz, CDCl3): δ ϭ 1.26 (t, J ϭ 7.3 Hz, 3
1
H, CH2CH3), 1.48 (s, 3 H, CH3), 3.10 (dd, J ϭ 3.4, 12.2 Hz, 1 H,
CH2Se), 3.49 (dd, J ϭ 12.2, 13.7 Hz, 1 H, CH2Se), 3.62 (dd, J ϭ
3.4, 13.7 Hz, 1 H, CHCϭO), 4.26 (q, J ϭ 7.3 Hz, 2 H, CH2CH3),
7.20 (dt, J ϭ 1.5, 7.8 Hz, 1 H, ArH), 7.34 (dt, J ϭ 1.5, 7.8 Hz, 1
H, ArH), 7.39 (dd, J ϭ 1.5, 7.8 Hz, 1 H, ArH), 8.06 (dd, J ϭ 1.5,
7.8 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 14.1
(q), 17.9 (t), 24.2 (q), 55.7 (d), 61.9 (t), 73.9 (s), 125.7 (d), 129.8
(d), 130.5 (d), 133.3 (d), 133.5 (s), 136.1 (s), 176.5 (s), 195.6 (s)
ppm. IR (NaCl): ν˜ ϭ 3490 (OH), 1734 (CϭO), 1672 cmϪ1 (CϭO).
MS (EI): m/z (%) ϭ 328 (15) [Mϩ], 49 (100). HRMS (EI) calcd.
for C14H16O4Se [Mϩ]: 328.0214; found 328.0207.
2-Hydroxy-3-methylene-4-[2-(methylseleno)phenyl]-1,2-diphenyl-
butane-1,4-dione (15a): Yellow oil. 1H NMR (400 MHz, CDCl3):
δ ϭ 2.28 (s, 3 H, SeCH3), 5.35 (s, 1 H, OH), 5.67 (s, 1 H, olefinic
H), 6.03 (s, 1 H, olefinic H), 7.26Ϫ7.48 (m, 9 H, ArH), 7.67 (dd,
J ϭ 1.3, 7.6 Hz, 2 H, ArH), 7.95 (dd, J ϭ 1.3, 7.6 Hz, 2 H, ArH),
8.08 (dd, J ϭ 1.3, 7.6 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3): δ ϭ 6.8 (q), 86.9 (s), 124.3 (d), 126.5 (d), 127.8 (d), 128.3
(d), 128.5 (d), 128.6 (d), 130.0 (t), 130.9 (d), 132.4 (d), 132.7 (d),
133.7 (d), 134.6 (s), 136.0 (s), 137.6 (s), 137.8 (s), 151.5 (s), 201.0
(s), 201.6 (s) ppm. IR (NaCl): ν˜ ϭ 3439 (OH), 1672 (CϭO), 1631
cmϪ1 (CϭO). MS (FAB, NBA): m/z (%) ϭ 437 (10) [Mϩ ϩ H],
154 (100). HRMS (FAB, NBA): calcd. for C24H21O3Se [Mϩ ϩ H]:
437.0578; found 437.0646.
Methyl
1-Hydroxy-1-(4-oxoselenochroman-3-yl)-1-phenylacetate
(16d): Pale yellow prisms (diethyl ether), m.p. 114Ϫ114.5 °C. 1H
NMR (400 MHz, CDCl3): δ ϭ 2.47 (dd, J ϭ 3.4, 12.7 Hz, 1 H, -
CH2Se), 3.38 (dd, J ϭ 12.7, 13.7 Hz, 1 H, -CH2Se), 3.78 (s, 3 H,
OCH3), 4.03 (br. s, 1 H, OH), 4.15 (dd, J ϭ 3.4, 13.7 Hz, 1 H,
CHCϭO), 7.21 (dt, J ϭ 1.5, 7.3 Hz, 1 H, ArH), 7.31Ϫ7.42 (m, 5
H, ArH), 7.70 (dd, J ϭ 1.5, 7.3 Hz, 2 H, ArH), 8.13 (dd, J ϭ 1.5,
7.3 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 18.1
(t), 53.2 (q), 57.0 (d), 78.4 (s), 125.6 (d), 125.7 (d), 128.2 (d), 128.7
(d), 129.9 (d), 130.1 (s), 130.6 (d), 133.4 (d), 136.5 (s), 138.5 (s),
174.6 (s), 195.8 (s) ppm. IR (KBr): ν˜ ϭ 3498 (OH), 1734 (CϭO),
1672 cmϪ1 (CϭO). MS (EI): m/z (%) ϭ 376 (10) [Mϩ], 105 (100).
C18H16O4Se (375.28): calcd. C 57.61, H 4.30; found C 57.56, H
4.40.
