An efficient synthesis of vinyl sulfones from alkenes and aryl sulfinates

Article abstract of DOI:10.1055/s-0030-1260142

Vinyl sulfones have been efficiently synthesized by treatment of alkenes with sodium arene sulfinates using potassium iodide and sodium periodate in the presence of a catalytic amount of acetic acid at room temperature. The products are formed in high yie

Full text of DOI:10.1055/s-0030-1260142

PAPER
2941
An Efficient Synthesis of Vinyl Sulfones from Alkenes and Aryl Sulfinates1
Synthesisof
V
iny
i
l
S
ulfo
s
nes wanath Das,* Maram Lingaiah, Kongara Damodar, Nisith Bhunia
Organic Chemistry Division-1, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)27193198; E-mail: biswanathdas@yahoo.com
Received 11 May 2011; revised 13 June 2011
Several olefinic compounds (aromatic and aliphatic) were
Abstract: Vinyl sulfones have been efficiently synthesized by
treatment of alkenes with sodium arene sulfinates using potassium
iodide and sodium periodate in the presence of a catalytic amount
of acetic acid at room temperature. The products are formed in high
yields (87–95%) within 2.5–8 hours.
converted into the corresponding vinyl sulfones by fol-
lowing the above method; the desired products were
formed in 2.5–8 hours and the yields were high (87–95%;
Table 1). In absence of a catalytic amount of acetic acid
the reaction times were longer and the yields were lower.
Olefins containing both electron-donating and electron-
withdrawing groups were tolerated, and homoallylic alco-
hols and homoallylic amines underwent the conversion
smoothly. The vinyl sulfone products derived from the
former type of compounds have important synthetic uses.8
An a,b-unsaturated ketone afforded a minor amount (7%)
of the corresponding Michael addition product (Table 1,
entry 3). Various functional groups such as halogen, hy-
droxy, amine, carbonyl, Cbz, Bn, and PMB remained un-
changed. The structures of the products were established
Key words: vinylsulfone, alkene, aryl sulfinate, synthetic methods
Vinyl sulfones are versatile intermediates in organic
synthesis2 that can easily participate in 1,4-addition and
cycloaddition reactions. Desulfonylation of these com-
pounds is an important method to generate substituted ole-
fins.3 Vinyl sulfones have also been utilized in the total
synthesis of bioactive natural products, such as mor-
phine,4a cephalotaxine,4b and magnofaragesin.4c
1
from their spectral (IR, H and 13C NMR, ESIMS) and
Biologically, vinyl sulfones are also highly valuable be-
cause they act as inhibitors of various types of enzymatic
processes.5 For example, such compounds have been
shown to inhibit cysteine protease, HIV-1 integrase, and
Staphylococcus aureus sortase.
physical analytical data. The (E) configuration of the dou-
ble bond of these compounds was established from the
coupling constant of the olefinic protons observed in their
NMR spectra.
Mechanistically, NaIO4 oxidizes KI to liberate I2,9 which
converts ArSO2Na into ArSO2I (Scheme 2).5 In the pres-
ence of acetic acid, the liberation of I2 was found to be rap-
id. Next, the reaction of ArSO2I with an olefin produces
the b-iodosulfone. Finally, spontaneous elimination of HI
from this b-iodosulfone furnishes the corresponding vinyl
sulfone.6b
The synthesis of vinyl sulfones has generally been accom-
plished through addition–elimination sequences, olefina-
tion reactions (Aldol, Wittig, Horner–Emmons–
Wadsworth (HEW), and Peterson), manipulation of
acetylic sulfones, or by using organometallic reagents.5,6
Here, we report a simple synthesis of these compounds
starting from alkenes.
In continuation of our work7 on the development of useful
synthetic methodologies, we have observed that the treat-
ment of alkenes with sodium arene sulfinates using KI and
NaIO4, in the presence of a catalytic amount of acetic acid,
afforded the corresponding vinyl sulfones at room tem-
perature (Scheme 1)
I2
KI + NaIO4
ArSO2I
I2 + ArSO2Na
I
– HI
SO2Ar
SO2Ar
R
ArSO2I
R
R
ArSO2Na
Scheme 2
KI + NaIO4
(10 mol% each)
SO2Ar
R
In conclusion, we have developed a simple and efficient
method for the synthesis of vinyl sulfones, starting from
alkenes, at room temperature. The mild reaction condi-
tions, high yields, and the applicability of both aromatic
and aliphatic alkenes are the notable advantages of this
method.
