An efficient preparation of β-dimethylaminovinyl sulfone and sulfoximide, and investigation of their reactivity as dipolarophiles

Article abstract of DOI:10.1002/jhet.5570420420

A simple reaction affording (E)-1-dimethylamino-2-phenylsulfonylethylene, and S-((E)-2-(N′N′-dimethylamino)ethenyl)-5-phenyl-N-(p- tolylsulfonyl) sulfoximide in high yields is described. A reversal in regioselectivity was observed when the ss-dimethylamin

Full text of DOI:10.1002/jhet.5570420420

An Efficient Preparation of β-Dimethylaminovinyl Sulfone and
Sulfoximide, and Investigation of Their Reactivity as Dipolarophiles
Nela Peša*, Chris J. Welch and Andrew N. Boa
May-Jun 2005
599
Department of Chemistry, University of Hull, Cottingham Road, Hull, HU6 7RX, U.K.
Received October 25, 2004
A simple reaction affording (E)-1-dimethylamino-2-phenylsulfonylethylene, and S-((E)-2-(N',N'-
dimethylamino)ethenyl)-S-phenyl-N-(p-tolylsulfonyl) sulfoximide in high yields is described. A reversal in
regioselectivity was observed when the β-dimethylaminovinyl sulfone was employed as a dipolarophile in
cycloadditions with nitrile oxides. The sulfone gives rise mainly to 4-substituted isoxazoles, after elimina-
tion of dimethyl amine. In comparison, phenyl vinyl sulfone cycloadds to give 5-substituted isoxazolines.
Although not showing comparable dipolarophilic activity in reactions with nitrile oxides and nitrile imides,
the β-dimethylaminovinyl sulfoximide was easily converted to S-((E)-(3-ethoxycarbonyl)prop-2-enyl)-S-
phenyl-N-(p-tolylsulfonyl) sulfoximide. This allylic sulfoximide cycloadds in good yield to both benzoni-
trile oxide and diphenylnitrile imide, but no stereoselectivity was observed in the process; and only modest
regioselectivity was detected in the case of benzonitrile oxide.
J. Heterocyclic Chem., 42, 599 (2005).
1,3-Dipolar cycloaddition reactions provide powerful
ful and can in many cases be used to make products with
high degrees of asymmetric induction [5]. Considering the
versatility of sulfonimidoyl functional group, and the pos-
sibility for obtaining chiral compounds with this moiety, it
was suggested that there should be more investigation of
dipolarophilic activity of vinylic sulfoximides [6].
synthetic methodology for the preparation of a wide range
of useful heterocycles, as well as advanced synthetic inter-
mediates [1]. The great scope of 1,3-dipolar cycloadditions
in organic synthesis stems from the large number of avail-
able 1,3-dipoles and the possibility of any double or triple
bond, including heteromultiple bonds, to react as dipo-
larophiles. As part of a program investigating novel dipo-
larophiles we decided to investigate methods for simple
preparation of new sulfur-containing alkenes, such as sub-
stituted vinyl sulfones and sulfoximides (sulfoximines
according to CAS). Barzaghi et al. reported the effect of
the sulfinyl and sulfonyl group on the reactivity of alkene
dipolarophiles and regioselectivity in 1,3-dipolar cycload-
ditions with diphenylnitrile imide and 3,5-dichloromesityl-
nitrile oxide [2]. Although similar results were obtained by
Shimizu et al. [3], their interpretations were different, sug-
gesting that the combination of both electron-withdrawing
effect of the sulfonyl group and the effect of other sub-
stituents on the double bond influence the regioselectivity
in cycloadditions. Thus, we were interested in investigat-
ing further such effects. Moreover, 1,3-dipolar cycloaddi-
tion reactions of sulfoximides has only briefly been
reported by Pyne et al. [4]. Reactants involving chiral moi-
eties in either dipole or dipolarophile are additionally use-
Herein, we report a facile synthesis of (E)-1-dimethy-
lamino-2-phenylsulfonylethylene (4) and its sulfoximide
analogue, S-((E)-2-(N',N'-dimethylamino)ethenyl)-S-
phenyl-N-(p-tolylsulfonyl) sulfoximide (5). In a previous
report, the sulfone 4 was prepared in moderate yield (60%)
by Peterson-type olefination reaction [7]. Although the
Peterson reaction is most often employed in olefin-synthe-
sis, this method involving multiple steps is quite difficult,
especially when applied to preparation of vinyl sulfox-
imides. Amongst several alternatives to the Peterson olefi-
nation, we found the method of Jackson [8] to work the
best, and by this method we prepared from S-methyl-S-
phenyl-N-(p-tolylsulfonyl)sulfoximide (1) several differ-
ent vinyl sulfoximides (2a-d), ranging from poor to good
yields (Scheme 1). Reaction of phenyl methyl sulfone (3)
with N,N-dimethylformamide dimethyl acetal in refluxing
dry DMF, however, gave dimethylamino vinyl sulfone 4 in
excellent yield, with high selectivity and only the E-isomer
was isolated. The reaction was equally successful with

600
N. Peša, C. J. Welch, and A. N. Boa
Vol. 42
S-methyl-S-phenyl-N-(p-tolylsulfonyl)sulfoximide (1),
affording the corresponding dimethylamino vinyl sulfox-
imide 5 (Scheme 2).
aldoxime 7a-d in DCM was added BTMA ICl and the
4
green suspension was stirred at room temperature for ten
minutes. In this period the hydroximoyl chloride formed as
indicated by the clear yellow solution, due to formation of
soluble BTMA ICl . The dipolarophile was then added,
2
followed by two equivalents of triethylamine. In the reac-
tions of nitrile oxides with phenyl vinyl sulfone (6), 5-
phenylsulfonyl-2-substituted isoxazolines 8a-d were
obtained almost exclusively, while the opposite regioiso-
mer 4-phenylsulfonyl-2-substituted isoxazoline was iso-
lated only in one case (9d, R = CH ). Barzaghi et al.
3
reported that 1,3-dipolar cycloaddition of 3,5-dichlorome-
sitylnitrile oxide with phenyl vinyl sulfone gave mostly 5-
phenylsulfonyl-2-isoxazoline (73%), with a small amount
of opposite regioisomer, 4-phenylsulfonyl-2-isoxazoline
(7%) [2]. Our results with different nitrile oxides are there-
fore generally in agreement with the 5-phenylsulfonyl-2
isoxazoles being isolated as the major or sole cycloadduct
(Scheme 3).
In reactions with enamine 4 isoxazolines were not
detected, rather the corresponding isoxazoles 10 and 11
resulting from elimination of dimethylamine were
obtained. A reversal in regioselectivity was also observed
and the 4-phenylsulfonyl isoxazoles were obtained in these
cases. The 5-phenylsulfonylisoxazole was only detected in
one case (10c). The yields however were at best modest,
one possible reason being the aforementioned stability of 4,
and the reaction with pivaladoxime and benzaldoxime were
When the same method was applied to the correspond-
ing sulfoxide there was unfortunately no reaction, not even
when catalytic p-TsOH was added. Paley and Snow have
prepared a variety of unsaturated sulfoximides from β-
tosyloxy-(E)-vinyl sulfoximide, which undergoes an addi-
tion-elimination process with higher-order cuprate nucle-
ophiles [9]. We hoped that the enamines 4 and 5 would
behave in a similar fashion so we investigated briefly the
possibility of preparing other unsaturated sulfones and sul-
foximides from these compounds. However, reaction of 4
and 5 with simple nucleophiles (e.g. malonate salts and
simple organometallic reagents) under a wide variety of
conditions were unsuccessful, but copper(I) catalysed
methods as per Paley and Snow have not yet been investi-
gated. Modest success in preparing new vinyl sulfoximides
was achieved with simple amine-exchange reactions. The
lack of reactivity of either the enamine or sulfonyl/sulfon-
imidoyl functions is most likely due to resonance stabilisa-
tion of 4 and 5 (Figure 1); a similar example can be found
in the work of Hyatt and Krutak [10].
unsuccessful with BTMA ICl ; many more by-products
4
formed and the desired adducts could not be conclusively
identified amongst them. An alternative procedure was
investigated to generate the dipole in the case of benzoni-
trile oxide. Following the method described previously
[12], benzaldehyde oxime was pre-chlorinated using N-
chlorosuccinimide (NCS). Without further purification, the
benzohydroximoyl chloride was dissolved in chloroform
with enamine 4, followed by addition of triethylamine. In
this case the reaction was cleaner, and after heating at reflux
for two days isoxazole 11a was isolated, along with the
furoxan dimer [13] of the dipole (Scheme 3).
