Efficient one-pot synthesis of 1-chlorovinyl p-tolyl sulfoxides from aldehydes and ketones by the Horner-Wadsworth-Emmons reaction

Article abstract of DOI:10.1002/hc.21395

A variety of 2-monosubstituted and 2,2-disubstituted 1-chlorovinyl p-tolyl sulfoxides was synthesized through a one-pot procedure by the Horner-Wadsworth-Emmons reaction of carbonyl compounds with [chloro(diethoxyphosphoryl)(p-tolylsulfinyl)methyl]lithium, which was generated from diethyl chlorophosphate, chloromethyl p-tolyl sulfoxide, and lithium diisopropylamide in advance. The in situ-prepared sulfoxides were directly converted into alkynes via the sulfoxide/magnesium exchange reaction with i-PrMgCl and the subsequent Fritsch-Buttenberg-Wiechell rearrangement of the resulting magnesium alkylidene carbenoids.

Full text of DOI:10.1002/hc.21395

Received: 27 July 2017
DOI: 10.1002/hc.21395
Revised: 13 September 2017
|
|
R E S E A R C H A R T I C L E
Efficient one-pot synthesis of 1-chlorovinyl p-tolyl sulfoxides
from aldehydes and ketones by the Horner-Wadsworth-Emmons
reaction
Tsutomu Kimura
Tsuyoshi Satoh
Gen Kobayashi
Shiori Ijima
Sae Saito
Aki Imafuji
|
|
|
|
|
Department of Chemistry, Graduate School
of Science, Tokyo University of Science,
Tokyo, Japan
Abstract
A variety of 2-monosubstituted and 2,2-disubstituted 1-chlorovinyl p-tolyl sulfox-
ides was synthesized through a one-pot procedure by the Horner-Wadsworth-
Emmons reaction of carbonyl compounds with [chloro(diethoxyphosphoryl)
(p-tolylsulfinyl)methyl]lithium, which was generated from diethyl chlorophosphate,
chloromethyl p-tolyl sulfoxide, and lithium diisopropylamide in advance. The in
situ-prepared sulfoxides were directly converted into alkynes via the sulfoxide/mag-
nesium exchange reaction with i-PrMgCl and the subsequent Fritsch-Buttenberg-
Wiechell rearrangement of the resulting magnesium alkylidene carbenoids.
Correspondence
Tsutomu Kimura, Department of Chemistry,
Graduate School of Science, Tokyo
University of Science, Tokyo, Japan.
Email: kimtwo@rs.tus.ac.jp
of adducts 4 to a leaving group, such as a mesyloxy or
1
INTRODUCTION
|
acetoxy group, and (3) β-elimination in the presence of an
1-Chlorovinyl p-tolyl sulfoxides 1 are versatile synthetic in-
termediates in organic synthesis.[1] The sulfoxide/magnesium
exchange reaction of sulfoxides 1 with i-PrMgCl generates
magnesium alkylidene carbenoids as reactive intermediates,
and the resulting magnesium alkylidene carbenoids are con-
verted into various compounds utilizing their diverse reac-
tivity.[2] For instance, the 1,2-rearrangement of magnesium
alkylidene carbenoids, referred to as Fritsch-Buttenberg-
Wiechell (FBW) rearrangement, leads to the formation of
alkynes (Scheme 1, Equation 1).[3,4] Sulfoxides 1 also act
as Michael acceptors toward nucleophiles. The conjugate
addition of lithium ester enolates to sulfoxides 1 occurs in
a highly diastereoselective manner to give adducts, and the
Pummerer-type cyclization of the adducts gives γ-lactones
(Scheme 1, Equation 2).[5] In several cases, 2 equivalents of
a nucleophile consecutively react with sulfoxides 1.[6] For in-
stance, the reaction of sulfoxides 1 with excess (cyanomethyl)
lithium affords 2-aminocyclopenta-1,3-dienecarbonitriles
(Scheme 1, Equation 3).
