Highly regioselective ring-opening of aziridines with arenesulfinates on water: A facile access to β-amino/vinyl sulfones

Article abstract of DOI:10.1016/j.tet.2012.12.028

We have developed a LiBr catalyzed efficient synthesis of β-amino sulfones from readily available aziridines and sodium sulfinates in good to excellent yields. The synthetic potential of β-amino sulfones has also been demonstrated by their facile conversion to the corresponding vinyl sulfones. The use of water as reaction media, atom-economy and isolation of products by simple filtration in the case of solid β-amino sulfones are certain green virtues of the synthetic protocol.

Full text of DOI:10.1016/j.tet.2012.12.028

Tetrahedron 69 (2013) 1720e1724
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Highly regioselective ring-opening of aziridines with arenesulfinates
on water: a facile access to
b
-amino/vinyl sulfones
*
Ruchi Chawla, Atul K. Singh, Lal Dhar S. Yadav
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211 002, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 October 2012
Received in revised form 7 December 2012
Accepted 11 December 2012
Available online 19 December 2012
We have developed a LiBr catalyzed efficient synthesis of
idines and sodium sulfinates in good to excellent yields. The synthetic potential of
b
-amino sulfones from readily available azir-
-amino sulfones has
also been demonstrated by their facile conversion to the corresponding vinyl sulfones. The use of water
b
as reaction media, atom-economy and isolation of products by simple filtration in the case of solid b-
amino sulfones are certain green virtues of the synthetic protocol.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Aziridines
Sodium sulfinates
b-Amino sulfones
Vinyl sulfones
Green methodology
1. Introduction
nitrogen heterocycles.9 Despite their importance, the synthesis of
b-amino sulfones has been less explored. The most common
b
-Amino sulfones have widely been recognized for their in-
methods available for their preparation include use of amino acids
as substrates,10 stereoselective addition of sulfonyl carbanions to
N-sulfinyl imines11 and intramolecular12 and intermolecular6,9a,13
teresting biological properties. They are valuable HIV protease in-
hibitors,1 matrix metalloproteinase inhibitors2 and DNA alkylating
agents for cancer treatment3 (Fig. 1). In addition, they readily un-
aza-Michael additions to
a,b-unsaturated sulfones. However,
dergo electrophilic substitution in the
intermediates in the synthesis of
substituted uridines and adenosines,6 alkaloids,7
a
-position acting as versatile
these methods suffer from drawbacks like tedious multi-step
transformations, low yields, non-green conditions and expensive
reagents.
a
-amino acids,4 amino alcohols,5
b
-lactams8 and
Aziridines are well-known synthetic intermediates and starting
materials owing to their inherent ring strain, which makes them
highly susceptible to nucleophilic attack. Nucleophilic ring-opening
reactions of aziridines hold a prominent place in organic synthesis
since they lead to 1,2-bifunctional systems, which are potent
structural motifs for the synthesis of wide variety of valuable
products. In view of the generation of such important functional-
ized systems, a plethora of oxygen, nitrogen and sulfur nucleophiles
have been reported for the ring-opening reactions of aziridines.14
To the best of our knowledge, there is no report on the ring-
opening reaction of aziridines with sulfinate nucleophiles al-
though it would offer a direct approach for the synthesis of
Ph
H
N
O
H
S
O
O
NHMs
(a)
OH
N
H
SPh
OHC
OH
O
S
O
O
N
HO
OCF3
N
H
S
O
O
NH
O
O
O
substituted b-amino sulfones. However, Hou and co-workers have
Cbz
(b)
(c)
reported an unexpected transfer of tosyl group of N-tosylimines to
aziridines catalyzed by N-heterocyclic carbene.15 The use of such
expensive and difficult-to-handle substrates and catalyst, strictly
limits the synthetic viability of the process. On the other hand,
numerous examples of the ring-opening reactions of epoxides
with sulfinates are reported in the literature.16 Recently, we have
Fig. 1. Examples of b-amino sulfone-containing enzyme inhibitors.
* Corresponding author. Tel.: þ91 5322500652; fax: þ91 5322460533; e-mail
address: ldsyadav@hotmail.com (L.D.S. Yadav).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.12.028

R. Chawla et al. / Tetrahedron 69 (2013) 1720e1724
1721
Table 1
disclosed a method for the synthesis of terminal as well as internal
Optimization of solvent for the synthesis of
b
-amino sulfonesa
CH3
vinyl sulfones employing the sulfinate nucleophile mediated ring-
opening reaction of terminal epoxides in aqueous medium.16g En-
couraged by our previous findings we became interested in the
nucleophilic ring-opening of aziridines with sulfinates.
