(Diphenoxyphosphoryl)methyl p -tolyl sulfoxide: A new reagent for Z -selective synthesis of racemic and optically active vinyl sulfoxides

Article abstract of DOI:10.1080/10426507.2015.1114489

Racemic and optically active (+)-(S)-(diphenoxyphosphoryl)methyl p-tolyl sulfoxide were prepared and used as Horner olefination reagents. Their reaction with aromatic and aliphatic aldehydes afforded the corresponding racemic and enantiomeric α,β-unsatura

Full text of DOI:10.1080/10426507.2015.1114489

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
(Diphenoxyphosphoryl)methyl p-tolyl sulfoxide: A
new reagent for Z-selective synthesis of racemic
and optically active vinyl sulfoxides
Wanda H. Midura, Ashraf M. Mohamed Ewas & Marian Mikołajczyk
To cite this article: Wanda H. Midura, Ashraf M. Mohamed Ewas & Marian Mikołajczyk (2016)
(Diphenoxyphosphoryl)methyl p-tolyl sulfoxide: A new reagent for Z-selective synthesis of
racemic and optically active vinyl sulfoxides, Phosphorus, Sulfur, and Silicon and the Related
Elements, 191:3, 535-540, DOI: 10.1080/10426507.2015.1114489
To link to this article: http://dx.doi.org/10.1080/10426507.2015.1114489
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Date: 21 March 2016, At: 13:17

PHOSPHORUS, SULFUR, AND SILICON
, VOL. , NO. , –
http://dx.doi.org/./..
(Diphenoxyphosphoryl)methyl p-tolyl sulfoxide: A new reagent for Z-selective
synthesis of racemic and optically active vinyl sulfoxides
Wanda H. Midura, Ashraf M. Mohamed Ewas, and Marian Mikołajczyk
´
Department of Heteroorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Łódz, Poland
ABSTRACT
ARTICLE HISTORY
Received  September 
Accepted  October 
Racemic and optically active (+)-(S)-(diphenoxyphosphoryl)methyl p-tolyl sulfoxide were prepared and
used as Horner olefination reagents. Their reaction with aromatic and aliphatic aldehydes afforded the cor-
responding racemic and enantiomeric α,β-unsaturated sulfoxides with moderate to high Z-selectivity. The
E/Z ratio was found to be dependent on the structure of aldehyde, nature of base, reaction conditions, and
addition of 18-crown-6.
KEYWORDS
Chiral (diphenoxyphospho-
ryl)methyl p-tolyl sulfoxide;
vinyl sulfoxides; Horner
reaction; Z-selectivity
GRAPHICAL ABSTRACT
for the synthesis of variously substituted vinyl sulfoxides, which
were usually formed as separable mixtures of (E)- and (Z)-
isomers. The Horner olefination reaction with racemic and
(+)-(S)-(diphenylphosphinoyl)methyl p-tolyl sulfoxide 1b gave
almost pure (E)-vinyl sulfoxides, as reported later by van Stee-
nis and his coworkers.5 In an extension of our studies on the
synthesis of vinyl sulfoxides, it has been found that the Wit-
tig reaction of the in situ generated α-sulfinylphosphonium
ylide 2 with carbonyl compounds results in the formation of
racemic and optically active vinyl sulfoxides as almost pure
(E)-isomers.6
Introduction
α,β-Unsaturated sulfoxides (vinyl sulfoxides), both in racemic
and enantiomeric forms, received a considerable attention as
useful building blocks in the synthesis of diverse biologically
active compounds and as valuable intermediates in a variety
synthetic transformations and asymmetric reactions.1 Among
many methods and reagents used for the synthesis of vinyl
sulfoxides, α-phosphoryl sulfoxides 1 (Scheme 1), first synthe-
sized in racemic2,3 and optically active forms4 in our laboratory,
turned out to be the best reagents in the Horner olefination
reaction that afforded in good to high yields vinyl sulfoxides.