Similarly, Zong et al. reported on reversed regioselectiv-
ity achieved by the cycloaddition of methyl 3-(p-nitroben-
zoyloxy)acrylate to a variety of substituted benzonitrile
oxides [14]. Also, only 4-substituted isoxazole was iso-
lated from the reaction of 2-methoxyvinyl phenyl ketone
with benzonitrile oxide [15]. Both dipolarophiles,
2-methoxyvinyl phenyl ketone and enamine 4, have one
electron-donating (EDG) and one electron-withdrawing
(EWG) group attached on the opposite sides of the double
bond. It is believed that such dipolarophiles have a HOMO
more polarised on the carbon adjacent to EWG, and the
To investigate the dipolarophilic activity of the enamine
4, and the possible effect of dimethylamino group on reac-
tivity and regioselectivity of cycloadditions, we decided to
carry out 1,3-dipolar cycloadditions of 4 with nitrile
oxides, and compare these results to the corresponding
reactions using unfunctionalised phenyl vinyl sulfone (6).
α-Chloroximes, precursors to the desired nitrile oxides,
were conveniently generated using benzyl trimethylammo-
LUMO has larger coefficient on the carbon where the EDG
is attached. In this case, both dipole LUMO-dipolarophile
nium tetrachloroiodate (BTMA ICl ) [11]. To a solution of
4

May-Jun 2005
An Efficient Preparation of β-Dimethylaminovinyl Sulfone and Sulfoximide
601
HOMO and dipole HOMO-dipolarophile LUMO interac-
tions lead to isoxazolines/isoxazoles with the EWG in
4-position. In our case, therefore, 4-phenylsulfonyl isoxa-
zoles 11 were isolated. It may be noticed that there is an
effect, possibly steric, of the substituent R on nitrile oxide,
on the reactivity and regioselectivity of the dipole in
cycloaddition. The best yield of the product was obtained
with methyl group as substituent. In the case of phenyl
substituent, it was more difficult to achieve cycloaddition
and an alternative route had to be found, affording lower
yield of the product. With ethyl, also a small amount of the
opposite regioisomer 10c was isolated, and for R = t-butyl
product could not be isolated.
Although slightly detrimental on the yield, the dimethyl-
amino group of the enamine 4 showed the effect of the
reversed regioselectivity in 1,3-dipolar cycloaddition reac-
tions with nitrile oxides. The sulfoximide analogue 5, on
the other hand, showed no dipolarophilic activity in the
same reactions. In fact, other vinyl sulfoximides, which we
prepared to the method of Jackson [8] as previously men-
tioned, were also unreactive using same nitrile oxides as
1,3-dipoles. Attempted cycloadditions of these vinyl sul-
foximides with diarylnitrile imides were unsuccessful as
well. These reactions were extensively investigated under
a range of conditions, and usually dipole dimerisations/self
condensation reactions appeared to take place and the
vinyl sulfoximide was recovered intact. Thus, we can only
confirm that vinyl sulfoximides are poor dipolarophiles,
with only one example of their dipolarophilic activity in
the reactions with nitrones [4]. Apart from attempting to
use different type of dipoles, molecular orbital calculations
might be needed to understand better how vinyl sulfox-
imides could be useful in 1,3-dipolar cycloaddition reac-
tions in the future.
pected result of one of the attempted cycloaddition reactions
using vinylic sulfoximide led us to believe that allylic sulfox-
imides actually might be interesting dipolarophiles to study.
This attempted cycloaddition undertaken was between α-
chlorobenzaldehyde phenylhydrazone (12) [16] and S-((E)-
prop-1-enyl)-S-phenyl-N-(p-tolylsulfonyl) sulfoximide (2b)
[8] in toluene. To enhance the dehydrohalogenation process
silver tetrafluoroborate was added and the mixture heated at
reflux for 24 h. None of the expected cycloadducts were
identified; however S-(prop-2-enyl)-S-phenyl-N-(p-tolylsul-
fonyl) sulfoximide (13) was recovered along with a small
amount of 1,3-diphenyl-5-([S-phenyl-N-toluene-4-
sulfonyl]sulfoximinylmethyl)-4,5-dihydro-1H pyrazoline
(14) as a 1:1 mixture of diastereoisomers. The allylic sulfox-
imide 13, formed presumably as the result of base-catalyzed
isomerization [17] of vinyl sulfoximide 2b, which then gave
rise to the pyrazoline 14 by cycloaddition (Scheme 4). We
decided therefore to look further at allylic sulfoximides.
There are only a few methods describing general prepa-
rations of allylic sulfoximides [6], but we envisaged a
Interestingly, to our knowledge, there are no reports on
dipolarophilic activity of allylic sulfoximides. An unex-

602
N. Peša, C. J. Welch, and A. N. Boa
Vol. 42
straightforward route to such sulfoximides using enamine
5. This was hydrolysed to S-(2-oxoethyl)-S-phenyl-N-(p-
tolylsulfonyl) sulfoximide (15). Although aldehyde 15
seemed to be obtained in very good yield, it was found to be
unstable and without further purification was then con-
densed with ethoxycarbonylmethylene triphenylphospho-
rane [18] to give S-((E)-(3-ethoxycarbonyl)prop-2-enyl)-S-
phenyl-N-(p-tolylsulfonyl) sulfoximide (16). Although not
further investigated, the aldehyde 15 should react in princi-
ple with a range of Wittig reagents, thus providing a general
stereospecific route to allylic sulfoximides. The corre-
sponding aldehyde from sulfone enamine 4 was found to be
quite water soluble and also volatile, so obtaining
reasonable yields proved very difficult using this
approach.
Allylic sulfoximide 16 reacted with diphenylnitrile
imide at room temperature to give a cycloadduct in excel-
lent yield (90%). However an inseparable 1:1 mixture of
two regioisomeric pyrazolines 17 and 18 was obtained.
From the proton nmr we could also deduce that each
regioisomer was present as a 1:1 mixture of diastereoiso-
mers due to the chirality at sulfur (Scheme 5).
16 was added to the chlorinated aldoximes at -78 ˚C. The
temperature of the mixture was then slowly brought to
room temperature but the same results were obtained as
before. Next, benzohydroximoyl chloride, preformed by
reaction of benzaldehyde oxime (7a) with NCS [12], was
dissolved in dichloromethane and at -78 ˚C was added
allylic sulfoximide 16, followed by triethylamine to gener-
ate the dipole. The mixture was warmed to room tempera-
ture slowly overnight with stirring, to afford cycloadducts
19 and 20 in good yield (72%). It proved impossible to
separate each of the isomers cleanly by column chro-
matography, but we determined that a slight excess of
regioisomer 20 was obtained. This deduction was based on
chemical shift information from the proton nmr spectrum,
and also the expected electronic factor favouring addition
of the oxygen of the dipole to the β-carbon of the eneoate
group. Again, each regioisomer was present as a 1:1 mix-
ture of diastereoisomers (Scheme 5).
In conclusion, a simple reaction afforded (E)-1-
dimethylamino-2-phenylsulfonylethylene and S-((E)-2-
(N',N'-dimethylamino)ethenyl)-S-phenyl-N-(p-tolylsul-
fonyl) sulfoximide. These compounds might be employed
to prepare other functionalised vinyl sulfones/sulfoximides,
thus avoiding the potentially more difficult Peterson ole-
fination. The dimethylamino group of the sulfone seems
to have an effect leading to reversed regioselectivity in
cycloadditions with nitrile oxides. The sulfoximide ana-
logue showed no dipolarophilic activity, just as many
other vinyl sulfoximides have proved to be poor reaction
partners in cycloadditions. On the other hand, during an
attempted cycloaddition, unexpected isomerisation of the
vinyl sulfoximide took place and the resulting allylic
isomer gave rise to a cycloadduct, indicating that allylic
sulfoximides could be better chiral dipolarophiles.