R
AcOH (cat.), MeCN
r.t, 2.5–8 h
1
2
R = aryl, alkyl
87–95%
Ar = Ph, 4-tolyl
Scheme 1
Silica gel F254 plates were used for thin layer chromatography
(TLC); spots were examined under UV light and then developed in
iodine vapor. Column chromatography was performed with silica
gel (BDH 100–200 mesh). Solvents were purified according to stan-
dard procedures. IR spectra were recorded with a Perkin–Elmer RX
SYNTHESIS 2011, No. 18, pp 2941–2944
Advanced online publication: 28.07.2011
DOI: 10.1055/s-0030-1260142; Art ID: Z49411SS
x
x.
x
x
.
2
0
1
1
© Georg Thieme Verlag Stuttgart · New York

2942
B. Das et al.
PAPER
Table 1 Synthesis of Vinyl Sulfones 2 from Alkenes and ArSO2Naa
r.t. for the appropriate time (progress of the reaction was monitored
by TLC). After completion of the reaction, the mixture was
quenched by the addition of a sat. aq Na2S2O3 (5 mL) and extracted
with EtOAc (2 × 10 mL). The organic layer was separated and con-
centrated, and the residue was subjected to column chromatography
(silica gel; hexane–EtOAc) to obtain the pure product. Compounds
2l–m are known sulfones.6b,c
Entry Substrate
Ar
Time Productb Yield
(h)
(%)c
1
Ph
Ph
6
2a
2b
89
3
OH
2
7
91
(E)-(Hex-1-en-1-ylsulfonyl)benzene (2a)
Colorless liquid; yield: 199 mg (89%).
Ph
IR (KBr): 1628, 1447, 1313, 1146 cm–1.
3
Ph
Ph
2.5
2c1, 2c2 87
O
1H NMR (200 MHz, CDCl3): d = 7.84 (d, J = 8.0 Hz, 2 H), 7.66–
7.48 (m, 3 H), 6.93 (m, 1 H), 6.29 (d, J = 14.0 Hz, 1 H), 2.30–2.21
(m, 2 H), 1.51–1.40 (m, 2 H), 1.39–1.28 (m, 2 H), 0.90 (t,
J = 7.0 Hz, 3 H).
13C NMR (50 MHz, CDCl3): d = 147.2, 140.9, 133.1, 130.0, 129.1,
127.2, 31.1, 29.6, 22.0, 13.3.
NHCbz
4
5
6
6
2d
2e
92
90
2
NHCbz
Ph
4
MS (ESI): m/z = 225 [M + H]+.
NHCbz
6
7
Ph
Ph
7
8
2f
90
88
Anal. Calcd for C12H16O2S: C, 64.29; H, 7.14. Found: C, 64.42; H,
7.11.
8
OH
(E)-1-Phenyl-4-(phenylsulfonyl)but-3-en-1-ol (2b)
White solid; yield: 262 mg (91%); mp 101–103 °C.
IR (KBr): 3522, 1626, 1449, 1285 cm–1.
2g
PMBO
1H NMR (200 MHz, CDCl3): d = 7.82 (d, J = 8.0 Hz, 2 H), 7.61–
7.46 (m, 3 H), 7.39–7.20 (m, 5 H), 6.96 (m, 1 H), 6.31 (d, J =
14.0 Hz, 1 H), 4.82 (m, 1 H), 3.22 (m, 1 H), 2.61 (m, 1 H).
13C NMR (50 MHz, CDCl3): d = 143.0, 142.9, 140.4, 133.2, 132.5,
129.2, 128.6, 128.0, 127.7, 125.3, 72.8, 40.9.
8
9
Ph
2.5
7
2h
2i
92
89
OH
4-MeC6H4
MS (ESI): m/z = 311 [M + Na]+.