Interestingly, racemic and (+)-(S)-(dimethoxyphosphoryl)
methyl p-tolyl sulfoxide 1a has become a reagent of choice
Recently, extensive effort has been devoted to the syn-
thesis of (Z)-α,β-unsaturated esters using α-phosphoryl
acetates 3 as the Horner olefination reagents. These stud-
ies have indicated that (Z)-selectivity depends essentially
on the structure of phosphonate moiety. Thus, a high (Z)-
selectivity may be achieved with cyclic five-membered phos-
phonates,7 cyclic five-membered diamidophosphonates,8
di(2,2,2-trifluoroethoxy)phosphonates,9
phosphonates10,11 (Scheme 2).
and di(aryloxy)-
Based on the above observations on the synthesis of
(Z)-vinylic esters, Kokin et al.12 prepared racemic (di-2,2,2-
trifluoroethoxyphosphoryl)methyl p-tolyl sulfoxide 1c and
found that (Z)-vinyl sulfoxides were predominantly formed in
its reaction with aldehydes. In our independent studies aimed
at the synthesis of racemic and optically active (Z)-vinyl sulfox-
ides, we decided to prepare both racemic and optically active
Scheme . Structure of α-phosphoryl sulfoxide 1 and reagents used for the synthe-
sis of vinyl sulfoxides.
CONTACT Marian Mikołajczyk
marmikol@cbmm.lodz.pl
Academy of Sciences, Sienkiewicza , - Łódz´, Poland.
Department of Heteroorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish
This paper is dedicated to late Professor Reinhard Schmutzler–founder of the phosphorus-fluorine chemistry.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/gpss.
©  Taylor and Francis Group, LLC

536
W. H. MIDURA ET AL.
the (Z/E)-selectivity of this reaction (Scheme 5). Generally,
the Horner reaction of 1d with aldehydes was performed in
a THF solution at low temperature (−78°C) using different
strong bases (NaH, n-BuLi, t-BuOK, KH, KHMDS, and Tri-
ton B) for the α-phosphonate carbanion generation. After addi-
tion of an aldehyde at −78°C and stirring for a proper time
(see Tables 1 and 2), the reaction mixture was warmed to
proper temperature and quenched. The usual work-up pro-
cedure afforded the crude sulfoxides 6. After the determina-
tion of (Z/E)-ratio by gas chromatography (GC), the crude
6 were separated into pure (Z)- and (E)-isomers by column
chromatography.
To begin with, the reaction of 1d with benzaldehyde was
investigated. This model reaction resulted in the formation of
the already known (Z)- and (E)-sulfoxides 6a4 and allowed us
to determine the effect of various factors on the (Z/E)-selectivity.
The results obtained are summarized in Table 1.
Scheme . α-Phosphoryl acetates 3 used in the synthesis of (Z)-α,β-unsaturated
esters.
(diphenoxyphosphoryl)methyl p-tolyl sulfoxide 1d and inves-
tigate (Z)-selectivity of its reaction with aldehydes. The results
obtained13 are reported herein.
Results and discussion
Synthesis of racemic and optically active sulfoxide 1d
An inspection of the results in Table 1 revealed that in
almost all cases investigated the reaction gave quantitatively 2-
phenylvinyl p-tolylsulfoxide 6a. The (Z)-selective Horner reac-
tion was observed with all bases used for the α-phosphonate
carbanion generation with the exception of n-butyllithium (n-
BuLi). The use of the latter base preferred the formation
of the (E)-isomer of 6a (from 58 to 61%). Moderate (Z)-
selectivity around 60% was observed with NaH, t-BuOK, KH,
and KHMDS. A sharp increase in (Z)-selectivity (78%) was
attained when KHMDS/18-crown-6 (5 eq) was applied as a
basic system (Table 1, entry 12). However, it should be noted
that the presence of such a big amount of crown ether in the
reaction mixture makes the isolation and purification of 6a
less effective. An important effect of 18-crown-6 on the (E/Z)-
selectivity of the Horner reaction under discussion was addi-
tionally demonstrated by carrying out the reaction of racemic
α-phosphoryl sulfoxide 1a with benzaldehyde using n-BuLi on
the one hand, and KHMDS/18-crown-6 as a basic system on the
other. Whereas in the former case the (E/Z)-ratio of sulfoxide 6a
was 2:1, the reverse relationship was observed in the latter case
(Scheme 6).
