Regioselective TfOH-mediated hydroamidation of ynamides with nitriles

Article abstract of DOI:10.1016/j.tet.2017.03.060

A new TfOH-mediated reaction of ynamides with nitriles as nucleophiles has been developed. The reaction works efficiently under mild reaction conditions to afford a new class of α-acylaminoenamides readily via the intermediacy of keteniminium ion. The reaction displays generality and a broad substrates scope. Additionally, the α-acylaminoenamides could be transformed to highly substituted pyridine, 4-aminopyrimidine or isoquinoline cores.

Full text of DOI:10.1016/j.tet.2017.03.060

Tetrahedron xxx (2017) 1e9
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Regioselective TfOH-mediated hydroamidation of ynamides with
nitriles
,
c
,
, b, c, *
Wan-Shu Wang a, Ping Chen b **, Yu Tang a
a School of Pharmaceutical Science and Technology, Key Laboratory for Modern Drug Delivery & High-Efficiency, Tianjin University, Tianjin, 300072,
PR China
b Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao,
PR China
c Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A new TfOH-mediated reaction of ynamides with nitriles as nucleophiles has been developed. The re-
Received 23 January 2017
Received in revised form
16 March 2017
Accepted 20 March 2017
Available online xxx
action works efficiently under mild reaction conditions to afford a new class of
readily via the intermediacy of keteniminium ion. The reaction displays generality and a broad substrates
scope. Additionally, the -acylaminoenamides could be transformed to highly substituted pyridine, 4-
aminopyrimidine or isoquinoline cores.
a-acylaminoenamides
a
© 2017 Elsevier Ltd. All rights reserved.
Keywords:
Ynamides
Trifluoromethanesulfonic acid
Nitriles
Acylaminoenamides
Keteniminium ions
1. Introduction
functionalized scaffolds with high efficiency, flexibility, and good
regioselectivity, remains an urgent and challenging synthetic goal.
Ynamides which constitute an important subgroup of alkynes,
represent one of the most significant and versatile N-containing
building blocks in organic synthesis.6 Cyclization reactions using
ynamides generally lead to heterocyclic compounds with very high
regio- and stereoselectivity.7 Recently, Zhao reported ynamides
could be used as coupling reagents to construct amide and peptide
bonds through the hydroacyloxylation of ynamides and the sub-
N-vinyl amide derivatives, a fundamental sort of compounds,
have been proved to be the elemental, significant, and versatile
building blocks in organic synthesis, as well as a skeletal part of the
massive and diverse natural products.1 For example, N-vinyl amides
have been widely used to construct nitrogen heterocyclic frame-
works, such as pyridines, pyrimidines, and isoquinolines.2 To the
best of our current knowledge, the conventional preparative
methods mainly depend on direct addition of amides to alkynes,3
the coupling reaction of amides with olefin,4 and acylation of im-
ines.5 However, these protocols suffered from either low yields or
lack of regiocontrol on the double bond geometry. Thus, the
development of novel approaches, especially as part of
sequent aminolysis of
a
-acyloxyenamide.8 Keteniminium ion, a
reactive cationic intermediate conveniently prepared from yna-
mide, has proven to be an especially useful subclass.9 A brønsted
acid introduced formal [2þ2þ2] cycloadditions of ynamides with
nitriles for de novo synthesis of highly substituted pyridine cores
were developed.10 Lately, our group developed the TfOH-mediated
[2þ2þ2] cycloadditions of ynamides with nitriles, which afforded
4-aminopyrimidine derivatives efficiently (Scheme 1).11 In this
paper, we describe such a TfOH-mediated amidation, allowing the
* Corresponding author. School of Pharmaceutical Science and Technology, Key
Laboratory for Modern Drug Delivery & High-Efficiency, Tianjin University, Tianjin,
300072, PR China.
facile and efficient synthesis of various
a-acylaminoenamides. And
** Corresponding author. Key Laboratory of Marine Drugs, Chinese Ministry of
Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan
Road, Qingdao, PR China.