Over the recent years, tremendous efforts have been devoted
towards the development of environmentally benign synthetic
methodologies. Replacement of hazardous classical solvents with
highly ecofriendly aqueous medium has emerged as one of the
most commendable moves in this direction.17 Besides being in-
expensive and environmentally benign, water as a reaction me-
dium offers an easy approach for the separation of organic reagents
or catalysts. As part of our efforts to devise novel greener synthetic
methodologies using easily available substrates16g,18,19a and to
CH3
Ts
O
Solvent
O
N
O
+
CH3
S
+
TsHN
TsHN
Ph
S
S
Temperature
Ph
NaO
O
O
Ph
2a
1a
3a
4a
Entry Solvent
Temp Time Yieldb (%) Regioselectivityc
(ꢀ C)
(h)
3a
4a
(3a:4a)
1
2
3
4
5
6
7
8
Water
Water
Water
1,4-Dioxane
Acetonitrile
rt
24
8
17
34
58
Nil
Nil
20
33
14
30
42
44
10
16
27
Nil
Nil
12
19
7
64:26
68:32
69:31
d
50e60
80e90
Reflux
Reflux
6
8
8
overcome the limitations associated with the synthesis of
sulfones, we herein report the first synthetic route to
b
b
-amino
-amino
d
Acetonitrileewater (9:1) rt
24
61:39
63:37
65:35
66:34
72:28
70:30
sulfones on water employing LiBr catalyzed nucleophilic ring-
opening of aziridines with arenesulfinates (Scheme 1).
Acetonitrileewater (9:1) Reflux 10
Dioxaneewater (9:1)
Dioxaneewater (9:1)
Methanol
rt
24
9
10
11
Reflux 10
15
16
19
Reflux
Reflux
8
8
R3
R3
Ethanol
a
Reaction conditions: N-tosylaziridine 1a (1.0 mmol), sodium p-toluenesulfinate
Ts
N
O
LiBr (10 mol %)
Water, 80-90 oC
(1.0 mmol), solvent (5 mL).
O
O
R3
+
S
b
+
TsHN
R2
TsHN
R1
S
S
R1
Isolated yield after column chromatography.
R2
NaO
c
As determined by 1H NMR integration of the
a- and b-proton signals of the two
O
O
R1
R2
regioisomeric sulfones 3a and 4a in the crude product.
1
R3 = CH3(2a), H(2b)
4
3
Scheme 1. Synthesis of b-amino sulfones in aqueous media.
The regioselectivity of the reaction was not satisfactory so we
decided to employ a Lewis acid. A number of Lewis acids were
tested and the best results were obtained with 10 mol % of LiBr
(Table 2). With the use of LiBr, the reaction could be performed
even at rt with decent yield and almost complete regioselectivity in
favour of 3a though longer time was needed (Table 2, entry 2). On
heating the reaction mixture to 80e90 ꢀC, the reaction was com-
pleted in 3.5 h without any appreciable change in regioselectivity
(Table 2, entry 3). Thus, the presence of 10 mol % of LiBr not only
accelerated the reaction but also enhanced the yield as well as
regioselectivity (Table 2, entries 3,11). The significant improvement
2. Results and discussion
We commenced our study with the model reaction of N-tosy-
laziridine 1a with sodium p-toluenesulfinate 2a on water at rt. Not
very encouraging results were obtained at rt even after 24 h, so we
heated the reaction mixture to 50e60 ꢀC. This resulted in the for-
mation of a mixture of regioisomers of b-amino sulfone 3a (34%)
and 4a (16%) after 8 h. It is quite evident from this fact that during
the nucleophilic attack, electronic factors were dominating the
steric factors since the attack of the bulky sulfinate nucleophile
took place at the hindered benzylic carbon of aziridine 1a to pro-
duce 3a as the major product. On increasing the temperature to
80e90 ꢀC, the overall yield of the reaction was increased but there
was not any significant change in the regioselectivity of the reaction
(Scheme 2) (Table 1, entries 1e3).