Having established the most favorable conditions for the syn-
thesis of (Z)-sulfoxide 6a (Table 1, entries 10–12), the effect
of the structure of an aldehyde on (E/Z)-selectivity in the
Horner reaction of 1d was examined as the second step of
the present study. Thus, the following aldehydes were used
as the Horner reaction partners with α-phosphoryl sulfox-
ide 1d: para-bromobenzaldehyde, ortho-bromobenzaldehyde,
acetaldehyde, and 4-pyridylcarboxyaldehyde. As in the case
of benzaldehyde, the corresponding vinyl sulfoxides 6b–
e were obtained in high yields (85–94%). Some experi-
mental data (base, conditions, Z/E-ratio) are collected in
Table 2.
The racemic sulfoxide ( )-1d was easily and efficiently pre-
pared in two steps (Scheme 3). At first, the Arbuzov reac-
tion of diphenylmethyl phosphite with chloromethyl p-tolyl sul-
fide gave upon heating the corresponding (diphenoxyphospho-
ryl)methyl p-tolyl sulfide 4 in 81% yield. This, in turn, was selec-
tively oxidized to ( )-1d by hydrogen peroxide in methanol in
the presence of a H2SO4/i-PrOH mixture as a catalyst.14 This
procedure afforded the desired sulfoxide ( )-1d in 83% yield as
a white solid. For comparison purposes, the corresponding sul-
fone 5 was synthesized by oxidation of ( )-1d with hydrogen
peroxide using selenium dioxide as a catalyst.
The synthesis of optically active sulfoxide 1d turned out
to be somewhat complicated and less effective. Our stan-
4
dard procedure
for the synthesis of optically active α-
phosphoryl sulfoxides 1 involving at first generation of α-
phosphonate carbanion and subsequent addition of (-)-(S)-
menthyl p-toluenesulfinate failed. It was found (31P NMR
assay) that the generated (diphenoxyphosphoryl)methyl car-
banion reacts at once with diphenyl methanephosphonate to
form the corresponding bis-phosphonate A (Scheme 4, reaction
a). This nucleophilic substitution reaction at P occurs due to a
good leaving group ability of the P-phenoxy substituent. There-
fore, in a modified procedure both diphenyl methanephos-
phonate and (-)-(S)-menthyl p-toluenesulfinate were placed in
the reaction vessel and then potassium hexamethyldisilazane
(KHMDS) was added to this mixture under standard conditions
(tetrahydrofuran (THF), −78°C). Analysis of the crude reaction
1
product by H NMR and 31P NMR spectra revealed that it
consisted of the starting phosphonate (50%), expected sul-
foxide 1d (30%), and menthylphenyl methanephosphonate B
as a side reaction product (Scheme 4, reaction b). The pure
optically active sulfoxide (+)-(S)-1d was obtained by flash
chromatography.
It was found that the reaction of 1d with bromo-substituted
benzaldehydes was highly Z-selective. The highest (Z/E)-ratio
(93/7) was obtained with ortho-bromobenzaldehyde, suggest-
ing that steric hindrance in the ortho position of the aromatic
ring may play essential role in controlling selectivity. Unex-
pectedly, 4-pyridinecarboxyaldehyde afforded under the same
experimental conditions an inseparable mixture of Z and E vinyl
sulfoxides 6e, the latter being the major one (Table 2, entry 5).