Cl
Anal. Calcd for C16H16O3S: C, 66.67; H, 5.56. Found: C, 66.78; H,
5.61.
Cl
10
4-MeC6H4
3
2j
95
(E)-1-(Phenylsulfonyl)pent-1-en-3-one (2c1)
White solid; yield: 161 mg (72%); mp 87–89 °C.
Cl
IR (KBr): 1703, 1618, 1450, 1315 cm–1.
11
12
4-MeC6H4 2.5
2k
2l
92
94
1H NMR (200 MHz, CDCl3): d = 7.91 (d, J = 8.0 Hz, 2 H), 7.60–
7.54 (m, 3 H), 7.12 (d, J = 14.0 Hz, 1 H), 7.02 (d, J = 14.0 Hz, 1 H),
2.68 (q, J = 7.0 Hz, 2 H), 1.12 (t, J = 7.0 Hz, 3 H).
13C NMR (50 MHz, CDCl3): d = 198.6, 140.1, 139.2, 135.2, 134.6,
129.9, 127.5, 35.3, 7.2.
Ph
2.5
MS (ESI): m/z = 247 [M + Na]+.
13
14
Ph
Ph
2.5
6
2m
2n
89
87
Anal. Calcd for C11H12O3S: C, 58.93; H, 5.36. Found: C, 58.81; H,
5.41.
5
1-(Phenylsulfonyl)pentan-3-one (2c2)
Colorless liquid; yield: 33 mg (15%).
IR (KBr): 1716, 1585, 1447, 1307, 1149 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.88 (d, J = 8.0 Hz, 2 H), 7.70–
7.56 (m, 3 H), 3.37 (t, J = 7.0 Hz, 2 H), 2.86 (t, J = 7.0 Hz, 2 H),
2.42 (q, J = 7.0 Hz, 2 H), 1.02 (t, J = 7.0 Hz, 3 H).
a Reaction conditions: Alkene (1 mmol), ArSO2Na (2 equiv), NaIO4
(10 mol%), KI (10 mol%), AcOH (cat), MeCN, r.t.
b The structures of the products were established from their spectral
(IR,1H and 13C NMR, ESI-MS) and physical analytical data.
c Isolated yields after purification.
13C NMR (50 MHz, CDCl3): d = 205.8, 138.6, 134.1, 129.6, 127.3,
FT-IR spectrophotometer; NMR spectra were recorded with a
Varian Gemini 200 MHz (1H) and 50 MHz (13C) spectrometer;
ESIMS spectra were recorded with a VG-Autospec micromass in-
strument. Organic extracts were dried over anhydrous Na2SO4.
49.9, 35.0, 34.4, 6.8.
MS (ESI): m/z = 227 [M + H]+, 249 [M + Na]+.
Anal. Calcd for C11H14O3S: C, 58.41; H, 6.20. Found: C, 58.32; H,
6.24.
Synthesis of Vinyl Sulfones; General Procedure
To a stirred solution of alkene (1.0 mmol) and ArSO2Na (2 equiv)
in MeCN (10 mL), NaIO4 and KI (each 10 mol%) and catalytic
amount of AcOH were added. The reaction mixture was stirred at
(E)-Benzyl[1-(phenylsulfonyl)hept-1-en-4-yl]carbamate (2d)
White solid; yield: 356 mg (92%); mp 86–88 °C.
Synthesis 2011, No. 18, 2941–2944 © Thieme Stuttgart · New York

PAPER
Synthesis of Vinyl Sulfones
2943
IR (KBr): 3299, 1686, 1538, 1450, 1282 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.94 (d, J = 8.0 Hz, 2 H), 7.63 (d,
J = 14.0 Hz, 1 H), 7.60–7.49 (m, 3 H), 7.42 (d, J = 8.0 Hz, 2 H),
7.35 (d, J = 8.0 Hz, 2 H), 6.75 (d, J = 14.0 Hz, 1 H), 1.30 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 155.1, 142.5, 140.9, 133.1, 129.3,
129.1, 128.3, 127.8, 126.2, 126.1, 34.9, 31.1.