β-Dimethylaminovinyl sulfoximide was easily converted
to S-((E)-(3-ethoxycarbonyl)prop-2-enyl)-S-phenyl-N-
(p-tolylsulfonyl) sulfoximide, offering a route for the
preparation of other allylic sulfoximides through the
aldehyde intermediate. The allylic sulfoximide we pre-
pared reacts with both benzonitrile oxide and diphenyl-
nitrile imide to give rise to cycloadducts in high yield.
Unfortunately, no stereoselectivity and only modest
regioselectivity in the case of benzonitrile oxide was
observed. Nevertheless, this preliminary investigation
indicates that allylic sulfoximides are more interesting
dipolarophiles, therefore, it might be worth investigating
further reaction conditions, the effects of the substituents
and which 1,3-dipoles to employ to achieve better regio-
and stereoselectivity in the future.
To study nitrile oxide cycloaddition reactions benzal-
doxime and acetaldoxime were first chlorinated with
BTMA ICl and then allylic sulfoximide 16 was added.
4
After a short period, starting materials were consumed but
many by-products formed. In a test reaction there was no
evidence that BTMA ICl reacted with the sulfoximide
4
directly, so the reactions with aldoximes were repeated
using low temperature conditions. The allylic sulfoximide
EXPERIMENTAL
Melting points were measured in glass capillary tubes using a
Gallenkamp melting point apparatus and are uncorrected. The ir

May-Jun 2005
An Efficient Preparation of β-Dimethylaminovinyl Sulfone and Sulfoximide
603
spectra were recorded on a Perkin Elmer 882 IR spectrophotometer.
ºC. At that temperature, aldehyde (4.8 mmole) was added to the
mixture. The mixture was warmed to 0 ºC and stirred for 45 min-
utes. Then, 0.5 ml (3.5 mmole) of dry triethylamine was added,
followed by 0.27 ml (3.5 mmole) of methanesulfonyl chloride
added dropwise at 0 ºC. After stirring at 0 ºC for 20 minutes, a
second equivalent of dry triethylamine (0.5 ml, 3.5 mmole) was
added to the mixture. The mixture was warmed to room tempera-
ture and stirred for another 20 minutes, then quenched with 2 ml
1
13
The H and C nmr spectra were recorded on a JEOL JNM-LA 400
1
13
or JEOL JNM-GX 270 at 400 MHz ( H) and 100 or 67.8 MHz ( C).
All chemical shifts are reported in ppm (δ) downfield from internal
tetramethylsilane and coupling constants are given in Hertz (Hz). The
mass spectra were recorded on a Finnigan MAT 1020 GC/MS mass
spectrometer. Chromatographic separations were carried out on silica
gel column (Prolabo silica gel 60, 35-75 µm, 230-400 mesh).
Reactions were monitored by tlc on silica plates (Merck Kieselgel 60
of diluted aqueous ammonium chloride solution (10% NH Cl)
4
F
). Elemental analyses were performed by staff at the Chemistry
and extracted with dichloromethane. After the solvent was dried
over magnesium sulfate, and removed by evaporation, the result-
ing yellow oil was purified by column chromatography on silica
gel (hexane/ethyl acetate = 1:1) as eluent to give the product.
254
Department at the University of Hull. Tetrahydrofuran was dried over
and distilled from sodium benzophenone ketal. Toluene was dried
over sodium wire. N,N-Dimethylformamide (DMF) and ethanol were
dried over 4 Å molecular sieves. Dichloromethane and triethylamine
were dried over calcium hydride powder.
S-Phenyl-N-(p-tolylsulfonyl)-vinylsulfoximide (2a).
This compound was obtained as white crystals (13%), mp 127
ºC; ir (potassium bromide): 3061, 1597, 1449 (CH=CH), 1314
S-Methyl-S-phenyl-N-(p-tolylsulfonyl)sulfoximide (1).
-1
1
S-Methyl-S-phenyl-N-(p-tolylsulfonyl)sulfoximide (1) was pre-
viously prepared and described by Johnson et al. [19]. However,
as part of our synthesis of this compound, we applied much sim-
pler method for the preparation of sulfilimines, recently reported
by Marzinzik and Sharpless [20]. Our simplified method for the
preparation of 1 is described here: To a stirred mixture of 2 g
(0.016 mole) of thioanisole dissolved in 50 ml of acetonitrile was
added 5.63 g (0.02 mole) of chloramine-T trihydrate. This mixture
was stirred overnight at room temperature. The reaction was
quenched with 60 ml of dichloromethane and the white precipitate
formed was removed by filtration and discarded. The solvent was
removed under reduced pressure to leave a viscous amber oil,
which was recrystallised from ethanol to yield 3.75 g (80%) of
pale yellow crystals (S-methyl-S-phenyl-N-(p-tolylsulfonyl)sulfil-
imine). Sulfilimine (1.56 g, 5.4 mmole) and 6 ml (0.144 mole) of
acetonitrile were dissolved in 120 ml of methanol. To this was
added a solution of 0.8 g (58 mmole) of potassium carbonate and
6 ml (60 mmole) of hydrogen peroxide in 120 ml of methanol.
The mixture was stirred at room temperature overnight, then the
solvent removed in vacuo to leave a cloudy white liquid. 80 ml of
dichloromethane and 80 ml of water were added and the organic
layer separated, washed with water and dried over magnesium
sulfate. The solvent was removed under reduced pressure leaving
an off white solid which was recrystallised from ethanol to yield
1.38 g (80%) of 1 as white crystals, mp 91-100 °C (from ethanol);
ir (potassium bromide): 3021, 2922, 1598, 1480, 1450, 1315 (SO),
(SO), 1289, 1232 (SO), 1152 (SO), 1087, 1059 cm ; H nmr
(400 MHz, deuteriochloroform): δ 2.43 (s, 3H, C H -CH ), 6.19
6
4
3
(dd, 1H, J = 9.6 Hz, J = 1.5 Hz, C=CH), 6.48 (dd, 1H, J = 16.3
Hz, J = 1.5 Hz, C=CH), 6.83 (dd, 1H, J = 16.3 Hz, J = 9.6 Hz,
SOCH=C), 7.24-7.26 (m, 2H, SO ArH, m), 7.56-7.60 (m, 2H,
2
SOPhH, m, ), 7.66-7.70 (m, 1H, SOPhH, p), 7.85-7.87 (m, 2H,
13
SOPhH, o), 7.96-7.99 (m, 2H, SO ArH, o); C nmr (100 MHz,
2
deuteriochloroform): δ 21.61, 126.76, 128.11, 128.33, 129.36,
129.76, 130.13, 134.37, 137.40, 137.69, 142.99, ms: m/z 321
+
(M , 6%), 139 (100), 125 (65), 91 (66), 77 (37), 65 (39).
Anal. Calcd. for C H NO S : C, 56.1; H, 4.7; N, 4.4; S,
15 15
3 2
20.0. Found: C, 56.5; H, 4.7; N, 4.3; S, 19.8.
S-((E)-Prop-1-enyl)-S-phenyl-N-(p-tolylsulfonyl)sulfoximide
(2b).
This compound was obtained as white crystals (30%), mp 126-
128 ºC (from ethanol); ir (potassium bromide): 3056, 1641
(CH=CH trans), 1596, 1450 (CH=CH trans), 1319 (SO), 1229
-1
1
(SO), 1150 (SO), 1087, 1059 cm ; H nmr (400 MHz, deuteri-
ochloroform): δ 1.95 (dd, 3H, J = 7.1 Hz, J = 1.7 Hz, CH-CH ),
3
2.39 (s, 3H, C H -CH ), 6.45 (dq, 1H, J = 14.8 Hz, J = 1.7 Hz,
6
4
3
CH=C), 6.99 (dq, 1H, J = 14.8 Hz, J = 7.1 Hz, CH=C), 7.24-7.26
(m, 2H, SO ArH, m), 7.54-7.67 (m, 3H, SOPhH, m, p), 7.83-7.96
2
13
(m, 4H, SOPhH, o + SO ArH, o); C nmr (100 MHz, deuteri-
2
ochloroform): δ 17.61, 21.60, 126.75, 127.78, 129.29, 129.62,
130.27, 133.96, 138.69, 140.96, 142.82, 144.53; ms: m/z 335
+
-1
1
(M , 3%), 278 (27), 139 (100), 125 (53), 91 (83), 77 (28).