E-mail addresses: chenping8315@126.com (P. Chen), yutang@tju.edu.cn
(Y. Tang).
the -acylaminoenamide reacted with nitriles or alkynes to further
generate highly substituted pyridine, 4-aminopyrimidine or iso-
quinoline cores.
a
http://dx.doi.org/10.1016/j.tet.2017.03.060
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Please cite this article in press as: Wang W-S, et al., Regioselective TfOH-mediated hydroamidation of ynamides with nitriles, Tetrahedron
(2017), http://dx.doi.org/10.1016/j.tet.2017.03.060

2
W.-S. Wang et al. / Tetrahedron xxx (2017) 1e9
such as methyl, methoxyl and trifluoromethyl) at the R1 position
were well tolerated, which afforded the desired products 2bee in
66e92% yields. Notably, when ynamide 1e was employed, the re-
action delivered the desired product as a Z/E isomer mixture with a
ratio of 1:2.6. The reaction still performed nicely when the yna-
mides 1feh containing fluoro, chloro and bromo groups to provide
the products in yields of 61e87%. Gratifyingly, the ynamides con-
taining ortho or meta-substituents (1i and 1j) of the phenyl group
were well tolerated, which converted to the corresponding target
products in fair to good yields. The ynamides 1kem (with different
substituents of the oxazolidinone groups) fruitfully delivered the
corresponding target products 2kem in good yields. We also
investigated the reactivity of ynamide substituted by alkyl chain at
the R1 position. In this case 2n was isolated in 71% yield and as Z/E
isomers with a ratio of 1:1. Among the oxazolidinone groups
evaluated, the reactions were also found to be compatible with
tosyl (2oeq) or mesyl (2r) as electron withdrawing group, and the
latter being inferior in terms of yields. Table 2 indicated that oxa-
zolidinone groups remain as the preferred protecting groups over
tosyl or mesyl because of the satisfactory yields. This phenomenon
could be attributed to a portion of the keteniminium ions protected
by tosyl or mesyl underwent hydrolysis to deliver the byproducts.
In addition, to further test the efficiency of the TfOH-mediated
reaction and push it to its limits, we next investigated the possi-
bility of ynamide 1a reacted with other nitriles in dichloromethane
(Scheme 2). In consideration of the decrease of concentration of
nitriles, we decided to raise the amount of TfOH to 2.0 equivalents
to perform the reaction. Firstly, we focused our attention on alkyl
nitriles. Not surprisingly, the valeronitrile and 2-(4-
methoxyphenyl) acetonitrile performed excellently to afford the
desired products 3a and 3b in 91% and 83% yields, respectively.
Interestingly, when benzonitrile, 4-chlorobenzonitrile or cinna-
monitrile were employed, phenylacetylamides 4aec were isolated
in the yields of 28%e47%.
Scheme 1. TfOH-mediated Intermolecular Reaction of Ynamides with Nitriles.
2. Results and discussion
In our previous work, N-vinyl amides could be isolated when the
ynamides reacted with acetonitrile in the presence of H2O. Based
on this result, we began our studies by utilizing 1a as model ma-
terial to optimize the reaction conditions. At the onset, the desired
product 2a was obtained in 86% yield when treated with 1.0
equivalent of TfOH in acetonitrile (Table 1, entry 1). Among the
TfOH evaluated, different intensity of acids were also tested, but the
latter were not superior in terms of yield and E/Z selectivity (entries
2e7). We also screened some other solvents, the reaction only
proceeded in dichloromethane, and we separated the target
product in 69% yield (entry 8). Attempts to change the amount of
the acid or temperature, resulted in the decrease of the yields
(entries 12e16).
