Silver-catalyzed three-component reaction of propargylic amines, carbon dioxide, and N-iodosuccinimide for stereoselective preparation of (E)-iodovinyloxazolidinones

Article abstract of DOI:10.1246/cl.150584

The silver-catalyzed three-component reaction of propargylic amines, carbon dioxide, and N-iodosuccinimide for the stereoselective synthesis of (E)-iodovinyloxazolidinones was developed. The silver-catalytic system could be applied to various propargylic amines to afford the corresponding iodovinyloxazolidinones in high yields. The structure of the oxazolidinone was confirmed by X-ray structure analysis to be the Eisomer for the geometry of the exo-olefin. The silver-catalyzed cyclization and replacement of silver with the iodine group in the intermediate were thought to be crucial steps.

Full text of DOI:10.1246/cl.150584

Received: June 16, 2015 | Accepted: July 16, 2015 | Web Released: October 5, 2015
CL-150584
Silver-catalyzed Three-component Reaction of Propargylic Amines, Carbon Dioxide,
and N-Iodosuccinimide for Stereoselective Preparation of (E)-Iodovinyloxazolidinones
Kohei Sekine, Ryo Kobayashi, and Tohru Yamada*
Department of Chemistry, Keio University, Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522
(E-mail: yamada@chem.keio.ac.jp)
The silver-catalyzed three-component reaction of propar-
gylic amines, carbon dioxide, and N-iodosuccinimide for the
stereoselective synthesis of (E)-iodovinyloxazolidinones was
developed. The silver-catalytic system could be applied to
various propargylic amines to afford the corresponding iodovi-
nyloxazolidinones in high yields. The structure of the oxazoli-
dinone was confirmed by X-ray structure analysis to be the E-
isomer for the geometry of the exo-olefin. The silver-catalyzed
cyclization and replacement of silver with the iodine group in
the intermediate were thought to be crucial steps.
silver with electrophiles would be persuasive evidence for the
vinylsilver intermediates in the present silver-catalytic systems.6
In recent publications, the transformation of the C(vinyl)-Ag
bond following the silver-catalyzed cyclization of allenylamine,
o-alkynylaniline or alkynyl silyl enol ether has been developed
to form the C(vinyl)-Cl bond,7a C(vinyl)-F bond,7b,7c C(vinyl)-I
bond,7d and C(vinyl)-SnBu3 bond.7e
The halovinyl component is one of the most reliable
structures for metal-catalyzed coupling reactions to form new
carbon frameworks. Thus, the successive introduction of carbon
dioxide and a halogen group into propargylic amines was
investigated to afford oxazolidinones bearing (E)-halovinyl
moieties. As an example for the sequential introduction of
carbon dioxide and a halogen group, the iodo-cyclization of
primary propargylic amines and carbon dioxide with t-BuOI was
reported,8 but the yields of the products and variations of the
substituents at the terminal position are not sufficient. According
to previous studies,6 it was expected that the silver-catalytic
system could be applied to various propargylic amines bearing
internal alkynes at around room temperature. In this communi-
cation, we report the silver-catalyzed three-component reaction
of propargylic amine, carbon dioxide, and halonium ions to
provide the corresponding oxazolidinone derivatives with an
(E)-halovinyl group.
Carbon dioxide is one of the most attractive carbon sources
due to its low toxicity, ease of handling, and abundance to
displace toxic reagents such as phosgene and carbon monoxide.
For the incorporation of carbon dioxide in fine chemicals,
much effort has been actively made;1 three- or four-component
reactions using aryne,2 allene,3 alkyne,4 or others5 have been
recently developed to afford diverse building blocks such as
carboxylic acid, lactone, carbonate, and carbamate derivatives.