1231 (SO), 1147 (SO), 1090, 1067 cm ; H nmr (400 MHz, deu-
teriochloroform): δ 2.40 (s, 3H, C H -CH ), 3.43 (s, 3H, SOCH ),
Anal. Calcd. for C H NO S : C, 57.3; H, 5.1; N, 4.1; S,
6
4
3
3
16 17
3 2
7.23-7.29 (m, 2H, SO ArH, m), 7.59-7.63 (m, 2H, SOPhH, m),
19.1. Found: C, 57.6; H, 5.2; N, 3.9; S, 19.3.
2
7.68-7.72 (m, 1H, SOPhH, p), 7.85-7.87 (m, 2H, SOPhH, o),
S-((E)-3,3-Dimethyl-but-1-enyl)-S-phenyl-N-(p-tolylsulfonyl)-
sulfoximide (2c).
13
8.01-8.03 (m, 2H, SO ArH, o); C nmr (100 MHz, deuteriochlo-
2
roform): δ 21.52, 46.65, 126.66, 127.49, 129.29, 129.72, 134.39,
+
This compound was obtained as pale yellow crystals (53%),
mp 166-168 ºC (from ethanol); ir (potassium bromide): 3043,
2964, 1621 (CH=CH trans), 1448 (CH=CH trans), 1317 (SO),
138.38, 140.64, 142.90; ms: m/z 309 (M , 4%), 294 (84), 139
(60), 91 (100), 77 (53), 65 (64).
Anal. Calcd. for C H NO S : C, 54.3; H, 4.9; N, 4.5; S,
14 15
3 2
-1
1
1252, 1216 (SO), 1152 (SO), 1101, 1070 cm ; H nmr (400
MHz, deuteriochloroform): δ 1.08 (s, 9H, C(CH ) ), 2.39 (s, 3H,
20.7. Found: C, 54.1; H, 5.0; N, 4.5; S, 21.8.
3 3
General Procedure for the Olefination of S-methyl-S-phenyl-N-
(p-tolylsulfonyl)sulfoximide (1).
C H -CH ), 6.29 (d, 1H, J = 15.1 Hz, CH=C), 6.96 (d, 1H, J =
6
4
3
15.1 Hz, CH=C), 7.23-7.26 (m, 2H, SO ArH, m), 7.54-7.68 (m,
2
3H, SOPhH, m, p), 7.82-7.95 (m, 4H, SOPhH, o + SO ArH, o);
C nmr (100 MHz, deuteriochloroform): δ 21.60, 28.26, 34.78,
To a solution of 1 g (3.2 mmole) of S-methyl-S-phenyl-N-(p-
tolylsulfonyl)sulfoximide (1) dissolved in 15 ml of dry tetrahy-
drofuran, 2 ml (3.2 mmole) of n-butyllithium was added drop-
wise at -78 ºC under nitrogen. The mixture was warmed to room
temperature and stirred for ten minutes, then cooled back to -78
2
13
125.45, 126.78, 127.74, 128.29, 129.29, 129.62, 133.91, 138.88,
+
141.00, 142.79; ms: m/z 378 (M , 1%), 155 (28), 139 (100), 125
(33), 91 (63), 77 (27).

604
N. Peša, C. J. Welch, and A. N. Boa
Vol. 42
Anal. Calcd. for C H NO S : C, 60.5; H, 6.1; N, 3.7; S,
17.0. Found: C, 60.8; H, 6.3; N, 3.5; S, 17.2.
General Procedure for the Reaction of Aldoximes 7a-d with
Phenyl vinyl sulfone (6).
19 23
3 2
All aldoximes (7a-d) were prepared according to the method
of Bashiardes et al. [21]. Benzyl trimethylammonium tetra-
S-2-((E)-2-Phenylethenyl)-S-phenyl-N-(p-tolylsulfonyl)sulfox-
imide (2d).
chloroiodate (BTMA ICl ) was prepared as previously described
[11]. To a solution of aldoxime (3.1 mmole) was added 1.3 g (3.1
4
This compound was obtained as white crystals (89%), mp 130-
132 ºC (from ethanol); ir (potassium bromide): 3058, 1608
(CH=CH trans), 1448 (CH=CH trans), 1319 (SO), 1235 (SO),
mmole) of BTMA ICl in 15 ml of dry dichloromethane under
4
nitrogen. The green suspension was stirred at room temperature
for ten minutes, during which period it became a clear yellow
solution. Then, 0.504 g (3 mmole) of phenyl vinyl sulfone was
added followed by 0.47 ml (3.3 mmole) of triethylamine added
dropwise. The mixture was then heated at reflux for three days.
-1
1
1223, 1152 (SO), 1086, 1058 cm ; H nmr (400 MHz, deuteri-
ochloroform): δ 2.38 (s, 3H, C H -CH ), 6.90 (d, 1H, J = 15.1 Hz,
6
4
3
CH=C), 7.23-7.26 (m, 3H, 2 ArH + CH=C), 7.37-7.47 (m, 4H,
ArH), 7.55-7.67 (m, 4H, ArH), 7.85-7.87 (m, 2H, SOPhH, o), 8.01-
13
8.03 (m, 2H, SO ArH, o); C nmr (100 MHz, deuteriochloroform):
2
Diethyl ether was added and the precipitate of BTMA ICl was
2
δ 21.59, 125.61, 126.84, 127.81, 128.97, 129.24, 129.35, 129.73,
removed by filtration. The solvent was removed in vacuo and the
resulting oil was purified by column chromatography on silica
gel (hexane/ethyl acetate = 1:1) as eluent to give the product as an
oil or a solid.
131.82, 131.90, 134.08, 138.82, 140.88, 142.92, 144.02; ms: m/z
+
398 (M , 4%), 368 (32), 139 (100), 125 (29), 91 (98), 77 (43).
Anal. Calcd. for C H NO S : C, 63.5; H, 4.8; N, 3.5; S,
21 19
3 2
16.1. Found: C, 63.8; H, 5.0; N, 3.5; S, 16.4.
5-Benzenesulfonyl-3-phenyl-4,5-dihydro-isoxazole (8a).
(E)- 1-Dimethylamino-2-phenylsulfonylethylene (4).
This compound was obtained as white crystals (78%), mp 136-
138 ºC (from ethanol); ir (potassium bromide): 2977, 1447, 1356,
To a solution of 1.0 g (6.40 mole) of methyl phenyl sulfone (3)
dissolved in 30 ml of dry N,N-dimethylformamide was added 4.4
ml (32 mole) of N,N-dimethylformamide dimethyl acetal under
nitrogen, and the solution was heated at reflux overnight. The sol-
vent and the excess of acetal were then removed by evaporation
in vacuo. The resulting solid was recrystallised from ethanol to
give 1.1 g (94%) of 4 as pale yellow crystals, mp 119-120 ºC
(from ethanol); ir (potassium bromide): 3073, 2915, 2817, 1623
(CH=CH), 1478, 1449 (CN), 1433, 1396, 1318 (SO), 1267 (SO),
-1
1
1311 (SO), 1145 (SO) cm ; H nmr (400 MHz, deuteriochloro-
form): δ 3.79 (dd, 1H, J = 18.3 Hz, J = 10.9 Hz), 4.06 (dd,
AB
AX
1H, J = 18.3 Hz, J = 4.5 Hz), 5.55 (dd, 1H, J = 10.9 Hz,
AB
BX
AX
J
= 4.5 Hz), 7.36-7.68 (m, 8H, PhH), 7.98-8.00 (m, 2H,
BX
13
SO ArH, o); C nmr (67.8 MHz, deuteriochloroform): δ 36.84,
2
93.27, 127.06, 127.27, 128.86, 129.23, 129.74, 131.10, 134.57,
+
+
135.19, 156.88; ms: m/z 288 (MH , 2%), 146 (M -SO Ar, 100),
2
144 (6), 118 (49), 91 (19), 77 (77).
-1 1
1132 (SO), 1080, 969, 898, 844, 754, 720, 690 cm ; H nmr (400
Anal. Calcd. for C H NO S: C, 62.7; H, 4.6; N, 4.9; S, 11.2.
15 13
3
MHz, deuteriochloroform): δ 2.74 (s, 3H, NCH ), 3.06 (s, 3H,
3
Found: C, 62.4; H, 4.6; N, 5.0; S, 10.8.