Having the optimized reaction conditions in hand, we then
explored the substrates scope and limitations of the reaction
(Table 2). We initially focused on the reactivity of ynamides 1aen
bearing oxazolidinone as an electron withdrawing group. Besides
ynamide 1a, compounds 1bee with a phenyl group bearing para-
substituents (electron donating groups or electron withdrawing,
Table 1
Optimization Studies.a
Further chemical transformation of the as synthesized N- vinyl
amides 2a or 2h were also explored, as depicted in Scheme 3. For
example, the reaction of amides with acetonitrile or valeronitrile in
dichloromethane could furnish the corresponding pyrimidine de-
rivative products in moderate yields. Phenylacetylene was also
tested in the same conditions, afforded the pyridine derivatives 6a
in 33% yield or 6b in 35% yield.12 And when dichloroethane was
used as solvent, the amides could generate the isoquinoline de-
rivatives 7a in 30% yield or 7b in 31% yield at 80 ꢀC.
entry
acid
solvent
T (ꢀC)
yieldb (%)
1
2
3
4
5
6
TfOH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH2Cl2
THF
toluene
dioxane
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
ꢁ40
15
86
80c
85e
0
0
0
31
69
0
0
0
75
46
21
25
81
Tf2NH
2.1. Proposed mechanism
d
HPF6
TsOH
CSA
HCl
We also proposed a plausible mechanism for the formation of 2
(3) and 4. As depicted in Scheme 4, ynamide 1a was activated by Hþ
in the presence of TfOH to produce keteniminium ion I.13 Nitriles
attacked keteniminium ion I to form intermediate II. Then inter-
mediate II was attacked by H2O to produce intermediate III. 2(3)
were subsequently obtained through tautomerization. With aryl-
nitriles (R3 ¼ Aryl) as the reactants, intermediate III was more
stable due to the conjugated structure and afforded the imine IV in
the presence of TfOH. Then H2O attacked the imine IV, forming the
hydroxyl-substituted amides V. Finally, the departure of 2-
oxazolidone of V gave the products 4.
7
BF3$Et2O
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
8f
9f
10f
11f
12
13
14
15g
16h
ꢁ20
0
20
ꢁ40
ꢁ40
a
Unless noted otherwise, all reactions were conducted using 0.15 mmol of
ynamide 1a in the presence of acid (1.0 equiv) and H2O (2.0 equiv) under N2 at-
mosphere for 0.5 h at ꢁ40 ꢀC.
3. Conclusion
b
Isolated yields.
c
Z:E ¼ 3:1.
In summary, we had demonstrated an efficient, facile, and
flexible strategy for the preparation of synthetically useful a-acy-
laminoenamides through TfOH-mediated amidation of ynamides
with nitriles. This reactivity could be exploited for other notable
features, providing a straightforward, modular access to desired
d
HPF6 (wt% 60e65% solution in water).
e
Z:E ¼ 3:1.
f
CH3CN (1.2 equiv) was added.
TfOH (0.2 equiv).
TfOH (2.0 equiv).
g
h
Please cite this article in press as: Wang W-S, et al., Regioselective TfOH-mediated hydroamidation of ynamides with nitriles, Tetrahedron
(2017), http://dx.doi.org/10.1016/j.tet.2017.03.060

W.-S. Wang et al. / Tetrahedron xxx (2017) 1e9
3
Table 2
Scope and limitations of ynamides reacted with Acetonitrile.a,b
conditions.
4. Experimental section
4.1. General information
All reactions were performed in standard glassware. Solvents
were distilled prior to use. All commercially available reagents were
used as purchased without further purification. 1H and 13C NMR
spectra were recorded on 500 MHz or 600 MHz spectrometers
using CDCl3 or DMSOed6 as solvent unless otherwise noted.
Chemical-shift values were given in ppm and referenced to the
internal standard TMS (tetramethylsilane). The peak patterns are
indicated as follows: s, singlet; d, doublet; t, triplet; q, quadruplet;
m, multiplet; dd, doublet of doublets, and br s, broad singlet. The
coupling constants (J) are reported in hertz (Hz). Melting points
were determined with a micromelting point apparatus without
corrections. Low-resolution mass spectra were obtained using LC/
MSD. High-resolution mass spectrometry (HRMS) was obtained on
a Q-TOF microspectrometer. Flash column chromatography was
aReaction condition: ynamide 1a (0.15 mmol), TfOH (2.0 equiv), H2O (2.0
equiv), R3CN (2.0 equiv), CH2Cl2 (2 mL), and under N2 atmosphere for 0.5 or
3 h.
bIsolated yields.