Sequential reactions in a one-pot operation would provide
promising methods to form various important frameworks in
the pharmaceutical and material science fields. Our group has
reported that carbon dioxide incorporation into propargylic
amines was effectively catalyzed by silver salts under mild
conditions to selectively afford (Z)-alkenyloxazolidinones
(Scheme 1, eq 1).6 Through the reaction, a vinylsilver inter-
mediate was expected to be stereoselectively generated as a
result of the anti-addition of carbamate to the C-C triple bond
activated by silver salts. This assumption was supported by DFT
calculations of the silver-catalyzed carbon dioxide incorporation
into propargylic alcohols.6b It is reasonable to assume that
the silver ion in the intermediate would be stereospecifically
replaced by a proton to produce (Z)-alkenyloxazolidinone and
regenerate the silver catalyst. This plausible mechanism sug-
gested that in the presence of appropriate electrophiles (E+),
the C(vinyl)-Ag bond could be stereospecifically trapped by the
electrophiles instead of the proton to afford the corresponding
oxazolidinones containing the C(vinyl)-E bond with high
geometry control (Scheme 1, eq 2). The exchange reaction of
For the initial screening, the propargylic amine 1a was
employed as the starting material using 10 mol % AgOAc in
DMSO under a 2.0 MPa CO2 atmosphere (Table 1, Entries 1-3).
The halonium ions were first examined using the corresponding
Table 1. Examination of halonium ion sources as electrophile
O
O
AgOAc (10 mol%)
NHBn
O
O
E
+ source (1 equiv)
NBn
NBn
Me
Me
Me
+
CO2
(E)
(Z)
Ph
Ph
Solvent (0.15 M)
25 °C
Ph
Me
Me
Me
E
H
1a
2
3a
CO2 pressure
Time
/h
Yielda 2
/%
Entry
E+ source
Solvent
/MPa
1
2
3
4
5
6
7
8
9
NCS
NBS
NIS
I2
I-Cl
I+ c
NIS
NIS
NIS
NIS
NIS
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
2.0
2.0
2.0
2.0
2.0
2.0
1.0
2.0
2.0
2.0
2.0
24
24
24
24
24
24
60
24
24
24
24
0b
0
92(2a)
trace
0
O
H+
0
O
NR4
(Z)
(1)
(2)
O
O
Previous Work R1
92(2a)
71(2a)
57(2a)
3(2a)
trace
NHR4
2 R3
O
O
cat. Ag+
CO2
R
O
NR4
NR4
2 R3
H
R3
R2
R1
R3
CH3CN
CH2Cl2
Toluene
E+
R2
Ag+
R1
R
(E+ = I+)
O
R1
10
11
Ag
NR4
2 R3
(E)
R1
vinylsilver
This Work
intermediate
R
b
aIsolated yield. The corresponding oxazolidinone 3a was obtained in
15% yield. cBis(2,4,6-trimethylpyridine)iodonium hexafluorophos-
phate was employed.
E
Scheme 1. Incorporation of carbon dioxide into propargylic amines.
Chem. Lett. 2015, 44, 1407–1409 | doi:10.1246/cl.150584
© 2015 The Chemical Society of Japan | 1407

Table 2. Comparative experiments
Table 3. Three-component reaction for secondary propargylic
amines
Ph
O
Cat. (10 mol%)
NHBn
O
+ (1 equiv)
O
N
I
AgOAc (10 mol%)
NHR4
NBn
Me
Me
Me
+
(E)
CO2
(2.0 MPa)
N-iodosuccinimide (1 equiv)
O
NR4
Ph
Me
Me
DMSO(0.15 M)
25 °C, 24 h
(E)
R3
+
CO2
(2.0 MPa)
R1
Ph
R2
Me
DMSO (0.15 M)
25 °C, 24 h
Ph
I
R1
3
R2
R
1a
2a
4a
I
1
2
Entry
Cat.
I+ source
Yielda 2a/%
4a/%
1a/%
Entry
Product
Yielda/%
1
2
3
AgOAc
none
NIS
NIS
I2
92
10
0
trace
20
5
0
26
71
O
1
2
R1 = Ph
(2a)
(2b)
92
none
O
CF3
Ac
(E)
NBn
Me
R1
R1
R1
=
=
89
aIsolated yield.