Table 2
Optimization of catalyst for the synthesis of b
-amino sulfonesa
CH3
CH3
Ts
O
Catalyst
N
O
O
CH3
S
+
TsHN
TsHN
Ph
+
S
S
Ph
Water, 80-90 o
C
NaO
O
O
Ph
2a
4a
1a
3a
CH3
CH3
Ts
N
Entry
Catalyst
Mol %
Time (h)
Yieldb (%)
Regioselectivityc
O
Water
O
O
+
CH3
S
+
TsHN
TsHN
Ph
S
S
3a
4a
(3a:4a)
80-90 oC
Ph
NaO
O
O
1
2
3
4
5
6
7
8
LiCl
10
10
10
5
15
10
10
10
10
10
d
8
15
3.5
8
3.5
7
9
9
8
7
48
68
89
73
89
50
32
40
26
32
58
10
4
83:17
94:6d
96:4
86:14
96:4
Ph
LiBr
LiBr
LiBr
LiBr
LiI
FeCl3
FeBr3
CuCl2
CuBr2
d
1a
2a
(27%)
4a
(58%)
3a
4
12
4
Scheme 2. Model reaction for the synthesis of
b-amino sulfones on water.
13
13
13
14
15
27
79:21e
70:30
76:24
66:34
69:31
69:31
The reaction was also tried in some organic solvents. At rt as well
as at reflux no product could be isolated in the case of less polar
solvents (Table 1, entries 4, 5). This may be attributed to the in-
solubility of salt 2a in these organic solvents. Addition of a few
drops of water to the reaction mixture in CH3CN or 1,4-dioxane,
slightly promoted the reaction at rt and heating the reaction mix-
ture to reflux did not produce any encouraging results (Table 1,
entries 6e9). Though the reaction proceeded well in polar solvents
like methanol and ethanol at reflux but the overall yield was lesser
than that in water without significant improvement in the regio-
selectivity as well (Table 1, entries 10, 11). So water remained the
solvent of choice for further study.
9
10
11
6
a
Reaction conditions: N-tosylaziridine 1a (1.0 mmol), sodium p-toluenesulfinate
(1.0 mmol), water (5 mL).
b
Isolated yield after column chromatography.
c
As determined by 1H NMR integration of the
a- and b-proton signals of the two
regioisomeric sulfones 3a and 4a in the crude product.
d
Reaction was carried out at rt.
In addition to 50% of 3a and 13% of 4a, 2-iodo-2-phenyl-N-tosylethanamine was
e
isolated in 18% yield.

1722
R. Chawla et al. / Tetrahedron 69 (2013) 1720e1724
in regioselectivity in the presence of LiBr may be attributed to the
fact that the carbocationic character of the benzylic carbon, induced
by the resonance effect of the phenyl group in N-tosylaziridine 1a,
is enhanced by the coordination of LiBr with the nitrogen atom of
the aziridine ring, which results in the predominant formation of
the ring-opened product 3a by the nucleophilic attack at the ben-
zylic carbon. LiBr is a mild Lewis acid, which has been employed as
an efficient, green, and inexpensive catalyst to carry out various
synthetic trasformations.16g,19
As far as the isolation of the product is concerned, when the
reaction was performed with 1 equiv of 1a and 1.2 equiv of 2a on
water at 80e90 ꢀC using LiBr (10 mol %), the product 3a could be
isolated as a white solid by simple filtration followed by successive
washing with water and toluene. Thus, water not only acted as
a solvent in the reaction but also very effectively facilitates isolation
of the product.
The presented methodology has remarkable potential for the
synthesis of vinyl sulfones, which have exceptional biological sig-
nificance20 and synthetic utility.21 Previously, we have prepared
vinyl sulfones by mere heating of epoxides and arenesulfinates on
water in the presence of LiBr.16g In the case of aziridines we did not
obtain any such results. Instead, the prepared b-amino sulfones 3
and 4 were treated with strong bases like NaH and tBuOK in dry THF
at rt to yield the corresponding vinyl sulfones in good yields. The
toluenesulfonamide group acted as the leaving group in the re-
action.22 The yield of vinyl sulfones was slightly better in the case of
NaH (76%) than with tBuOK (68%). We also attempted the reaction
in water with NaOH but a complex mixture containing aziridine as
the major product was formed. The protocol is superior to other
methods of vinyl sulfone synthesis as it gives the opportunity to
prepare terminal vinyl sulfones for which lesser methods are
available in the literature as compared to the other internal iso-
mer.23 The process is general and works well with good yields of
vinyl sulfones (Table 4).