appropriate base.[3,7] While this synthetic route is faithful
and highly reproducible, the number of steps is a consid-
erable drawback. Alternatively, 3 independent groups have
reported the synthesis of 2-monosubstituted 1-chlorovinyl
sulfoxides 1 by the Horner-Wadsworth-Emmons (HWE)
reaction of aldehydes with P-[(arylsulfinyl)chloromethyl]-
substituted phosphonates or phosphine oxides 5 (Scheme 2,
Equation 3).[8-10] This synthetic approach is potentially
attractive because sulfoxides 1 can be prepared from car-
bonyl compounds 2 in a single step; however, the key phos-
phorus reagents 5 have to be elaborated over several steps
from commercially available materials. In addition, only
the synthesis of 2-monosubstituted sulfoxides 1 from alde-
hydes has been attempted, and the synthesis of more chal-
lenging 2,2-disubstituted sulfoxides from ketones has not
been examined. The development of an efficient synthetic
method that permits convenient access to a wide range of
sulfoxides 1 is expected to facilitate further advancement
of the chemistry using sulfoxides 1.[1-6] Herein, we report
a one-pot synthesis of 1-chlorovinyl p-tolyl sulfoxides
from chloromethyl p-tolyl sulfoxide, diethyl chlorophos-
phate, and carbonyl compounds. The one-pot synthesis
of one-carbon elongated terminal alkynes from aldehydes
A conventional synthetic method for sulfoxides 1 con-
sists of 3 steps (Scheme 2, eqs 1 and 2): (1) nucleophilic
addition of [chloro(p-tolylsulfinyl)methyl]lithium to car-
bonyl compounds 2, (2) conversion of the hydroxy group
|
Heteroatom Chemistry. 2017;28:e21395.
https://doi.org/10.1002/hc.21395
wileyonlinelibrary.com/journal/hc
© 2017 Wiley Periodicals, Inc.
1 of 6

2 of 6
KIMURA et Al.
|
SCHEME 3 Generation of [chloro(diethoxyphosphoryl)(p-
tolylsulfinyl)methyl]lithium (6a) from chloromethyl p-tolyl sulfoxide
(3) and diethyl chlorophosphate (7)
temperature for 15 minutes. As a result, diethyl [chloro(p-
tolylsulfinyl)methyl]phosphonate (5a) was obtained in 94%
yield.
SCHEME 1 Synthetic applications of 1-chlorovinyl p-tolyl
sulfoxides 1
As phosphonate 5a could be prepared from sulfoxide 3 and
chlorophosphate 7 with high efficiency, we then examined the
one-pot synthesis of 2-monosubstituted 1-chlorovinyl p-tolyl
sulfoxides 1a-l from aldehydes 2a-l (Table 1). To a solution
of deprotonated phosphonate 6a (one equiv) in THF, which
was prepared from sulfoxide 3, chlorophosphate 7, and LDA
in advances, was added benzaldehyde (2a) at −60°C, and the
reaction mixture was stirred at 0°C for 30 minutes (entry 1).
The desired 2-phenyl-substituted sulfoxide 1a was formed
in 72% yield as a 1:1 mixture of geometric isomers. The re-
action of aldehyde 2a with 1.25 equivalents of deprotonated
phosphonate 6a gave the product 1a in an improved yield
(entry 2). A variety of 2-monoaryl-substituted sulfoxides 1b-
g was synthesized from aryl and heteroaryl aldehydes 2b-g
through the one-pot procedure in 86%-96% yields (entries
3-8). When paraformaldehyde was subjected to the reaction
with deprotonated phosphonate 6a, 2-unsubstituted sulfoxide
1h was obtained in 76% yield (entry 9). Enolizable aliphatic
aldehydes, such as acetaldehyde (2i), hydrocinnamaldehyde
(2j), and cyclohexanecarboxaldehyde (2k), could also be
converted into the corresponding 2-monoalkyl-substituted
sulfoxides 1i-k in 72%-96% yields, whereas pivalaldehyde
(2l) was less reactive at 0°C (entries 10-13). The reaction of
aldehyde 2l with 3 equivalents of deprotonated phosphonate
6a at room temperature for 3 hours gave sulfoxide 1l in an
improved yield (entry 14).
SCHEME 2 Synthetic routes to 1-chlorovinyl p-tolyl sulfoxides 1
via the FBW rearrangement of magnesium alkylidene car-
benoids generated from sulfoxides 1 and i-PrMgCl is also
described.