Me
I
succinimides. In the case of N-chlorosuccinimide and N-
bromosuccinimide, the corresponding oxazolidinone 2 was not
obtained (Table 1, Entries 1 and 2). On the other hand, when N-
iodosuccinimide (NIS) was employed, the propargylic amine 1a
was completely consumed in 24 h to produce the oxazolidinone
2a bearing the iodovinyl group in 92% yield (Table 1, Entry 3).
3
(2c)
(2d)
(2e)
82
91
91
Me
4b
5b
R1
R1
=
=
OMe
1
According to the H NMR spectroscopic analysis, the oxazoli-
dinone 2a was obtained as the sole isomer. The structure of the
oxazolidinone 2a was confirmed by X-ray analysis, and the
geometry of the exo-olefin in 2a was suggested to be the E-
isomer (Figure S1). To our surprise, the oxazolidinone 3a was
not observed at all, which suggested that the silver ion was
effectively replaced with the iodonium ion prior to the proton
derived from the amino group. Several iodine sources were then
examined to determine variations in the effective iodonium
sources. It was revealed that iodine, iodine monochloride, or
bis(2,4,6-trimethylpyridine)iodonium hexafluorophosphate were
not effective (Table 1, Entries 4-6). When the carbon dioxide
pressure was reduced to 1.0 MPa, the corresponding iodovinyl
derivative 2a was produced in 92% yield, though a longer
reaction time was required (Table 1, Entry 7). After evaluation
of the solvents (Table 1, Entries 8-11), aprotic polar solvents,
such as CH3CN, DMF, and DMSO, turned out to be suitable to
produce the oxazolidinone 2a in good yields.
For a detailed study of the reaction, some comparative
experiments were carried out (Table 2). The halonium ion is
typically employed as an activator for alkenes and alkynes for
halocyclization, such as halolactonization.9 Therefore, it was a
concern that, without silver catalysts, NIS itself promoted the
cyclization to afford the oxazolidinone 2a. In the absence of
AgOAc, the oxazolidinone 2a was obtained in 10% yield along
with a 20% yield of the imine 4a. The imine 4a was supposed to
be produced by the oxidation of benzylamine by the iodonium
ion (Table 2, Entry 2).10 When iodine was employed instead of
NIS, the reaction did not afford the oxazolidinone 2a at all
(Table 2, Entry 3). It was assumed that the iodo-cyclization
pathway was not dominant in the present silver-catalyzed
reaction and that the vinylsilver intermediate could be trapped
by the iodonium ion to stereoselectively afford corresponding
(E)-oxazolidinones. In addition, it was notable that the silver
catalysts were necessary to promote the cyclization reaction
prior to oxidation of benzylamine by the iodonium ion. Next, the
oxazolidinone 3a, which was synthesized under the previous
conditions,6 was exposed to the reaction conditions in order to
confirm whether the oxazolidinone 3a was transformed into the
iodine-introduced 2a (Scheme S1). As a result, the vinyl iodine
2a was not detected at all and the starting oxazolidinone 3a was
6
R1
R1
=
=
(2f)
96
95
7b
(2g)
S
8
R1
=
(2h)
(2i)
90
86
O
O
9b
NBn
Me
I
O
10b,c
11
R2 = Me, R3 = Me (2j)
92
92
b
O
NPMB
2 R3
(E)
Me
Ph
R2
=
, R3 = H (2k)
Me
R
I
aIsolated yield. E-Isomer was selectively obtained in every case. The
reaction was carried out for 48 h. The reaction was carried out under
1.0 MPa CO2.
c
recovered in 99% yield, which suggested that the iodovinyl
moiety did not form through the oxazolidinone 3a.