With the optimized conditions, scope of the reaction was in-
vestigated for the synthesis of various b-amino sulfones and the re-
sults are compiled in Table 3. The generality of the protocol was
demonstrated across a range of aziridines using two sulfinate salts. In
general, 2-arylaziridines bearing an electron-donating substituent
Table 4
Synthesis of vinyl sulfonesa
afford better yield of b-amino sulfones than that with an electron-
R3
R3
withdrawing group (Table 3, entries 1e6). The more nucleophilic
p-toluenesulfinate gave slightly higher yields than benzenesulfinate.
In the case of terminal aliphatic aziridines (Table 3, entries 8e10,
14e16), the nucleophilic attack took place exclusively at the terminal
carbon atom of the aziridine ring. Aziridines bearing an aryl sub-
stituent were preferably attacked at the benzylic carbon to produce
the ring-opened products (Table 3, entries 1e6,12,18). Under similar
conditions, cyclic aziridines gave trans products as confirmed by
coupling constants in 1H NMR spectroscopy (Table 3, entries 11, 17).
NaH (2 eqiv)
dry THF, rt
O
O
S
TsHN
R2
S
O
O
R2
R1
R1
5
3
OR
R3
R3
NaH (2 eqiv)
dry THF, rt
O
S
O
S
TsHN
R1
Table 3
O
O
Synthesis of b
-amino sulfones 3 and 4a
R1
R2
R2
R3
R3
5'
4
Ts
N
O
LiBr (10 mol %)
Water, 80-90 oC
Entry
Compound 3 or 4
Productb
Time (h)
Yieldc (%)
O
O
+
R3
S
+
TsHN
R2
TsHN
R1
S
S
R1
R2
1
2
3
4
5
3a
3c
3e
4k
4n
5a
5c
5e
5’k
5’n
12
14
10
15
18
72
67
75
68
65
NaO
O
O
R1
R2
R3 = CH3(2a), H(2b)
1
4
3
Entry R1
R2
2
Product Time Yieldc,d (%)
(h)
Regioselectivitye
(3:4)
a
For the experimental procedure, see Experimental.
Vinyl sulfones 5 and 5’ are known compounds and their spectroscopic data were
b
3
4
in agreement with the literature data.16g,24
1
Ph
H
H
H
H
H
H
H
H
H
H
2a 3ab, 4a 3.5
89
77
91
82
74
82
d
d
d
d
d
75
d
d
d
d
d
71
4
8
3
4
7
5
86
77
71
69
74
10
82
73
68
67
66
11
96:4
91:9
97:3
95:5
92:8
94:6
d
c
Isolated yield after column chromatography.
2
3
4
p-ClC6H4
p-MeC6H4
Ph
2a 3b, 4b
2a 3c, 4c
2b 3d, 4d
2b 3e, 4e
2b 3f, 4f
2a 4gb
4.5
4.0
4.0
5.5
4.5
3.5
3. Conclusions
5
6
7
p-ClC6H4
p-MeC6H4
H
In summary, we have described a LiBr catalyzed highly regio-
2a 3hb, 4h 5.5
0:100
0:100
0:100
d
selective approach for the synthesis of b-amino sulfones from easily
8
n-Bu
9
n-Hexyl
C16H33
e(CH2)4e
Ph
H
n-Bu
n-Hexyl
C16H33
e(CH2)4e
Ph
2a 3ib, 4i
2a 3jb, 4j
2a 4kb
5.0
7.0
5.5
4.0
3.5
7.0
7.0
7.5
6.5
6.0
accessible starting materials on water. This is the first report on
the aziridine ring-opening with the commercially available in-
expensive arenesulfinates. Environmentally benign reaction con-
ditions and easier purification of products opens up a new green
pathway for the synthesis of
tential of the prepared -amino sulfones has been demonstrated by
10
11
12
13
14
15
16
17
18
CH3 2a 3lb, 4l
88:12
d
H
H
H
H
2b 4m
b-amino sulfones. The synthetic po-
2b 3n, 4n
2b 3o, 4o
2b 3p, 4p
2b 4q
0:100
0:100
0:100
d
b
their conversion to vinyl sulfones in good yields.
CH3 2b 3r, 4r
86:14
a
4. Experimental
4.1. General
For the experimental procedure, see Experimental.
b
b
-Amino sulfones 3/4 are known compounds and their spectroscopic data were
in agreement with the literature data.15
c
Isolated yield after column chromatography/filtration.