1H NMR (200 MHz, CDCl3): d = 7.82 (d, J = 8.0 Hz, 2 H), 7.51 (t,
J = 8.0 Hz, 1 H), 7.46 (d, J = 8.0 Hz, 2 H), 7.34–7.20 (m, 5 H), 6.96
(m, 1 H), 6.31 (d, J = 14.0 Hz, 1 H), 5.11 (br s, 1 H), 4.99 (s, 2 H),
3.72 (m, 1 H), 2.49–2.22 (m, 2 H), 1.49–1.22 (m, 4 H), 0.85 (t, J =
7.0 Hz, 3 H).
13C NMR (50 MHz, CDCl3): d = 156.0, 143.1, 140.2, 136.2, 133.5,
133.0, 129.2, 128.1, 127.8, 127.7, 127.2, 67.1, 50.0, 37.1, 37.0,
21.0, 13.9.
MS (ESI): m/z = 301 [M + H]+, 318 [M + NH4]+.
Anal. Calcd for C18H20O2S: C, 72.00; H, 6.67. Found: C, 72.18; H,
6.63.
MS (ESI): m/z = 388 [M + H]+.
(E)-1-(4-Chlorophenyl)-4-tosylbut-3-en-1-ol (2i)
White solid; yield: 299 mg (89%); mp 117–119 °C.
IR (KBr): 3502, 1638, 1595, 1488, 1310 cm–1.
Anal. Calcd for C21H25O4S: C, 65.12; H, 6.46. Found: C, 65.24; H,
6.42.
1H NMR (200 MHz, CDCl3): d = 7.69 (d, J = 8.0 Hz, 2 H), 7.38–
7.19 (m, 6 H), 6.90 (m, 1 H), 6.29 (d, J = 14 Hz, 1 H), 4.83 (t, J =
7.0 Hz, 1 H), 2.68–2.53 (m, 2 H), 2.48 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 144.3, 141.7, 141.4, 137.2, 133.2,
129.8, 127.5, 127.2, 127.0, 71.7, 40.7, 21.6.
(E)-Benzyl[1-(phenylsulfonyl)non-1-en-4-yl]carbamate (2e)
White solid; yield: 373 mg (90%); mp 90–92 °C.
IR (KBr): 3294, 1685, 1540, 1450, 1249 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.82 (d, J = 8.0 Hz, 2 H), 7.60–
7.41 (m, 3 H), 7.35–7.21 (m, 5 H), 6.91 (m, 1 H), 6.32 (d,
J = 14.0 Hz, 1 H), 5.17–4.98 (m, 3 H), 3.72 (m, 1 H), 2.48–2.23 (m,
2 H), 1.46–1.12 (m, 8 H), 0.82 (t, J = 7.0 Hz, 3 H).
13C NMR (50 MHz, CDCl3): d = 155.9, 143.0, 142.7, 140.2, 133.1,
132.9, 129.1, 128.3, 128.1, 128.0, 127.8, 66.8, 50.1, 37.0, 34.9,
31.3, 25.4, 22.2, 13.9.
MS (ESI): m/z = 354 [M + NH4]+, 359 [M + Na]+.
Anal. Calcd for C17H17ClO3S: C, 60.62; H, 5.05. Found: C, 60.73;
H, 5.01.
(E)-1,3-Dichloro-2-(2-tosylvinyl)benzene (2j)
White solid; yield: 310 mg (95%); mp 91–93 °C.
IR (KBr): 1614, 1593, 1435, 1303, 1142 cm–1.
MS (ESI): m/z = 416 [M + H]+, 433 [M + Na]+.
Anal. Calcd for C23H29NO4S: C, 66.50; H, 6.98. Found: C, 66.84; H,
6.81.
1H NMR (200 MHz, CDCl3): d = 7.88 (m, 3 H), 7.34 (d, J = 8.0 Hz,
4 H), 7.21 (d, J = 14.0 Hz, 1 H), 7.09 (d, J = 14.0 Hz, 1 H), 2.45 (s,
3 H).
13C NMR (50 MHz, CDCl3): d = 144.8, 137.1, 135.9, 135.1, 130.6,
129.9, 128.9, 128.0, 21.6.
