Radical β-addition to acyclic α-(arylsulfinyl) enones: Pummerer-type rearrangement

Article abstract of DOI:10.1039/a800828k

The reaction of (S,E)-3-(p-tolylsulfinyl)pent-3-en-2-one with an isopropyl radical, generated from isopropyl iodide and triethylborane, gives the non-stereoselective addition product and an unexpected α-(arylsulfanyl) enone which is formed through a radical addition and subsequent Pummerer-type rearrangement. The formation of the α-(arylsulfanyl) enone depends upon the additives used as well as the aryl group on the sulfur.

Full text of DOI:10.1039/a800828k

View Article Online / Journal Homepage / Table of Contents for this issue
Radical â-addition to acyclic á-(arylsulfinyl) enones: Pummerer-type
rearrangement
Nobuyuki Mase, Yoshihiko Watanabe, Yoshio Ueno and Takeshi Toru*
Department of Applied Chemistry, Nagoya Institute of Technology, Gokiso, Showa-ku,
Nagoya 466-8555, Japan
The reaction of (S,E)-3-(p-tolylsulfinyl)pent-3-en-2-one with an isopropyl radical, generated from
isopropyl iodide and triethylborane, gives the non-stereoselective addition product and an unexpected
á-(arylsulfanyl) enone which is formed through a radical addition and subsequent Pummerer-type
rearrangement. The formation of the á-(arylsulfanyl) enone depends upon the additives used as well
as the aryl group on the sulfur.
O
S
Introduction
O
i
Recently, radical reactions have been recognized as a means for
Ar
S
stereoselective carbon᎐carbon bond formation.1 There are a
RO
Ar
number of reports of asymmetric radical reactions using chiral
auxiliaries.2 While the sulfinyl group has been recognized as an
attractive chiral auxiliary in radical 1,2-asymmetric induction,3
there are only a few reports on radical β-addition to chiral vinyl
sulfoxides.4 We have reported a stereoselective intermolecular
radical β-addition reaction of 2-(arylsulfinyl)cycloalk-2-
enones,5 in which a chiral sulfinyl group having a sterically
bulky aryl group such as a 2,4,6-triisopropylphenyl or 2,4,6-
trimethylphenyl group shows extremely high diastereoselectiv-
ity in the radical β-addition. We report herein the results of an
intermolecular β-addition of alkyl radicals to acyclic α-(aryl-
sulfinyl) enones.
1–4
5a (95%)
5b (91%)
5c (90%)
5d (81%)
ii
O
O
O
OH
S
S
iii
Ar
Ar
7a (85%)
7b (58%)
7c (86%)
7d (72%)
6a (87%)
6b (69%)
6c (53%)
6d (91%)
a: Ar = (S)-p-tolyl
b: Ar = 4-methoxyphenyl
c: Ar = 4-chlorophenyl
Results and discussion
We studied the radical β-addition to acyclic α-(arylsulfinyl)
enones 7a–d which were prepared from the sulfinates 1–4 in
d: Ar = (S)-2,4,6-triisopropylphenyl
Scheme
1
Reagents and conditions: i, CH3CH᎐CHMgBr, THF,
᎐
0 ЊC → rt; ii, LDA, CH3CHO, THF, Ϫ100 ЊC; iii, Jones oxidation or
Swern oxidation, and subsequent purification by recrystallization (7a
and 7d) or flash column chromatography (7c)
O
S
O
S
Pri
O
menthyl
O
which was composed mainly of the (E)-isomer due to cis–trans
isomerization during the reaction.7 Oxidation of 6 was accom-
plished by Jones oxidation8 or Swern oxidation7a to give the
3-(arylsulfinyl)pent-3-en-2-one 7. (E)-7a and (E)-7d could be
isolated by recrystallization from diethyl ether and (E)-7c by
flash column chromatography. A mixture of (E)- and (Z)-7b in
an E:Z ratio of 72:28 was used without separation of the
isomers in the following radical reaction.
The β-addition of an isopropyl radical to α-(arlysulfinyl)
enones 7a–7d was carried out as follows. To a degassed solution
of the α-(arylsulfinyl) enone 7 in CH2Cl2 (0.01 mol dmϪ3) was
added isopropyl iodide (10 equiv.) and triethylborane (10 equiv.)
as a radical initiator9 at 0 ЊC, and air was continuously passed
through the solution via a needle by a microfeeder.10 The results
are shown in Table 1.
The reaction of (S,E)-3-(p-tolylsulfinyl)pent-3-en-2-one 7a
with an isopropyl radical gave a diastereomeric mixture of the
addition products 8a with low diastereoselectivity (entry 1). The
addition product with an ethyl radical generated from triethyl-
borane was not formed.11 Reactions in the presence of
TiCl2(OPi)2,12 Ti(OPri)4, ZnBr2, BF3ؒOEt2 or K2CO3 did not
alter the stereoselectivity substantially (entries 2–6). We
expected a low stereoselectivity, as the p-tolyl group is not as
effective as the 2,4,6-triisopropylphenyl or 2,4,6-trimethyl-
phenyl group in inducing high stereoselectivity as we observed
OMe
(S)-1
2
O
S
O
S
Pri
Pri
O
DAG
O
Cl
Pri
(S)-4
Pri
3
O
O
O
DAG =
O
O
O
three steps. The reaction of sulfinates 1–4 with prop-1-enyl-
magnesium bromide, which was prepared from magnesium and
a mixture of (E)- and (Z)-1-bromoprop-1-ene, gave a mixture
of (E)- and (Z)-aryl prop-1-enyl sulfoxides 5 in good yields
(Scheme 1).6 A mixture of (E)- and (Z)-5 was treated with 2
equiv. of LDA at Ϫ100 ЊC and subsequently with an excess of
acetaldehyde to afford the 3-(arylsulfinyl)pent-3-en-2-ol 6
J. Chem. Soc., Perkin Trans. 1, 1998
1613

View Article Online
Table 1 Radical β-addition to α-(arylsulfinyl) enones 7 with isopropyl iodide and triethylborane
O
Et3B, PriI
additive
air
O
O
O
O
S
S
S
Ar
Ar
+
Ar
CH2Cl2, 0 °C
Pri
Pri
7
9
8
a: Ar = (S)-p-tolyl
b: Ar = 4-methoxyphenyl
c: Ar = 4-chlorophenyl
d: Ar = (S)-2,4,6-triisopropylphenyl
8
9
Entry
Enone
Additive
t/h
Yield (%)
Ratio
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
7a
7a
7a
7a
7a
7a
7a
7ba
7c
7d
7d
7d
7d
7d
none
1
1
1
1
1
1
1
2
1
75
60
80
79
79
80
0
77
91
0
21:13:41:19
13:20:35:32
26:14:48:12
39:11:40:10
45:10:35:10
30:15:42:13
—
17:11:56:16
21:13:49:17
—
12
23
10
16
17
6
57
21
6
58
23
33
99
TiCl2(OPri)2
Ti(OPi)4
ZnBr2
BF3ؒOEt2
K2CO3
p-TsOH
none
none
none
1.5
45
1.5
0.7
3 days
TiCl2(OPi)2
SiMe3Cl
p-TsOH
galvinoxyl
0
0
0
—
—
—
no reaction
a An E:Z = 72:28 mixture was used.