Scheme 2. Amidation of other Nitriles with Ynamide 1a.a,b
products in a single operation and with a high atom economy. a-
Acylaminoenamides could be converted to highly substituted pyr-
idine, 4-aminopyrimidine and isoquinoline cores under mild
Please cite this article in press as: Wang W-S, et al., Regioselective TfOH-mediated hydroamidation of ynamides with nitriles, Tetrahedron
(2017), http://dx.doi.org/10.1016/j.tet.2017.03.060

4
W.-S. Wang et al. / Tetrahedron xxx (2017) 1e9
methyl-N-phenylbenzenesulfonamide (1.2 g, 5.0 mmol, 5.0 equiv)
and Na2CO3 (212 mg, 2.0 mmol, 2.0 equiv) were combined. The
reaction flask was purged with oxygen gas for 15 min. A solution of
pyridine (2.0 mmol) in 5.0 mL dry toluene was added to the reac-
tion flask via a syringe. A balloon filled with oxygen gas was con-
nected to the reaction flask via a needle. The flask was placed in an
oil-bath and heated to 70 ꢀC. A solution of 3, 3-dimethylbut-1-yne
(82 mg, 1.0 mmol, 1.0 equiv) in 5.0 mL dry toluene was added to the
flask over 4 h by using a syringe pump. After the addition of 3, 3-
dimethylbut-1-yne/toluene solution, the reaction mixture was
allowed to stir at 70 ꢀC for another 4 h and then cooled to room
temperature. After the crude mixture was concentrated under
vacuum, the reaction mixture was purified by flash chromatog-
raphy on silica gel [gradient eluent: EtOAc/petroleum ether] to
yield the ynamides.
aIsolated yields.
bReaction condition: 2a or 2h (0.1 mmol), Tf2O (2.0 equiv), 2-Cl-pyridine
(1.2 equiv), CH2Cl2 (2 mL) and under N2 atmosphere at -78 to 45 oC.
cReaction condition: 2a or 2h (0.1 mmol), Tf2O (2.0 equiv), 2-Cl-pyridine
(1.2 equiv), DCE (2 mL) and under N2 atmosphere at -30 to 80 oC.
4.2.1. 2-(phenylethynyl) isoxazolidin-3-one (1a)
Following the general procedure 1: white solid, mp: 84 e 85 ꢀC,
62%; Rf ¼ 0.6 (30% EtOAc/Petroleum Ether); 1H NMR (600 MHz,
CDCl3)
d
7.45 e 7.43 (m, 2H), 7.31 e 7.30 (m, 3H), 4.48 (t, J ¼ 8.0 Hz,
2H), 4.01 (t, J ¼ 8.0 Hz, 2H); 13C NMR (150 MHz, CDCl3)
d 155.90,
Scheme 3. Further Transformation of
a
-Acylaminoenamides 2a and 2h.a
131.58, 128.31, 128.22, 122.16, 78.96, 71.21, 63.05, 47.06; mass
spectrum (ESI): m/e (% relative intensity) 210.1 (100) (MþNa)þ.
4.2.2. 3-(P-tolylethynyl) oxazolidin-2-one (1b)
Following the general procedure1: white solid, mp: 124 e
126 ꢀC, 52%; Rf ¼ 0.3 (20% EtOAc/Petroleum Ether); 1H NMR
(600 MHz, CDCl3)
d
7.34 (d, J ¼ 7.8 Hz, 2H), 7.11 (d, J ¼ 7.8 Hz, 2H),
4.48 (t, J ¼ 8.4 Hz, 2H), 4.00 (t, J ¼ 8.4 Hz, 2H), 2.34 (s, 3H); 13C NMR
(150 MHz, CDCl3)
d 155.97, 138.42, 131.63, 129.07, 118.99, 78.24,
71.22, 63.00, 47.10, 21.48; mass spectrum (ESI): m/e (% relative in-
tensity) 224.1 (100) (MþNa)þ.