NCH ), 4.87 (d, 1H, J = 12.7 Hz, C=CH), 7.32 (d, 1H, J = 12.7
3
5-Benzenesulfonyl-3-tert-butyl-4,5-dihydro-isoxazole (8b).
Hz, C=CH), 7.44-7.52 (m, 3H, PhH, m, p), 7.85-7.88 (m, 2H,
13
PhH, o); C nmr (100 MHz, deuteriochloroform): δ 37.11,
This compound was obtained as white crystals (63%), mp 120-
121 ºC (from ethanol); ir (potassium bromide): 3852, 3440, 3075,
44.48, 92.31, 126.11, 128.78, 131.52, 145.12, 151.01; ms: m/z
+
211 (M , 100%), 146 (35), 134 (15), 91 (29), 77 (62), 69 (94).
2970, 2935 ((CH ) ), 2906, 2871, 2359, 2340, 1909, 1825, 1700
3 3
Anal. Calcd. for C H NO S: C, 56.9; H, 6.2; N, 6.6; S, 15.2.
(C=N), 1616, 1585, 1477, 1452 ((CH ) ), 1436, 1396, 1370
10 13
2
3 3
Found: C, 56.8; H, 6.2; N, 6.3; S, 14.9.
(C(CH ) ), 1321, 1312 (SO), 1276 (SO), 1260, 1145 (SO), 1086,
3 3
-1 1
1015, 962, 855, 792, 766, 740, 689 cm ; H nmr (400 MHz, deu-
S-((E)-2-(N',N'-Dimethylamino)ethenyl)-S-phenyl-N-(p-tolylsul-
fonyl) Sulfoximide (5).
teriochloroform): δ 1.13 (s, 3H, (CH ) ), 3.43 (dd, 1H, J
=
3 3
AB
18.6 Hz, J = 10.7 Hz), 3.62 (dd, 1H, J = 18.6 Hz, J = 4.2
AX
AB
BX
To a solution of 1.0 g (3.20 mole) of S-methyl-S-phenyl-N-(p-
tolylsulfonyl)sulfoximide (1) dissolved in 20 ml of dry N,N-
dimethylformamide was added 2.2 ml (16.5 mole) of N,N-
dimethylformamide dimethyl acetal under nitrogen, and the solu-
tion was heated at reflux overnight. The solvent and the excess of
acetal were then removed by evaporation in vacuo. The resulting
solid was recrystallised from ethyl acetate to give 1.1 g (94%) of
5 as yellow solid, mp 108-110 ºC (from ethyl acetate); ir (potas-
sium bromide): 3078, 2920, 1627 (CH=CH), 1446 (CN), 1319
Hz), 5.40 (dd, 1H, J = 10.7 Hz, J = 4.2 Hz), 7.57-7.61 (m,
AX
BX
2H, PhH, m), 7.68-7.72 (m, 1H, PhH, p), 7.98-8.00 (m, 2H, PhH,
13
o); C nmr (100 MHz, deuteriochloroform): δ 27.97, 33.21,
36.62, 93.20, 129.28, 130.03, 134.55, 135.28, 166.18; ms: m/z
+
268 (MH , 1%), 149 (7), 126 (100), 97 (5), 77 (64), 70 (10).
Anal. Calcd. for C H NO S: C, 58.4; H, 6.4; N, 5.2; S, 12.0
13 17
3
Found: C, 58.5; H, 6.3; N, 5.5; S, 12.1.
5-Benzenesulfonyl-3-ethyl-4,5-dihydro-isoxazole (8c).
-1
1
(SO), 1212 (SO), 1154 (SO), 1098, 1050 cm ; H nmr (400
This compound was obtained as yellow oil (37%); ir (neat):
3630, 3066, 2978, 2942 (CH CH ), 2883, 2361, 2342, 1981,
MHz, deuteriochloroform): δ 2.38 (s, 3H, C H -CH ), 2.74 (s,
6
4
3
2
3
3H, NCH ), 3.08 (s, 3H, NCH ), 4.79 (d, 1H, J = 12.2 Hz,
1908, 1743, 1696 (C=N), 1631, 1585, 1478, 1462, 1448
(CH CH ), 1429, 1378, 1348, 1309 (SO), 1213 (SO), 1178, 1151
3
3
C=CH), 7.20-7.22 (m, 2H, SO ArH, m), 7.34 (d, 1H, J = 12.2 Hz,
2
2
3
C=CH), 7.44-7.54 (m, 3H, SOPhH, m, p), 7.81-7.91 (m, 4H,
(SO), 1086, 1024, 999, 956, 878, 837, 801, 765, 735, 691, 633
13
-1
1
SOPhH, o + SO ArH, o); C nmr (100 MHz, deuteriochloro-
cm ; H nmr (400 MHz, deuteriochloroform): δ 1.08 (t, 3H, J =
7.6 Hz, CH ), 2.28-2.35 (m, 2H, CH ), 3.43 (dd, 1H, J = 18.8
2
form): δ 21.55, 37.50, 45.06, 88.60, 126.46, 126.76, 128.81,
3
2
AB
129.08, 132.36, 141.62, 142.17, 143.62, 151.77; ms: m/z 364
Hz, J = 10.7 Hz), 3.59 (dd, 1H, J = 18.8 Hz, J = 4.2 Hz),
AX
AB
BX
+
(M , 1%), 194 (5), 161 (26), 91 (32), 86 (100), 69 (44).
5.41 (1 H, dd, J = 10.7 Hz, J = 4.2 Hz), 7.56-7.61 (m, 2H,
AX
BX
Anal. Calcd. for C H N O S : C, 56.0; H, 5.5; N, 7.7; S,
17.6. Found: C, 56.0; H, 5.6; N, 7.6; S, 17.6.
PhH, m), 7.68-7.72 (m, 1H, PhH, p), 7.95-7.98 (m, 2H, PhH, o);
C nmr (67.8 MHz, deuteriochloroform): δ 10.52, 20.53, 38.70,
17 20
2 3 2
13

May-Jun 2005
An Efficient Preparation of β-Dimethylaminovinyl Sulfone and Sulfoximide
605
92.57, 129.18, 129.73, 134.46, 135.21, 160.33; ms: m/z 240
(MH , 1%), 125 (7), 104 (10), 98 (100), 77 (75), 70 (89).
Anal. Calcd. for C H NO S: C, 53.8; H, 4.1; N, 6.3; S, 14.4
10 9 3
Found: C, 53.8; H, 4.0; N, 6.3; S, 14.3.
+
5-Benzenesulfonyl-3-methyl-4,5-dihydro-isoxazole (8d).
Modified Method for the Preparation of 4-Benzenesulfonyl-3-
phenyl-isoxazole (11a).
This compound was obtained as white crystals (26%), mp 83-
85 ºC; ir (potassium bromide): 2976, 2927, 1450, 1432, 1304
(SO), 1146 (SO) cm ; H nmr (400 MHz, deuteriochloroform): δ
To a solution of 0.266 g (2.2 mmole) of benzaldehyde oxime
(7a) dissolved in 10 ml of dry N,N-dimethylformamide was added
0.297 g (2.2 mmole) of solid N-chlorosuccinimide with stirring.
The solution was stirred at room temperature for one hour before
it was poured into cold water and extracted with diethyl ether. The
combined extracts were washed with cold water and dried over
magnesium sulfate, then the solvent was removed by evaporation.
The resulting yellow oil of benzohydroximoyl chloride was dis-
solved in 12 ml of chloroform and 0.422 g (2 mmole) of enamine
4 was added at room temperature. Then, 0.32 ml (2.2 mmole) of
triethylamine was added dropwise over 15 minutes, and the mix-
ture was then heated at reflux for two days. The solvent was
removed in vacuo, and the resulting oil was purified by column
chromatography on silica gel (hexane/ethyl acetate = 2:1) as elu-
ent to give the product 11a as white solid (0.12 g, 21%); ir (potas-
sium bromide): 3108, 3064, 1447, 1366, 1328 (SO), 1146 (SO),
-1 1
1.96 (s, 3H, CH ), 3.43 (dd, 1H, J = 18.8 Hz, J = 10.7 Hz),
3
AB
AX
3.60 (dd, 1H, J = 18.8 Hz, J = 4.4 Hz), 5.40 (dd, 1H, J =
AB
BX
AX
10.7 Hz, J = 4.4 Hz), 7.57-7.61 (m, 2H, PhH, m), 7.68-7.72 (m,
BX
13
1H, PhH, p), 7.95-7.97 (m, 2H, PhH, o); C nmr (67.8 MHz,
dimethylsulfoxide-d ): δ 12.34, 40.18, 92.67, 129.25, 129.74,
6
+
134.57, 135.29 and 155.92; ms: m/z 226 (MH , 1%), 125 (13),
104 (16), 97 (13), 84 (100), 65 (14).
