40
Chemistry Letters Vol.37, No.1 (2008)
Regio- and Stereoselective Hydrothiolation Reactions of Ynamides
with Diphenyldithiophosphinic Acid: Straightforward Synthesis
of Ketene N,S-Acetal Derivatives
Hiroto Yasui, Hideki Yorimitsu,ꢀ and Koichiro Oshimaꢀ
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510
(Received September 21, 2007; CL-071048;
E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp, oshima@orgrxn.mbox.media.kyoto-u.ac.jp)
Treatment of N-1-alkynyl-N-methylarenesulfonamides
corresponding products in high yields (Entries 2 and 3). In addi-
tion, N-arylethynylamides having an electron-donating group or
an electron-withdrawing group on the aromatic rings provided
the corresponding hydrothiolation products without difficulty
(Entries 4–7). It is worth noting that the keto group in 1g sur-
vived under the reaction conditions (Entry 7). Ynamide 1h,
which has a silyl group on the terminus of the triple bond, also
furnished the desired product 3h (Entry 8). Even N-methyl-N-
phenylethynyl-p-nitrobenzenesulfonamide (1j), the carbon–car-
bon triple bond of which would be more electron-deficient,
reacted with 2 smoothly to afford the corresponding product 3j
in 97% isolated yield (Entry 10).
Treatment of ynamide 1c with thiobenzoic acid (4) instead
of 2 under otherwise the same conditions furnished ketene ami-
nal 5 in 51% isolated yield (Scheme 1). When the adduct 5 react-
ed with butylmagnesium bromide in tetrahydrofuran (THF),
amide 6 was obtained in 66% yield. Therefore, the result sug-
gested that the adduct 5 was not S-alkenyl thioester but O-alken-
yl thioester. On the other hand, when ynamide 1c was treated
with thiols such as benzenethiol and 1-dodecanethiol under
otherwise the same conditions, no hydrothiolation reactions
took place.5 The result suggests that the acidity of the reagents
is important.6
In order to reveal the mechanism of the hydrothiolation, the
reaction of deuterium-labeled ynamide 1k was performed. As a
result, a mixture of adducts 3k, 3a, and 3l was obtained in 93%
combined yield in a ratio of 75:18:7 (Scheme 2). It is worth not-
ing that 3k was obtained as a 1:1 mixtuer of the E and Z isomers.
The formation of the stereoisomeric mixture of 3k suggests
the stepwise mechanism for the hydrothiolation as shown in
Scheme 3. Namely, protonation of 1k with 2 would generate ke-
teniminium intermediate 7-d and diphenyldithiophosphinate
anion 20 as the first step.7 Next 20 would add to the intermediate
7-d to furnish 3k. Instead of the addition of 20 to 7-d, when 20
abstracted the deuterium in 7-d, 1a and 2-d were generated.
Then, the reaction of 1a with 2 would afford 3a. In addition,
with diphenyldithiophosphinic acid resulted in hydrothiolation
reactions to provide ketene N,S-acetal derivatives regio- and
stereoselectively.
Ynamides are ynamines having both good reactivity and
sufficient stability to handle, thanks to the electron-withdrawing
group on the nitrogen. In the past few years, the chemistry of
ynamides has attracted considerable attention.1 Reactions of
ynamides have been developed on the basis of the reactivity of
the electron-rich carbon–carbon triple bonds. Among them,
Brønsted acid- or Lewis acid-promoted addition reactions to
ynamides have been actively explored.2 We report here hydro-
thiolation of ynamides with diphenyldithiophosphinic acid3
leading to ketene N,S-acetal derivatives.
Treatment of N-ethynyl-N-methyl-p-toluenesulfonamide
(1a) with diphenyldithiophosphinic acid (2) in 1,2-dimethoxy-
ethane (DME) at room temperature for 1 h afforded 1-[meth-
yl(p-tolylsufonyl)amino]ethenyl
diphenyldithiophosphinate
(3a) in 86% isolated yield regioselectively (Table 1, Entry 1).
A wide range of ynamides 1 were tested for the hydrothio-
lation reactions with 2. Interestingly, internal ynamides also
reacted with 2 smoothly. All the reactions proceeded in a syn
fashion to furnish E isomers as the sole isomers.4 Both N-1-
propynylamide 1b and N-phenylethynylamide 1c afforded the
Table 1. Hydrothiolation reactions of ynamides with diphenyl-
dithiophosphinic acid
S
P
S
EWG
R'
Ph
Ph
S
N
+
R
C
C N
P
Ph
HS
Ph
DME, rt, 1 h
R
EWG
R'
1
2 (1.2 equiv.)
3
Entry
1
R
H
R0
EWG
3
Yield/%a
1
2
1a
1b
1c
1d
1e
1f
Me
Me
Me
Me
Me
Ts
Ts
3a
3b
3c
3d
3e
3f
86
76
87
91
97
88
97
63b
95
97
Me
Ph
S
3
Ts
Ts
O
4
p-tolyl
o-tolyl
Ts
O
Ph
Ts
5
Ts
Ts
+
Ph C C N
Ph
N
DME, rt, 1 h
51%
HS
Ph
6
p-ClC6H4
p-AcC6H4
TMS
Me
Me
Me
allyl
Me
Me
Me
1c
4 (1.2 equiv.)
7
1g
1h
1i
Ts
Ts
3g
3h
3i
5
(E/Z = 92:8)
8
O
9
10
Ph
Ph
Ts
p-Nsc
n-BuMgBr (2.2 equiv.)
Ph
Ts
N
1j
3j
THF, 20 °C to 0 °C
aIsolated yields by silica-gel column chromatography unless otherwise
noted. bIsolated yield obtained by recrystallization. cp-Nitrophenylsul-
fonyl.
6
Me
66%
Scheme 1.
Copyright Ó 2008 The Chemical Society of Japan
Yasui, Hiroto
