Efficient diastereoselective synthesis of phosphonato vinylsulfones via a multicomponent method

Article abstract of DOI:10.1055/s-0028-1083176

The phosphonato vinylsulfone building block was prepared by a facile three-component reaction of an acetylene, a sulfonyl chloride and a trialkyl phosphite. Georg Thieme Verlag.

Full text of DOI:10.1055/s-0028-1083176

PAPER
3447
Efficient Diastereoselective Synthesis of Phosphonato Vinylsulfones via a
Multicomponent Method
D
iastereoselective
b
Synthesis of
d
Phosphonato Vinylsulfon
l
e
s
ali Alizadeh,* Sadegh Rostamnia
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran 18716, Iran
Fax +98(21)88006544; E-mail: aalizadeh@modares.ac.ir
Received 9 May 2008; revised 14 July 2008
The reaction of trialkyl phosphites 1 with dialkyl acety-
lenedicarboxylates 2 in the presence of sulfonyl chlorides
3 in toluene under reflux conditions, produced diethyl (E)-
2-(dialkoxyphosphoryl)-3-(arylsulfonyl)-2-butenedioate
derivatives 4 in 83–97% yields after four hours (Table 1).
Abstract: The phosphonato vinylsulfone building block was pre-
pared by a facile three-component reaction of an acetylene, a sulfo-
nyl chloride and a trialkyl phosphite.
Key words: vinylsulfone, dialky acetylenedicarboxylate, trialkyl
phosphate, multicomponent reaction, zwitterion
The IR spectrum of 4a exhibited absorption bands due to
the carbonyl group of esters at 1737 cm–1, the C=C group
at 1650 cm–1, and the absorption bands of the sulfone
[1338 and 1177 (SO2) cm–1] and phosphonate [1272
(P=O), 1098 and 1037 (PO–Me), and 856 (P–O) cm–1]
Vinylsulfones, as unsaturated sulfones, are extensively
used as intermediates in organic synthesis1a–e due to the
chemical versatility of the sulfone moiety. Vinyl sulfones
are also excellent acceptors in Michael additions and 2p
partners in cycloaddition reactions.1f,g Several biological-
Table 1 Reaction of Trialkyl Phosphites 1 with Dialkyl Acetylene-
ly active sulfone molecules, prepared from alkenyl sul- dicarboxylates 2 in the Presence of Sulfonyl Chlorides 3
fones,1h–j and a,b-unsaturated sulfones, have been found
O
O
to have anticancer1k and carcinogenesis-suppressing ac-
tivity.1l Moreover, the sulfone group can be removed at
the end of a synthetic sequence by a variety of reductive,
alkylative, or oxidative methods.2 In our investigation, vi-
nylsulfones with phosphonate substituents have been syn-
thesized. Organo phosphonates have been used as
substitutes for the corresponding esters and acids with
high biological activity;3a,b vinylphosphonates have been
used as intermediates in the stereoselective synthesis of
trisubstituted olefins.3c–e
S
Cl
R4
R3
CO2R2
3
+
O O
S
PO(OR1)2
CO2R2
toluene, reflux
4 h
R2O2C
CO2R2
2
+
R4
R3
(R1O)3P
1
4
a
b
c
d
e
f
R1
R2
R3
R4
H
Yield of 4 (%)a
Numerous methods have been developed for the synthesis
of vinylsulfones,4a–g however, these methods are some-
times complex, do not tolerate sensitive functional
groups, and the reagents and starting materials are not al-
ways readily available.
Me
Me
Me
Me
Me
Me
Me
Et
Me
Me
Me
Me
Et
H
H
H
Et
H
H
Et
H
H
Et
H
H
H
Et
92
89
90
83
90
91
89
94
90
84
95
97
96
87
Me
Et
H
A general way to improve synthetic efficiency and also to
address the other criteria is the development of types of
multicomponent reactions.5 Multicomponent reactions
(MCRs), by virtue of their convergence, productivity, fac-
ile execution, and generally high yields of products, have
attracted much attention from the point of view of combi-
natorial chemistry.6–8
H
Et
Et
H
g
h
i
Et
Et
H
We recently reported a new class of multicomponent reac-
tions mediated by zwitterionic intermediates.9 We were
interested in applying this zwitterionic method to the dia-
stereoselective synthesis of (E)-phosphonato vinylsul-
fones using acetylenes and phosphites in the presence of
sulfonyl chlorides.
Et
Et
Et
H
j
Et
Et
k
l
Et
Me
Me
Me
Me
H
Et
Me
Et
H
m
Et
SYNTHESIS 2008, No. 21, pp 3447–3452
x
x.
x
x
.
2
0
0
8
n
Et
Advanced online publication: 16.10.2008
DOI: 10.1055/s-0028-1083176; Art ID: Z09608SS
© Georg Thieme Verlag Stuttgart · New York
a Isolated yield.

3448
A. Alizadeh, S. Rostamnia
PAPER
1
moieties. The H NMR spectrum of 4a exhibited one Dimethyl and diethyl acetylenedicarboxylates, and trialkyl phos-
phites were obtained from Merck (Germany) and Fluka (Switzer-
sharp doublet readily recognized as arising from the meth-
land) and were used without further purification. Melting points
were measured on an Electrothermal 9100 apparatus. Elemental
analyses for C, H and N were performed using a Heraeus CHN-O-
Rapid analyzer. Mass spectra were recorded on a Finnigan–Matt
oxy group attached to the phosphorus (d = 3.79 ppm,
3JH–P = 11.7 Hz), and two sharp singlets arising from the
methoxy groups (d = 3.82 and 3.96 ppm). The aryl moiety
exhibited characteristic signals in the aromatic region of
the spectrum. The 1H-decoupled 13C NMR spectrum of 4a
showed 11 distinct resonances in agreement with the di-
methyl (E)-2-(dimethoxyphosphoryl)-3-(phenylsulfonyl)-
8430 mass spectrometer operating at an ionization potential of 70
1
eV. H and 13C NMR spectra were measured as CDCl3 solutions
with a Bruker DRX-500 Avance spectrometer at 500.1 and 125.8
MHz, respectively. IR spectra were recorded on a Shimadzu IR-460
spectrometer. Chromatography columns were prepared from Merck
silica gel 230–240 mesh.