All compounds (3 and 4) gave C, H and N analyses within ꢁ0.36% and satis-
d
Melting points were determined by open glass capillary method
and are uncorrected. IR spectra in KBr were recorded on a Per-
kineElmer 993 IR spectrophotometer and 1H NMR spectra were
factory spectral (IR, 1H NMR, 13C NMR and EIMS) data.
e
As determined by 1H NMR integration of the
a- and b-proton signals of the two
regioisomeric sulfones 3a and 4a in the crude product.

R. Chawla et al. / Tetrahedron 69 (2013) 1720e1724
1723
recorded on a Bruker Avance II (400 MHz) FT spectrometer in CDCl3
using TMS as internal reference. 13C NMR spectra were recorded on
the same instrument at 100 MHz in CDCl3 and TMS was used as
internal reference. Mass (EI) spectra were recorded on JEOL D-300
mass spectrometer. Elemental analyses were carried out in a Cole-
man automatic carbon, hydrogen and nitrogen analyzer. All
chemicals used were reagent grade and were used as received
without further purification. Reactions for the synthesis of vinyl
sulfones (Section 4.3) were performed using oven-dried glassware.
Organic solutions were concentrated using a Buchi rotary evapo-
rator. Column chromatography was carried out over silica gel
(Merck 100e200 mesh) and TLC was performed using silica gel
GF254 (Merck) plates.
127.3,128.0,128.5,128.9,129.7,130.3,132.2,134.9,137.1,136.6,143.0;
EIMS (m/z) 415 (Mþ).
4.2.4. N-[2-(4-Chlorophenyl)-2-(phenylsulfonyl)ethyl]-4-methylben-
zenesulfonamide (3e). Yield (0.33 g, 74%) as a white solid; mp
188e191 ꢀC; [found: C, 56.26; H, 4.36; N, 3.03 C21H20ClNO4S2 re-
quires C, 56.05; H, 4.48; N, 3.11%]; Rf (20% EtOAc/hexane) 0.32; IR
(KBr) nmax 3285, 1597, 1334, 1315, 1303, 1289, 1156, 740 cmꢃ1 1H
;
NMR (400 MHz; CDCl3) 2.46 (s, 3H), 3.59e3.69 (m, 1H), 3.88e3.97
(m, 1H), 4.15e4.20 (m, 1H), 5.22e5.26 (dd, 1H, J¼7.9, 5.2 Hz),
6.91e6.93 (d, 2H, J¼7.7 Hz), 7.12e7.43 (m, 9H), 7.70e7.73 (d, 2H,
J¼8.2 Hz); 13C NMR (100 MHz, CDCl3) 21.1, 41.1, 68.8, 127.4, 128.1,
128.5,129.0,129.9,130.3,131.1,132.0,133.5,136.6,137.2,143.0; EIMS
(m/z) 449, 451 (Mþ, Mþþ2).
4.2. General procedure for the synthesis of
3 and 4
b
-amino sulfones
4.2.5. N-[2-(Phenylsulfonyl)-2-p-tolylethyl]-4-methylbenzenesulfona-
mide (3f). Yield (0.35 g, 82%) as a white solid; mp 220e223 ꢀC;
[found: C, 61.36; H, 5.49; N, 3.08 C22H23NO4S2 requires C, 61.51; H,
5.40; N, 3.26%]; Rf (20% EtOAc/hexane) 0.34; IR (KBr) nmax 3283,1598,
A mixture of aziridine 1 (1.0 mmol), LiBr (10 mol %) and sodium
sulfinate 2 (1.2 mmol) in water (5 mL) was stirred at 80e90 ꢀC for
3.5e7.5 h (Table 3). After completion of the reaction (monitored
by TLC), the mixture was cooled to rt and extracted with EtOAc
(3ꢂ5 mL). The combined organic phases were dried over anhyd
Na2SO4, filtered and concentrated under reduced pressure. The
resulting crude product was purified by silica gel column chro-
matography using a mixture of EtOAc/n-hexane (1:19) as eluent to
1335, 1315, 1303, 1289, 1157, 745 cmꢃ1 1H NMR (400 MHz; CDCl3)
;
2.35 (s, 3H), 2.47 (s, 3H), 3.59e3.66 (m, 1H), 3.88e3.94 (m, 1H),
4.13e4.17 (m,1H), 5.21e5.25 (dd,1H, J¼7.9, 5.3 Hz), 6.91e6.93 (d, 2H,
J¼7.9 Hz), 7.01e7.38 (m, 9H), 7.71e7.73 (d, 2H, J¼8.3 Hz); 13C NMR
(100 MHz, CDCl3) 21.1, 24.2, 41.1, 69.0,127.3,128.0,128.5,128.9,129.7,
130.3, 134.9, 135.3, 135.9, 136.6, 137.1, 143.1; EIMS (m/z) 429 (Mþ).
