A mild and convenient procedure for desulfinylation of p-toluenesulfinyl amines

Article abstract of DOI:10.1055/s-2005-862352

Reaction of p-toluenesulfinyl amines with thiophenol in the presence of catalytic amount of ZnCl₂ provides the corresponding desulfinylated amines in high yield. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-862352

LETTER
535
A Mild and Convenient Procedure for Desulfinylation of p-Toluenesulfinyl
Amines
D
B
esulfinylation o
i
f
p
-Tol
n
uenesulfinyl
Amin
F
es eng Li, Ke Yuan, Li Xin Dai, Xue Long Hou*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
54 Fenglin Lu, Shanghai 200032, P. R. China
3
E-mail: xlhou@mail.sioc.ac.cn
Received 12 November 2004
reaction with a little bit lower yield (entries 6 and 7,
Abstract: Reaction of p-toluenesulfinyl amines with thiophenol in
Table 1), but no product was detected using FeCl as the
3
the presence of catalytic amount of ZnCl provides the correspond-
2
Lewis acid (entry 8, Table 1). This desulfinylation reac-
tion has been tested in several normal solvents (entries 1
and 3–5, Table 1). Among them CH Cl gives the highest
ing desulfinylated amines in high yield.
Key word: desulfinylation, Lewis acid catalyst, amine, sulfinamide
2
2
yield (entry 1, Table 1). So the best condition for this de-
sulfinylation reaction is using 3 equivalents of thiophenol
and 10 mol% ZnCl in CH Cl at room temperature for 3
Enantiopure sulfinimines have recently become very pop-
ular chiral building blocks, as the electron-withdrawing
2
2
2
1
hours.
sulfinyl group in sulfinimines activates the carbon-nitro-
gen double bond and exerts powerful stereodirecting
effects in the reactions. Moreover, in sulfinamide the N-
sulfinyl group can be used for further elaboration of the
Under this optimal reaction condition, a number of p-tol-
uenesulfinyl amines were employed and the results were
summarized in Table 2.9
2
1
product. Since the pioneer work of Davis, many asym- It can be seen that sulfonamides derived from primary
metric transformations based upon enantiopure p-toluene- amines provided corresponding products in higher yield
3
,4
sulfinimines have been documented. After successful (entries 1–7, Table 2), and those derived from secondary
nucleophilic addition to sulfinimines giving diastereomer- amines afforded the products in a little bit lower yield
ic p-toluenesulfinyl amines, the challenge became the se- (entries 9 and 10, Table 2). However, no reaction took
lective removal of the p-toluenesulfinyl group to give free place for compound 1h with two phenyl groups on
amines under mild conditions. So far, several very simple nitrogen (entry 8, Table 2). It should be pointed out that
3
f,5–7
procedures have been reported in literature.
However, sulfonamide 1g containing a nitrile group, which would
3f
5
some of them involved harsh, strong acidic (HCl, TFA ) be hydrolyzed under strong acidic or basic condition, also
or strong basic (KOH ) reaction conditions. Very recent-
6
ly, Davis reported another procedure to remove the sulfi-
Table 1 Desulfinylation Reaction Catalyzed with Lewis Acida
7
nyl group using Dess–Martin periodinane. During the
course of studying the reaction of aziridines and imines,4
,8
NH2
O
S
we inadvertently found out that desulfinylated amine was
obtained in moderate yield from the reaction of (p-tol-
uenesulfinylamino)-a-(1-benzylaziridinyl-2)-acetonitrile
with p-chlorothiophenol in the presence of catalytic
3
00 mol% PhSH
N
H
1
0 mol% Lewis acid
2a
1a
amount of ZnCl . Further study showed that p-toluene-
sulfinyl group can be easily removed from sulfinamide in
2
Yield (%)b
Entry
Solvent
CH Cl
Lewis acid Time (h)
the presence of thiophenol and ZnCl . In this letter, we
1
2
3
4
5
6
7
ZnCl2
None
3
12
3
80
0
2
2
2
2
will disclose our preliminary results on this simple, mild
and convenient desulfinylation procedure.
CH Cl
2
THF
ZnCl2
77
60
55
65
60
0
Reaction of p-toluenesulfinylaniline with 3 equivalents of
thiophenol in the presence of catalytic amount of ZnCl at
2
Et O
ZnCl2
8
2
room temperature provided aniline in 80% yield (entry 1,
Toluene
CH Cl
ZnCl2
10
Table 1). The presence of both thiophenol and ZnCl is
2
important for the reaction. In the absence of ZnCl , no
2
CuSO4
4.5
2
2
2
2
2
desulfinylated product was detected (entry 2, Table 1).
From Table 1, it can also be seen that several other Lewis
acids (CuSO and AlCl ) are also suitable to promote the
CH
Cl
AlCl
4
8
3
4
3
8
CH Cl
2
FeCl3
a
Reaction proceeds at r.t. using 1 mmol p-toluenesulfinylaniline,
mmol PhSH, 10 mol% Lewis acid, 4 mL of solvent.
Determined by GC.
SYNLETT 2005, No. 3, pp 0535–0537
1
6.
0
2.
2
0
0
5
3
Advanced online publication: 17.01.2005
DOI: 10.1055/s-2005-862352; Art ID: U24504ST
b
©
Georg Thieme Verlag Stuttgart · New York