1
2-butenedioate structure. The H- and 13C-decoupled 31P
NMR spectrum of 4a exhibited one sharp singlet readily
recognized as arising from phosphonate (d = 9.32 ppm).
The relative stereochemistry of 4 was determined on the
basis of the 31P–13C coupling constants from the vi-
nylphosphonate. Vicinal 31P–13C coupling through a p-
bond is a useful tool for assigning Z, E structure. In gen-
Dimethyl (E)-2-(Dimethoxyphosphoryl)-3-(phenylsulfonyl)-2-
butenedioate (4a); Typical Procedure
To a magnetically stirred solution of sulfonyl chloride (0.18 g, 1
mmol) and dimethyl acetylenedicarboxylate (0.14 g, 1 mmol) in tol-
uene (3 mL), was added dropwise a solution of trimethyl phosphite
(0.12 g, 1 mmol) in anhydrous toluene (3 mL) at r.t. over 10 min.
The reaction mixture was then allowed to stir for 4 h under reflux.
The solvent was removed under reduced pressure, and the residue
was separated by silica gel column chromatography (silica gel, hex-
ane–EtOAc, 4:1) to give the product 4a.
3
3
eral, JC–P-trans coupling is much larger than JC–P-cis.10
In the 13C NMR spectrum of 4a, the 3JC–P coupling of 8.5
Hz (d = 163.23 ppm, CO2Me) was diagnostic for their E
relationship.10a Partial assignment of these resonances is
given in the experimental section. The H, 13C and 31P
1
Yield: 0.36 g (92%); colorless crystals; mp 119–121 °C.
NMR spectra of compounds 4b–n were similar to those of
4a except for the alkoxy group, ester groups and the aryl
moiety, which exhibited characteristic signals with appro-
priate chemical shifts (see Experimental section).
IR (KBr): 1737 (2 × C=O of CO2Me), 1650 (C=C), 1594 and 1451
(Ph), 1348 and 1177 (SO2), 1272 (P=O), 1235 and 1142 (C–O),
1098 and 1037 (POMe), 856 cm–1 (P–O).
3
1H NMR (500 MHz, CDCl3): d = 3.79 [6 H, d, JH–P = 11.7 Hz,
Although we have not established the mechanism of the
reaction between the phosphites 1 and the acetylenic es-
ters 2 in the presence of the sulfonyl chloride 3 in an ex-
perimental manner, a possible explanation is proposed in
Scheme 1.
P(OMe)2], 3.82 (3 H, s, OMe), 3.96 (3 H, s, OMe), 7.57 (2 H, t,
3JH–H = 8.1 Hz, 2 × CH of Ph), 7.69 (1 H, t, 3JH–H = 7.5 Hz, CH of
Ph), 7.97 (2 H, d, 3JH–H = 7.9 Hz, 2 × CH of Ph).
13C NMR (125 MHz, CDCl3): d = 53.71 and 53.78 (2 × OMe), 54.28
[d, 2JC–P = 5.3 Hz, P(OMe)2], 129.18 (2 × CH of Ph), 129.53 (2 ×
CH of Ph), 134.61 (d, 1JC–P = 159.5 Hz, PC=C), 134.91 (CH of Ph),
137.81 (Cipso-SO2), 148.22 (d, 2JC–P = 6.0 Hz, PC=C), 161.61 (d,
2JC–P = 9.8 Hz, CO2Me), 163.23 (d, 3JC–P = 8.5 Hz, CO2Me).
31P NMR (202 MHz, CDCl3): d = 9.32.
MS: m/z (%) = 393 (4) [M+ + 1], 361 (52), 327 (3), 296 (100), 281
(57), 207 (18), 155 (14), 125 (41), 109 (48), 93 (27), 77 (72), 59
(10), 45 (3).
R2O2C
SO2Ar
CO2R2
R2O2C
3
R1O
P
4
1
+
2
– R1Cl
R1O
(R1O)3P
CO2R2
O
R1
Cl
5
6
Scheme 1
Anal. Calcd for C14H17O9PS: C, 42.86; H, 4.37. Found: C, 42.90; H,
4.30.
On the basis of the well-established chemistry of acetylen-
ic esters,9a,e,i,11 it is reasonable to assume that the phospho-
nato vinylsulfone derivatives 4 apparently result from
initial addition of the phosphite to the acetylenic ester and
subsequent attack of the resulting zwitterion 5 on the sul-
fonyl chloride 3 to yield ion pair 6. This intermediate, un-
der the reflux conditions, then suffers attack by the
chloride ion to produce the (E)-phosphonato vinylsulfone
4 derivatives (Scheme 1).
Dimethyl (E)-2-(Dimethoxyphosphoryl)-3-[(4-methylphe-
nyl)sulfonyl]-2-butenedioate (4b)
Yield: 0.36 g (89%); colorless viscous liquid.
IR (KBr): 1730 (2 × C=O of CO2Me), 1613 (C=C), 1586 and 1429
(Ar), 1333 and 1152 (SO2), 1275 (P=O), 1198 and 1115 (C–O),
1061 and 1028 (POMe), 852 cm–1 (P–O).
1H NMR (500 MHz, CDCl3): d = 2.43 (3 H, s, Me), 3.77 [6 H, d,
3JH–P = 11.7 Hz, P(OMe)2], 3.80 (3 H, s, OMe), 3.93 (3 H, s, OMe),
7.34 (2 H, d, 3JH–H = 8.3 Hz, 2 × CH of Ar), 7.81 (2 H, d, 3JH–H = 8.3
Hz, 2 × CH of Ar).
In summary, the reaction between phosphites and dialkyl
acetylenedicarboxylates, in the presence of sulfonyl chlo-
rides, provides a simple one-pot entry into the synthesis of
(E)-phosphonato vinylsulfone derivatives of potential
synthetic and biological interest. The present method car-
ries the advantage of being performed under the neutral
conditions and requires no activation or modification of
the educts.
