A novel method for the synthesis of vicinal disulfonamides promoted by metallic samarium in aqueous media

Article abstract of DOI:10.1016/S0040-4039(02)01509-5

A new method to synthesize vicinal disulfonamides by reductive coupling of N-sulfonylimines in Sm/HCl/THF has been developed and various reaction conditions have been studied.

Full text of DOI:10.1016/S0040-4039(02)01509-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6787–6789
A novel method for the synthesis of vicinal disulfonamides
promoted by metallic samarium in aqueous media
a
a
a,b,
Xi Liu, Yunkui Liu and Yongmin Zhang
*
a
Department of Chemistry, Zhejiang University (Campus Xixi), Hangzhou 310028, PR China
b
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, PR China
Received 28 May 2002; revised 10 July 2002; accepted 19 July 2002
Abstract—A new method to synthesize vicinal disulfonamides by reductive coupling of N-sulfonylimines in Sm/HCl/THF has
been developed and various reaction conditions have been studied. © 2002 Elsevier Science Ltd. All rights reserved.
8
Recently, growing interest has been focused on syn-
thetic organic reactions in aqueous media. Water pos-
sesses many advantages over traditional organic
solvents: simple operation, safety, low cost, the mini-
mization of tedious protection and deprotection, etc.
Many organic reactions have been successfully carried
out in aqueous media, such as Diels–Alder reactions,
Barbier reactions, Claisen rearrangements and aldol
promoted by Zn/TMSCl in DMF. When performing
cross coupling of N-sulfonylimines and aromatic
ketones we found that SmI could promote the dimer-
ization of N-sulfonylimines to afford vicinal disulfon-
amides. Here we report a convenient and practical
method to synthesize vicinal disulfonamides via the
reductive coupling of N-sulfonylimines promoted by
metallic samarium in HCl/THF (Scheme 1).
2
9
1
reactions. Reactions in aqueous media promoted by a
metal (such as In, Zn, Sn, etc.) have been extensively
Various activators and reaction media were studied to
1
a,2
reported.
Metallic samarium is stable in air and its
optimize the reaction conditions (Table 1). Our group
3+
10
reducing power (Sm /Sm=−2.41 V) is similar to that
has reported that saturated NH Cl can activate Sm.
4
2+
of magnesium (Mg /Mg=−2.37 V) and superior to
However, Sm/NH Cl/THF does not provide vicinal
4
2+
that of zinc (Zn /Zn=−0.71 V). However, the reac-
disulfonamides without catalytic I2 (entry a). Better
yields were obtained by adding a catalytic amount of I2
tions promoted by samarium in aqueous media have
3,4
been investigated less.
(entries b and c). Thus, we deduced that I might have
2
an important effect on the activation of Sm, so we used
On the other hand, compared with vicinal diamines,
which are of interest due to their application in asym-
a catalytic amount of I alone to perform the reductive
2
coupling, however, only a trace amount of the product
5
6
metric synthesis and medicinal chemistry and which
was obtained (entry d). When 2 equiv. of I were used,
2
7
have been synthesized by various methods, vicinal
the conversion of 1a was nearly 100% but the chemose-
lectivity was poor (entries e and f). We also investigated
8
disulfonamides have rarely been studied. Pansare
reported that cyclic sulfamides can be synthesized via
intramolecular coupling of dibenzylidine sulfamides
the reaction promoted by Sm/Me SiCl and Sm/
3
Me SiCl in anhydrous THF and moderate yields of 2a
2
2
1
1
Ar SO HN
NHSO Ar
Sm/HCl/THF
r.t.
2
2
Ar SO N CHAr2
1
1
2
2
+
Ar SO NH CH Ar
2
2
Ar2
Ar2
1
2 (dl/meso) (major)
3 (minor)
Scheme 1.
Keywords: vicinal disulfonamides; samarium reagents; aqueous media; reductive coupling.
*
0
Corresponding author. E-mail: yminzhang@mail.hz.zj.cn
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01509-5