4.2.3. 3-((4-methoxyphenyl)ethynyl)oxazolidin-2-one (1c)
Following the general procedure 1: white solid, mp: 99 e 101 ꢀC,
51%; Rf ¼ 0.7 (30% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
CDCl3)
d
7.39 (d, J ¼ 8.5 Hz, 2H),
d
6.84 (d, J ¼ 8.5 Hz, 2H), 4.48 (t,
Scheme 4. Proposed Reaction Mechanism.
J ¼ 8.0 Hz, 2H), 4.00 (t, J ¼ 8.0 Hz, 2H), 3.82 (s, 3H); 13C NMR
(125 MHz, CDCl3)
d 159.71, 156.03, 133.47, 114.05, 113.93, 77.56,
70.92, 62.95, 55.28, 47.12; mass spectrum (ESI): m/e (% relative
performed over silica gel 200e300 mesh.
intensity) 240.1 (100) (MþNa)þ.
4.2. General procedure 1 for the synthesis of ynamides (1ae1d,
1fe1m, 1o, 1p, 1r)10c and procedure 2 for (1e, 1n, 1q)14
4.2.4. 2-((4-(trifluoromethyl) phenyl) ethynyl) isoxazolidin-3-one
(1d)
Following the general procedure 1: white solid, mp: 96 e 97 ꢀC,
45%; Rf ¼ 0.4 (30% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
Procedure 1: To a solution of alkyne (9.80 mmol, 1.0 equiv) in
acetone (10 mL) was added NBS (10.78 mmol, 1.1 equiv) and AgNO3
(0.98 mmol, 0.1 equiv). The resulting solution was stirred under
nitrogen at room temperature for 4 h. After removing excess
acetone the reaction was quenched with water and extracted with
petroleum ether three times, dried over MgSO4, and concentrated
under reduced pressure. The residue was eluted through a short
silica column (petroleum ether) to obtain the bromoalkyne.
To a dried flask was added 2-oxazolidone (4.8 mmol, 1.2 equiv),
CuSO4$5H2O (100 mg, 0.4 mmol, 0.1 equiv), 1, 10-phenanthroline
(144 mg, 0.8 mmol, 0.2 equiv) and K2CO3 (1.38 g, 10.0 mmol, 2.5
equiv), bromoalkyne (4.0 mmol, 1.0 equiv) and this mixture was
subsequently treated with anhydrous toluene (10 mL). The flask
was charged with nitrogen, and the solution was heated at 80 ꢀC
overnight. After completion, the crude reaction mixture was cooled
to room temperature, filtered and concentrated in vacuo. Purifica-
tion of the crude residue using silica gel flash column chromatog-
raphy yielded the pure ynamides.
CDCl3)
d
7.57 (d, J ¼ 8.5 Hz, 2H), 7.53 (d, J ¼ 8.5 Hz, 2H), 4.52 (t,
J ¼ 8.0 Hz, 2H), 4.05 (t, J ¼ 8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3)
d
155.59, 131.34, 130.10e129.32 (q,
J
¼
32.5 Hz), 126.17,
125.28e125.29 (q, J ¼ 3.75 Hz), 124.97, 81.31, 70.45, 63.11, 46.89; 19
F
NMR (470 MHz, CDCl3)
d e62.82 (s, 3F); mass spectrum (ESI): m/e
(% relative intensity) 278.0 (100) (MþNa)þ.