13C NMR (125 MHz, CDCl3): d = 21.65 (Me), 53.54 and 53.61 (2 ×
OMe), 54.13 [d, 2JC–P = 5.4 Hz, P(OMe)2], 129.45 (2 × CH of Ar),
129.76 (2 × CH of Ar), 134.00 (d, 1JC–P = 159.7 Hz, PC=C), 134.71
2
(Cipso-SO2), 146.27 (Cipso-Me), 148.47 (d, JC–P =4.6 Hz, PC=C),
2
3
161.56 (d, JC–P = 9.5 Hz, CO2Me), 163.12 (d, JC–P = 7.8 Hz,
CO2Me).
31P NMR (202 MHz, CDCl3): d = 9.38.
MS: m/z (%) = 407 (3) [M+ + 1], 375 (22), 341 (3), 310 (100), 295
(56), 283 (11), 221 (49), 155 (24), 119 (26), 109 (34), 91 (53), 79
(14), 65 (20), 59 (7), 45 (3).
Synthesis 2008, No. 21, 3447–3452 © Thieme Stuttgart · New York

PAPER
Diastereoselective Synthesis of Phosphonato Vinylsulfones
3449
Anal. Calcd for C15H19O9PS: C, 44.34; H, 4.71. Found: C, 44.50; H,
4.60.
2 × CH of Ph), 7.65 (1 H, t, 3JH–H = 7.5 Hz, CH of Ph), 7.95 (2 H, d,
3JH–H = 7.3 Hz, 2 × CH of Ph).
13C NMR (125 MHz, CDCl3): d = 13.44 and 13.61 (2 × OCH2CH3),
Dimethyl (E)-2-(Dimethoxyphosphoryl)-3-[(4-ethylphenyl)sul-
fonyl]-2-butenedioate (4c)
Yield: 0.38 g (90%); colorless viscous liquid.
2
54.07 [d, JC–P = 5.5 Hz, P(OMe)2], 63.04 and 63.22 (2 ×
OCH2CH3), 129.00 (2 × CH of Ph), 129.33 (2 × CH of Ph), 134.48
(d, 1JC–P = 159.0 Hz, PC=C), 134.72 (CH of Ph), 137.98 (Cipso-SO2),
147.97 (d, 2JC–P = 6.0 Hz, PC=C), 160.97 (d, 2JC–P = 9.4 Hz, CO2Et),
162.59 (d, 3JC–P = 7.8 Hz, CO2Et).
31P NMR (202 MHz, CDCl3): d = 8.34.
MS: m/z (%) = 421 (12) [M+ + 1], 375 (66), 347 (19), 310 (100), 281
(96), 272 (6), 240 (16), 207 (67), 193 (5), 161 (39), 125 (80), 109
(35), 93 (28), 77 (83), 53 (27).
IR (KBr): 1734 (2 × C=O of CO2Me), 1620 (C=C), 1586 and 1427
(Ar), 1331 and 1153 (SO2), 1266 (P=O), 1175 and 1153 (C–O),
1063 and 1022 (PO–Me), 885 cm–1 (P–O).
3
1H NMR (500 MHz, CDCl3): d = 1.25 (3 H, t, JH–H = 7.6 Hz,
3
CH2CH3), 2.72 (2 H, q, JH–H = 7.6 Hz, CH2CH3), 3.78 [6 H, d,
3JH–P = 11.8 Hz, P(OMe)2], 3.81 (3 H, s, OMe), 3.94 (3 H, s, OMe),
7.37 (2 H, d, 3JH–H = 8.3 Hz, 2 × CH of Ar), 7.85 (2 H, d, 3JH–H = 8.3
Hz, 2 × CH of Ar).
Anal. Calcd for C16H21O9PS: C, 45.72; H, 5.04. Found: C, 45.80; H,
5.10.
13C NMR (125 MHz, CDCl3): d = 14.76 (CH2CH3), 28.89
2
(CH2CH3), 53.55 and 53.62 (2 × OMe), 54.15 [d, JC–P = 5.1 Hz,
Diethyl (E)-2-(Dimethoxyphosphoryl)-3-[(4-ethylphenyl)sulfo-
nyl]-2-butenedioate (4f)
Yield: 0.41 g (91%); colorless viscous liquid.
P(OMe)2], 128.61 (2 × CH of Ar), 129.60 (2 × CH of Ar), 133.95
(d, 1JC–P = 159.5 Hz, PC=C), 134.88 (Cipso-SO2), 148.50 (d, 2JC–P
=
2
4.7 Hz, PC=C), 152.29 (Cipso-Et), 161.57 (d, JC–P = 9.7 Hz,
CO2Me), 163.13 (d, 3JC–P = 7.8 Hz, CO2Me).
IR (KBr): 1731 (2 × C=O of CO2Et), 1650 (C=C), 1586 and 1451
(Ar), 1331 and 1154 (SO2), 1271 (P=O), 1182 and 1100 (C–O),
1055 and 1023 (PO–Me), 857 cm–1 (P–O).
31P NMR (202 MHz, CDCl3): d = 9.42.
MS: m/z (%) = 421 (4) [M+ + 1], 389 (46), 324 (100), 309 (65), 297
(14), 265 (12), 221 (44), 153 (27), 133 (27), 109 (53), 93 (28), 79
(41), 65 (4), 59 (11), 45 (4).
3
1H NMR (500 MHz, CDCl3): d = 1.07 (3 H, t, JH–H = 7.4 Hz,
3
CH2CH3), 1.27 (3 H, t, JH–H = 7.1 Hz, OCH2CH3), 1.42 (3 H, t,
3JH–H = 7.1 Hz, OCH2CH3), 3.03 (2 H, q, 3JH–H = 7.4 Hz, CH2CH3),
3
3
Anal. Calcd for C16H21O9PS: C, 45.72; H, 5.04. Found: C, 45.90; H,
5.10.
3.83 [6 H, d, JH–P = 11.5 Hz, P(OMe)2], 4.05 (2 H, q, JH–H = 7.1
Hz, OCH2CH3), 4.39 (2 H, q, 3JH–H = 7.1 Hz, OCH2CH3), 7.40 (2 H,
t, 3JH–H = 8.3 Hz, 2 × CH of Ar), 7.92 (2 H, t, 3JH–H = 8.3 Hz, 2 × CH
of Ar).
Dimethyl (E)-2-(Dimethoxyphosphoryl)-3-[(2-ethylphenyl)sul-
fonyl]-2-butenedioate (4d)
Yield: 0.35 g (83%); colorless viscous liquid.