3-Hydroxy-3-methyl-2-methylene-1-[2-(methylseleno)phenyl]-
pentane-1,4-dione (15b): Yellow powder, m.p. 117.5Ϫ118 °C. 1H
NMR (400 MHz, CDCl3): δ ϭ 1.56 (s, 3 H, Me), 2.26 (s, 3 H,
SeMe), 2.34 (s, 3 H, COMe), 4.56 (s, 1 H, OH), 5.67 (s, 1 H, olefinic
H), 6.11 (s, 1 H, olefinic H), 7.22 (dt, J ϭ 1.0, 7.5 Hz, 1 H, ArH),
7.43 (dt, J ϭ 1.0, 7.5 Hz, 1 H, ArH), 7.46 (dd, J ϭ 1.0, 7.5 Hz, 1
H, ArH), 7.74 (dd, J ϭ 1.0, 7.5 Hz, 1 H, ArH) ppm. 13C NMR Synthesis of 17: A solution of p-nitrobenzaldehyde (5a; 6.25 g,
(100 MHz, CDCl3): δ ϭ 6.8 (q), 22.9 (q), 23.3 (q), 79.3 (s), 124.3 41.4 mmol) and 4-(trimethylsilyloxy)thiochrom-3-ene[15] (7.74 g,
(d), 125.0 (t), 128.6 (d), 132.4 (d), 132.9 (d), 135.9 (s), 137.6 (s),
45.5 mmol) in dry THF (50 mL) was added to a suspension of
149.9 (s), 198.1 (s), 209.1 (s) ppm. IR (NaCl): ν˜ ϭ 3440 (OH), 1714 TBAF (540 mg, 2.1 mmol) in THF (5 mL) at Ϫ78 °C. After stirring
(CϭO), 1645 cmϪ1 (CϭO). MS (EI): m/z (%) ϭ 312 (2) [Mϩ], 269 at that temperature for 3 h and at Ϫ40 °C for 1 h, the reaction
4860
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4852Ϫ4861

Chalcogeno MoritaϪBaylisϪHillman Reaction of 2-(Methylchalcogeno)phenyl Vinyl Ketones
FULL PAPER
mixture was quenched by adding AcOH/H2O (40 mL) and stirred
at room temperature overnight. The reaction mixture was neu-
Acknowledgments
This work was supported in part by a Grant-in-Aid (No. 3824) for
JSPS Fellows from the Japan Society for the Promotion of Science.
tralized with saturated aqueous NaHCO3 and extracted with
CH2Cl2 (100 mL, three times). The combined extracts were dried
with MgSO4 and concentrated under reduced pressure. The residue
was purified by column chromatography (hexane/EtOAc, 3:1) to
yield 17 as a yellow powder (syn/anti ϭ 4:1, 7.84 g, 60%). The mix-
ture of diastereomers 17 was separated into syn and anti isomers
by recycling preparative HPLC with CHCl3.
[1] [1a]
S. E. Drewes, G. H. P. Roos, Tetrahedron 1988, 44,
[1b]
4653Ϫ4670.
D. Basavaiah, P. D. Rao, R. S. Hyma, Tetra-
hedron 1996, 52, 8001Ϫ8062. [1c] E. Ciganek, Org. React. 1997,
[1d]
51, 201Ϫ350.
P. Langer, Angew. Chem. 2000, 112,
[1e]
3177Ϫ3180; Angew. Chem. Int. Ed. 2000, 39, 3049Ϫ3052.
D. Basavaiah, A. J. Rao, T. Satyanarayana, Chem. Rev. 2003,
103, 811Ϫ891.
(1ЈR*,3R*)-3-[1-Hydroxy-1-(4-nitrophenyl)methyl]thiochroman-4-
one (syn-17): Yellow needles (from CH2Cl2/hexane), m.p.
130Ϫ131.5 °C. 1H NMR (400 MHz, CDCl3): δ ϭ 2.67 (dd, J ϭ
3.2, 13.4 Hz, 1 H, SCH2), 2.97 (br. s, 1 H, OH), 3.19 (dt, J ϭ 3.2,
13.4 Hz, 1 H, COCH), 3.48 (t, J ϭ 13.4 Hz, 1 H, SCH2), 5.84 (d,
J ϭ 3.2 Hz, 1 H, benzylic H), 7.19Ϫ7.30 (m, 2 H, ArH), 7.42 (dt,
J ϭ 1.2, 7.8 Hz, 1 H, ArH), 7.58 (d, J ϭ 8.3 Hz, 2 H, ArH), 8.12
(dd, J ϭ 1.2, 7.8 Hz, 1 H, ArH), 8.27 (d, J ϭ 8.3 Hz, 2 H, ArH)
ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 25.3 (t), 54.4 (d), 69.9 (d),
123.7 (d), 125.0 (d), 126.7 (d), 127.4 (d), 129.5 (d), 130.7 (s), 133.7
(d), 142.0 (s), 147.3 (s), 148.5 (s), 195.2 (s) ppm. IR (KBr): ν˜ ϭ
3414 (OH), 1671 (CϭO), 1518 (NO2), 1345 cmϪ1 (NO2). MS (EI):
m/z (%) ϭ 315 (2) [Mϩ], 136 (100). C16H12NO4S (315.34): calcd. C
60.94, H 4.16, N 4.44; found C 60.72, H 4.25, N 4.32.