(E)-Benzyl[1-(phenylsulfonyl)tridec-1-en-4-yl]carbamate (2f)
White solid; yield: 423 mg (90%); mp 95–97 °C.
IR (KBr): 3294, 1685, 1541, 1453, 1250 cm–1.
MS (ESI): m/z = 327, 329, 331 [M + H]+.
1H NMR (200 MHz, CDCl3): d = 7.82 (d, J = 8.0 Hz, 2 H), 7.80–
7.41 (m, 5 H), 7.38–7.20 (m, 5 H), 6.90 (m, 1 H), 6.33 (d,
J = 14.0 Hz, 1 H), 5.09–4.97 (m, 2 H), 4.58 (d, J = 8.0 Hz, 1 H),
3.75 (m, 1 H), 2.52–2.28 (m, 2 H), 1.51–1.15 (m, 14 H), 0.89 (t,
J = 7.0 Hz, 3 H).
13C NMR (50 MHz, CDCl3): d = 155.8, 143.1, 142.7, 140.3, 133.2,
132.8, 129.1, 128.7, 128.1, 128.0, 127.5, 66.9, 50.2, 37.1, 34.5,
32.0, 29.9–29.1 (overlapped peaks), 25.8, 22.7, 14.0.
Anal. Calcd for C15H12Cl2O2S: C, 55.05; H, 3.67. Found: C, 55.12;
H, 3.63.
(E)-1,3-Dimethyl-2-(2-tosylvinyl)benzene (2k)
White solid; yield: 263 mg (92%); mp 93–95 °C.
IR (KBr): 1604, 1495, 1302, 1142 cm–1.
1H NMR (200 MHz, CDCl3): d = 7.87–7.78 (m, 3 H), 7.31 (d,
J = 8.0 Hz, 4 H), 6.95 (d, J = 14.0 Hz, 1 H), 6.69 (d, J = 14.0 Hz,
1 H), 2.45 (s, 3 H), 2.42 (s, 3 H), 2.31 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 144.2, 141.5, 139.8, 138.0, 132.0,
130.1, 128.7, 127.9, 127.6, 127.1, 21.9, 21.7, 19.8.
MS (ESI): m/z = 472 [M + H]+, 489 [M + NH4]+, 494 [M + Na]+.
Anal. Calcd for C27H37NO4S: C, 68.79; H, 7.86. Found: C, 68.87; H,
7.82.
MS (ESI): m/z = 287 [M + H]+.
(E)-5-[(4-Methoxybenzyl)oxy]-1-(phenylsulfonyl)pent-1-en-3-
ol (2g)
Light yellow liquid; yield: 318 mg (88%).
IR (KBr): 3504, 1611, 1512, 1446, 1304, 1246 cm–1.
Anal. Calcd for C17H18O2S: C, 71.33; H, 6.29. Found: C, 71.42; H,
6.24.
1H NMR (200 MHz, CDCl3): d = 7.86 (d, J = 8.0 Hz, 2 H), 7.62–
7.48 (m, 3 H), 7.18 (d, J = 8.0 Hz, 2 H), 6.91 (dd, J = 14.0, 4.0 Hz,
1 H), 6.81 (d, J = 8.0 Hz, 2 H), 6.58 (d, J = 14.0 Hz, 1 H), 4.50 (m,
1 H), 4.35 (s, 2 H), 3.74 (s, 3 H), 3.62–3.41 (m, 2 H), 1.98 (m, 1 H),
1.71 (m, 1 H).
Acknowledgment
The authors thank CSIR and UGC, New Delhi for financial assis-
tance.
13C NMR (50 MHz, CDCl3): d = 159.8, 148.2, 140.1, 133.1, 130.3,
129.2, 129.0, 127.9, 133.8, 73.0, 70.1, 68.0, 55.0, 35.1.
References
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White solid; yield: 276 mg (92%); mp 115–117 °C.
IR (KBr): 2960, 1612, 1311, 1146 cm–1.
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PAPER
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Synthesis 2011, No. 18, 2941–2944 © Thieme Stuttgart · New York