13C NMR (125 MHz, CDCl3): d = 13.60 and 13.83 (2 × OCH2CH3),
2
14.92 (CH2CH3), 29.02 (CH2CH3), 54.13 [d, JC–P = 4.9 Hz,
IR (KBr): 1734 (2 × C=O of CO2Me), 1621 (C=C), 1586 and 1429
(Ar), 1331 and 1153 (SO2), 1266 (P=O), 1246 and 1175 (C–O),
1063 and 1020 (PO–Me), 852 cm–1 (P–O).
P(OMe)2], 63.13 and 63.31 (2 × OCH2CH3), 128.62 (2 × CH of Ar),
129.76 (2 × CH of Ar), 132.79 (d, 1JC–P = 147.7 Hz, PC=C), 135.22
2
(Cipso-SO2), 148.51 (d, JC–P = 5.0 Hz, PC=C), 152.23 (Cipso-Et),
161.26 (d, 2JC–P = 9.5 Hz, CO2Et), 162.83 (d, 3JC–P = 8.2 Hz, CO2Et).
31P NMR (202 MHz, CDCl3): d = 8.56.
3
1H NMR (500 MHz, CDCl3): d = 1.27 (3 H, t, JH–H = 7.4 Hz,
3
CH2CH3), 2.97 (2 H, q, JH–H = 7.4 Hz, CH2CH3), 3.58 (3 H, s,
OMe), 3.79 [6 H, d, 3JH–P = 11.6 Hz, P(OMe)2], 3.89 (3 H, s, OMe),
7.33–7.39 (2 H, m, 2 × CH of Ar), 7.58 (1 H, t, 3JH–H = 7.2 Hz, CH
of Ar), 7.94 (1 H, d, 3JH–H = 8.1 Hz, CH of Ar).
MS: m/z (%) = 449 (12) [M+ + 1], 437 (2), 404 (10), 377 (30), 331
(38), 285 (58), 265 (100), 237 (62), 211 (85), 193 (42), 149 (42),
109 (61), 75 (96), 59 (40), 45 (17).
13C NMR (125 MHz, CDCl3): d = 15.27 (CH2CH3), 25.57
Anal. Calcd for C18H25O9PS: C, 48.21; H, 5.62. Found: C, 48.20; H,
5.70.
2
(CH2CH3), 53.50 and 53.63 (2 × OMe), 54.15 [d, JC–P = 5.1 Hz,
P(OMe)2], 126.26, 130.70, 130.94 and 134.93 (4 × CH of Ar),
1
132.00 (d, JC–P = 159.0 Hz, PC=C), 135.97 (Cipso-SO2), 146.11
Diethyl (E)-2-(Dimethoxyphosphoryl)-3-[(2-ethylphenyl)sulfo-
nyl]-2-butenedioate (4g)
Yield: 0.40 g (89%); colorless viscous liquid.
(Cipso-Et), 149.49 (d, 2JC–P = 4.6 Hz, PC=C), 161.13 (d, 2JC–P = 9.7
Hz, CO2Me), 162.77 (d, 3JC–P = 7.8 Hz, CO2Me).
31P NMR (202 MHz, CDCl3): d = 9.47.
MS: m/z (%) = 421 (4) [M+ + 1], 370 (8), 325 (32), 324 (100), 309
(65), 292 (12), 265 (12), 221 (44), 169 (23), 153 (27), 133 (27), 109
(53), 93 (28), 79 (41), 65 (5), 59 (12), 45 (3).
IR (KBr): 1731 (2 × C=O of CO2Et), 1650 (C=C), 1586 and 1451
(Ar), 1331 and 1154 (SO2), 1271 (P=O), 1182 and 1100 (C–O),
1055 and 1023 (PO–Me), 857 cm–1 (P–O).
3
1H NMR (500 MHz, CDCl3): d = 1.29 (3 H, t, JH–H = 7.5 Hz,
3
Anal. Calcd for C16H21O9PS: C, 45.72; H, 5.04. Found: C, 45.80; H,
5.00.
CH2CH3), 1.32 (3 H, t, JH–H = 7.1 Hz, OCH2CH3), 1.38 (3 H, t,
3JH–H = 7.1 Hz, OCH2CH3), 2.76 (2 H, q, 3JH–H = 7.5 Hz, CH2CH3),
3
3
3.84 [6 H, d, JH–P = 11.5 Hz, P(OMe)2], 4.29 (2 H, q, JH–H = 7.1
Hz, OCH2CH3), 4.45 (2 H, q, 3JH–H = 7.1 Hz, OCH2CH3), 7.36–7.45
(2 H, m, 2 × CH of Ar), 7.61 (1 H, t, 3JH–H = 7.5 Hz, CH of Ar), 8.01
(1 H, d, 3JH–H = 7.9 Hz, CH of Ar).
Diethyl (E)-2-(Dimethoxyphosphoryl)-3-(phenylsulfonyl)-2-
butenedioate (4e)
Yield: 0.38 g (90%); colorless crystals; mp 72–74 °C.
IR (KBr): 1726 (2 × C=O of CO2Et), 1650 (C=C), 1574 and 1459
(Ph), 1332 and 1152 (SO2), 1263 (P=O), 1109 and 1040 (C–O),
1063 and 1013 (PO–Me), 859 cm–1 (P–O).
13C NMR (125 MHz, CDCl3): d = 13.41 and 13.74 (2 × OCH2CH3),
2
15.29 (CH2CH3), 25.60 (CH2CH3), 54.17 [d, JC–P = 5.4 Hz,
P(OMe)2], 63.08 and 63.18 (2 × OCH2CH3), 126.26, 130.86, 130.88
1
and 134.85 (4 × CH of Ar), 134.06 (d, JC–P = 147.7 Hz, PC=C),
3
1H NMR (500 MHz, CDCl3): d = 1.21 (3 H, t, JH–H = 7.2 Hz,
2
135.04 (Cipso-SO2), 146.19 (Cipso-Et), 148.67 (d, JC–P = 4.9 Hz,
OCH2CH3), 1.35 (3 H, t, 3JH–H = 7.2 Hz, OCH2CH3), 3.75 [6 H, d,
3JH–P = 11.7 Hz, P(OMe)2], 4.22 (2 H, q, 3JH–H = 7.2 Hz, OCH2CH3),
4.39 (2 H, q, 3JH–H = 7.2 Hz, OCH2CH3), 7.53 (2 H, t, 3JH–H = 7.7 Hz,
PC=C), 160.75 (d, 2JC–P = 9.5 Hz, CO2Et), 162.46 (d, 3JC–P = 8.1 Hz,
CO2Et).