α-(arylsulfanyl) enone 9d seemed to proceed via a radical path-
way at least in the first step of the alkyl radical addition,
because both reactions were completely suppressed by a radical
scavenger (entry 14). The presumed reaction mechanism is
shown in Scheme 2.
O
O
S
S
O
O
It is well recognized that enones react with alkyl radicals
generated from trialkylborane to form a boron enolate via a
carbon radical α to the carbonyl group.9,13 Thus, an isopropyl
radical generated from isopropyl iodide by the action of tri-
ethylborane with oxygen, attacks the olefinic carbon β to the
carbonyl to form a carbon radical α to the carbonyl (A), which
then reacts with triethylborane to form the cyclic interme-
diate B or the rapidly equilibrated boron enolates C and D.
Hydrolysis of the intermediate gives the addition product 8.
However, the Pummerer-type products 9 are formed in the
present reaction of α-(arylsulfinyl) enones probably because of
the easy formation of the thionium intermediate E from the
intermediate B. On the other hand, the radical reaction of the
2-(arylsulfinyl)cycloalk-2-enones produced no such Pummerer-
type products and induced no racemization of the substrate (see
below), due to the difficult formation of the corresponding
intermediate BЈ and the subsequent intermediate EЈ, shown in
Scheme 2.5 The S᎐O bond fission in B forms E and the sub-
sequent proton abstraction from the β-carbon gives the α-(aryl-
sulfanyl) enone 9 as a mixture of (E)- and (Z)-isomers. Since
the S᎐O bond fission is the rate-determining step in the Pum-
merer reaction of sulfoxides having an electron-withdrawing
group at the α-position,14 the electronic nature of the substitu-
ent on the sulfur should have an influence on this step. In the
reaction of the α-(arylsulfinyl) enone 7b having an electron-
donating 4-methoxyphenyl group, the formation of α-(aryl-
sulfanyl) enone 9b increases due to its thionium-stabilizing
effect (Table 1, entry 8), whereas the reaction of the α-
(arylsulfanyl) enone 7c having an electron-withdrawing 4-
chlorophenyl group decreases the stability of intermediate E
and hence the yield of α-(arylsulfanyl) enone 9c (Table 1, entry
9). p-TsOH would accelerate the S᎐O bond fission to form the
thionium ion intermediate E, thus leading to the α-(aryl-
sulfanyl) enone 9 exclusively (Table 1, entries 7 and 13). This
assumption is quite reasonable, since acids are known to
H
Hβ
H
Hβ
11% NOE
9% NOE
7d
High diastereoselectivity
Fig. 1
in the reaction of 2-(arylsulfinyl)cyclopent-2-enones.5 It was,
however, surprising that an unexpected product, 4,5-dimethyl-
3-(p-tolylsulfanyl)hex-3-en-2-one 9a, was formed besides the
addition products 8a. The yield of the α-(arylsulfanyl) enone 9a
increased when the reaction was carried out in the presence of
p-TsOH, where the addition product was not obtained at all
(entry 7). The yield of the α-(arylsulfanyl) enone 9 increased in
the reaction of (E)-3-(4-methoxyphenylsulfinyl)pent-3-en-2-
one 7b (entry 8) and decreased in the case of 3-(4-chloro-
phenylsulfinyl)pent-3-en-2-one 7c (entry 9). Next, we examined
the radical β-addition to (S,E)-3-(2,4,6-triisopropylphenyl-
sulfinyl)pent-3-en-2-one 7d which has a significant nuclear
Overhauser effect (11%) between the methine proton of the
o-isopropyl group and the β-vinyl proton in the 1H NMR spec-
trum. Since 2-(2,4,6-triisopropylphenylsulfinyl)cyclopent-2-
enone, which also has a significant nuclear Overhauser effect
between these protons, shows extremely high stereoselection in
the radical β-addition,5 high stereoselectivity was anticipated in
the radical β-addition to α-(arylsulfinyl) enone 7d (see Fig. 1).
However, formation of the α-(arylsulfanyl) enone 9d was
observed in the reaction of α-(arylsulfinyl) enone 7d, with no
addition product 8d being formed (entries 10–12). The α-(aryl-
sulfanyl) enone 9d was even obtained almost quantitatively
when p-TsOH was added to the reaction mixture (entry 13).