Anal. Calcd. for C H NO S: C, 53.3; H, 4.9; N, 6.2; S, 14.2
10 11
3
Found: C, 53.4; H, 4.9; N, 6.5; S, 14.0.
4-Benzenesulfonyl-3-methyl-4,5-dihydro-isoxazole (9d).
1
This compound was obtained as yellow oil (5%); H nmr (400
MHz, deuteriochloroform): δ 2.26 (s, 3H, CH ), 4.40 (dd, 1H,
3
J
= 10.7 Hz, J = 10.5 Hz), 4.61 (dq, 1H, J = 10.5 Hz, J
AX
AB AB BX
-1
1
1135 (SO) cm ; H nmr (400 MHz, deuteriochloroform): δ 7.22-
= 4.4 Hz), 4.73 (dd, 1H, J = 10.7 Hz, J = 4.4 Hz), 7.58-7.62
AX
BX
7.53 (m, 8H, PhH), 8.08-8.11 (m, 2H, SO PhH, o), 8.96 (s, 1H,
C=CH); ms: m/z 285 (M , 24%), 220 (7), 143 (84), 90 (21), 77
(m, 2H, PhH, m), 7.69-7.74 (m, 1H, PhH, p), 7.86-7.89 (m, 2H,
PhH, o); C nmr (67.8 MHz, deuteriochloroform): δ 12.88,
2
+
13
(100), 63 (14). Another product was obtained as the first fraction,
dimer of the dipole, furoxan, as white crystals (0.06 g, 13%); ir
(potassium bromide): 3062, 1598, 1575 (C=N), 1444 (N-O), 1422
70.51, 75.40, 128.91, 129.27, 129.54, 134.95, 149.47; ms: m/z
226 (MH , 8%), 168 (14), 125 (82), 97 (28), 84 (100), 65 (34).
+
General Procedure for the Reaction of Aldoximes 7a-d with (E)-
1-Dimethylamino-2-phenylsulfonylethylene (4).
-1
1
(N-O) cm ; H nmr (400 MHz, deuteriochloroform): δ 7.41-7.64
+
(m, 8H, PhH), 8.16-8.24 (m, 2H, PhH); ms: m/z 238 (M , 6%),
+
The procedure is the same as for the reaction of aldoximes 7a-
d with Phenyl vinyl sulfone (6), only the reaction mixture was
heated at reflux for four days.
222 (M -O, 29), 178 (100), 119 (46), 91 (11), 77 (14).
1,3-Dipolar Cycloaddition Reaction of δ-Chlorobenzaldehyde
Phenylhydrazone (12) and S-((E)-Prop-1-enyl)-S-phenyl-N-(p-
tolylsulfonyl) Sulfoximide 2b; an Unexpected Isomerisation and
Cycloaddition of Allylic Sulfoximide: S-(Prop-2-enyl)-S-phenyl-
N-(p-tolylsulfonyl) Sulfoximide (13) and (R,S/S,R)- and
(S,S/R,R)-1,3-Diphenyl-5-([S-phenyl-N-toluene-4-sulfonyl]sul-
foximinylmethyl)-4,5-dihydro-1H-pyrazole (14).
5-Benzenesulfonyl-3-ethyl-isoxazole (10c) and 4-Benzene-
sulfonyl-3-ethyl-isoxazole (11c).
The compound 11c was obtained as yellow oil (27%) and a
mixture containing some of the other regioisomer 10c, as shown
1
13
by H and C nmr, which could not be separated. The ratio of
1
regioisomers 11c and 10c is estimated from H nmr to be 5:1,
To a solution of 0.078 g (0.34 mmole) of α-chlorobenzalde-
hyde phenylhydrazone (12) [16] and 0.11 g (0.33 mmole) of
vinyl sulfoximide 2b in 10 ml of dry toluene, 0.19 ml (1.36
mmole) of dry triethylamine was added dropwise, followed by
0.066 g (0.34 mmole) of silver tetrafluoroborate. The mixture
was kept in the dark, under nitrogen and heated at reflux for one
day. The solid formed was removed by filtration, and then the
solvent removed in vacuo. The crude product was purified by
column chromatography on silica gel (hexane/ethyl acetate = 3:1)
as eluent to give 13, which was formed by isomerisation of vinyl
sulfoximide 2b. The isomer was obtained as brown oil (0.023 g,
thus, the yield can be calculated as 25% for 11c and 5% for 10c;
1
the following data in H nmr refer to the regioisomer 11c except
1
where assigned to the minor regioisomer 10c - H nmr (400
MHz, deuteriochloroform): δ 1.24 (t, 3H, J 7.6 Hz, CH ), 1.35 (t,
3
J 7.3 Hz, CH , 10c), 2.56 (q, J 7.3 Hz, CH , 10c), 2.75 (q, 2H, J
3
2
7.6 Hz, CH ), 6.42 (s, C=CH, 10c), 7.57-7.82 (m, 3H, PhH, m, p),
2
13
7.95-8.06 (m, 2H, PhH, o), 8.90 (s, 1H, C=CH); C nmr (100
MHz, deuteriochloroform): δ 9.87, 11.04, 11.35, 16.01, 18.48,
19.34, 127.50, 129.13, 129.30, 129.59, 130.88, 131.22, 134.11,
+
135.26, 135.59, 140.62, 160.71, 162.35; ms: m/z 237 (M , 14%),
1
141 (44), 125 (17), 96 (21), 77 (100), 68 (9).
21%); H nmr (400 MHz, deuteriochloroform): δ 2.39 (s, 3H,
C H -CH ), 4.23-4.34 (m, 2H, J = 7.6 Hz, SOCH ), 5.13 (dd, 1H,
6
4
3
2
4-Benzenesulfonyl-3-methyl-isoxazole (11d).
J
J
= 18.2 Hz, J
= 1.0 Hz, H ), 5.36 (dd, 1H, J
= 10.4 Hz,
AB
AA'
A
A'B
This compound was obtained as white crystals (30%), mp 85-
86 ºC; ir (potassium bromide): 3139, 3110, 1566, 1449, 1400,
1318 (SO), 1168 (SO), 1138 (SO), 1119, 1072 cm ; H nmr (400
= 1.0 Hz, H ), 5.73 (ddt, 1H, J = 18.2 Hz, J = 10.4 Hz,
AA'
A'
AB
A'B
J = 7.6 Hz H ), 7.24-7.27 (m, 2H, ArH), 7.55-7.59 (m, 2H, ArH),
B
-1
1
7.66-7.70 (m, 1H, ArH, p), 7.86-7.93 (m, 4H, SO ArH, o +
2
13
MHz, deuteriochloroform): δ 2.35 (s, 3H, CH ), 7.56-7.61 (m,
SOPhH, o); C nmr (67.8 MHz, deuteriochloroform): δ 21.54,
3
2H, PhH, m), 7.65-7.70 (m, 1H, PhH, p), 7.96-7.99 (m, 2H, PhH,
o), 8.92 (s, 1H, C=CH); C nmr (67.8 MHz, deuteriochloro-
62.55, 123.57, 126.68, 126.72, 128.78, 129.02, 129.28, 129.29,
134.41, 135.36, 142.85; ms: m/z 335 (M , 1%), 180 (16), 155
13
+
form): δ 9.92, 127.54, 129.63, 134.14, 134.17, 140.50, 156.24,
162.19; ms: m/z 223 (M , 100%), 130 (44), 116 (12), 102 (11),
77 (83), 65 (13).