31P NMR (202 MHz, CDCl3): d = 8.51.
Synthesis 2008, No. 21, 3447–3452 © Thieme Stuttgart · New York

3450
A. Alizadeh, S. Rostamnia
PAPER
Diethyl (E)-2-(Diethoxyphosphoryl)-3-[(2-ethylphenyl)sulfo-
nyl]-2-butenedioate (4j)
Yield: 0.40 g (84%); colorless viscous liquid.
MS: m/z (%) = 448 (12) [M+], 437 (2), 421 (11), 404 (10), 377 (30),
331 (38), 303 (31), 285 (58), 265 (100), 237 (62), 211 (85), 193
(42), 149 (42), 109 (61), 75 (96), 59 (40), 45 (17).
Anal. Calcd for C18H25O9PS: C, 48.21; H, 5.62. Found: C, 48.10; H,
5.60.
IR (KBr): 1736 (2 × C=O of CO2Et), 1655 (C=C), 1580 and 1454
(Ar), 1360 and 1141 (SO2), 1387 (P=O), 1180 and 1051 (C–O),
1104 and 1073 (PO–Et), 944 cm–1 (P–O).
Diethyl (E)-2-(Diethoxyphosphoryl)-3-(phenylsulfonyl)-2-
butenedioate (4h)
Yield: 0.42 g (94%); colorless viscous liquid.
3
1H NMR (500 MHz, CDCl3): d = 1.21 (3 H, t, JH–H = 7.5 Hz,
CH2CH3), 1.23 (3 H, t, 3JH–H = 7.1 Hz, OCH2CH3), 1.27 [6 H, d,
3
3JH–H = 7.4 Hz, P(OCH2CH3)2], 1.38 (3 H, t, JH–H = 7.1 Hz,
3
IR (KBr): 1745 (2 × C=O of CO2Et), 1697 (C=C), 1580 and 1453
(Ph), 1371 and 1170 (SO2), 1272 (P=O), 1178 and 1146 (C–O),
1096 and 1019 (PO–Et), 900 cm–1 (P–O).
OCH2CH3), 2.98 (2 H, q, JH–H = 7.5 Hz, CH2CH3), 3.98 (2 H, q,
3JH–H = 7.1 Hz, OCH2CH3), 4.10–4.18 [4 H, m, P(OCH2CH3)2], 4.38
(2 H, q, 3JH–H = 7.1 Hz, OCH2CH3], 7.28–7.40 (2 H, m, 2 × CH of
Ar), 7.56 (1 H, t, 3JH–H = 7.6 Hz, CH of Ar), 7.94 (1 H, d, 3JH–H = 8.0
Hz, CH of Ar).
3
1H NMR (500 MHz, CDCl3): d = 1.28 (3 H, t, JH–H = 7.6 Hz,
OCH2CH3), 1.33 [6 H, t, 3JH–H = 7.0 Hz, P(OCH2CH3)2], 1.41 (3 H,
t, 3JH–H = 7.7 Hz, OCH2CH3), 4.14–4.4.22 [4 H, m, P(OCH2CH3)2],
4.28 (2 H, q, 3JH–H = 7.7 Hz, OCH2CH3), 4.44 (2 H, q, 3JH–H = 7.6
13C NMR (125 MHz, CDCl3): d = 13.35 and 13.72 (2 × OCH2CH3),
15.19 (CH2CH3), 16.01 [d, JC–P = 6.5 Hz, P(OCH2CH3)2], 25.52
(CH2CH3), 62.86 and 62.99 (2 × OCH2CH3), 64.08 [d, JC–P = 6.3
Hz, P(OCH2CH3)2], 126.21, 130.74, 130.80 and 134.82 (4 × CH of
Ar), 135.42 (d, 1JC–P = 152.6 Hz, PC=C), 134.82 (Cipso-SO2), 146.05
(Cipso-Et), 147.92 (d, 2JC–P = 6.1 Hz, PC=C), 160.75 (d, 2JC–P = 9.5
Hz, CO2Et), 162.46 (d, 3JC–P = 7.4 Hz, CO2Et).
3
3
2
Hz, OCH2CH3), 7.58 (2 H, t, JH–H = 8.6 Hz, 2 × CH of Ph), 7.70
(1 H, t, 3JH–H = 7.6 Hz, CH of Ph), 8.02 (2 H, d, 3JH–H = 7.8 Hz, 2 ×
CH of Ph).
13C NMR (125 MHz, CDCl3): d = 13.58 and 13.85 (2 × OCH2CH3),
3
16.02 [d, JC–P = 6.5 Hz, P(OCH2CH3)2], 63.04 and 63.25 (2 ×
OCH2CH3), 64.19 [d, 2JC–P = 6.28 Hz, P(OCH2CH3)2], 129.06 (2 ×
CH of Ph), 129.48 (2 × CH of Ph), 134.70 (CH of Ph), 135.52 (d,
1JC–P = 156.2 Hz, PC=C), 138.18 (Cipso-SO2), 147.48 (d, 2JC–P = 6.2
Hz, PC=C), 161.21 (d, 2JC–P = 9.4 Hz, CO2Et), 162.89 (d, 3JC–P = 8.2
Hz, CO2Et).
31P NMR (202 MHz, CDCl3): d = 5.35.
MS: m/z (%) = 476 (2) [M+], 461 (1), 378 (3), 349 (9), 317 (2), 299
(11), 271 (12), 211 (3), 197 (3), 105 (100), 99 (25), 93 (9), 77 (25),
65 (25), 59 (5), 45 (2).
Anal. Calcd for C20H29O9PS: C, 50.42; H, 6.13. Found: C, 50.50; H,
6.00.
31P NMR (202 MHz, CDCl3): d= 7.72.
MS: m/z (%) = 448 (2) [M+], 403 (22), 375 (11), 338 (46), 309 (32),
301 (14), 281 (6), 207 (17), 179 (35), 150 (23), 125 (62), 99 (25), 97
(18), 77 (100), 65 (25), 53 (45), 45 (28).