afford an analytically pure sample of
b
-amino sulfones 3 or 4
4.2.6. N-[2-(Phenylsulfonyl)]-4-methylbenzenesulfonamide
(4m). Yield (0.28 g, 82%) as a white solid; mp 130e133 ꢀC; [found:
C, 53.19; H, 4.94; N, 4.01 C15H17NO4S2 requires C, 53.08; H, 5.05; N,
4.13%]; Rf (20% EtOAc/hexane) 0.25; IR (KBr) nmax 3281, 1596, 1335,
1289,1162,1146,1082 cmꢃ1; 1H NMR (400 MHz; CDCl3) 2.46 (s, 3H),
3.18e3.23 (m, 2H), 3.33e3.41 (m, 2H), 5.38e5.41 (t, 1H, J¼6.1 Hz),
7.31e7.85 (m, 9H); 13C NMR (100 MHz, CDCl3) 21.5, 37.0, 55.2, 127.1,
127.9, 129.7, 130.1, 135.8, 136.4, 138.2, 143.8; EIMS (m/z) 339 (Mþ).
(Table 3, entries 8e11, 14e17). In the case of solid products, after
completion of the reaction, the resulting solution was cooled to rt,
the precipitate was filtered and washed with cold water and then
with toluene to afford an analytically pure sample of
sulfones 3 (Table 3, entries 1e6, 12, 18) or 4 (Table 3, entries 7
b-amino
and 13).
4.2.1. N-[2-(4-Chlorophenyl)-2-tosylethyl]-4-methylbenzenesulfona-
mide (3b). Yield (0.36 g, 77%) as a white solid; mp 169e171 ꢀC;
[found: C, 57.01; H, 4.62; N, 3.19 C22H22ClNO4S2 requires C, 56.95; H,
4.78; N, 3.02%]; Rf (20% EtOAc/hexane) 0.31; IR (KBr) nmax 3281,
4.2.7. N-[1-(Phenylsulfonylhexan-2-yl)]-4-methylbenzenesulfonamide
(4n). Yield (0.29 g, 73%) as a colourless oil; [found: C, 57.52; H, 6.44;
N, 3.26 C19H25NO4S2 requires C, 57.69; H, 6.37; N, 3.54%]; Rf (20%
EtOAc/hexane) 0.22; IR (KBr) nmax 3282, 2959, 2932, 2871, 1598,1317,
1292, 1159, 1145, 1086 cmꢃ1; 1H NMR (400 MHz; CDCl3) 0.75 (t, 3H,
J¼5.2 Hz), 1.02e1.12 (m, 4H), 1.59e1.62 (m, 1H), 1.80e1.88 (m, 1H),
2.47 (s, 3H), 3.09e3.13 (dd, 1H, J¼6.6, 14.4 Hz), 3.31e3.36 (dd, 1H,
J¼4.5, 14.1 Hz), 3.50e3.56 (m, 1H), 5.23e5.26 (d, 1H, J¼7.2 Hz),
7.30e7.78 (m, 9H); 13C NMR (100 MHz, CDCl3) 13.6, 21.0, 21.5, 22.2,
28.1, 49.6, 59.6, 127.0, 127.7, 129.5, 130.1, 133.5, 136.8, 139.1, 143.5;
EIMS (m/z) 395 (Mþ).
1598, 1335, 1315, 1302, 1289, 1159, 742 cmꢃ1 1H NMR (400 MHz;
;
CDCl3) 2.40 (s, 3H), 2.47 (s, 3H), 3.59e3.69 (m, 1H), 3.88e3.97 (m,
1H), 4.13e4.19 (m, 1H), 5.22e5.26 (dd, 1H, J¼7.9, 5.3 Hz), 6.90e6.92
(d, 2H, J¼7.8 Hz), 7.12e7.40 (m, 8H), 7.71e7.74 (d, 2H, J¼8.3 Hz); 13C
NMR (100 MHz, CDCl3) 20.8, 21.3, 41.0, 68.8, 127.4, 128.0, 128.5,
128.9, 129.7, 130.4, 131.1, 132.0, 134.1, 136.6, 143.0, 144.7; EIMS (m/z)
463, 465 (Mþ, Mþþ2).