Synthesis of vinyl sulfoxides by the Horner reaction of
(diphenoxyphosphoryl)methyl p-tolyl sulfoxide with
aldehydes and (Z/E)-selectivity
Having a new Horner olefination reagent 1d in hand, we could
use it for the synthesis of vinyl sulfoxides 6 and investigate

PHOSPHORUS, SULFUR, AND SILICON
537
Scheme . Synthesis of racemic olefination reagent 1d.
Scheme . Synthesis of optically active α-phosphoryl sulfoxide 1d and accompanying side reactions.
Scheme . Vinyl sulfoxides 6 from the Horner reaction of 1d with aldehydes.
examined. Although the reaction of racemic sulfoxide ( )-1d
with aromatic aldehydes showed the highest Z-selectivity in the
presence of KHMDS/5 eq 18-c-6 as a basic system (Table 1,
entry 12), the reaction of (+)-1d with benzaldehyde was per-
formed with 1 equivalent of crown ether and that with o-
bromobenzaldehyde in its absence to avoid some problems con-
nected with isolation of products and separation of pure (Z)- and
(E)-isomers. In Scheme 7, some experimental data for these two
reactions performed according to a general procedure are given.
Since the synthesis of optically active α-phosphoryl sulfox-
ide (+)-(S)-1d described above was not efficient, the (Z)- and
(E)-isomers of both optically active sulfoxides 6a and 6c were
also prepared by a one-pot procedure described by Craig et al.15
from three components: diphenyl methanephosphonate, (-)-
(S)-menthyl p-toluenesulfinate, and benzaldehyde in the pres-
ence of KHMDS as a base. In this procedure, α-phosphoryl
sulfoxide 1d is not isolated since its carbanion generated from
phosphonate and sulfinate reacts in situ with aldehyde. In
our hands, this one-pot procedure gave the desired optically
active vinylic sulfoxides 6a and 6c, however, with lower (Z/E)-
selectivity (ca. 1:1) and lower yields of the isolated products (ca.
40%).
Scheme. Dependenceof(E/Z)-selectivityonthenatureofbaseintheHornerreac-
tion of 1a.
As vinyl sulfoxides 6b, 6c, and 6e are new compounds, their
Z- and E-isomers were characterized by 1H NMR spectroscopy.
Assignment of configurations Z and E to the respective isomers
of the above-mentioned sulfoxides was based on the well-known
geometrical dependence of vicinal proton coupling constants in
olefins. The 1H NMR spectra of these three sulfoxides reveal AB
systems for trans and cis vinyl protons with 3JH–H of ca. 15.5 and
10.5 Hz, respectively.
Finally, the synthesis of optically active vinyl sulfoxides using
(+)-(S)-1d as a new chiral Horner olefination reagent was briefly

538
W. H. MIDURA ET AL.
Scheme . Synthesis of optically active vinyl sulfoxides 6.
Table . Reaction of α-phosphoryl sulfoxide 1d with benzaldehyde.
ultraviolet (UV) light. THF was freshly distilled over potas-
sium/benzophenone.