Dimethyl (E)-2-(Diethoxyphosphoryl)-3-(phenylsulfonyl)-2-
butenedioate (4k)
Yield: 0.40 g (95%); colorless crystals; mp 69–71 °C.
Anal. Calcd for C18H25O9PS: C, 48.21; H, 5.62. Found: C, 48.20; H,
5.50.
IR (KBr): 1739 (2 × C=O of CO2Me), 1655 (C=C), 1587 and 1452
(Ph), 1369 and 1173 (SO2), 1260 (P=O), 1219 and 1173 (C–O),
1097 and 1023 (PO–Et), 896 cm–1 (P–O).
Diethyl (E)-2-(Diethoxyphosphoryl)-3-[(4-ethylphenyl)sulfo-
nyl]-2-butenedioate (4i)
Yield: 0.43 g (90%); colorless viscous liquid.
3
1H NMR (500 MHz, CDCl3): d = 1.25 [6 H, t, JH–H = 7.0 Hz,
P(OCH2CH3)2], 3.76 (3 H, s, OMe), 3.90 (3 H, s, OMe), 4.08–4.14
[4 H, m, P(OCH2CH3)2], 7.15 (2 H, t, 3JH–H = 8.1 Hz, 2 × CH of Ph),
7.64 (1 H, t, 3JH–H = 7.9 Hz, CH of Ph), 7.91 (2 H, d, 3JH–H = 8.6 Hz,
2 × CH of Ph).
IR (KBr): 1736 (2 × C=O of CO2Et), 1655 (C=C), 1584 and 1454
(Ar), 1360 and 1181 (SO2), 1268 (P=O), 1141 and 1073 (C–O),
1104 and 1051 (PO–Et), 901 cm–1 (P–O).
3
3
1H NMR (500 MHz, CDCl3): d = 1.00 (3 H, t, JH–H = 7.5 Hz,
13C NMR (125 MHz, CDCl3): d = 15.99 [d, JC–P = 6.5 Hz,
3
2
CH2CH3), 1.27 (3 H, t, JH–H = 7.1 Hz, OCH2CH3), 1.31 [6 H, t,
P(OCH2CH3)2], 53.50 and 53.63 (2 × OMe), 64.29 [d, JC–P = 5.5
3
3JH–H = 7.5 Hz, P(OCH2CH3)2], 1.38 (3 H, t, JH–H = 7.1 Hz,
Hz, P(OCH2CH3)2], 129.14 (2 × CH of Ar), 129.41 (2 × CH of Ph),
1
OCH2CH3), 2.70 (2 H, q, 3JH–H = 7.5 Hz, CH2CH3), 4.07–4.15 [4 H,
134.85 (CH of Ph), 135.75 (d, JC–P = 158.0 Hz, PC=C), 137.98
3
m, P(OCH2CH3)2], 4.27 (2 H, q, JH–H = 7.1 Hz, OCH2CH3), 4.40
(Cipso-SO2), 147.53 (d, 2JC–P = 4.9 Hz, PC=C), 161.63 (d, 2JC–P = 9.4
(2 H, q, 3JH–H = 7.1 Hz, OCH2CH3), 7.35 (2 H, d, 3JH–H = 8.1 Hz, 2
× CH of Ar), 7.86 (2 H, d, 3JH–H = 8.1 Hz, 2 × CH of Ar).
Hz, CO2Me), 163.27 (d, 3JC–P = 7.5 Hz, CO2Me).
31P NMR (202 MHz, CDCl3): d = 6.15.
MS: m/z (%) = 421 (3) [M+ + 1], 390 (3), 389 (15), 378 (3), 361 (7),
324 (100), 309 (30), 223 (9), 207 (5), 129 (23), 125 (47), 109 (29),
77 (67), 65 (11), 51 (13), 45 (4).
13C NMR (125 MHz, CDCl3): d = 13.55 and 13.81 (2 × OCH2CH3),
3
14.89 (CH2CH3), 16.01 [d, JC–P = 6.5 Hz, P(OCH2CH3)2], 28.94
2
(CH2CH3), 62.92 and 63.13 (2 × OCH2CH3), 64.10 [d, JC–P = 6.3
Hz, P(OCH2CH3)2], 128.55 (2 × CH of Ar), 129.65 (2 × CH of Ar),
133.86 (d, 1JC–P = 156.3 Hz, PC=C), 135.30 (Cipso-SO2), 147.77 (d,
2JC–P = 6.1 Hz, PC=C), 152.12 (Cipso-Et), 161.27 (d, 2JC–P = 9.5 Hz,
CO2Et), 162.72 (d, 3JC–P = 7.6 Hz, CO2Et).
Anal. Calcd for C16H21O9PS: C, 45.72; H, 5.04. Found: C, 45.90; H,
5.10.
Dimethyl (E)-2-(Diethoxyphosphoryl)-3-[(4-methylphenyl)sul-
fonyl]-2-butenedioate (4l)
Yield: 0.42 g (97%); colorless viscous liquid.
31P NMR (202 MHz, CDCl3): d = 5.31.
MS: m/z (%) = 476 (4) [M+], 461 (2), 408 (3), 349 (9), 325 (9), 317
(2), 299 (11), 271 (12), 211 (3), 197 (3), 105 (100), 99 (25), 93 (9),
77 (25), 65 (25), 59 (5), 45 (1).
IR (KBr): 1741 (2 × C=O of CO2Me), 1604 (C=C), 1502 and 1454
(Ar), 1362 and 1172 (SO2), 1261 (P=O), 1172 and 1100 (C–O),
1066 and 1034 (PO–Et), 902 cm–1 (P–O).
Anal. Calcd for C20H29O9PS: C, 50.42; H, 6.13. Found: C, 50.50; H,
6.00.
3
1H NMR (500 MHz, CDCl3): d = 1.29 [6 H, t, JH–H = 7.0 Hz,
P(OCH2CH3)2], 2.43 (3 H, s, Me), 3.80 (3 H, s, OMe), 3.93 (3 H, s,
OMe), 4.11–4.16 [4 H, m, P(OCH2CH3)2], 7.34 (2 H, d, 3JH–H = 8.1
Hz, 2 × CH of Ar), 7.82 (2 H, d, 3JH–H = 8.1 Hz, 2 × CH of Ar).