Both reactions to form the addition product 8d and the
1614
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
Et3B, PriI, O2
Pri•
racemic
O
S
O
S
O
O
O
O
1) LDA
O
2) AcOEt
*
*
S
S
Ar
Ar
Tol
Tol
THF, –78 °C → rt
1 h, 74%
Pri
Pri
Pri
7
A
11
10
four stereoisomers
25 : 29 : 26 : 20
Et3B
–Et•
chiral
O
Et
O
Et
O
S
O
S
O
O
B
Et2BO
O
OBEt2
Et3B, PriI
air
O
S
S
S
Tol
Ar
Ar
Ar
CH2Cl2, 0 °C
44%
Tol
Pri
Pri
Pri
Pri
B
C
11
D
12
four stereoisomers
4 : 54 : 11 : 31
O
S
O
H2O
Scheme 3
Ar
Ar
Pri
acid or p-anisaldehyde in ethanol. Column chromatography
was carried out on a column packed with Fuji Silysia silica gel
BW-200. Melting points were measured on a Yanaco micro-
8
O
O
1
melting point apparatus and are uncorrected. H NMR (200
S
MHz) and 13C NMR (50.3 MHz) spectra for solutions in CDCl3
were recorded on a Varian Gemini-200 instrument, chemical
shifts (δ) are expressed in ppm downfield from internal tetra-
methylsilane, and J values are given in Hz. Infrared spectra were
recorded on a JASCO FTIR-200 spectrometer. Mass spectra
(eV) were recorded on a Hitachi M-2000 spectrometer. Micro-
analyses were performed with a Perkin-Elmer-240 instrument.
Optical rotations were measured on a JASCO DIP-4 polar-
imeter operating at λ = 589 nm corresponding to the sodium D
line, in the indicated solvent with concentration in grams of
solute per 100 cm3. HPLC analyses were performed on a
JASCO TRI ROTOR IV using 4.6 × 150 mm COSMOSIL and
4.6 × 250 mm CHIRALCEL OB-H packed columns (flow rate,
0.5 cm3 minϪ1).
S
Ar
Pri
H
–OBEt2
Pri
9
E
Et
Et
B
O
O
O
S
S
Ar
Ar
R
R
E'
B'
Scheme 2
Preparation of the acyclic á-sulfinyl enones
catalyze Pummerer-type reactions from sulfoxides to α-(aryl-
sulfanyl) enones.15 If this mechanistic pathway is correct then
the sulfoxide should racemize during the formation of the cyclic
boron enolate B. To verify this the following experiment was
carried out.
4-Methoxyphenyl prop-1-enyl sulfoxide 5b. To a solution of
isopropyl 4-methoxybenzenesulfinate17 2 (2.28 g, 10.7 mmol)
in THF (11 cm3) was added dropwise a solution of prop-1-
enylmagnesium bromide, prepared from 1-bromoprop-1-ene
(1.46 cm3, 17.1 mmol) and magnesium (389 mg, 16 mmol) in
THF (26 cm3), at 0 ЊC over a period of 5 min. After stirring for
10 min at room temperature, the mixture was quenched with
saturated aqueous NH4Cl (10 cm3) at 0 ЊC and concentrated
under reduced pressure. The aqueous mixture was extracted
with Et2O (3 × 5 cm3). The combined organic extracts were
washed with saturated aqueous NaHCO3 (5 cm3), brine (5 cm3),
dried over Na2SO4, and concentrated to give the crude sulfox-
ide, which was purified by column chromatography (hexane–
ethyl acetate, 40:60) to give the sulfoxide 5b (1.91 g, 91%) in an
E:Z ratio of 73:27. (E)-5b (Found: C, 61.18; H, 6.31.
C10H12O2S requires C, 61.20; H, 6.16%); TLC Rf 0.37 (hexane–
ethyl acetate, 40:60); νmax(neat)/cmϪ1 2950, 1595, 1500, 1440,
(S)-3-(p-Tolylsulfinyl)but-3-en-2-one 12, prepared according
to the literature,8,16 was treated with isopropyl iodide and tri-
ethylborane as described above to give the addition product 11
in 44% yield and the ethyl adduct (38% yield) (Scheme 3).
HPLC analysis (CHIRALCEL OB-H) of the addition product
11 showed four stereoisomers in a ratio of 4:54:11:31 in order
of elution. The retention times for these four stereoisomers
were in accord with those for the products obtained on treat-
ment of the racemic isopentyl p-tolyl sulfoxide 10 with lithium
diisopropylamide and subsequently with ethyl acetate. These
results show that the radical addition gives the racemized sulf-
oxide 11, supporting the formation of the cyclic boron enolate
intermediate B.
1305, 1260 and 1030; δH 1.91 (3 H, dd, J 1.6, 6.8, CH CH᎐),
᎐
3
3.85 (3 H, s, OCH ), 6.23 (1 H, dq, J 1.6, 15.1, CH CH᎐CH),
᎐
3
3
6.58 (1 H, dq, J 6.8, 15.1, CH CH᎐CH), 6.94–7.08 (2 H, m,
᎐
3
Experimental
ArH) and 7.50–7.62 (2 H, m, ArH); δC 17.4, 55.3, 114.6, 126.3,
135.0, 135.3, 136.1 and 161.6; m/z (EI) 196 (Mϩ, 10%), 155 (50)
and 148 (100). (Z)-5b: TLC Rf = 0.27 (hexane–ethyl acetate,
40:60); νmax(neat)/cmϪ1 2945, 1590, 1500, 1460, 1305, 1250 and
General
Diethyl ether (ether) and THF were distilled before use from a
deep blue solution resulting from addition of benzophenone
and sodium. CH2Cl2 was distilled from calcium hydride. All
reactions were monitored by thin layer chromatography on 0.25
mm Merck silica gel (60F-254) precoated glass plates. TLC
plates were visualized with UV light and 7% phosphomolybdic
1035; δH 2.13 (3 H, d, J 5.5, CH CH᎐), 3.85 (3 H, s, OCH ),
᎐
3
3
6.12–6.33 (2 H, m, CH᎐CH), 6.94–7.08 (2 H, m, ArH) and
᎐
7.50–7.62 (2 H, m, ArH); δC 15.0, 55.4, 114.8, 125.8, 135.5,
136.2, 138.0 and 161.7.