2
RESULTS AND DISCUSSION
One-pot synthesis of 2-monosubstituted
|
2.1
|
2.2
One-pot synthesis of 2,2-disubstituted
1-chlorovinyl p-tolyl sulfoxides from aldehydes
|
1-chlorovinyl p-tolyl sulfoxides from ketones
Initially,
we
tested
the
generation
of
Encouraged by the successful one-pot synthesis of
2-monosubstituted sulfoxides 1a-l, the synthesis of
2,2-disubstituted sulfoxides 1m-p from ketones 2m-p was
carried out (Table 2). When acetone (2m) was subjected to
the HWE reaction under the reaction conditions described
above, the desired 2,2-dimethyl-substituted sulfoxide 1m
[chloro(diethoxyphosphoryl)(p-tolylsulfinyl)methyl]lithium
(6a) from chloromethyl p-tolyl sulfoxide (3) and diethyl chlo-
rophosphate (7) as readily available materials (Scheme 3).
Sulfoxide 3 was treated with 2 equivalents of lithium diiso-
propylamide (LDA), and the resulting [chloro(p-tolylsulfinyl)
methyl]lithium was reacted with chlorophosphate 7 at low

KIMURA et Al.
3 of 6
|
TABLE 1 One-pot synthesis of 2-monosubstituted 1-chlorovinyl
p-tolyl sulfoxides 1a-l from aldehydes 2a-la
TABLE 2 One-pot synthesis of 2,2-disubstituted 1-chlorovinyl
p-tolyl sulfoxides 1m-p from ketones 2m-pa
Entry
1b
2
3
4
5
6
7
2
R
1
Yield (%)
E/Z ratio
Entry
1b,c
2
3
4
2
R
R′
1
Yield (%)
2a
2a
2b
2c
2d
2e
2f
Ph
Ph
1a
1a
1b
1c
1d
1e
1f
72
96
96
93
90
90
92
1:1
1:1
2m
2m
2n
2o
2p
2p
Me
Me
Ph
–(CH2)4–
–(CH2)5–
–(CH2)5–
Me
Me
Me
1m
1m
1n
1o
1p
1p
49
82
67d
89
96
93
4-MeOC6H4
4-CF3C6H4
4-ClC6H4
4-NCC6H4
1:1.2
1:2.3
1:1.7
1.7:1
1:1
5
6e
aThe molar ratio of LDA/3/7/2 = 6/3/3/1 (except entries 1 and 6).
bThe molar ratio of LDA/3/7/2 = 2.5/1.25/1.25/1.
cThe reaction was carried out at 0°C for 30 minutes.
dE/Z ratio = 3.3:1.
8
2g
2h
2i
2j
2k
2l
2-thienyl
H
Me
PhCH2CH2
cyclo-C6H11
t-Bu
1g
1h
1i
1j
1k
1l
86
76d
96
92
72
4
1.1:1
–
1:2
1:1.7
1.2:1
3.6:1
3.3:1
9c
eRecovered HWE reagent 5a (3 equiv) and LDA (3.3 equiv) were used.
10
11
12
13
14e
homologation, and Ohira-Bestmann modification have
been developed. If magnesium alkylidene carbenoids can
be directly generated from in situ-prepared 1-chlorovinyl
p-tolyl sulfoxides 1 and a Grignard reagent via the sul-
foxide/magnesium exchange reaction, the following
FBW rearrangement of the resulting magnesium alky-
lidene carbenoids is expected to give alkynes (Scheme 1,
Equation 1).[3,4] We examined the one-pot conversion
of aldehydes into alkynes through the sequential HWE
reaction-sulfoxide/magnesium exchange reaction-FBW
rearrangement (Scheme 4). A solution of i-PrMgCl
in THF was added to a solution of 1-chlorovinyl p-
tolyl sulfoxide 1b in THF, which was prepared from
p-anisaldehyde (2b) and deprotonated phosphonate 6a
according to the procedure described above, at −78°C,
and the reaction mixture was allowed to warm to 0°C.