(68), 117 (37), 91 (100), 77 (39). Another product was obtained
as a first fraction, cycloadduct of allylic sulfoximide 13 and
hydrazone 12. The cycloadduct 14 was obtained as a mixture of
+

606
N. Peša, C. J. Welch, and A. N. Boa
Vol. 42
diastereoisomers (due to chirality at sulphur) in the ratio 1:1, as
brown oil (0.016 g, 9%); H nmr (400 MHz, deuteriochloroform)*:
14.19, 21.61, 60.74, 61.10, 126.75, 128.60, 129.41, 129.68,
131.17, 131.44, 134.92, 135.27, 140.63, 143.15, 164.53; ms: m/z
407 (M , 1%), 294 (64), 155 (78), 91 (100), 77 (28), 65 (22).
1
+
δ 2.41 (s, 3H, C H -CH ), 3.28-3.84 (m, 4H, SOCH , H H ),
6
4
3
2
A A'
4.65-4.72 (tdd, 1/2H, J = 10.1 Hz, J = 4.5 Hz, J = 1.7 Hz, H ), 4.96-
Anal. Calcd. for C H NO S : C, 56.0; H, 5.2; N, 3.4; S,
B
19 21 5 2
5.02 (tdd, 1/2H, J = 10.1 Hz, J = 4.5 Hz, J = 1.7 Hz, H ), 6.75-8.07
(m, 19H, ArH); C nmr (100 MHz, deuteriochloroform)**: δ
15.7. Found: C, 56.3; H, 5.5; N, 3.6; S, 15.8.
B'
13
1,3-Dipolar Cycloaddition Reaction of α-Chlorobenzaldehyde
Phenylhydrazone (12) and S-((E)-(3-Ethoxycarbonyl)prop-2-
enyl)-S-phenyl-N-(p-tolylsulfonyl) sulfoximide (16): Ethyl
(4S,5R,R/S)- and (4R,5S,R/S)-1,3-diphenyl-4-([S-phenyl-N-
toluene-4-sulfonyl]sulfoximidylmethyl)-4,5-dihydro-1H-pyra-
zole-5-carboxylate (17) and Ethyl (4R, 5S, R/S)- and (4S, 5R,
R/S)-1,3-diphenyl-5-([S-phenyl-N-toluene-4-sulfonyl]sulfox-
imidylmethyl)-4,5-dihydro-1H-pyrazole-4-carboxylate (18).
21.63, 38.41, 39.10, 54.03, 54.47, 57.30, 57.54, 113.58, 125.96,
126.36, 126.74, 128.24, 128.41, 128.48, 128.72, 129.32, 129.44,
129.52, 129.61, 129.93, 130.03, 149.02, 155.73; ms: m/z 529 (M ,
5%), 234 (100), 221 (53), 105 (29), 91 (71), 77 (58).
* Some signals were overlapping, so it was not possible to cal-
culate all coupling constants.
** The aromatic region appears to be too complicated to assign
signals accurately to all carbons and it seems that many signals
are overlapping.
+
To a solution of 0.169 g (0.736 mmole) of α-chlorobenzalde-
hyde phenylhydrazone (12) and 0.3 g (0.736 mmole) of allylic
sulfoximide 16 in 15 ml of dry toluene, 0.41 ml (2.944 mmole) of
dry triethylamine was added dropwise over 15 minutes. The mix-
ture was stirred under nitrogen at room temperature for two days.
The solvent was removed in vacuo, and the crude product was
purified by column chromatography on silica gel (hexane/ethyl
acetate = 3:1) as eluent to give a mixture of regioisomers 17 and
18 and their diastereoisomers (due to chirality at sulphur) in the
ratio 1:1:1:1. The isomers could not be separated and the mixture
was obtained as a yellow solid (0.4 g, 90%), mp 57-62 ºC; ir
(potassium bromide): 3061, 2980, 2927, 1735 (C=O), 1598
(C=N), 1559, 1496 (C-N), 1447, 1388, 1320 (SO), 1235 (SO),
1196 (C-O), 1152 (SO), 1089, 1061, 1018, 997, 904, 843, 815,
S-(2-Oxoethyl)-S-phenyl-N-(p-tolylsulfonyl) Sulfoximide (15).
To a solution of 0.5 g (1.35 mmole) of S-((E)-2-(N',N'-
Dimethylamino)ethenyl)-S-phenyl-N-(p-tolylsulfonyl) sulfox-
imide (5) in 20 ml of tetrahydrofuran, hydrochloric acid (20%)
was added until the pH was 1. The two-phase system was stirred
at room temperature overnight. Then, a saturated solution of
sodium bicarbonate was added until the pH was 7, followed by
extraction with dichloromethane. The organic layer was dried
over magnesium sulfate and the solvent removed by evaporation,
to give 15 as white crystals (0.42 g, 92%), mp 55-57 ºC; ir (potas-
sium bromide): 3063, 2927, 1726 (CO), 1598, 1448, 1316 (SO),
-1
1
1241 (SO), 1152 (SO), 1088, 1060 cm ; H nmr (400 MHz, deu-
-1
1
teriochloroform): δ 2.41 (s, 3H, C H -CH ), 4.64 (d, 2H, J = 2.6
749, 692, 670 cm ; H nmr (400 MHz, deuteriochloroform): δ
6
4
3
Hz, CH ), 7.21-7.30 (m, 2H, SO ArH, m), 7.50-7.66 (m, 2H,
1.11-1.17 (m, 3H, CH CH ), 2.40 (s, 3H, C H -CH ), 3.43-3.87
2
2
2
3
6
4
3
SOPhH, m), 7.71-7.83 (m, 1H, SOPhH, p), 7.89 (d, 2H, J = 8.4
(many doublets overlapping, 2H, CH SO), 4.03 (dt, 1/4H, H ),
2
B
Hz, SOPhH, o), 7.96 (d, 2H, J = 7.8 Hz, SO ArH, o), 9.83 (br s,
1H, CHO); C nmr (100 MHz, deuteriochloroform): δ 21.64,
4.06-4.16 (m, 2H, CH CH ), 4.41 (dt, 1/4H, H ), 4.73 (d, 1/4H, J
2
2
3
B
13
= 2.7 Hz, H ), 4.78 (d, 1/4H, J = 2.7 Hz, H ), 5.05 (dt, 1/4H,
A
A
66.75, 126.78, 128.14, 129.43, 129.55, 130.02, 135.28, 136.17,
143.57, 188.48; ms: m/z 338(MH , 3%), 139 (48), 105 (55), 91
H ), 5.11 (d, 1/4H, J = 2.0 Hz, H ), 5.19 (d, 1/4H, J = 2.0 Hz,
B
A
+
13
H ), 5.30 (dt, 1/4H, H ), 6.82-8.12 (m, 19H, ArH); C nmr (100
A
B
(100), 77 (51), 65 (49).
* This aldehyde was not stable enough to obtain good elemen-
tal analysis.
MHz, deuteriochloroform): δ 14.02, 14.21, 21.07, 21.55, 44.01,
44.18, 55.23, 55.63, 55.75, 56.18, 56.39, 56.69, 58.15, 58.66,
61.99, 62.14, 65.40, 65.66, 113.56, 113.62, 113.66, 120.42,
120.58, 125.69, 125.84, 126.73, 128.42, 128.59, 128.82, 128.99,
129.15, 129.33, 129.48, 129.98, 131.21, 134.92, 135.06, 136.04,
136.34, 136.88, 140.46, 141.70, 143.01, 143.09, 143.72, 145.32,
S-((E)-(3-Ethoxycarbonyl)prop-2-enyl)-S-phenyl-N-(p-tolylsul-
fonyl) Sulfoximide (16).
+
To a solution of 0.4 g (1.19 mmole) of S-(2-oxoethyl)-S-
phenyl-N-(p-tolylsulfonyl)sulfoximide (15) in 20 ml of ethanol,
0.42 g (1.19 mmole) of ethoxycarbonylmethylene(triphenyl)-
phosphorane [18] was added, and the mixture was stirred at room
temperature for half an hour. The product was extracted with
dichloromethane, and the organic extracts dried over magnesium
sulfate, before the solvent was removed in vacuo. The resulting
oil was purified by column chromatography on silica gel
(hexane/ethyl acetate = 1:1) as eluent to give 16 as white crystals
(0.42 g, 87%), mp 95-97 ºC; ir (potassium bromide): 3422, 3069,
2982, 2924, 1719 (C=O), 1654 (CH=CH trans), 1600, 1495,
1473, 1445 (CH=CH trans), 1408, 1367, 1320 (SO), 1299, 1266
(CO), 1234 (SO), 1200 (CO), 1152 (SO), 1090, 1053, 1014, 996,
168.33, 168.39, 168.87, 169.05; ms: m/z 601 (M , 4%), 306 (42),
293 (100), 233 (87), 91 (32), 77 (30).