6
788
X. Liu et al. / Tetrahedron Letters 43 (2002) 6787–6789
Table 1. The reductive coupling of N-sulfonylimine (1a, 1 mmol) under various conditions
Entry
Sm (mmol)
Reaction medium, additive
Reaction time
Yield (%)a of 2a
Yield (%)a of 3a
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
4
4
4
4
4
4
2
1.2
1.2
4
4
4
4
4
2
Satd. NH Cl/THF (5:1)
12 h
12 h
24 h
24 h
12 h
24 h
24 h
15 h
B5
37
42
B2
54
55
41
73
76
85
83
74
75
0
B5
7
8
B2
44
44
30
10
8
9
9
18
8
0
4
Satd. NH Cl/THF (5:1), I (cat.)
4
2
Satd. NH Cl/THF (5:1), I (cat.)
4
2
H O/THF (5:1), I (10% mmol)
2
2
H O/THF (5:1), I (2 mmol)
2
2
H O/THF (5:1), I (2 mmol)
2
2
H O/THF (5:1), I (1 mmol)
2
2
THF, Me SiCl (4 mmol)
3
THF, Me SiCl (4 mmol)
10 h
2
2
1 HCl/THF (5:1)
1 HCl/EtOH (5:1)
2 HCl/THF (5:1)
0.1 HCl/THF (5:1)
30 min
30 min
30 min
30 min
30 min
30 min
1 M HCl/H O (5:1)
2
1 M HCl/THF (5:1)
63
4
a
Isolated yields.
1
1
were obtained (entries h and i). Finally we used
hydrochloric acid to perform the reductive coupling of
1
matic N-sulfonylimines, the reactions of aliphatic N-
sulfonylimines in Sm/HCl/THF gave exclusively the
corresponding sulfonamides (1i–k) in quite low yields.
a and obtained a satisfactory result (entry j). A certain
amount of organic solvent is still necessary for the
reductive coupling (entry n), both THF and EtOH are
useful (entries j and k). The concentration of hydro-
chloric acid also influences the yields of the products,
for example, 2 M HCl decreases the yield of 2a but
increases the yield of 3a (entry l), and 0.1 M HCl
reduces the yields of both 2a and 3a (entry m). Com-
pared with the other methods mentioned above, the
Sm/HCl/THF system needs a shorter reaction time and
does not require the exclusion of oxygen.
On the basis of previous work on reductive coupling
4a
reaction in Sm/HCl, a possible mechanism is postu-
lated (Scheme 2). Perhaps the samarium powder is
activated by the hydrochloric acid and an electron
transfer to the substrate forms the radical anion (A),
which then dimerizes and is protonated to afford the
product 2a, but the real nature of the reducing species
4a,12
[Sm*] in this system is unclear.
The radical anion of
the aliphatic N-sulfonylimines may be too unstable to
dimerize and the reductive products formed exclusively.
Similar to the Sm/I /H O/THF system, when satd.
When 1 M hydrochloric acid was added dropwise to a
suspension of Sm powder and the substrate in THF
under air, hydrogen was released immediately and the
reaction was completed within 30 min (Scheme 1). All
the aromatic N-sulfonylimines (1a–h) investigated here
give vicinal disulfonamides (2a–h) in good yields. The
ratio of dl/meso is almost 1:1 (Table 2). Unlike aro-
2
2
NH Cl/THF/I (cat.) is used, a deep blue solution was
4
2
observed, which turned yellow when the reaction was
completed. However, in the absence of I (10% mmol),
2
we did not see a blue solution. Since divalent samarium
shows a deep blue color, these phenomena suggest that
I2 might help to form the divalent samarium. In the
14,15
Table 2. The reductive coupling of N-sulfonylimines (1a–h)
Entry
Ar1 of 1
Ar2 (R) of 1
Yield (%)a
Ratio of dl/mesob
Yield (%)
a
b
c
d
e
f
4-CH -C H
4-CH -C H
85 (2a)
80 (2b)
78 (2c)
79 (2d)
77 (2e)
83 (2f)
85 (2g)
51:49
50:50
45:55
48:52
50:50
46:54
50:50
9 (3a)
8 (3b)
6 (3c)
10 (3d)
12 (3e)
4 (3f)
3
6
4
4
4
4
3
6
4
4
C H
4-CH -C H
6
5
3 6
4-CH -C H
C H
6 5
3
6
C H
4-CH O-C H
6
5
3 6
4
4
4-CH -C H
4-CH O-C H
3
6
3
6
C H
4-Cl-C H
6
5
6
4
g
4-CH -C H
4-Cl-C H
3 (3g)
3
6
6
4
h
4-CH -C H
72 (2h)
50:50
15 (3h)
3
6
4
O
i
j
k
4-CH -C H
CH (CH )
2 3
0
0
0
–
–
–
41 (3i)
35 (3j)
48 (3k)
3
6
4
4
4
3
4-CH -C H
(CH ) CHCH
3
6
3 2
2
4-CH -C H
CH CH CH
2
3
6
3
2
a
Isolated yields.
b
The ratio of dl/meso was determined from the 1H NMR spectra.