Gratifyingly, the reaction gave the desired alkyne 8a in
2l
t-Bu
1l
73
aThe molar ratio of LDA/3/7/2 = 2.5/1.25/1.25/1 (except entries 1, 9, and 14).
bThe molar ratio of LDA/3/7/2 = 2/1/1/1.
cParaformaldehyde (5 equiv) was used.
dYield based on sulfoxide 3.
eThe reaction was carried out with 3 equivalents of deprotonated phosphonate 6a
at room temperature for 3 hours.
was formed in only 49% yield (entry 1). To improve the reac-
tion efficiency, 3 equivalents of deprotonated phosphonate
6a were used, and the reaction was performed at room tem-
perature for 3 hours. Consequently, sulfoxide 1m was ob-
tained in 82% yield (entry 2). The reaction of aryl and cyclic
aliphatic ketones 2n-p with deprotonated phosphonate 6a
gave the corresponding 2,2-disubstituted sulfoxides 1n-p in
67%-96% yields (entries 3-5). Excess HWE reagent 5a in the
reaction of entry 5 was recovered by column chromatography
on silica gel and used for the reaction with cyclohexanone
(2p) in the presence of LDA (entry 6). Sulfoxide 1p was ob-
tained in 93% yield. Benzophenone was unreactive toward
deprotonated phosphonate 6a.
2.3
Conversion of aldehydes into alkynes
|
with one-carbon elongation
The conversion of aldehydes into alkynes with one-
carbon elongation is a useful method for the synthesis
of terminal alkynes.[11] Much effort has been devoted
to developing a synthetic method of alkynes from al-
dehydes, and Corey-Fuchs reaction, Seyferth-Gilbert
SCHEME 4 One-pot synthesis of terminal alkynes 8 from
aldehydes 2

4 of 6
KIMURA et Al.
|
84% yield. Terminal alkynes 8b and 8c were also ob-
tained from aldehydes 2e and 2f in 54% and 61% yields,
respectively.
was added to the solution of LDA in THF at −78°C, and the
mixture was stirred at −78°C for 15 minutes. Diethyl chloro-
phosphate (7, 1.73 g, 10.0 mmol) was added to the solution
of [chloro(p-tolylsulfinyl)methyl]lithium in THF at −78°C,
and the mixture was allowed to warm to −60°C over a pe-
riod of 15 minutes. The reaction was quenched with sat. aq
NH4Cl (1.0 mL), and the mixture was extracted with CHCl3
(3 × 20 mL). The combined organic layer was washed with
water (60 mL), dried over MgSO4, and concentrated under
reduced pressure. The residue was purified by column chro-
matography on silica gel (hexane–EtOAc, 1:1) to give 5a
(3.04 g, 9.36 mmol, 94%, Rf = 0.18 [hexane–EtOAc, 1:1])
as a 7:3 mixture of diastereomers. One of the diastereomers
isomerized to the other diastereomer spontaneously at room
temperature within several hours, and the diastereomeric mix-
ture became a single diastereomer; colorless crystals (hex-
ane/EtOAc); mp 91.2-93.6°C; IR (ATR) 2985, 2904, 1592,
1496, 1441, 1399, 1240, 1158, 1090, 1059, 1013, 847, 815,
770, 717 cm−1; 1H NMR (399 MHz, CDCl3) δ 1.35-1.43 (m,
3H), 2.43 (s, 3H), 4.24-4.37 (m, 4H), 4.50 (d, J = 11.4 Hz,
1H), 7.36 (d, J = 8.1 Hz, 2H), 7.57 (d, J = 8.1 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 16.28 (d, J = 6.0 Hz), 16.29 (d,
J = 6.3 Hz), 21.5, 64.7 (d, J = 7.0 Hz), 64.8 (d, J = 6.5 Hz),
70.8 (d, J = 150.5 Hz), 124.9, 129.9, 137.6 (d, J = 7.7 Hz),
142.7; MS (FAB+): m/z (%) 325 ([M+H]+, 100), 186 (21),
123 (19); HRMS (FAB+) calcd for C12H19ClO4PS: 325.0430,
found: 325.0431.
3
CONCLUSION
|
We developed an efficient one-pot synthetic method of
1-chlorovinyl p-tolyl sulfoxides from readily available ma-
terials by the HWE reaction. The synthetic method was ap-
plied to the one-pot conversion of aldehydes into alkynes
with one-carbon elongation. This efficient synthetic method
will help advance the chemistry using 1-chlorovinyl p-tolyl
sulfoxides.