4.2.5. 3-((4-nitrophenyl)ethynyl)oxazolidin-2-one (1e)
Following the general procedure 2: yellow solid, mp:
156e158 ꢀC, 43%; Rf ¼ 0.7 (30% EtOAc/Petroleum Ether); 1H NMR
(500 MHz, CDCl3)
d
8.18 (d, J ¼ 9.0 Hz, 2H), 7.56 (d, J ¼ 9.0 Hz, 2H),
4.56e4.53 (m, 2H), 4.08e4.05 (m, 2H); 13C NMR (125 MHz, CDCl3)
155.35, 146.71, 131.45, 129.47, 123.63, 84.32, 70.59, 63.23, 46.80;
d
mass spectrum (ESI): m/e (% relative intensity) 255.0 (100)
(MþNa)þ.
4.2.6. 3-((4-fluorophenyl)ethynyl)oxazolidin-2-one (1f)
Procedure 2: In a 250 mL three-neck round-bottom flask
equipped with a stir-bar, CuCl2 (27.0 mg, 0.2 mmol, 0.2 equiv), 4-
Following the general procedure 1: white solid, mp: 114e116 ꢀC,
56%; Rf ¼ 0.3 (20% EtOAc/Petroleum Ether); 1H NMR (600 MHz,
Please cite this article in press as: Wang W-S, et al., Regioselective TfOH-mediated hydroamidation of ynamides with nitriles, Tetrahedron
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W.-S. Wang et al. / Tetrahedron xxx (2017) 1e9
5
CDCl3)
d
7.43e7.41 (m, 2H), 7.00 (t, J ¼ 7.8 Hz, 2H), 4.49 (t, J ¼ 7.8 Hz,
50%; Rf ¼ 0.4 (30% EtOAc/Petroleum Ether); 1H NMR (600 MHz,
2H), 4.00 (t, J ¼ 7.8 Hz, 2H); 13C NMR (150 MHz, CDCl3)
CDCl3)
d
7.47e7.39 (m, 5H), 7.26e7.21 (m, 5H), 5.14 (t, J ¼ 7.8 Hz,
163.34e161.70 (d,
J
¼
247.5 Hz), 155.92, 133.72e133.66 (d,
1H), 4.78 (t, J ¼ 8.4 Hz, 1H), 4.31 (t, J ¼ 7.8 Hz, 1H); 13C NMR
J ¼ 9.0 Hz), 118.19e118.17 (d, J ¼ 3.0 Hz), 115.68e115.54 (d,
J ¼ 22.5 Hz), 78.58, 70.16, 63.07, 47.00; mass spectrum (ESI): m/e (%
relative intensity) 228.0 (100) (MþNa)þ.
(150 MHz, CDCl3) d 155.61, 136.02, 131.48, 129.56, 129.35, 128.17,
128.09, 126.93, 122.10, 78.02, 72.84, 70.81, 62.22; mass spectrum
(ESI): m/e (% relative intensity) 286.1 (100) (MþNa)þ.
4.2.7. 3-((4-chlorophenyl)ethynyl)oxazolidin-2-one (1g)
4.2.14. (R)-3-(hex-1-yn-1-yl)-4-phenyloxazolidin-2-one (1n)
Following the general procedure 2: yellow oil, 50%; Rf ¼ 0.7(30%
Following the general procedure 1: white solid, mp: 131e132 ꢀC,
48%; Rf ¼ 0.5 (20% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
EtOAc/Petroleum Ether); 1H NMR (500 MHz, CDCl3)
d 7.46e7.39 (m,
CDCl3)
d
7.36 (d, J ¼ 8.5 Hz, 2H), 7.28 (d, J ¼ 8.5 Hz, 2H), 4.50 (t,
3H), 7.35e7.33 (m, 2H), 5.00 (dd, J ¼ 7.0 Hz, 1.5 Hz, 1H), 4.70 (t,
J ¼ 8.0 Hz, 2H), 4.01 (t, J ¼ 8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3)
J ¼ 9.0 Hz, 1H), 4.22 (dd, J ¼ 7.0 Hz, 2.0 Hz, 1H), 2.16 (t, J ¼ 7.0 Hz,
d
155.75, 134.20, 132.75, 128.64, 120.69, 79.81, 70.26, 63.07, 46.96;
2H),1.36e1.30 (m, 2H),1.22e1.14 (m, 2H), 0.77 (t, J ¼ 7.0 Hz, 3H); 13
C
mass spectrum (ESI): m/e (% relative intensity) 243.9 (100)
NMR (125 MHz, CDCl3) d 156.28, 136.38, 129.29, 129.15, 126.88,
(MþNa)þ.