J. Chem. Soc., Perkin Trans. 1, 1998
1615

View Article Online
4-Chlorophenyl prop-1-enyl sulfoxide 5c. The reaction was
carried out as described above using isopropyl 4-chlorobenzene-
sulfinate17 3 (2.46 g, 11.3 mmol) to give the sulfoxide 5c (2.04 g,
90%) in an E:Z ratio of 71:29. (E)-5c (Found: C, 53.66; H,
4.59. C9H9ClOS requires C, 53.87; H, 4.52%); TLC Rf = 0.54
(hexane–ethyl acetate, 40:60); νmax(neat)/cmϪ1 3015, 2910, 1630,
1580, 1480, 1445, 1390, 1090 and 1040; δH 1.92 (3 H, dd, J 1.5,
CH᎐C), 6.90–7.12 (2 H, m, ArH) and 7.39–7.67 (2 H, m, ArH);
᎐
m/z (EI) 240 (Mϩ, 17%), 192 (9) and 156 (100).
3-(4-Chlorophenylsulfinyl)pent-3-en-2-ol 6c. The reaction was
carried out as described above using the sulfoxide 5c (1.20 g,
5.98 mmol) to give the alcohol 6c (769 mg, 53%) as a mixture of
four diastereomers; TLC Rf = 0.31 (hexane–ethyl acetate,
50:50); νmax(neat)/cmϪ1 3370, 2980, 1580, 1480, 1395, 1090 and
1030; δH 1.02–1.40 [3 H, m, CH(OH)CH3], 1.90–2.24 (3 H,
6.7, CH ), 6.24 (1 H, dq, J 1.5, 15.2, CH CH᎐CH), 6.64 (1 H,
᎐
3
3
dq, J 6.7, 15.2, CH CH᎐CH) and 7.40–7.62 (4 H, m, ArH);
m, CH CH᎐C), 2.42–2.85 (1 H, m, OH), 4.40–4.92 [1 H, m,
᎐
3
᎐
3
δC 17.7, 125.7, 129.4, 136.0, 136.9, 137.2 and 142.7; m/z (EI) 200
(Mϩ, 21%), 152 (100) and 117 (54). (Z)-5c: TLC Rf = 0.44
(hexane–ethyl acetate, 40:60); νmax(neat)/cmϪ1 3015, 2950, 1630,
1480, 1390, 1090 and 1040; δH 2.16 (3 H, dd, J 1.2, 6.7, CH3),
CH(OH)], 6.30–6.63 (1 H, m, CH᎐C) and 7.39–7.67 (4 H, m,
᎐
ArH); m/z (EI) 244 (Mϩ, 13%), 226 (16) and 160 (100).
(SS)-3-(2,4,6-Triisopropylphenylsulfinyl)pent-3-en-2-ol
6d.
The reaction was carried out as described above using the
sulfoxide 5d (1.06 g, 3.62 mmol) to give the alcohol 6d (1.11 g,
91%) as a diastereomeric mixture of (E)-isomers in a ratio of
57:43 (Found: C, 71.49; H, 9.71. C20H32O2S requires C, 71.38;
H, 9.58%); TLC Rf = 0.26 (hexane–ethyl acetate, 70:30);
νmax(neat)/cmϪ1 3315, 2970, 1600, 1460, 1370, 1110 and 1020;
δH 1.05–1.34 [18 H, m, 3 × CH(CH3)2], 1.36 and 1.59 [3 H,
2 × d, J 6.5 and 6.7, CH(OH)CH3], 1.81 and 1.87 (3 H, 2 × d,
J 7.2 and 7.3, CH CH᎐C), 2.59 and 3.83 (1 H, 2 × d, J 7.1 and
6.15–6.42 (2 H, m, CH᎐CH) and 7.40–7.62 (4 H, m, ArH);
᎐
δC 15.0, 125.2, 129.2, 136.5, 137.1, 137.5 and 142.9.
(R)-Prop-1-enyl 2,4,6-triisopropylphenyl sulfoxide 5d. The
reaction was carried out as described above using (S)-diacetone
-glucosyl 2,4,6-triisopropylbenzenesulfinate5 (S)-4 (4.94 g,
9.67 mmol) to give the sulfoxide 5d (2.29 g, 81%). (E)-5d
(Found: C, 73.68; H, 9.51. C18H28OS requires C, 73.92; H,
9.65%); TLC Rf = 0.26 (hexane–ethyl acetate, 80:20); [α]D24 Ϫ63.1
(c 0.482 in CHCl3); νmax(neat)/cmϪ1 2960, 1600, 1470, 1050 and
1030; δH 1.23, 1.25 and 1.32 [18 H, 3 × d, J 6.7, 6.8, 6.8,
᎐
3
7.8, OH), 2.76–3.03 [1 H, m, CH(CH3)2], 3.58–4.02 [2 H, m,
2 × CH(CH3)2], 4.61–5.06 [1 H, m, CH(OH)], 5.51 and 5.77
3 × CH(CH ) ], 2.10 (3 H, dd, J 1.6, 7.1, CH CH᎐CH), 2.75–
(1 H, 2 × q, J 7.2 and 7.3, CH᎐C) and 7.07 and 7.10 (2 H, 2 × s,
᎐
᎐
3
2
3
3.01 [1 H, m, CH(CH3)2], 3.85–4.08 [2 H, m, 2 × CH(CH3)2],
6.27 (1 H, dq, J 7.1, 9.9, CH CH᎐CH), 6.75 (1 H, dq, J 1.6, 9.9,
ArH); m/z (EI) 336 (Mϩ, 3%), 318 (46), 301 (61), 275 (36) and
255 (100).
᎐
3
CH CH᎐CH) and 7.08 (2 H, s, ArH); δ 14.7, 24.0, 24.8, 28.8,
(S,E)-3-(p-Tolylsulfinyl)pent-3-en-2-one 7a.—Method A via
the Swern oxidation.7a To a solution of oxalyl chloride
(55.5 × 10Ϫ3 cm3, 0.636 mmol) in CH2Cl2 (1 cm3) was added
dimethyl sulfoxide (60.2 × 10Ϫ3 cm3, 0.848 mmol) at Ϫ78 ЊC.
After the mixture was stirred for 5 min, a solution of the alco-
hol 6a (95.1 mg, 0.424 mmol) in CH2Cl2 (0.8 cm3) was added.