4
EXPERIMENTAL
General methods
|
4.1
|
All reactions involving air- or water-sensitive compounds
were conducted under an argon atmosphere. Argon gas was
dried by passage through P2O5. Anhydrous THF was pur-
chased and used as supplied. Acetaldehyde and acetone were
distilled before use. Silica gel (60N) containing 0.5% fluores-
cence reagent 254 and a quartz column were used for column
chromatography, and the products that absorbed UV light
were detected by UV irradiation. Gel permeation chromatog-
raphy (GPC) was performed on JAIGEL-1HH and JAIGEL-
2HH using a recycling preparative HPLC LC-9210 II NEXT
system (Japan Analytical Industry, Tokyo, Japan). The melt-
ing points were measured using a Yanaco MP-S3 apparatus
(Yanaco, Kyoto, Japan) and are uncorrected. IR spectra were
recorded on a Perkin-Elmer Frontier FT IR in ATR mode.
NMR spectra were measured in a CDCl3 solution with JEOL
JNM-LA 300, JEOL JNM-LA 500 (JEOL, Tokyo, Japan),
Bruker AVANCE DPX 300, and Bruker AVANCE DPX 400
spectrometers (Bruker Biospin, Billerica, MA, USA). Mass
spectra (MS) were obtained at 70 eV by direct injection with
a HITACHI M-80B mass spectrometer. Fast atom bombard-
ment (FAB) mass spectra were obtained with a mixture of
m-nitrobenzyl alcohol and glycerol as the matrix. Sulfoxides
4.3
Typical procedure for the
|
synthesis of 2-monosubstituted 1-chlorovinyl
p-tolyl sulfoxides 1 from aldehydes
A 1.60 mol/L solution of BuLi in hexane (1.68 mL,
2.69 mmol) was added to a solution of i-Pr2NH (274 mg,
2.71 mmol) in THF (3.0 mL) at 0°C, and the mixture was
stirred at 0°C for 15 minutes. A solution of chloromethyl
p-tolyl sulfoxide (3, 253 mg, 1.34 mmol) in THF (2.0 mL)
was added to the solution of LDA in THF at −78°C, and
the mixture was stirred at −78°C for 15 minutes. Diethyl
chlorophosphate (7, 234 mg, 1.36 mmol) was added to the
solution of [chloro(p-tolylsulfinyl)methyl]lithium in THF
at −78°C, and the mixture was allowed to warm to −60°C
over a period of 15 minutes. 4-Methoxybenzaldehyde (2b,
146 mg, 1.07 mmol) was added to the solution of 6a in THF
at −60°C. The reaction mixture was immediately warmed
to 0°C and stirred at 0°C for 30 minutes. The reaction was
quenched with sat. aq NH4Cl (3.0 mL), and the mixture was
extracted with CHCl3 (3 × 3.0 mL). The combined organic
layer was washed with water (3.0 mL), dried over MgSO4,
and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel (hexane-
EtOAc, 3:1) to give 1b (317 mg, 1.03 mmol, 96%, Rf = 0.28
[hexane–EtOAc, 3:1]) as a colorless solid.
1a, 1b, and 1e-p and alkynes 8 are known compounds.[3b,6a,
7,8c,12,13]
4.2
Synthesis of diethyl [chloro(p-
|
tolylsulfinyl)methyl]phosphonate (5a)
A 1.60 mol/L solution of BuLi in hexane (12.5 mL,
20.0 mmol) was added to a solution of i-Pr2NH (2.02 g,
20.0 mmol) in THF (15.0 mL) at 0°C, and the mixture was
stirred at 0°C for 15 minutes. A solution of chloromethyl
p-tolyl sulfoxide (3, 1.89 g, 10.0 mmol) in THF (5.0 mL)

KIMURA et Al.
5 of 6
|
13C NMR (126 MHz, CDCl3) δ 21.8, 126.2, 127.5, 129.2,
130.3, 130.9, 131.2, 136.0, 136.3, 138.7, 143.2; MS (FAB+):
m/z (%) 311 ([M+H]+, 100), 185 (18), 154 (20), 137 (16),
93 (24); HRMS (FAB+) calcd for C15H13Cl2OS: 311.0064,
found: 311.0063.
