Published on the web August 1, 2013
1233
One-pot Preparation of Homopropargylic N-Sulfonylamines Catalyzed by Zinc Powder
Chao Wu, Wangyong Huang, Weimin He,* and Jiannan Xiang*
College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China
(Received July 24, 2013; CL-130626; E-mail: jnxiang@hnu.edu.cn)
Table 1. Examination of reaction conditionsa
A new one-pot method for synthesis of homopropargylic
N-sulfonylamines from aldehydes catalyzed by zinc powder is
described. The procedure is lauded by its simplicity, good
yields, and adaptability to a wide variety of aldehydes.
1) TsNH2, Zn,
BnBr, THF
2) propragyl
bromide, rt
NTs
NTs
CHO
4a
2a
1a
not observed
Aldehyde
/equiv
Zn
/equiv
Temp
Yield
Entry
Owing to the versatility of homopropargylic N-sulfonyl-
amines as intermediates in organic synthesis,1 extensive studies
on their preparation have been well documented.2 Among them,
the addition of organometallic reagents to imines has long been
recognized as a highly versatile method. Transition metals such
as magensium,3 silver,4 chromium,5 indium,6 and palladium7
have been used for this purpose. In addition, ring-opening
reactions of aziridines with acetylides also provide a useful
protocol.8 However, the reported methods are associated with
one or more of the following drawbacks: harsh conditions,
complex experimental manipulations, and the use of hazardous
and expensive reagents. Furthermore, some methods require
multistep procedures.9 On the other hand, the aliphatic N-
tosylimines are labile to decomposition during purification by
silica gel column chromatography or during distillation at high
temperature. It is difficult to purify aliphatic N-tosylimines even
though recrystallization is feasible. As a result, the substrate
scope of electrophilic addition to imines is limited.
/°Cb
/%c
1d
2
3
4
5
6
7
8
9
1.5
1.5
1.5
1.5
1.5
1.1
1.0
0.9
1.1
1.1
1.1
1.1
3.0
3.0
2.0
4.0
5.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
25
25
25
25
25
25
25
25
40
46
44
39
49
48
58
50
38
63
71
76
9
10
11
12e
60
reflux
reflux
aThe reactions were conducted on a 1 mmol scale. Temper-
b
c
ature of reaction step 1. Isolated yield based on the amide.
e
dN2 atmosphere. No BnBr was used.
As an important catalyst,10 zinc has been reported to be
applied in the allylation and benzylation of imines. In the
presence of zinc powder, homobenzylamines and homoallyl-
amines were prepared in good yields in THF, and the reactions
were also carried out under solvent-free conditions.11 Never-
theless, the propargylation of N-sulfonylimines has received
much less scrutiny, and only one example of a zinc-mediated
addition to imines has been reported.1c
We describe herein the first zinc-catalyzed synthesis of
homopropargylic N-sulfonylamines using an efficient and simple
one-pot procedure for the direct condensation of aldehydes with
p-toluenesulfonamide.
A systematic study was undertaken to define the best
condition, and the representative data are listed in Table 1.12
In general, a mixture of benzyl bromide and activated zinc
powder13 was stirred for 30 min, then p-toluenesulfonamide
(1 mmol) and benzaldehyde were successively added. The
mixture was stirred until the amide disappeared as monitored
by TLC. Then, propargyl bromide was added dropwise.
The reactions of organozinc reagents always require strict
reaction conditions such as inert atmosphere.11c However, our
present route proceeded well in air (Table 1, Entries 1 and 2).
Then we studied the effect of catalyst amount on the conversion
of the reaction. By changing the amount of zinc powder from 2
to 4 equiv, the yield increased to 49% (Entries 2-4), but higher
amount of zinc powder (5 equiv) did not improve the yield.
Variation of the ratio of aldehyde to N-tosylamide had significant
impact on the conversion. With a 1.5:1 ratio, the yield was 49%.
The excessive aldehyde led to an increased by-product homo-
propargyl alcohol 1-phenylbut-3-yn-1-ol (3a).14 When we
decreased the amount of aldehyde to a ratio of 1.1:1, the yield
did increase significantly (58%) (Entry 6). However, when the
ratio reached 1:1 or less, the yields decreased (Entries 7 and 8).
By changing the temperature of reaction step 1 from 25 °C to
reflux, the yield increased to 76% (Entries 9-11). This suggested
that high temperature could enhance the reaction. Due to the
weak nucleophilicity of p-toluenesulfonamide, high temperature
was usually required.15 To get more information on the optimal
catalytic conditions, we also carried out intensive investigations
to define the necessity of benzyl bromide. Only 14% conversion
of imine was detected by 1H NMR and 9% isolated yield of
compound 1a was obtained without addition of benzyl bromide.
It is known that propargylic organometallic reagents exist as
an equilibrium mixture of allenic and propargylic species.16
Hence, the use of metal-catalyzed additions of propargylic
reagents to electrophiles has been previously limited by low
regioselectivity. Interestingly, in our work its regioisomer (i.e.,
4a) was not observed by H NMR. Significantly, both H NMR
and GC-MS for the reaction mixture confirmed the formation of
toluene, which should be the product of BnBr.
After optimization of the reaction conditions, a range of
structurally diverse aromatic and aliphatic aldehydes were
studied, and the results are summarized in Table 2.12 It was
clear from the table that the reactions proceeded efficiently and
the desired products were obtained in good yields. For aromatic
1
1
Chem. Lett. 2013, 42, 1233-1234
© 2013 The Chemical Society of Japan
Wu, Chao