Entry Base
Reaction conditions
(Z/E)-ratiob Conversion (%)a













n-BuLi
n-BuLi
NaH
NaH
NaH
t-BuOK
t-BuOK
KH
KHMDS
KHMDS
−°C,  min
−°C,  min → −°C
−°C,  h → −°C
−°C,  h
/
/
/
/
/
/
/
/
/
/
/
/
-












c
Diphenoxyphosphoryl)methyl p-tolyl sulfide (4)
−°C → rt
A mixture of diphenylmethyl phosphite (12.4 g, 0.05 mol) and
chloromethyl p-tolyl sulfide (8.5 g, 0.05 mol) was heated at 150–
160°C for 10 h. The crude α-phosphoryl sulfide 4 formed was
purified by column chromatography to give sulfide 4 (15.2 g)
−°C,  min → −°C
−°C,  min → −°C
−°C,  min → −°C
−°C,  h
−°C → -°C,  h
1
in 82% yield as a semi-solid, m.p. 21°C, H NMR (300 MHz,
KHMDS −°C → rt,  eq -crown-
KHMDS −°C → rt,  eq -crown-
CDCl3) δ: 2.32 (s, 3H, CH3), 3.40 (d, 2H, J = 13.4 Hz, CH2P),
7.1–7.4 (m, 14H, HAr); 31P NMR (24.3 MHz, CDCl3) δ: 17.3;
13C NMR (80 MHz, CDCl3) δ: 20.6, 29.1 (d, J = 148 Hz, CH2P),
115.9, 120.2, 120.3, 125.1, 128.9, 129.4, 129.6, 131.1, 137.4, 149.6,
149.8, 156.6; MS (EI, 70 eV) m/z: 370.0 (M+, 100%), 247.8
(M+-STol, 8.3%), 137.0 [M+-(PhO)2P(O), 83%]; Anal. calc for
C20H19O3PS (370.4): C 64.85, H 5.17, S 8.65; Found: C 64.79, H
5.20, S 8.68.
Triton B
−°C → −°C
a
b
c
Determined by H NMR spectra of the crude reaction product.
Determined by gas chromatography.
Starting sulfoxide 1d was recovered.
Experimental
General experimental details
1H NMR and 13C NMR spectra were recorded on Bruker DRX
500, Bruker MSL 300, and Bruker AC 200 spectrometers using
(Diphenoxyphosphoryl)methyl p-tolyl sulfoxide (1d)
deuterochloroform as a solvent. 31P NMR spectra were recorded To a solution of 4 (1.85 g, 0.05 mol) and catalyst (1.2 g, prepared
on a Jeol JNM-FX 60 spectrometer. Mass spectra were recorded from 1.38 g of 96% H2SO4 and 30 g of isopropanol) in MeOH
on Finnigan MAT95. The optical rotations were measured on (10 mL), 30% hydrogen peroxide (1.2 g, 0.011 mol) was added
a Perkin-Elmer 241 MC photopolarimeter at 20°C. The micro- at once to the stirred reaction mixture. The progress of oxida-
analyses were performed on an Elemental Analyzer EA 1108. tion was followed by TLC (silica gel, benzene/methanol (10:1),
Thin-layer chromatography (TLC) was carried out on silica iodine vapors as developer). After 10 h, oxidation was complete
gel plates (Merck F254). Silica Gel 60 (70-230 ASTM) was and water (150 mL) was added to the reaction mixture. Aque-
used for chromatography, and visualization was achieved by ous phase was extracted with CHCl3 (3 × 30 mL) and com-
bined chloroform extracts were dried over anhydrous MgSO4
and evaporated to give crude α-phosphoryl sulfoxide 1d. Purifi-
Table . Reaction of α-phosphoryl sulfoxide 1d with aldehydes, RCHO.
cation by column chromatography provided sulfoxide 1d (1.6 g,
83%) as a white solid, m.p. 57°C. 1H NMR (300 MHz, CDCl3) δ:
2.40 (s, 3H, CH3), 3.50–3.65 (d, 2H, CH2, AB part of ABX sys-
tem), 7.10–7.35 (m, 12H, HAr), 7.64–7.68 (d, 2H, J = 8.2 Hz,
Entry
R
Base
Conditions
6/y (%) Z/E-ratio

CH
KHMDS/-c- −°C → rt, overnight 6a/
/
/
/
/
/
/





p-BrCH KHMDS/-c- −°C → rt, overnight 6b/
o-BrCH KHMDS
−°C → rt, overnight 6c/
part of [AB]2 system); 31P NMR (24.3 MHz, CDCl3) δ: 9.7; 13
C
o-BrCH KHMDS/-c- −°C → rt, overnight 6c/
NMR (80 MHz, CDCl3) δ: 21.4, 54.1 (d, J = 140.4 Hz, CH2P),
115.3, 119.9, 120.4, 120.5, 124.3, 125.7, 129.3, 129.8, 130.2; MS
(EI, 70eV) m/z: 386 (M+, 8.3%), 247 [M+-S(O)Tol, 16.6%], 293
Me
KHMDS
KHMDS
−°C → rt, overnight 6d/
−°C → rt, overnight 6e/
-CHN

PHOSPHORUS, SULFUR, AND SILICON
539
(M+-PhO, 100%); Anal. calc. for C20H19O4PS (386.4): C 62.17,
H 4.95, S 8.29; Found: C 62.20, H 4.91, S 8.28.