The reaction mixture was stirred for an additional 1 h at
Ϫ78 ЊC. Then triethylamine (0.12 cm3, 0.848 mmol) was added
to the reaction mixture, which was stirred for 5 min. The reac-
tion mixture was poured into ice-cooled 1 mol dmϪ3 aqueous
HCl (10 cm3). The aqueous layer was extracted with CH2Cl2
(3 × 5 cm3). The combined organic extracts were washed with
ice–water (10 cm3), dried over Na2SO4, and concentrated to give
the crude enone, which was purified by column chrom-
atography (hexane–ethyl acetate, 60:40) to give the enone 7a
(64.1 mg, 68%) as a mixture of two diastereomers.
᎐
3
C
34.3, 123.1, 135.3, 135.9, 136.9, 149.8 and 152.4; m/z (EI) 292
(Mϩ, 19%), 275 (100), 233 (39), 191 (74) and 149 (66). (Z)-5d
(Found: C, 73.62; H, 9.64. C18H28OS requires C, 73.92; H,
9.65%); TLC Rf = 0.37 (hexane–ethyl acetate, 80:20); [α]D23 ϩ203
(c 0.350 in CHCl3); νmax(neat)/cmϪ1 2960, 1600, 1470 and 1055;
δH 1.18–1.39 [18 H, m, 3 × CH(CH3)2], 1.92 (3 H, d, J 5.0,
CH CH᎐CH), 2.75–3.01 [1 H, m, CH(CH ) ], 3.79–4.05 [2 H,
᎐
3
3 2
m, 2 × CH(CH ) ], 6.36–6.51 (2 H, m, CH᎐CH) and 7.06 (2 H,
᎐
3
2
s, ArH); δC 17.8, 23.7, 24.8, 28.2, 34.3, 123.0, 133.5, 134.0,
134.7, 150.3 and 152.6; m/z (EI) 292 (Mϩ, 16%), 275 (100), 233
(40), 191 (77) and 149 (69).
(SS)-3-(p-Tolylsulfinyl)pent-3-en-2-ol 6a. To a solution of
LDA (13.0 mmol) was added a solution of (R)-prop-1-enyl
p-tolyl sulfoxide 5a6 (1.06 g, 5.89 mmol) in THF (6 cm3) at
Ϫ100 ЊC over a period of 3 min. After the reaction mixture
was stirred for 2 min, a solution of acetaldehyde (25.2 cm3,
1.17 mol cmϪ3 in THF, 29.5 mmol) was added. The reaction
mixture was stirred for 15 min, then quenched with saturated
aqueous NH4Cl (10 cm3), and concentrated under reduced
pressure. The aqueous mixture was extracted with CH2Cl2
(3 × 5 cm3). The combined organic extracts were washed with
brine (10 cm3), dried over Na2SO4, and concentrated to give
the crude alcohol, which was purified by column chrom-
atography (silica gel, CH2Cl2–ethyl acetate, 60:40) to give the
alcohol 6a (1.14 g, 87%) as a mixture of four diastereomers
composed mainly of the (E)-isomers. (E)-6a (Found: C,
64.28; H, 7.30. C12H16O2S requires C, 64.25; H, 7.19%); TLC
Rf = 0.17 (hexane–ethyl acetate, 50:50); νmax(neat)/cmϪ1 3370,
2980, 1600, 1495, 1450, 1400, 1380, 1080 and 1030; δH 1.07
and 1.22 [3 H, 2 × d, J 6.7 and 6.8, CH(OH)CH3], 1.98 (3 H,
Method B via the Jones oxidation.8 To a solution of the alco-
hol 6a (103 mg, 0.458 mmol) in acetone (3 cm3) was added at
0 ЊC the Jones reagent [prepared from chromium() oxide
(9.99 g, 100 mmol), 97% sulfuric acid (11.0 cm3, 200 mmol) and
water (50 cm3)], until the starting alcohol disappeared on TLC.
The reaction mixture was quenched with water (3 cm3) and
concentrated under reduced pressure. The aqueous mixture was
extracted with Et2O. The combined organic extracts were
washed with brine (5 cm3), dried over Na2SO4, and concen-
trated to give the crude enone, which was purified by column
chromatography (hexane–ethyl acetate, 60:40) to give the
enone 7a (86.5 mg, 85%) as a mixture of two diastereomers. The
(E)-isomer was further purified by recrystallization from Et2O
(Found: C, 64.80; H, 6.46. C12H14O2S requires C, 64.84; H,
6.35%); TLC Rf = 0.24 (hexane–ethyl acetate, 60:40); mp 61–
62 ЊC (from Et2O); [α]D22 ϩ255 (c 0.434 in CHCl3); νmax(KBr)/
cmϪ1 2920, 1660, 1625, 1430, 1380, 1220 and 1050; δH 2.22 (3 H,
d, J 7.4, CH3CH), 2.24 (3 H, s, CH3CO), 2.38 (3 H, s, ArCH3),
d, J 7.2, CH CH᎐C), 2.41 (3 H, s, ArCH ), 2.70–2.84 (1 H,
᎐
3
3
m, OH), 4.61–4.85 [1 H, m, CH(OH)], 6.43 and 6.53 (1 H,
2 × q, J 7.2 and 7.2, CH᎐C), 7.22–7.37 (2 H, m, ArH) and
᎐
7.43–7.59 (2 H, m, ArH); m/z (EI) 224 (Mϩ, 12%), 206 (6)
and 140 (100).
7.05 (1 H, q, J 7.4, CH᎐C), 7.25 (2 H, d, J 8.3, ArH) and 7.52 (2
᎐
H, d, J 8.3, ArH); δC 15.7, 21.3, 31.4, 125.6, 129.8, 139.4, 140.1,
141.8, 146.2 and 195.9; m/z (EI) 222 (Mϩ, 29%), 149 (28), 140
(53) and 139 (100).
3-(4-Methoxyphenylsulfinyl)pent-3-en-2-one 7b. The reaction
was carried out as described above (Method A) using the alco-
hol 6b (700 mg, 2.91 mmol) to give the enone 7b (399 mg, 58%).