Synthesis 2008, No. 21, 3447–3452 © Thieme Stuttgart · New York

PAPER
Diastereoselective Synthesis of Phosphonato Vinylsulfones
3451
3
13C NMR (125 MHz, CDCl3): d = 15.93 [d, JC–P = 6.4 Hz,
P(OCH2CH3)2], 21.67 (Me), 53.40 and 53.54 (2 × OMe), 64.16 [d,
2JC–P = 5.4 Hz, P(OCH2CH3)2], 129.45 (2 × CH of Ar), 129.73 (2 ×
CH of Ar), 135.10 (d, 1JC–P = 158.2 Hz, PC=C), 134.87 (Cipso-SO2),
Anal. Calcd for C18H25O9PS: C, 48.21; H, 5.62. Found: C, 48.20; H,
5.60.
2
References
146.15 (Cipso-Me), 147.79 (d, JC–P = 4.8 Hz, PC=C), 161.67 (d,
2JC–P = 9.4 Hz, CO2Me), 163.27 (d, 3JC–P = 7.5 Hz, CO2Me).
31P NMR (202 MHz, CDCl3): d = 5.10.
(1) (a) Simpkins, N. S. Sulfones in Organic Synthesis;
Pergamon: Oxford, 1993. (b) Tanaka, K.; Kaji, A. In The
Chemistry of Sulfones and Sulfoxides; Patai, S.; Rapoport,
Z.; Stirling, C. J. M., Eds.; Wiley: Chechester, 1988, Chap.
15. (c) Carreno, M. C. Chem. Rev. 1995, 95, 1717.
(d) Kazuhiro, Y.; Tamio, H. J. Am. Chem. Soc. 2003, 125,
2872. (e) Ranu, B. C.; Guchhait, S. K.; Ghosh, K. J. Org.
Chem. 1998, 63, 5250. (f) Fuchs, P. L.; Braish, T. F. Chem.
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Tetrahedron 1988, 44, 6755. (h) Wang, G.; Mahesh, U.;
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7203. (k) Reddy, P. E.; Reddy, R. M. V. PCT Int. Appl.
W09918068, 1999; Chem. Abstr. 1999, 130, 281870.
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Kunikowski, A. J.; Asao, T.; Nishino, H.; Yamada, Y. Jpn.
Patent JP 9003037, 1997; Chem. Abstr. 1997, 126, 185889.
(2) For a review of desulfonylation, see: Najera, C.; Yus, M.
Tetrahedron 1999, 55, 10547.
(3) (a) Kaboudin, B.; Nazari, R. Tetrahedron Lett. 2001, 42,
8211. (b) Kim, D. Y.; Rhie, D. Y. Tetrahedron 1997, 53,
13603; and references therein. (c) Thomas, A. A.;
Sharpless, K. B. J. Org. Chem. 1999, 64, 8379. (d) Shen,
Y.; Jiang, G. F. Synthesis 2000, 99. (e) Tago, K.; Kogen, H.
Org. Lett. 2000, 2, 1975.
(4) (a) Huang, X.; Duan, D.; Zheng, W. J. Org. Chem. 2003, 68,
1958. (b) Duan, D.-H.; Huang, X. Synlett 1999, 317.
(c) Huang, X.; Liang, C.-G.; Xu, Q.; He, Q.-W. J. Org.
Chem. 2001, 66, 74. (d) Nair, V.; Augustine, A.; George,
T. G.; Nair, L. G. Tetrahedron Lett. 2001, 42, 6763.
(e) Qian, H.; Huang, X. Synlett 2001, 1913. (f) Berteina, S.;
Wendeborn, S.; Brill, W. K.-D.; Mesmaeker, A. D. Synlett
1998, 676. (g) Matano, Y.; Yoshimune, M.; Azuma, N.;
Suzuki, H. J. Chem. Soc., Perkin Trans. 1 1996, 1971.
(5) Tietze, L. F. Chem. Rev. 1996, 96, 115.
MS: m/z (%) = 435 (22) [M+ + 1], 403 (34), 389 (6), 375 (4), 338
(100), 323 (36), 311 (6), 235 (11), 139 (54), 119 (21), 109 (30), 91
(86), 81 (23), 65 (39), 53 (9), 45 (5).
Anal. Calcd for C17H23O9PS: C, 47.01; H, 5.34. Found: C, 47.00; H,
5.20.
Dimethyl (E)-2-(Diethoxyphosphoryl)-3-[(4-ethylphenyl)sulfo-
nyl]-2-butenedioate (4m)
Yield: 0.43 g (96%); colorless viscous liquid.
IR (KBr): 1732 (2 × C=O of CO2Me), 1612 (C=C), 1586 and 1427
(Ar), 1330 and 1154 (SO2), 1257 (P=O), 1186 and 1013 (C–O),
1063 and 1036 (PO–Et), 884 cm–1 (P–O).
3
1H NMR (500 MHz, CDCl3): d = 1.24 (3 H, t, JH–H = 7.6 Hz,
CH2CH3), 1.29 [6 H, t, 3JH–H = 7.1 Hz, P(OCH2CH3)2], 2.72 (2 H, q,
3JH–H = 7.6 Hz, CH2CH3), 3.56 (3 H, s, OMe), 3.80 (3 H, s, OMe),
3
4.10–4.18 [4 H, m, P(OCH2CH3)2], 7.36 (2 H, d, JH–H = 8.1 Hz,
2 × CH of Ar), 7.84 (2 H, d, 3JH–H = 8.1 Hz, 2 × CH of Ar).
13C NMR (125 MHz, CDCl3): d = 14.84 (CH2CH3), 15.98 [d, 3JC–P
= 6.6 Hz, P(OCH2CH3)2], 28.94 (CH2CH3), 53.44 and 53.58 (2 ×
OMe), 64.22 [d, 2JC–P = 5.4 Hz, P(OCH2CH3)2], 128.62 (2 × CH of
1
Ar), 129.63 (2 × CH of Ar), 133.88 (d, JC–P = 158.6 Hz, PC=C),
135.08 (Cipso-SO2), 147.86 (d, 2JC–P = 4.8 Hz, PC=C), 152.23 (Cipso
-
Et), 161.74 (d, 2JC–P = 9.4 Hz, CO2Me), 163.31 (d, JC–P = 7.7 Hz,
3
CO2Me).