4.3.1
(E)-1-({1-Chloro-2-[4-
|
(trifluoromethyl)phenyl]vinyl}sulfinyl)-4-
methylbenzene [(E)-2c]
Colorless crystals (hexane/EtOAc); mp 111.8-112.4°C; IR
(ATR) 3009, 1616, 1493, 1415, 1323, 1164, 1108, 1086, 1068,
1058, 1015, 920, 908, 834, 820, 802, 756 cm−1; H NMR
1
4.4
Typical procedure for the
|
(400 MHz, CDCl3) δ 2.42 (s, 3H), 7.32 (d, J = 8.1 Hz, 2H),
7.34 (s, 1H), 7.47 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 8.5 Hz,
2H), 7.72 (d, J = 8.5 Hz, 2H); 13C NMR (126 MHz, CDCl3)
δ 21.8, 124.0 (q, J = 272.4 Hz), 125.0, 126.1 (q, J = 3.6 Hz),
130.0, 130.3, 131.6 (q, J = 33.1 Hz), 136.3, 136.8, 137.9,
142.7, 143.3; MS (FAB+): m/z (%) 345 ([M+H]+, 100);
HRMS (FAB+) calcd for C16H13ClF3OS: 345.0328, found:
345.0329.
synthesis of 2,2-disubstituted 1-chlorovinyl p-
tolyl sulfoxides 1 from ketones
A 1.60 mol/L solution of BuLi in hexane (3.63 mL, 5.81 mmol)
wasaddedtoasolutionofi-Pr2NH(587 mg, 5.80 mmol)inTHF
(3.0 mL) at 0°C, and the mixture was stirred at 0°C for 15 min-
utes. A solution of chloromethyl p-tolyl sulfoxide (3, 547 mg,
2.90 mmol) in THF (2.0 mL) was added to the solution of LDA
in THF at −78°C, and the mixture was stirred at −78°C for
15 minutes. Diethyl chlorophosphate (7, 499 mg, 2.89 mmol)
was added to the solution of [chloro(p-tolylsulfinyl)methyl]
lithium in THF at −78°C, and the mixture was allowed to warm
to −60°C over a period of 15 minutes. Cyclohexanone (2p,
94.8 mg, 0.966 mmol) was added to the solution of 6a in THF
at −60°C. The reaction mixture was immediately warmed to
room temperature and stirred at room temperature for 3 hours.
The reaction was quenched with sat. aq NH4Cl (1 mL), and
the mixture was extracted with CHCl3 (3 × 5 mL). The com-
bined organic layer was washed with water (15 mL), dried over
MgSO4, and concentrated under reduced pressure. The residue
was purified by column chromatography on silica gel (hexane–
EtOAc, 3:1) to give 1p (250 mg, 0.930 mmol, 96%, Rf = 0.30
[hexane–EtOAc, 3:1]) as a colorless solid.
4.3.2
(Z)-1-({1-Chloro-2-[4-
|
(trifluoromethyl)phenyl]vinyl}sulfinyl)-4-
methylbenzene [(Z)-2c]
Colorless crystals (hexane/EtOAc); mp 90.8-93.1°C; IR
(ATR) 3001, 1617, 1412, 1323, 1194, 1171, 1114, 1086,
1067, 1017, 899, 885, 821 cm−1; 1H NMR (400 MHz,
CDCl3) δ 2.43 (s, 3H), 7.34 (d, J = 8.0 Hz, 2H), 7.656 (d,
J = 8.0 Hz, 2H), 7.660 (d, J = 8.5 Hz, 2H), 7.68 (s, 1H), 7.84
(d, J = 8.5 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 21.6,
123.8 (q, J = 272.1 Hz), 125.6 (q, J = 3.8 Hz), 126.0, 126.5,
129.9, 130.2, 131.2 (q, J = 32.7 Hz), 135.6 (q, J = 1.5 Hz),
138.2, 138.3, 143.2; MS (FAB+): m/z (%) 345 ([M+H]+,
100); HRMS (FAB+) calcd for C16H13ClF3OS: 345.0328,
found: 345.0328.
4.5
Typical procedure for the synthesis of
|
4.3.3
(E)-1-Chloro-4-[2-chloro-2-(p-
alkynes from aldehydes
|
tolylsulfinyl)vinyl]benzene [(E)-2d]
A 1.60 mol/L solution of BuLi in hexane (1.68 mL, 2.69 mmol)
was added to a solution of i-Pr2NH (274 mg, 2.71 mmol)
in THF (3.0 mL) at 0°C, and the mixture was stirred at 0°C
for 15 minutes. A solution of chloromethyl p-tolyl sulfox-
ide (3, 253 mg, 1.34 mmol) in THF (2.0 mL) was added to
the solution of LDA in THF at −78°C, and the mixture was
stirred at −78°C for 15 minutes. Diethyl chlorophosphate (7,
234 mg, 1.36 mmol) was added to the solution of [chloro(p-
tolylsulfinyl)methyl]lithium in THF at −78°C, and the mixture
was allowed to warm to −60°C over a period of 15 minutes.