An E:Z = 72:28 mixture was used for the radical reaction,
since attempts to isolate the (E)-isomer were unsuccessful
(Found: C, 60.31; H, 5.89. C12H14O3S requires C, 60.48; H,
3-(4-Methoxyphenylsulfinyl)pent-3-en-2-ol 6b. The reaction
was carried out as described above using the sulfoxide 5b (1.20
g, 6.11 mmol) to give the alcohol 6b (1.01 g, 69%) as a mixture
of four diastereomers; TLC Rf = 0.17 (hexane–ethyl acetate,
30:70); νmax(neat)/cmϪ1 3370, 2975, 1595, 1500, 1250, 1090 and
1025; δH 1.01–1.46 [3 H, m, CH(OH)CH3], 1.89–2.22 (3 H, m,
CH CH᎐C), 2.56–292 (1 H, m, OH), 3.85 and 3.86 (3 H, 2 × s,
᎐
3
OCH3), 4.05–4.85 [1 H, m, CH(OH)], 6.23–6.62 (1 H, m,
1616
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
5.92%); TLC Rf = 0.51 (hexane–ethyl acetate, 50:50); νmax
-
6.68%); TLC Rf = 0.65 (hexane–ethyl acetate, 50:50); νmax(neat)/
(KBr)/cmϪ1 2940, 1655, 1600, 1500, 1255 and 1040; δH 2.22 and
2.24 (3 H, 2 × s, CH3CO), 2.24 and 2.38 (3 H, 2 × d, J 7.6 and
7.5, CH3CH), 3.83 and 3.85 (3 H, 2 × s, OCH3), 6.90–7.07 (2 H,
cmϪ1 2970, 1705, 1480, 1395, 1360, 1280 and 1050; δH 0.72–1.39
[9 H, m, CH(CH3)2 and CHCH3], 1.87, 1.96, 1.99 and 2.00 (3 H,
4 × s, CH3CO), 1.50–2.70 [2 H, m, CH(CH3)2 and CHCH3],
3.13, 3.23, 3.94 and 3.99 (1 H, 4 × d, J 12.3, 11.0, 6.5 and 9.5,
COCHSO) and 7.37–7.62 (4 H, m, ArH); m/z (EI) 286 (Mϩ,
3%), 217 (5), 202 (8), 160 (100) and 127 (92).
m, ArH), 7.05 and 7.32 (3 H, 2 × q, J 7.6 and 7.5, CH᎐C) and
᎐
7.48–7.63 (2 H, m, ArH); m/z (EI) 238 (Mϩ, 51%), 190 (40) and
155 (100).
(E)-3-(4-Chlorophenylsulfinyl)pent-3-en-2-one 7c. The reac-
tion was carried out as described above (Method A) using the
alcohol 6c (500 mg, 2.04 mmol) to give the enone 7c (424 mg,
86%) (Found: C, 54.32; H, 4.51. C11H11ClO2S requires C, 54.43;
H, 4.57%); TLC Rf = 0.29 (hexane–ethyl acetate, 50:50);
νmax(KBr)/cmϪ1 3080, 2930, 1660, 1620, 1480, 1380, 1210 and
1050; δH 2.26 (3 H, d, J 7.6, CH3CH), 2.31 (3 H, s, CH3CO),
4,5-Dimethyl-3-(p-tolylsulfanyl)hex-3-en-2-one 9a. (Found:
C, 72.55; H, 8.17. C15H20OS requires C, 72.54; H, 8.12%); TLC
Rf = 0.80 (hexane–ethyl acetate, 60:40); νmax(neat)/cmϪ1 2970,
1730, 1690, 1490 and 1270; δH 1.06 and 1.08 [6 H, 2 × d, J 6.8
and 6.8, CH(CH ) ], 1.91 and 1.98 (3 H, 2 × s, CH C᎐), 2.23
᎐
3
3
2
and 2.24 (3 H, 2 × s, CH3CO), 2.28 (3 H, s, ArCH3), 2.92–3.03
and 3.43–3.64 [1 H, 2 × m, CH(CH3)2] and 7.07 (4 H, s, ArH);
m/z (EI) 248 (Mϩ, 100%), 233 (16) and 137 (33).
7.11 (1 H, q, J 7.6, CH᎐C) and 7.36–7.65 (4 H, m, ArH);
᎐
δC 15.8, 31.5, 126.8, 129.3, 137.3, 140.2, 142.2, 146.1 and 195.6;
m/z (EI) 242 (Mϩ, 51%), 183 (25), 144 (46) and 112 (100).
(S,E)-3-(2,4,6-Triisopropylphenylsulfinyl)pent-3-en-2-one 7d.
The reaction was carried out as described above (Method B)
using the alcohol 6d (338 mg, 1.00 mmol) to give the enone 7d
(242 mg, 72%), which was further purified by recrystallization
from Et2O (Found: C, 71.65; H, 9.22. C20H30O2S requires C,
71.81; H, 9.04%); TLC Rf = 0.43 (hexane–ethyl acetate, 70:30);
mp 70–71 ЊC (from Et2O); [α]D22 ϩ286 (c 0.402 in CHCl3);
νmax(KBr)/cmϪ1 2970, 1675, 1600, 1470, 1375, 1190 and 1050;
δH 1.20, 1.22 and 1.27 [18 H, 3 × d, J 6.9, 6.9, 6.9, 3 ×
CH(CH3)2], 2.17 (3 H, d, J 7.6, CH3CH), 2.20 (3 H, s, CH3CO),
2.73–3.00 [1 H, m, CH(CH3)2], 3.72–4.00 [2 H, m, 2 ×
4,5-Dimethyl-3-(4-methoxyphenylsulfanyl)hex-3-en-2-one 9b.
(Found: C, 68.17; H, 7.48. C15H20O2S requires C, 68.15; H,
7.62%); TLC Rf = 0.88 (hexane–ethyl acetate, 50:50); νmax(neat)/
cmϪ1 2960, 1690, 1600, 1500, 1295 and 1245; δH 1.06 and 1.07
[6 H, 2 × d, J 6.9 and 6.8, CH(CH3)2], 1.87 and 1.98 (3 H, 2 × s,
CH C᎐), 2.22 and 2.23 (3 H, 2 × s, CH CO), 2.85–3.05 and
᎐
3
3
3.45–3.68 [1 H, 2 × m, CH(CH3)2], 3.77 (3 H, s, OCH3), 6.82–
6.90 (2 H, m, ArH) and 7.10–7.22 (2 H, m, ArH); m/z (EI) 264
(Mϩ, 100%), 250 (10), 151 (28), 140 (50) and 113 (75).