4.2.2. N-[2-(p-Tolyl)-2-tosylethyl]-4-methylbenzenesulfonamide
(3c). Yield (0.40 g, 91%) as a white solid; mp 210e213 ꢀC; [found: C,
62.16; H, 5.50; N, 3.24 C23H25NO4S2 requires C, 62.28; H, 5.68; N,
3.16%]; Rf (20% EtOAc/hexane) 0.35; IR (KBr) nmax 3283, 1599, 1336,
1312,1306,1288,1158, 745 cmꢃ1; 1H NMR (400 MHz; CDCl3) 2.34 (s,
3H), 2.39 (s, 3H), 2.47 (s, 3H), 3.57e3.66 (m, 1H), 3.86e3.94 (m, 1H),
4.12e4.17 (m, 1H), 5.21e5.25 (dd, 1H, J¼7.8, 5.3 Hz), 6.91e6.93 (d,
2H, J¼7.7 Hz), 7.00e7.38 (m, 8H), 7.71e7.73 (d, 2H, J¼8.2 Hz); 13C
NMR (100 MHz, CDCl3) 20.8, 21.3, 24.2, 41.0, 68.9, 127.4, 128.1, 128.5,
128.9, 129.7, 130.3, 133.3, 134.1, 135.3, 136.6, 143.1, 144.8; EIMS (m/z)
443 (Mþ).
4.2.8. N-[1-(Phenylsulfonyl)octan-2-yl]-4-methylbenzenesulfonamide
(4o). Yield (0.29 g, 68%) as a colourless oil; [found: C, 59.67; H, 6.81;
N, 3.37 C21H29NO4S2 requires C, 59.54; H, 6.90; N, 3.31%]; Rf (20%
EtOAc/hexane) 0.23; IR (KBr) nmax 3283, 2957, 2928, 2860, 1598,
1319, 1290, 1163, 1088 cmꢃ1; 1H NMR (400 MHz; CDCl3) 0.80 (t, 3H,
J¼7.2 Hz), 0.93e1.17 (m, 8H), 1.47e1.58 (m, 1H), 1.73e1.85 (m, 1H),
2.46 (s, 3H), 3.09e3.17 (m, 1H), 3.33e3.39 (m, 1H), 3.43e3.52 (m,
1H), 5.56e5.58 (d, 1H, J¼7.7 Hz), 7.23e7.35 (m, 5H), 7.61e7.67 (m,
4H); 13C NMR (100 MHz, CDCl3) 13.8, 21.5, 22.3, 24.9, 28.3, 31.3, 33.8,
49.5, 59.6, 127.0, 127.8, 129.5, 129.9, 134.5, 136.7, 139.3, 143.4; EIMS
(m/z) 423 (Mþ).
4.2.3. N-[2-Phenyl-2-(phenylsulfonyl)ethyl]-4-methylbenzenesulfona-
mide (3d). Yield (0.34 g, 82%) as a white solid; mp 173e175 ꢀC;
[found: C, 60.34; H, 5.04; N, 3.49 C21H21NO4S2 requires C, 60.70; H,
5.09; N, 3.37%]; Rf (20% EtOAc/hexane) 0.34; IR (KBr) nmax 3284,
1598, 1336, 1314, 1305, 1289, 1158 cmꢃ1; 1H NMR (400 MHz; CDCl3)
2.47 (s, 3H), 3.59e3.66 (m, 1H), 3.88e3.94 (m, 1H), 4.14e4.18 (m,
1H), 5.21e5.25 (dd, 1H, J¼7.8, 5.2 Hz), 6.90e6.92 (d, 2H, J¼7.8 Hz),
7.15e7.83 (m,12H); 13C NMR (100 MHz, CDCl3) 21.2, 41.0, 68.9,126.5,
4.2.9. N-[1-(Phenylsulfonyl)octadecan-2-yl]-4-methylbenzenesulfon-
amide (4p). Yield (0.38 g, 67%) as a colourless oil; [found: C, 66.01;
H, 8.64; N, 2.64 C31H49NO4S2 requires C, 66.03; H, 8.76; N, 2.48%]; Rf
(20% EtOAc/hexane) 0.20; IR (KBr) nmax 3281, 2919, 2849, 1599,
1321, 1150, 1094 cmꢃ1 1H NMR (400 MHz; CDCl3) 0.88 (t, 3H,
;
J¼6.6 Hz), 0.97e1.32 (m, 28H), 1.59e1.67 (m, 1H), 1.79e1.88 (m, 1H),
2.47 (s, 3H), 3.13 (dd, 1H, J¼6.0, 13.6 Hz), 3.36 (dd, 1H, J¼4.5,

1724
R. Chawla et al. / Tetrahedron 69 (2013) 1720e1724
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13.6 Hz), 3.49e3.61 (m, 1H), 5.10e5.13 (d, 1H, J¼6.9 Hz), 7.26e7.38
(m, 5H), 7.61e7.67 (m, 4H); 13C NMR (100 MHz, CDCl3) 14.06, 21.5,
22.6, 25.2, 28.8, 29.2, 29.6, 31.8, 33.9, 49.8, 59.6, 127.2, 127.8, 129.5,
129.9, 134.7, 136.9, 139.6, 143.5; EIMS (m/z) 563 (Mþ).