Anal. Calcd. for C H N O S : C, 63.9; H, 5.2; N, 7.0; S,
32 31
3 5 2
10.7. Found: C, 63.6; H, 5.4; N, 6.8; S, 10.4.
1
13
* Many signals were overlapping in both H and C nmr, so it
was not possible to calculate some coupling constants and assign
the signals to all atoms.
1,3-Dipolar Cycloaddition Reaction of Benzohydroximoyl
Chloride and S-((E)-(3-Ethoxycarbonyl)prop-2-enyl)-S-phenyl-
N-(p-tolylsulfonyl) Sulfoximide (16): Ethyl (4S,5S,R/S)- and
(4R,5R,R/S)-3-phenyl-4-([S-phenyl-N-toluene-4-sulfonyl]sulfox-
imidylmethyl)-4,5-dihydroisoxazole-5-carboxylate (19) and
Ethyl (4S,5S,R/S)- and (4R,5R,R/S)-3-phenyl-5-([S-phenyl-N-
toluene-4-sulfonyl]sulfoximidylmethyl)-4,5-dihydroisoxazole-4-
carboxylate (20).
-1
1
980, 809, 783, 767, 742, 718, 685, 665 cm ; H nmr (400 MHz,
deuteriochloroform): δ 1.26 (t, 3H J = 7.2 Hz, CH CH ), 1.40 (s,
2
3
3H, C H -CH ), 4.17 (q, 2H, J = 7.2 Hz, CH CH ), 4.46 (m, 2H,
6
4
3
2
3
CH CH=C), 5.85 (d, 1H, J = 15.7 Hz, C=CHCO ), 6.66 (dt, 1H,
To a solution of 0.067 g (0.55 mmole) of benzaldehyde oxime
(7a) in 5 ml of dry N,N-dimethylformamide, 0.149 g (1.1 mmole)
of solid N-chlorosuccinimide was added with stirring. The solu-
tion was stirred at room temperature for one hour before it was
2
2
J = 15.7 Hz, J = 7.8 Hz, CH CH=C), 7.26-7.28 (m, 2H, SO ArH,
2
2
m), 7.56-7.73 (m, 3H, SOPhH, m, p), 7.86-7.94 (m, 4H, SOPhH,
13
o + SO ArH, o); C nmr (100 MHz, deuteriochloroform): δ
2

May-Jun 2005
An Efficient Preparation of β-Dimethylaminovinyl Sulfone and Sulfoximide
607
REFERENCES AND NOTES
poured into cold water and extracted with diethyl ether. The com-
bined extracts were washed with cold water and dried over mag-
nesium sulfate, then the solvent was removed by evaporation.
The resulting yellow oil of benzohydroximoyl chloride was dis-
solved in 8 ml of dichloromethane and 0.18 g (0.42 mmole) of
allylic sulfoximide 16 was added at -78 ºC, followed by 0.08 ml
(0.55 mmole) of dry triethylamine, added dropwise. The mixture
was left to warm to room temperature and stir overnight. The sol-
vent was removed in vacuo, and the crude product was purified
by column chromatography on silica gel (hexane/ethyl acetate =
2:1) as eluent to give a mixture of regioisomers 19 and 20 in the
ratio ~ 1:3, with each regioisomer obtained as a pair of
diastereoisomers (due to chirality at sulphur) in the ratio 1:1. The
isomers could not be separated and the mixture was obtained as a
yellow solid (0.16 g, 72%), mp 41-43 ºC; ir (potassium bromide):
3854, 3463, 3062, 2981, 2928, 2361, 2339, 1734 (C=O), 1700,
1653, 1602, 1559, 1498, 1448, 1374, 1319 (SO), 1235 (SO), 1153
[1] 1,3-Dipolar Cycloaddition Chemistry, A. Padwa, ed, Wiley &
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Chem. Soc., Perkin Trans. I, 343 (1993).
-1
1
(SO), 1090, 1061, 1018, 998, 886, 816, 749, 684, 667 cm ; H
nmr (400 MHz, deuteriochloroform): δ 1.11-1.31 (m, 3H,
CH CH ), 2.36 and 2.37 (2 s, 3H, 2 _ C H -CH ), 3.44-4.29
2
3
6
4
3
[9] R. S. Paley and S. R. Snow, Tetrahedron Lett., 31, 5853
(1990).
(many peaks overlapping, 4H, CH SO, CH CH ), 4.36-4.39 (m,
2
2
3
J
J
= 2.8 Hz, H ), 4.62 (d, J
= 4.8 Hz, H ), 4.66-4.68 (m,
[10] J. A. Hyatt and J. J. Krutak, J. Org. Chem., 42, 169 (1977).
[11] S. Kanemasa, H. Matsuda, A. Kamimura and T. Kakinami,
Tetrahedron, 56, 1057 (2000).
A'B'
B'
C'D' C'
= 3.1 Hz, H ), 4.71 (d, J = 5.3 Hz, H ), 5.11 (d, J
= 2.8
= 4.8
AB
B
CD
C
A'B'
Hz, H ), 5.28 (d, J = 3.1 Hz, H ), 5.35-5.40 (dt, J
A'
AB
A
C'D'
[12] J. E. Johnson, D. Nwoko, M. Hotema, N. Sanchez, R.
Alderman and V. Lynch, J. Heterocyclic Chem., 33, 1583 (1996).
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Chemistry, Vol. 1, A. Padwa, ed, Wiley & Sons, New York, 1984, p 291;
N. Arai, M. Iwakoshi, K. Tanabe and K. Narasaka, Bull. Soc. Chem. Jpn.,
72, 2277 (1999).
[14] K. Zong, S. I. Shin, D. J. Jeon, J. N. Lee and E. K. Ryu, J.
Heterocyclic Chem., 37, 75, (2000).
[15] E. C. Argyropoulou and E. Thessalonikeos, J. Heterocyclic
Chem., 28, 429, (1991).
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(1971).
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[18] J. R. Anderson, R. L. Edwards and A. J. S. Whalley, J. Chem.
Soc., Perkin Trans. I, 1481 (1985).
Hz, H ), 5.46-5.50 (dt, J = 5.3 Hz, H ), 7.21-8.06 (m, 14H,
D'
13
CD
D
ArH); C nmr (67.8 MHz, deuteriochloroform): δ 13.80, 14.01,
21.49, 45.03, 45.35, 56.21, 56.80, 58.13, 58.18, 58.40, 58.45,
60.18, 60.50, 60.59, 60.95, 62.33, 62.39, 62.44, 62.51, 78.52,
79.28, 82.10, 82.15, 82.44, 125.96, 126.00, 126.61, 126.88,
127.02, 127.33, 127.45, 128.30, 128.44, 128.64, 129.27, 129.54,
129.68, 129.97, 130.69, 130.76, 131.01, 131.07, 131.30, 134.80,
135.04, 135.34, 136.22, 136.35, 140.30, 140.36, 143.03, 143.12,
154.48, 154.62, 155.61, 164.38, 167.49, 168.30, 168.51; ms: m/z
+
No M , 294 (57%), 155 (91), 125 (41), 91 (100), 77 (61), 65 (39).
Anal. Calcd. for C H N O S : C, 59.3; H, 5.0; N, 5.3; S,
26 26
2 6 2
12.2. Found: C, 58.7; H, 5.0; N, 5.3; S, 10.5.
1
13
* Many signals were overlapping in both H and C nmr, so it
was not possible to calculate some coupling constants and assign
the signals to all atoms.
[19] C. R. Johnson, R. A. Kirchhoff, R. J. Reischer and G. F.
Katekar, J. Am. Chem. Soc., 95, 4287 (1973).
[20] A. L. Marzinzik and B. K. Sharpless, J. Org. Chem., 66, 594
(2001).
[21] G. Bashiardes, G. J. Bodwell and S. G. Davies, J. Chem. Soc.,
Perkin Trans. I, 459 (1993).
Acknowledgment.
We wish to thank the Ministry of Science and Technology of
Republic of Croatia for financial support.