4,5-Dimethyl-3-(4-chlorophenylsulfanyl)hex-3-en-2-one
9c.
(Found: C, 62.66; H, 6.39. C14H17ClOS requires C, 62.56;
H, 6.37%); TLC Rf = 0.85 (hexane–ethyl acetate, 50:50);
νmax(neat)/cmϪ1 2970, 1690, 1480, 1350, 1205 and 1100; δH 1.03
and 1.07 [6 H, 2 × d, J 6.8 and 6.8, CH(CH3)2], 1.91 and 1.95
CH(CH ) ], 6.77 (1 H, q, J 7.6, CH᎐C) and 7.03 (2 H, s, ArH);
᎐
3
2
δC 15.7, 23.7, 25.0, 27.8, 31.3, 34.3, 123.1, 132.1, 135.8, 146.7,
151.3, 153.0 and 197.0; m/z (EI) 334 (Mϩ, 6%), 317 (4) and 291
(100).
(3 H, 2 × s, CH C᎐), 2.23 (3 H, s, CH CO), 2.90–3.14 and 3.30–
᎐
3 3
3.57 [1 H, 2 × m, CH(CH3)2] and 7.00–7.25 (4 H, m, ArH); m/z
(EI) 268 (Mϩ, 100%), 254 (20), 225 (12), 155 (24), 143 (13) and
125 (20).
General procedure for radical â-addition to á-(arylsulfinyl)
enones 7
4,5-Dimethyl-3-(2,4,6-triisopropylphenylsulfanyl)hex-3-en-2-
one 9d. (Found: C, 76.55; H, 10.20. C23H36OS requires C, 76.61;
H, 10.06%); TLC Rf = 0.72 (hexane–ethyl acetate, 80:20);
νmax(neat)/cmϪ1 2970, 1700, 1600, 1470, 1370 and 1205; δH 1.02
and 1.09 [6 H, 2 × d, J 6.8 and 6.8, CH(CH3)2], 1.13–1.69 [21 H,
A solution of the α-(arlysulfinyl) enone 7 in CH2Cl2 (0.01 mol
dmϪ3) was degassed under reduced pressure using a sonicator.
To this solution was added triethylborane (10 equiv.) and iso-
propyl iodide (10 equiv.) at 0 ЊC. In the reaction using an addi-
tive, the additive (1.1 equiv.) was added at 0 ЊC and the mixture
was stirred for 1 h before the addition of triethylborane and
isopropyl iodide. Then air was passed through the solution by a
microfeeder at a rate of 90.0 × 10Ϫ3 cm3 minϪ1 per 1 mmol of
triethylborane. The reaction mixture was poured into saturated
aqueous NaH2PO4, and extracted with Et2O. The combined
organic extracts were dried over Na2SO4 and concentrated to
give the crude product which was purified by column chrom-
atography to give the addition product 8 and the Pummerer-
type product 9.
4,5-Dimethyl-3-(p-tolylsulfinyl)hexan-2-one 8a. (Found: C,
67.47; H, 8.48. C15H22O2S requires C, 67.63; H, 8.32%); TLC
Rf = 0.51 (hexane–ethyl acetate, 60:40); νmax(neat)/cmϪ1 2970,
1705, 1360, 1215 and 1060; δH 0.63–1.39 [9 H, m, CH(CH3)2
and CHCH3], 1.81, 1.196 and 2.00 (3 H, 3 × s, CH3CO), 2.17–
2.70 [2 H, m, CH(CH3)2 and CHCH3], 2.41 (3 H, s, ArCH3),
3.13, 3.23, 3.93 and 3.95 (1 H, 4 × d, J 11.7, 11.0, 6.3 and 9.7,
COCHSO) and 7.22–7.56 (4 H, m, ArH); m/z (EI) 266 (Mϩ,
1%), 140 (100) and 127 (70).
m, 3 × CH(CH3)2 and CH C᎐], 1.91 and 1.97 (3 H, 2 × s,
᎐
3
CH3CO), 2.50–2.73 and 3.48–3.75 [1 H, 2 × m, CH(CH3)2],
2.72–2.98 [1 H, m, CH(CH3)2], 3.53–3.82 [2 H, m, 2 ×
CH(CH3)2] and 6.96 (2 H, s, ArH); m/z (EI) 360 (Mϩ, 52%), 317
(7), 204 (100) and 189 (67).
5-Methyl-3-(p-tolylsulfinyl)hexan-2-one 11. (Found: C, 66.52;
H, 7.91. C14H20O2S requires C, 66.63; H, 7.99%); TLC Rf = 0.17
(hexane–ethyl acetate, 80:20); HPLC tR = 29.02, 31.70, 33.18
and 37.44 min (hexane–propan-2-ol, 98:2); νmax(neat)/cmϪ1
2960, 1710, 1680, 1625, 1580, 1355, 1290, 1170 and 1040;
δH 0.80–1.00 [6 H, m, CH(CH3)2], 1.15–1.41 (2 H, m, CH2),
1.49–1.75 [1 H, m, CH(CH3)2], 1.90, 2.16 (3 H, 2 × s, CH3CO),
2.42 (3 H, s, ArCH3), 3.54 and 3.76 (1 H, 2 × dd, J 5.4, 9.8 and
4.4, 9.6, COCHSO) and 7.27–7.53 (4 H, m, ArH); m/z (EI) 252
(Mϩ, 5%), 201 (3), 140 (100) and 139 (89).
Acknowledgements
This work was partly supported by the Ministry of Education,
Science and Culture of Japan (Grant-in-Aid for Scientific
Research No. 06805079).
4,5-Dimethyl-3-(4-methoxyphenylsulfinyl)hexan-2-one
8b.