[2]
[2a] T. Kataoka, T. Iwama, S. Tsujiyama, Chem. Commun. 1998,
197Ϫ198. [2b] T. Kataoka, T. Iwama, S. Tsujiyama, T. Iwamura,
[2c]
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Iwama, H. Kinoshita, T. Kataoka, Tetrahedron Lett. 1999, 40,
[2d]
3741Ϫ3744.
T. Kataoka, H. Kinoshita, T. Iwama, S. Tsuji-
yama, T. Iwamura, S. Watanabe, O. Muraoka, G. Tanabe,
Tetrahedron 2000, 56, 4725Ϫ4731.
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[3b]
rukami, T. Iwamura, S. Watanabe, Synlett 1999, 197Ϫ198.
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2000, 112, 2448Ϫ2450; Angew. Chem. Int. Ed. 2000, 39,
2358Ϫ2360. [3d] S. Kinoshita, H. Kinoshita, T. Iwamura, S. Wa-
tanabe, T. Kataoka, Chem. Eur. J. 2003, 9, 1496Ϫ1502.
(1ЈR*,3S*)-3-[1-Hydroxy-1-(4-nitrophenyl)methyl]thiochroman-4-
one (anti-17): Yellow solid, m.p. 133Ϫ133.5 °C. 1H NMR
(400 MHz, CDCl3): δ ϭ 2.72 (dd, J ϭ 3.4, 13.4 Hz, 1 H, SCH2),
2.97 (dd, J ϭ 12.2, 13.4 Hz, 1 H, SCH2), 3.14 (ddd, J ϭ 3.4, 8.3,
12.2 Hz, 1 H, COCH), 4.17 (br. s, 1 H, OH), 5.25 (d, J ϭ 8.3 Hz,
1 H, benzylic H), 7.19Ϫ7.26 (m, 2 H, ArH), 7.43 (dt, J ϭ 1.2,
7.6 Hz, 1 H, ArH), 7.65 (d, J ϭ 8.8 Hz, 1 H, ArH), 8.13 (dd, J ϭ
1.2, 7.6 Hz, 1 H, ArH), 8.26 (d, J ϭ 7.6 Hz, 2 H, ArH) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 27.7 (t), 53.4 (d), 72.8 (d), 123.5
(d), 124.9 (d), 127.1 (d), 127.7 (d), 129.5 (d), 130.0 (s), 133.7 (d),
141.5 (s), 147.2 (s), 147.6 (s), 196.3 (s) ppm. IR (KBr): ν˜ ϭ 3391
(OH), 1674 (CϭO), 1518 (NO2), 1346 cmϪ1 (NO2). MS (EI): m/z
(%) ϭ 315 (1) [Mϩ], 136 (100). C16H12NO4S (315.34): calcd. C
60.94, H 4.16, N 4.44; found C 60.81, H 4.22, N 4.37.
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[8] [8a]
Preparation and Reactivity of Sulfonium Salt 8a: AgBF4 (15 mg,
0.08 mmol) was slowly added to a stirred mixture of 17 (22 mg,
0.07 mmol) and MeI (102 mg, 0.69 mmol) in dry CH2Cl2 (2 mL) at
0 °C. The reaction mixture was allowed to warm to room tempera-
ture, stirred for 3 h, and then concentrated under reduced pressure.
The residue was dissolved in CH3CN (0.5 mL), and then saturated
aqueous NaHCO3 (0.5 mL) was added. The mixture was stirred
at room temperature for 5 min and concentrated to dryness under
reduced pressure. The residue was dissolved in CD3CN and submit-
J. S. Hill, N. S. Isaacs, Tetrahedron Lett. 1986, 27,
5007Ϫ5010. [8b] J. S. Hill, N. S. Isaacs, J. Chem. Res. (S) 1988,
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1
ted to H NMR spectroscopy.
Demethylation of anti-Sulfonium Salt 8: KI (25 mg, 0.15 mmol) was
added to a solution of anti-sulfonium salt 8 (21 mg, 0.05 mmol) in
CH3CN (1 mL). The reaction mixture was stirred at room tempera-
ture for 1 h, concentrated under reduced pressure, and submitted
[13]
[14]
[15]
1
to H NMR spectroscopy in CDCl3.
Received September 1, 2003
Eur. J. Org. Chem. 2003, 4852Ϫ4861
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4861