2-Phenylvinyl p-tolyl sulfoxide (6a)
The crude product (0.05 g, 87%) obtained from benzaldehyde
(0.03 g, 0.23 mmol) consisted of Z- and E-isomers in a ratio 78:22
(1H NMR assay), which were separated by column chromatog-
raphy.
(Diphenoxyphosphoryl)methyl p-tolyl sulfone (5)
Z-6a: 1H NMR (300 MHz, CDCl3) δ: 2.40 (s, 3H, CH3), 6.40
(AB system, 1H, JAB = 10.6 Hz, Hvinyl), 7.01 (AB system, 1H,
JHH = 10.5 Hz, Hvinyl), 7.10–7.50 (m, 9H, HAr); Anal. calc. for
C15H14OS (242.3) C 74.35, H 5.82, Found: C 74.39, H 5.78.
E-6a: 1H NMR (300 MHz, CDCl3) δ: 2.40 (s, 3H, CH3), 6.80
(AB system, 1H, JAB = 15.5 Hz, Hvinyl), 7.10–7.50 (m, 9H, HAr
+ 1H, part of AB system, Hvinyl); Anal. calc. for C15H14OS
(242.3) C 74.35, H 5.82, Found: C 74.32 H 5.85.
To a solution of sulfoxide 4 (1.93 g, 0.005 mol) and SeO2
(0.06 g) in methanol (15 mL), hydrogen peroxide (0.25 mL) was
added. The progress of oxidation was followed by TLC (silica
gel, petroleum ether–acetone, 2:1). After completion of oxida-
tion (15 h), water (50 mL) was added to the reaction mixture.
Aqueous phase was extracted with CHCl3 (3 × 15 mL) and
the extract was dried over anhydrous MgSO4. Removal of chlo-
roform gave α-phosphoryl sulfone 5 (1.93 g, 96%) as a white
1
solid, m.p. 62°C; H NMR (300 MHz, CDCl3) δ: 2.40 (s, 3H,
CH3), 4.01 (d, 2H, JHP = 16.9 Hz, CH2P), 7.10–7.30 (m, 12H,
HAr), 7.69–7.80 (d, 2H, [AB]2 system, J = 8.3 Hz); 31P NMR
(24.3 MHz, CDCl3) δ: 4.9; 13C NMR (80 MHz, CDCl3) δ: 21.1,
53.0 (d, J = 139.8 Hz, CH2P), 120.4, 120.5, 125.3, 128.1, 129.4,
129.5, 137.1, 144.8, 149.6; MS (EI, 70eV) m/z: 402 (M+, 16%),
247 [M+-S(O)2Tol, 100%], 309 (M+-PhO, 8.4%); Anal. calc. for
C20H19O5PS (402.4): C 59.69, H 4.76, S 7.96; Found: C 59.66, H
4.79, S 7.94.
2-(4-Bromophenyl)vinyl p-tolyl sulfoxide (6b)
The crude product (0.15 g, 94%) obtained from p-
bromobenzaldehyde (0.1 g, 0.5 mmol) was a mixture of Z-
and E-isomers in a ratio 76:24. These were separated by col-
umn chromatography (petroleum ether–acetone (100:2)) and
obtained in analytically pure state.