(Found: C, 63.97; H, 7.92. C15H22O3S requires C, 63.80; H,
7.85%); TLC Rf = 0.53 (hexane–ethyl acetate, 50:50); νmax(neat)/
cmϪ1 2960, 1700, 1600, 1500, 1360, 1090 and 1055; δH 0.65–1.34
[9 H, m, CH(CH3)2 and CHCH3], 1.95 and 2.02 (3 H, 2 × s,
CH3CO), 2.17–2.68 [2 H, m, CH(CH3)2 and CHCH3], 3.13 and
3.26 (1 H, 2 × d, J 11.8 and 10.8, COCHSO) and 3.73–3.90
(1 H, m, COCHSO), 3.84 and 3.85 (3 H, 2 × s, OCH3), 6.96–
7.10 (2 H, m, ArH) and 7.37–7.51 (2 H, m, ArH); m/z (EI) 282
(Mϩ, 20%), 156 (81) and 155 (100).
References
1 D. P. Curran, N. A. Porter and B. Giese, Stereochemistry of Radical
Reactions, VCH, Weinheim, 1995; W. Smadja, Synlett, 1994, 1; N. A.
Porter, B. Giese and D. P. Curran, Acc. Chem. Res., 1991, 24, 296.
2 M. Nishida, H. Hayashi, Y. Yamaura, E. Yanaginuma and
O. Yonemitsu, Tetrahedron Lett., 1995, 36, 269; M. P. Sibi, C. P.
Jasperse and J. Ji, J. Am. Chem. Soc., 1995, 117, 10 779; Q. Zhang,
R. M. Mohan, L. Cook, S. Kazanis, D. Peisach, B. M. Foxman and
B. B. Snider, J. Org. Chem., 1993, 58, 7640; J. G. Stack, D. P. Curran,
S. V. Geib, J. Rebek, Jr. and P. Ballester, J. Am. Chem. Soc., 1992,
4,5-Dimethyl-3-(4-chlorophenylsulfinyl)hexan-2-one
8c.
(Found: C, 58.48; H, 6.56. C14H19ClO2S requires C, 58.63; H,
J. Chem. Soc., Perkin Trans. 1, 1998
1617

View Article Online
114, 7007; N. A. Porter, I. J. Rosenstein, R. A. Breyer, J. D. Bruhnke,
W.-X. Wu and A. T. McPhail, J. Am. Chem. Soc., 1992, 114, 7664;
N. A. Porter, D. S. Scott, I. J. Rosenstein, B. Giese, A. Veit and H. G.
Zeitz, J. Am. Chem. Soc., 1991, 113, 1791; D. P. Curran, W. Shen,
J. Zhang and T. A. Heffner, J. Am. Chem. Soc., 1990, 112, 6738.
3 R. Angelaud and Y. Landais, Tetrahedron Lett., 1997, 38, 233;
M. Zahouily, G. Caron, P.-A. Carrupt, N. Knouzi and P. Renaud,
Tetrahedron Lett., 1996, 37, 8387; P. Renaud and T. Bourquard,
Synlett, 1995, 1021 and references cited therein; P. Renaud,
N. Moufid, L. H. Kuo and D. P. Curran, J. Org. Chem., 1994, 59,
3547; A. De Mesmaeker, A. Waldner, P. Hoffmann and T. Mindt,
Synlett, 1993, 871; A. L. J. Beckwith, R. Hersperger and J. M.
White, J. Chem. Soc., Chem. Commun., 1991, 1151; B. B. Snider,
B. Y.-F. Wan, B. O. Buckman and B. M. Foxman, J. Org. Chem.,
1991, 56, 328; Y.-M. Tsai, B.-W. Ke and C.-H. Lin, Tetrahedron
Lett., 1990, 31, 6047.
4 M. Zahouily, M. Journet and M. Malacria, Synlett, 1994, 366.
5 N. Mase, Y. Watanabe, Y. Ueno and T. Toru, J. Org. Chem., 1997,
62, 7794; T. Toru, Y. Watanabe, N. Mase, M. Tsusaka, T. Hayakawa
and Y. Ueno, Pure Appl. Chem., 1996, 68, 711; T. Toru, Y. Watanabe,
M. Tsusaka and Y. Ueno, J. Am. Chem. Soc., 1993, 115, 10 464.
6 D. J. Abbott, S. Colona and C. J. M. Stirling, J. Chem. Soc., Perkin
Trans. 1, 1976, 492.
literature: (a) J. Fawcett, S. House, P. R. Jenkins, N. J. Lawrence and
D. R. Russell, J. Chem. Soc., Perkin Trans. 1, 1993, 67; (b)
H. Okamura, Y. Mitsuhira, M. Miura and H. Takei, Chem. Lett.,
1978, 517.
8 C. Maignan, A. Guessous and F. Rouessac, Tetrahedron Lett., 1986,
27, 2603.
9 K. Nozaki, K. Oshima and K. Utimoto, Bull. Chem. Soc. Jpn., 1991,
64, 403.
10 H. C. Brown and G. W. Kabalka, J. Am. Chem. Soc., 1970, 92, 714.
11 Formation of the competitive ethyl adduct depends on the amount
of isopropyl iodide used: see ref. 5.
12 This reagent was produced according to the method reported, see
K. Mikami, M. Terada and T. Nakai, J. Am. Chem. Soc., 1990, 112,
3949.
13 G. W. Kabalka, H. C. Brown, A. Suzuki, S. Honma, A. Arase and
M. Itoh, J. Am. Chem. Soc., 1970, 92, 710.
14 T. Numata and S. Oae, Tetrahedron Lett., 1977, 1337.
15 H. J. Monteiro and A. L. Gemal, Synthesis, 1975, 437.
16 C. Alexandre, O. Belkadi and C. Maignan, Synthesis, 1992, 547.
17 J. Drabowicz, Phosphorus Sulfur Relat. Elem., 1987, 31, 123.
Paper 8/00828K
Received 30th January 1998
Accepted 10th March 1998
7 The Michael addition product of the generated vinyl anion to prop-
1-enyl sulfoxide 5 was mainly formed, when less than 2 equiv. of
LDA were used as in the procedures reported in the following
1618
J. Chem. Soc., Perkin Trans. 1, 1998