X. Liu et al. / Tetrahedron Letters 43 (2002) 6787–6789
6789
activator
Sm
[Sm*]
_
electron transfer
.
1
2
Ar SO N CHAr
2
Ar SO N CHAr2
1
2
A
_
_
1
NHSO2Ar1
Ar2
1
1
Ar SO2HN
Ar SO N
NSO Ar
2
2
protonation
coupling
Ar2
Ar2
Ar2
B
Scheme 2.
Sm/Me SiCl and Sm/Me SiCl systems, we assumed
8. Pansare, S. V.; Malusare, M. G. Tetrahedron Lett. 1996,
37, 2859.
9. Liu, Y.-K.; Zhang, Y.-M.; Liu, X. Chin. J. Chem. 2001, 19,
3
2
2
that the mechanism is similar to that of pinacolic
11,13
coupling promoted by Sm/Me SiCl.
3
500.
In summary, reductive coupling of N-sulfonylimines
promoted by Sm/HCl/THF is a convenient and practi-
cal method to synthesize vicinal disulfonamides. This
method adds to the reactions in aqueous media pro-
moted by samarium reagents. Its advantages include no
need for a nitrogen atmosphere, good yields, mild
10. (a) Wang, L.; Zhang, Y.-M. Tetrahedron Lett. 1998, 39,
5257; (b) Wang, L.; Zhang, Y.-M. Chin. J. Chem. 1999, 17,
550.
11. Sm/TMSCl/THF system has been used to promote pina-
colic coupling: Wang, L.; Zhang, Y.-M. Tetrahedron 1998,
54, 11129.
12. (a) Moeller, T. In Comprehensive Inorganic Chemistry;
Bailar, J. C.; Emeleus, H. J.; Nyholm, R.; Trotman-
Dichenson, A. F.; Eds.; Pergamon Press: Oxford, 1973;
Vol. 7, pp. 3599 and 3615; (b) Enemaerke, R. J.; Daasbjerg,
K.; Skrydstrup, T. Chem. Commun. 1999, 343; (c) Fuchs,
J. R.; Mitchall, M. L.; Shabangi, M.; Flowers, R. A., II
Tetrahedron Lett. 1997, 38, 8157; (d) Leonard, E.; Dun-
bach, E.; Pericho, J. Chem. Commun. 1989, 276.
14,15
reaction conditions and simple operation.
Acknowledgements
We are grateful to the National Natural Science Foun-
dation of China (Project No. 20072003) and the NSF of
Zhejiang province for financial support.
1
3. Me SiCl can activate the metal by the removal of the
3
metal–oxide coating on the metal surface: (a) Takai, K.;
Ueda, T.; Hayashi, T.; Moriwake, T. Tetrahedron Lett.
1996, 37, 7049; (b) Takai, K.; Kakauchi, T.; Utimoto, K.
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14. General procedure: to a suspension of the substrate (1
mmol) and samarium powder (0.66 g, 4 mmol) in THF (2
mL) 1 M hydrochloric acid (10 mL) was added dropwise
with stirring at room temperature. After the reaction was
completed (monitored by TLC), the mixture was extracted
by AcOEt (3×20 mL) and the AcOEt solution was washed
with saturated NaCl (10 mL) and dried over anhydrous
9
19; (b) Yanada, R.; Harada, Y.; Inanaga, J.; Yamaguchi,
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Na SO . The solvent was evaporated under reduced pres-
sure and the crude product was purified by preparative
TLC (cyclohexane–ethyl acetate (2:1) as eluent).
2 4
(
1
5
6
7
15. Typical physical data of compounds 2a (N-(2-(4-
methyl)benzenesulfonylamino-1,2-di(4-methyl)phenylethyl)-
4-methylbenzenesulfonamide): colourless crystals, mp
1
−
1
3
142–147°C; wmax: 3277, 3030, 1595, 1495, 1323, 1159, cm ;
1
. (a) Lucet, D.; Le Gall, T.; Mioskowski, C. Angew. Chem.,
Int. Ed. Engl. 1998, 37, 2580; (b) Enholm, E. J.; Forbes,
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H NMR (400 MHz, DMSO): 8.00 (2H, d, NH), 7.14 (4H,
d, ArH), 6.96 (4H, d, ArH), 6.74 (4H, d, ArH), 6.66 (4H,
d, ArH), 4.48 (dl) and 4.45 (meso) (2H, s, CH), 2.24 (6H,
s, ArCH
(88.69), 155 (31.62), 91 (100), 77 (12.13). Anal.
. Calcd: C, 65.69; H, 5.84; N, 5.11; S, 11.68.
Found C, 65.72; H, 5.86; N, 5.11; S, 11.65%.
), 2.11 (6H, s, ArCH ); m/z (%): 393 (0.95), 274
3
3
C H N O S
30 32 2 4 2