Z-6b: 1H NMR (300 MHz, CDCl3) δ: 2.40 (s, 3H, CH3), 6.40
(d, 1H, JAB = 10.6 Hz, Hvinyl), 6.90 (d, 1H, J = 10.5 Hz, Hvinyl),
7.20–7.50 (m, 8H, HAr); Anal. calc. for C15H13OSBr (321.2): C
56.09, H 4.08; Found: C 56.04, H 4.20.
1
(+)-(S)-(Diphenoxyphosphoryl)metyl p-tolyl sulfoxide (1d)
E-6b: H NMR (300 MHz, CDCl3) δ: 2.40 (s, 3H, CH3),
6.80 (d, 1H, JAB = 15.3 Hz, Hvinyl), 7.10–7.50 (m, 8H, HAr +
1H, Hvinyl); Anal. calc. for C15H14OS (321.2): C 56.09, H 4.08;
Found: C 56.12 H 4.04.
To a solution of diphenyl methanephosphonate (0.55 g,
0.0022 mol) and (-)-(S)-menthyl p-toluenesulfinate (0.56 g,
0.002 mol) in THF (50 mL), KHDMS (4.84 mL) was added
dropwise at −78°C. The reaction mixture was stirred at −78°C
for 1 h and then allowed to warm up to −40°C. The reaction
was quenched at this temperature with aqueous NH4Cl solution. 2-(2-Bromophenyl)vinyl p-tolyl sulfoxide (6c)
The aqueous phase was extracted with CHCl3 (3 × 100 mL),
The crude product (0.14 g, 87.5%) obtained from o-
and chloroform extract was dried over anhydrous MgSO4 and
bromobenzaldehyde (0.11 g, 0.5 mmol) and comprising Z-
evaporated. The residue containing unreacted diphenyl phos-
and E-isomers in a ratio of 93:7 gave after column chromatog-
phonate (ca. 50%, δ = 24 ppm), desired sulfoxide 1d (ca. 30%,
P
raphy (petroleum ether–acetone (100:2)) both pure isomers.
δ = 9.7 ppm), and menthylphenyl phosphonate B (ca. 20%,
P
Z-6c: 1H NMR (300 MHz, CDCl3) δ: 1.90 (s, 3H, CH3), 6.20
δ
= 27.2–26.6 ppm) was purified by flash chromatography
P
(d, 1H, JAB = 10.3 Hz, Hvinyl), 6.60 (d, 1H, JAB = 10.4 Hz,
Hvinyl), 6.90–7.80 (m, 8H, HAr); Anal. calc. for C15H13OSBr
(321.2): C 56.09, H 4.08; Found: C 56.05, H 4.12.
(petroleum ether/acetone). The separated sulfoxide (+)-(S)-1d,
[α]D = +68.0 (c 1.2, Me2CO), (0.22 g, 28%) exhibited the same
spectral properties as ( )-1d.
1
E-6c: H NMR (300 MHz, CDCl3) δ: 1.90 (s, 3H, CH3),
6.50 (d, 1H, JAB = 15.3 Hz, Hvinyl), 6.90–7.80 (m, 8H, HAr +
1H, Hvinyl); Anal. calc. for C15H14OS (321.2): C 56.09, H 4.08;
Found: C 56.14 H 4.03.
General procedure for synthesis of vinyl sulfoxides 6a–e
To a solution of α-phosphoryl sulfoxide 1d (0.193 g, 0.5 mmol)
in THF (15 mL), solution of a base (0.6 mmol) in THF was
added at −78°C. After 30 min, the reaction solution became
2-(4-Pyridyl)vinyl p-tolyl sulfoxide (6e)
yellow. Then a solution of an aldehyde (0.05 mmol) in THF The crude product (0.1 g, 85%) arising from the reaction with
(5 mL) was added dropwise at −78°C and the reaction mixture 4-pyridinecarboxyaldehyde (0.03 mL, 0.3 mmol) comprised Z-
was stirred for 30 min at this temperature. After warming the and E-isomers in a ratio 34:66. This mixture was purified by flash
1
reaction solution to a desired temperature it was quenched with chromatography. Analysis of H NMR spectrum of the above
aqueous NH4Cl. Aqueous phase was extracted with CHCl3 (3 × Z/E mixture allowed to assign proton resonances to the corre-
25 mL), and organic phase was dried over anhydrous MgSO4 sponding isomers.