4-Methoxybenzaldehyde (2b, 146 mg, 1.07 mmol) was added
to the solution of 6a in THF at −60°C. The reaction mixture
was immediately warmed to 0°C and stirred at 0°C for 30 min-
utes. A 2.0 mol/L solution of i-PrMgCl in THF (1.88 mL,
3.76 mmol) was added to the reaction mixture at −78°C, and
the reaction mixture was allowed to warm to 0°C over a pe-
riod of 2 hours. The reaction was quenched with sat. aq NH4Cl
(1 mL), and the mixture was extracted with CHCl3 (3 × 5 mL).
The combined organic layer was washed with water (15 mL),
Colorless crystals (hexane/EtOAc); mp 148.4-150.8°C; IR
(ATR) 3031, 1591, 1488, 1403, 1084, 1050, 1013, 918,
1
887, 825, 802 cm−1; H NMR (500 MHz, CDCl3) δ 2.42
(s, 3H), 7.27 (s, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.41-7.49
(m, 6H); 13C NMR (76 MHz, CDCl3) δ 21.1, 124.3, 128.8,
129.6, 130.4, 130.6, 135.3, 136.7, 137.3, 140.7, 141.8; MS
(FAB+): m/z (%) 311 ([M+H]+, 100), 154 (17), 136 (16),
93 (24); HRMS (FAB+) calcd for C15H13Cl2OS: 311.0064,
found: 311.0062.
4.3.4
(Z)-1-Chloro-4-[2-chloro-2-(p-
|
tolylsulfinyl)vinyl]benzene [(Z)-2d]
Colorless crystals (hexane/EtOAc); mp 131.0-134.1°C; IR
(ATR) 3031, 1592, 1490, 1403, 1084, 1051, 1013, 919, 886,
1
817, 671, 622 cm−1; H NMR (400 MHz, CDCl3) δ 2.42 (s,
3H), 7.33 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 8.6 Hz, 2H), 7.58
(s, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.70 (d, J = 8.6 Hz, 2H);

6 of 6
KIMURA et Al.
|
[6] a) T. Satoh, H. Ota, Tetrahedron 2000, 56, 5113; b) T. Satoh, J.
Endo, H. Ota, T. Chyouma, Tetrahedron 2007, 63, 4806; c) T.
Kimura, Y. Nishimura, N. Ishida, H. Momochi, H. Yamashita,
T. Satoh, Tetrahedron Lett. 2013, 54, 1049; d) T. Kimura, H.
Momochi, K. Moriuchi, T. Katagiri, Tetrahedron 2017, 58, 3505.
[7] T. Satoh, T. Kawashima, S. Takahashi, K. Sakai, Tetrahedron
2003, 59, 9599.
dried over MgSO4, and concentrated under reduced pressure.
The residue was purified by column chromatography on silica
gel (hexane–EtOAc, 50:1) and gel permeation chromatogra-
phy (CHCl3) to give 8a (119 mg, 0.900 mmol, 84%, Rf = 0.28
[hexane–EtOAc, 50:1]) as colorless oil.
[8] a) M. Mikołajczyk, W. Midura, M. Kajtar, Phosphorus, Sulfur
Silicon Relat. Elem. 1988, 36, 79; b) M. Mikołajczyk, W. H.
Midura, S. Grzejszczak, F. Montanari, M. Cinquini, M. W.
Wieczorek, J. Karolak-Wojciechowska, Tetrahedron 1994, 50,
8053; c) M. Mikołajczyk, J. A. Krysiak, W. H. Midura, M. W.
Wieczorek, J. Błaszczyk, Tetrahedron 1996, 7, 3513.
[9] a) P. A. Otten, H. M. Davies, A. van der Gen, Tetrahedron Lett.
1995, 36, 781; b) P. A. Otten, H. M. Davies, A. van der Gen,
Phosphorus, Sulfur Silicon Relat. Elem. 1996, 109, 449; c) P. A.