31P NMR (202 MHz, CDCl3): d = 6.35.
MS: m/z (%) = 449 (72) [M+ + 1], 417 (77), 352 (100), 337 (37), 293
(17), 235 (9), 215 (47), 187 (19), 153 (28), 105 (33), 91 (22), 79
(35), 65 (12), 53 (11), 45 (7).
Anal. Calcd for C18H25O9PS: C, 48.21; H, 5.62. Found: C, 48.30; H,
5.50.
Dimethyl (E)-2-(Diethoxyphosphoryl)-3-[(2-ethylphenyl)sulfo-
nyl]-2-butenedioate (4n)
(6) Ugi, I. Angew. Chem., Int. Ed. Engl. 1982, 21, 810.
(7) Dömling, A.; Ugi, I. Angew. Chem. Int. Ed. 2000, 39, 3169.
(8) Dömling, A. Chem. Rev. 2006, 106, 17.
Yield: 0.39 g (87%); colorless viscous liquid.
IR (KBr): 1732 (2 × C=O of CO2Me), 1612 (C=C), 1586 and 1427
(Ar), 1330 and 1186 (SO2), 1257 (P=O), 1154 and 976 (C–O), 1036
and 1013 (PO–Et), 847 cm–1 (P–O).
(9) (a) Alizadeh, A.; Masrouri, H.; Rostamnia, S.; Movahedi, F.
Helv. Chim. Acta. 2006, 89, 923. (b) Alizadeh, A.;
Rostamnia, S.; Hu, M. L. Synlett 2006, 1592. (c) Alizadeh,
A.; Rostamnia, S.; Esmaili, A. A. Synthesis 2007, 709.
(d) Alizadeh, A.; Oskueyan, Q.; Rostamnia, S. Synthesis
2007, 2637. (e) Alizadeh, A.; Zohreh, N.; Rostamnia, S.
Tetrahedron 2007, 63, 8083. (f)Alizadeh, A.;Rostamnia, S.
Synthesis 2008, 57. (g) Alizadeh, A.; Rostamnia, S.; Zohreh,
N.; Bijanzadeh, H. R. Monatsh. Chem. 2008, 139, 49.
(h) Alizadeh, A.; Rostamnia, S.; Zhu, L. G. Tetrahedron
2006, 62, 5641. (i) Alizadeh, A.; Rostamnia, S.; Zohreh, N.;
Oskueyan, Q. Synlett. 2007, 1610.
(10) (a) Phosphorus-31 NMR Spectroscopy in Stereochemical
Analysis: Organic Compounds and Metal Complexes, Vol.
8; Verkade, J. G.; Quin, L. D., Eds.; VCH: New York, 1987,
401. (b) Duncan, M.; Gallagher, M. J. Org. Magn. Reson.
1981, 15, 37. (c) Ahlbrecht, H.; Farnung, W. Chem. Ber.
1984, 117, 1. (d) Macomber, R. S.; Krudy, G. A. J. Org.
Chem. 1981, 46, 4038.
3
1H NMR (500 MHz, CDCl3): d = 1.26 (3 H, t, JH–H = 7.4 Hz,
CH2CH3), 1.31 [6 H, t, 3JH–H = 7.1 Hz, P(OCH2CH3)2], 2.81 (2 H, q,
3JH–H = 7.4 Hz, CH2CH3), 3.86 (3 H, s, OMe), 3.93 (3 H, s, OMe),
4.11–4.17 [4 H, m, P(OCH2CH3)2], 7.32–7.39 (2 H, m, 2 × CH of
Ar), 7.57 (1 H, t, 3JH–H = 7.5 Hz, CH of Ar), 7.93 (1 H, d, 3JH–H = 8.0
Hz, CH of Ar).
13C NMR (125 MHz, CDCl3): d = 15.27 (CH2CH3), 15.98 [d,
3JC–P = 6.6 Hz, P(OCH2CH3)2], 25.58 (CH2CH3), 53.43 and 53.46 (2
× OMe), 64.20 [d, 2JC–P = 5.3 Hz, P(OCH2CH3)2], 126.27, 130.74,
130.91 and 134.91 (4 × CH of Ar), 134.74 (Cipso-SO2), 135.17 (d,
1JC–P = 162.1 Hz, PC=C), 146.12 (Cipso-Et), 148.02 (d, JC–P = 4.8
2
Hz, PC=C), 161.27 (d, 2JC–P = 9.4 Hz, CO2Me), 162.94 (d, 3JC–P
7.7 Hz, CO2Me).
=
31P NMR (202 MHz, CDCl3): d = 6.37.
MS: m/z (%) = 448 (16) [M+], 418 (14), 352 (100), 325 (7), 293
(17), 235 (9), 215 (47), 187 (19), 153 (28), 105 (33), 91 (22), 79
(35), 65 (12), 53 (11).
Synthesis 2008, No. 21, 3447–3452 © Thieme Stuttgart · New York

3452
A. Alizadeh, S. Rostamnia
PAPER
Soc., Perkin Trans. 1 1997, 3129. (f) Nair, V.; Nair, J. S.;
Vinod, A. U. Synthesis 2000, 1713. (g) Yavari, I.; Alizadeh,
A.; Mohebbi, H. Phosphorus, Sulfur 2003, 178, 1741.
(h) Yavari, I.; Maghsoodlou, M. T. Tetrahedron Lett. 1998,
39, 4579.
(11) (a) Johnson, A. W.; Tebby, J. C. J. Chem. Soc. 1961, 2126.
(b) Tebby, J. C.; Wilson, I. F.; Griffiths, D. V. J. Chem. Soc.,
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H.-J. Chem. Ber. 1966, 99, 1558. (d) Nozaki, K.; Sato, N.;
Ikeda, K.; Takaya, H. J. Org. Chem. 1996, 61, 4516.
(e) Nair, V.; Nair, J. S.; Vinod, A. U.; Rath, N. P. J. Chem.
Synthesis 2008, No. 21, 3447–3452 © Thieme Stuttgart · New York