and evaporated. The crude sulfoxides 6 obtained were purified
Z-6e: 1H NMR (300 MHz, CDCl3) δ: 2.42 (s, 3H, CH3), 6.60
by flash chromatography (petroleum ether) and separated into (d, 1H, JAB = 10.6 Hz, Hvinyl), 7.15 (d, 1H, JAB = 10.5 Hz,
corresponding Z- and E-isomers. Hvinyl), 7.20–7.70 (m, 8H, HAr).

540
W. H. MIDURA ET AL.
E-6e: 1H NMR (300 MHz, CDCl3) δ: 2.42 (s, 3H, CH3), 7.00
sulfoxide 6c, which upon column chromatography was sep-
arated into Z-(-)-(R)-6c: [α]D = −450.0 (c 1.1, Me2CO) and
E-(+)-(R)-6c: [α]D = +76.5 (c 1.4, Me2CO) in almost equal
amounts.
(d, 1H, JAB = 15.5 Hz, Hvinyl), 7.20–7.80 (m, 8H, HAr + 1H,
Hvinyl);
Anal. calc. for C14H13ONS (243.3): C 69.11, H 5.38; Found:
C 69.14 H 5.35.
References
One-pot synthesis of (S)-2-phenylvinyl p-tolyl sulfoxide
(6a)
1. Mikołajczyk, M.; Drabowicz, J.; Kiełbasin´ski, P. Chiral Sulfur Reagents:
Applications in Asymmetric and Stereoselective Synthesis; CRC Press
LLC: Boca Raton, FL, 1997, pp. 144–178.
A solution of KHMDS (2 mmol) in THF was added dropwise to
a solution of diphenyl methanephosphonate (0.26 g, 1 mmol),
(-)-(S)-menthyl p-toluenesulfinate (0.29 g, 1 mmol), and 18-
crown-6 (1.9 g, 1 mmol) in THF (30 mL) at −78°C. The result-
ing reaction mixture was stirred for 1 h. A solution of benzalde-
hyde (0.2 mL, 2 mmol) in THF was then added. The reaction
mixture was warmed slowly to room temperature and stirred
overnight. The reaction was quenched with saturated aqueous
NH4Cl (10 mL). The water phase was extracted with diethyl
ether (3 × 30 mL). Organic phase was dried over anhydrous
MgSO4, filtered off, and evaporated. The residue was purified
by column chromatography (benzene–acetone), and Z- and E-
isomers of 6a formed in equal amounts were separated.
Z-(R)-6a: [α]D = −735.0 (c 1.4, CHCl3); E-(R)-6a:
[α]D = +166.0 (c 1.1, CHCl3).
2. Mikołajczyk, M.; Zatorski, A. Synthesis 1973, 669–670.
3. Mikołajczyk, M.; Grzejszczak, S.; Zatorski, A. J. Org. Chem. 1975, 40,
1979–1984.
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Chefczyn´ska, A. J. Org. Chem. 1978, 43, 473–478.
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640.
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Some Heteroorganic Compounds of Possible Biological Activities, Ain
Shams University, Cairo, 2001.
One-pot synthesis of 2-(2-bromophenyl)winyl p-tolyl
sulfoxide (6c)
14. Drabowicz, J.; Łyz˙wa, P.; Popielarczyk, M.; Mikołajczyk, M. Synthesis
1990, 937–938.
The same procedure as described above with 2-
bromobenzaldehyde (0.4 mL, 2 mmol) gave the crude vinyl
15. Craig, D.G.; Daniels, K.; Marsh, A.; Reinford, D.; Smith, A. M. Synlett
1990, 531–532.