Otten, H. M. Davies, J. H. van Steenis, S. Gorter, A. van der Gen,
Tetrahedron 1997, 53, 10527.
ORCID
Tsutomu Kimura
http://orcid.org/0000-0003-0370-2836
REFERENCES
[1] T. Satoh, Chem. Rec. 2004, 3, 329.
[2] a) M. Watanabe, M. Nakamura, T. Satoh, Tetrahedron 2005, 61,
4409; b) T. Satoh, Y. Ogino, K. Ando, Tetrahedron 2005, 61,
10262; c) J. Sakurada, T. Satoh, Tetrahedron 2007, 63, 3806; d)
N. Mori, K. Obuchi, T. Katae, J. Sakurada, T. Satoh, Tetrahedron
2009, 65, 3509; e) T. Kimura, G. Kobayashi, M. Ishigaki, M.
Inumaru, J. Sakurada, T. Satoh, Synthesis 2012, 44, 3623; f)
T. Kimura, T. Satoh, J. Organomet. Chem. 2012, 715, 1; g) T.
Kimura, M. Watanabe, G. Kashiwamura, J. Sakurada, T. Satoh,
Synthesis 2013, 45, 659; h) T. Kimura, T. Satoh, Tetrahedron
2013, 69, 6371; i) T. Kimura, T. Satoh, Tetrahedron Lett. 2013,
54, 5072; j) T. Satoh, T. Kimura, J. Synth. Org. Chem Jpn. 2013,
71, 1033; k) T. Kimura, K. Fukuda, G. Kashiwamura, T. Satoh,
Heterocycles 2015, 90, 163.
[10] T. H. Kim, E. J. Lee, D. Y. Oh, Bull. Korean Chem. Soc. 1996, 17,
4.
[11] a) F. Eymery, B. Iorga, P. Savignac, Synthesis 2000, 2000, 185; b)
D. Habrant, V. Rauhala, A. M. P. Koskinen, Chem. Soc. Rev. 2010,
39, 2007.
[12] a) H. Yamashita, T. Satoh, Tetrahedron 2009, 65, 613; b) T. Satoh,
T. Sakamoto, M. Watanabe, K. Takano, Chem. Pharm. Bull.
2003, 51, 966; c) M. Kido, S. Sugiyama, T. Satoh, Tetrahedron
2007, 18, 1934.
[13] a) Y.-S. Feng, C.-Q. Xie, W.-L. Qiao, H.-J. Xu, Org. Lett. 2013,
15, 936; b) S. N. Aslam, P. C. Stevenson, S. J. Phythian, N. C.
Veitch, D. R. Hall, Tetrahedron 2006, 62, 4214.
[3] a) T. Satoh, Y. Hayashi, K. Yamakawa, Bull. Chem. Soc. Jpn.
1993, 66, 1866; b) T. Satoh, K. Takano, H. Ota, H. Someya, K.
Matsuda, M. Koyama, Tetrahedron 1998, 54, 5557.
[4] a) M. Braun, Angew. Chem. Int. Ed. 1998, 37, 430; b) G. Boche, J.
C. W. Lohrenz, Chem. Rev. 2001, 101, 697; c) R. Knorr, Chem. Rev.
2004, 104, 3795; d) E. Jahnke, R. R. Tykwinski, Chem. Commun.
2010, 46, 3235; e) V. Capriati, S. Florio, Chem. Eur. J. 2010, 16,
4152; https://doi.org/10.1055/s-0036-1590894
[5] a) T. Satoh, S. Sugiyama, Y. Kamide, H. Ota, Tetrahedron 2003,
59, 4327; b) T. Satoh, Y. Kamide, S. Sugiyama, Tetrahedron
2004, 60, 11805; c) H. Shimizu, S. Fukuda, S. Sugiyama, T.
Satoh, Synthesis 2009, 2009, 1323; d) T. Katae, S. Sugiyama, T.
Satoh, Synthesis 2011, 2011, 1435.
How to cite this article: Kimura T, Kobayashi G,
Ijima S, Saito S, Imafuji A, Satoh T. Efficient one-pot
synthesis of 1-chlorovinyl p-tolyl sulfoxides from
aldehydes and ketones by the Horner-Wadsworth-
Emmons reaction. Heteroatom Chem.
2017;28:e21395. https://doi.org/10.1002/hc.21395