5
36
B. F. Li et al.
LETTER
gave the product in 85% yield, keeping the nitrile group Table 2a Desulfinylation Reaction of Different p-Toluenesulfinyl
Amines (continued)
unchanged. Also, no epimerization reaction took place in
a conversion of compounds 1d and 1g to the correspond-
O
S
1
0
ing amines (entries 4 and 7, Table 2). It entails that the
method can be applied in the syntheses of optical active
compounds.
R2
3
00 mol% PhSH
H
N
N
R1
10 mol% ZnCl2, CH2Cl2
R1
R2
1
a–i
2a–i
In summary, a simple, mild and efficient procedure for the
removal of p-toluenesulfinyl group in sulfinamide has
been developed. It provides an easier way from sulfin-
amides to free amines and widens the synthetic utility of
sulfinimines and sulfinamides.
Entry p-Toluenesulfinyl amines
Time
(h)
Yield
(%)
7
O
S
2
85
Cl
HN
Table 2a Desulfinylation Reaction of Different p-Toluenesulfinyl
Amines
S
CN
O
NHBn
R2
S
300 mol% PhSH
H
N
1g
N
R1
10 mol% ZnCl2, CH2Cl2
R1
R2
8
9
24
14
7
NR
50c
70c
Ph
N
1a–i
2a–i
Ph
S
Entry p-Toluenesulfinyl amines
Time
h)
Yield
(%)
O
(
1
h
O
S
1
3
80
O
N
S
N
H
1
i
1
a
10
2
3
4
5
6
O
S
3
87b
85b
81
N
Bn
Ph
S
N
H
O
1
j
1
1
1
1
b
a
O
S
2.5
Reaction condition: 1 mmol p-toluenesulfinyl amine, 3 mmol PhSH,
1
0 mol% ZnCl , 4 mL of CH Cl , at r.t.
2
2
2
b
c
N
H
Determined by GC.
Separated as acylated product.
c
O
S
6
Acknowledgment
This work was supported by National Natural Science Foundation
of China, the Major Basic Research Development Program (grant
No. G2000077506), National Outstanding Youth Fund and Chinese
Academy of Sciences.
N
H
d
e
4
83b
90
O
S
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N
H
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Synlett 2005, No. 3, 535–537 © Thieme Stuttgart · New York

LETTER
Desulfinylation of p-Toluenesulfinyl Amines
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2
1
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D
1
–
3
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Synlett 2005, No. 3, 535–537 © Thieme Stuttgart · New York