The scope of the substrates was investigated under the
optimized reaction conditions (Table 3). First, substituents on
the aromatics were evaluated using secondary propargylic
amines. In the case of the substrates 1b (p-CF3) and 1c (p-Ac)
bearing electron-withdrawing groups, the corresponding (E)-
oxazolidinones 2b and 2c were obtained in 89% and 82% yields,
respectively. Propargylic amines 1d (p-Me) and 1e (p-OMe)
were transformed into the corresponding oxazolidinones 2d and
2e in 91% and 91% yields, respectively. The reaction of the
propargylic amines 1f and 1g having a 1-naphthyl or 2-naphthyl
group proceeded to give the oxazolidinones 2f and 2g in high
yields, respectively. The 2-thienyl- and alkyl-substituted alkynes
substrates 1h and 1i were also suitable for the reaction to
furnish the corresponding products 2h and 2i in 90% and 86%
yields, respectively. The p-methoxybenzyl propargylic amines
1j-1l were found to be good substrates. Substrates 1j and 1k
were converted to oxazolidinones 2j and 2k in 92% yields,
1408 | Chem. Lett. 2015, 44, 1407–1409 | doi:10.1246/cl.150584
© 2015 The Chemical Society of Japan

Table 4. Evaluation of primary amine derivatives
E-selective synthesis. The structure of the oxazolidinone 2a
was confirmed by an X-ray structure analysis to be the E-isomer
for the geometry of the exo-olefin. The silver-catalyzed cycliza-
tion and replacement of silver with the iodine group in the
intermediate were supposed to be crucial steps. The trans-
formation should provide persuasive evidence for the vinylsilver
intermediates for the previously reported silver-catalytic incor-
poration of carbon dioxide.
O
O
Cat. (10 mol%)
NH2
NIS (X equiv)
O
O
NH
Me
NH
Me
(E)
Me
Me
(Z)
+
CO2
(1.0 MPa)
R
I
DMSO
25 °C, 24 h
R
Me
Me
I
R
1
(E)-2
(Z)-2
X
Conc. Yielda
Entry
R
Cat.
E:Zb
/equiv
/M
/%
1
2
3
4
5
6
7
8d
Ph (1l)
Ph (1l)
Ph (1l)
Ph (1l)
Ph (1l)
Ph (1l)
AgOAc
none
AgOAc
AgSbF6
AgNO3
AgNO3
1.2
1.2
1.0
1.0
1.0
1.0
1.0
1.0
0.30
0.30
0.15
0.15
0.15
0.05
0.05
0.05
86
79c
95
95
90
94
91
98
58:42
22:78
83:17
88:12
91:9
95:5
96:4
97:3
This work was financially supported by JSPS Research
Fellowships for Young Scientists.
Supporting Information is available electronically on J-STAGE.
4-MeC6H4 (1m) AgNO3
4-CF3C6H4 (1n) AgNO3
References and Notes
1
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94% yield with the ratios of 95:5 (Table 4, Entry 6). Substrates
containing an electron-donating group 1m (p-Me) and an
electron-withdrawing group 1n (p-CF3) on the aromatics were
transformed into corresponding the oxazolidinones 2m and 2n
in high yields with the ratios of 96:4 and 97:3, respectively
(Table 4, Entries 7 and 8).
2
3
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In conclusion, the silver-catalyzed three-component reaction
of propargylic amines, carbon dioxide, and NIS for the stereo-
selective synthesis of (E)-iodovinyloxazolidinones was devel-
oped. The silver-catalytic system could be applied to various
secondary propargylic amines to afford the corresponding
iodovinyloxazolidinones in high yields. It should be noted that
prior to the other possibility of oxidation and protodeauration,
silver catalysts could control the reaction to selectively afford
(E)-iodovinyloxazolidinones. In the case of primary amines,
a low concentration was found to be suitable for the highly
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Chem. Lett. 2015, 44, 1407–1409 | doi:10.1246/cl.150584
© 2015 The Chemical Society of Japan | 1409