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4.2.10. N-[2-(Phenylsulfonyl)cyclohexyl]-4-methylbenzenesulfonamide
(4q). Yield (0.26 g, 66%) as a colourless oil; [found: C, 57.75; H, 5.76;
N, 3.44 C19H23NO4S2 requires C, 57.99; H, 5.89; N, 3.56%]; Rf (20%
EtOAc/hexane) 0.22; IR (KBr) nmax 3255, 2940, 2865,1596,1452,1335,
8. DiPetro, D.; Borzilleri, R. M.; Weinreb, S. M. J. Org. Chem. 1994, 59, 5856e5857.
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1312, 1302, 1290, 1161, 1143 cmꢃ1 1H NMR (400 MHz; CDCl3)
;
1.14e1.37 (m, 4H),1.53e1.61 (m,1H),1.69e1.74 (m,1H),1.82e1.89 (m,
1H), 2.41e2.46 (m, 1H), 2.46 (s, 3H), 3.01 (td, 1H, J¼10.5, 3.6 Hz),
3.28e3.38 (m,1H), 6.32 (s,1H), 7.30e7.38 (m, 5H), 7.63e7.78 (m, 4H);
13C NMR (100 MHz, CDCl3) 21.5, 22.5, 23.2, 25.3, 28.7, 51.4, 64.6,127.2,
128.8, 129.5, 129.9, 133.5, 135.1, 139.9, 143.4; EIMS (m/z) 393 (Mþ).
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4.2.11. N-[1-Phenyl-1-(phenylsulfonyl)propan-2-yl]-4-methyl-
benzenesulfonamide (3r). Yield (0.30 g, 71%) as a white solid; mp
134e138 ꢀC; [found: C, 61.83; H, 5.68; N, 3.17 C22H23NO4S2 requires
C, 61.51; H, 5.40; N, 3.26%]; Rf (20% EtOAc/hexane) 0.33; IR (KBr)
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nmax 3226, 1597, 1325, 1287, 1163, 1136, 1083 cmꢃ1 1H NMR
;
15. Chen, D.-D.; Hou, X.-L.; Dai, L.-X. J. Org. Chem. 2008, 73, 5578e5581.
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(400 MHz; CDCl3) 1.53 (d, 3H, J¼5.7 Hz), 2.43 (s, 3H), 4.12e4.18 (m,
2H), 5.72 (d, 1H, J¼7.7 Hz), 7.01e7.18 (m, 6H), 7.21e7.34 (m, 6H),
7.69e7.75 (m, 2H); 13C NMR (100 MHz, CDCl3) 19.5, 21.5, 51.5, 74.2,
127.1, 128.0, 128.4, 128.9, 129.3, 129.9, 130.4, 130.8, 133.6, 138.3,
137.4, 143.4; EIMS (m/z) 429 (Mþ).
4.3. General procedure for the synthesis of vinyl sulfones 5/50
A mixture of
b-amino sulfone 3 or 4 (1.0 mmol) and NaH
(2.0 mmol) in dry THF was stirred at rt for the required time (Table
4). After completion of the reaction (monitored by TLC), the mix-
ture was extracted with EtOAc (3ꢂ5 mL). The combined organic
phases were dried over anhyd Na2SO4, filtered and concentrated
under reduced pressure. The resulting crude product was purified
by silica gel column chromatography using a mixture of EtOAc/n-
hexane (1:24) as eluent to afford an analytically pure sample of
vinyl sulfones 5/50 (Table 4).
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Acknowledgements
We sincerely thank SAIF, Punjab University, Chandigarh, for
providing microanalyses and spectra.
References and notes
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