72.85, 70.54, 69.03, 62.12, 30.57, 21.53, 17.95, 13.45; mass spectrum
(ESI): m/e (% relative intensity) 266.1 (100) (MþNa)þ.
4.2.8. 3-((4-bromophenyl)ethynyl)oxazolidin-2-one (1h)
Following the general procedure 1: white solid, mp: 152e153 ꢀC,
50%; Rf ¼ 0.5 (20% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
4.2.15. 4-methyl-N-phenyl-N-(phenylethynyl)benzenesulfonamide
(1o)
CDCl3)
d
7.44 (d, J ¼ 8.5 Hz, 2H), 7.30 (d, J ¼ 8.5 Hz, 2H), 4.49 (t,
Following the general procedure 1: white solid, mp: 103e105 ꢀC,
55%; Rf ¼ 0.6 (20% EtOAc/Petroleum Ether); 1H NMR (600 MHz,
J ¼ 8.0 Hz, 2H), 4.01 (t, J ¼ 8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3)
d
155.74, 132.91, 131.56, 122.36, 121.18, 80.02, 70.34, 63.10, 46.94;
CDCl3)
d
7.61 (d, J ¼ 7.0 Hz, 2H), 7.39e7.38 (m, 2H), 7.35e7.30 (m,
mass spectrum (ESI): m/e (% relative intensity) 288.0 (100)
10H), 2.44 (s, 3H); 13C NMR (150 MHz, CDCl3)
d 145.01, 138.93,
(MþNa)þ.
132.87, 131.46, 129.53, 129.12, 128.31, 128.28, 127.99, 126.31, 122.61,
82.97, 70.48, 21.76; mass spectrum (ESI): m/e (% relative intensity)
370.0 (100) (MþNa)þ;
4.2.9. 3-((2-chlorophenyl)ethynyl)oxazolidin-2-one (1i)
Following the general procedure 1: white solid, mp: 119.0 e
119.8 ꢀC, 75%; Rf ¼ 0.6 (30% EtOAc/Petroleum Ether); 1H NMR
4.2.16. N-phenyl-N-(phenylethynyl)methanesulfonamide (1p)
Following the general procedure 1: white solid, mp: 70e72 ꢀC,
43%; Rf ¼ 0.6 (20% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
(500 MHz, CDCl3)
d 7.50e7.48 (m, 1H), d 7.41e7.39 (m, 1H),
d
7.26e7.19 (m, 2H), 4.52 (t, J ¼ 8.0 Hz, 2H), 4.06 (t, J ¼ 8.0 Hz, 2H);
13C NMR (125 MHz, CDCl3)
d
155.54, 135.43, 133.00, 129.18, 129.06,
CDCl3)
d
7.80 (d, J ¼ 8.5 Hz, 2H), 7.35e7.31 (m, 7H), 7.25e7.24 (m,
126.44, 122.28, 83.83, 68.52, 63.11, 47.01; mass spectrum (ESI): m/e
5H), 4.59 (s, 2H), 2.46 (s, 3H); 13C NMR (125 MHz, CDCl3)
d 144.60,
(% relative intensity) 244.0 (100) (MþNa)þ.
134.69, 134.43, 131.10, 129.69, 128.86, 128.50, 128.31, 128.16, 127.75,
127.63, 122.80, 82.66, 71.37, 55.70, 21.65; mass spectrum (ESI): m/e
(% relative intensity) 384.0 (100) (M þ Na)þ;
4.2.10. 3-((3-chlorophenyl)ethynyl)oxazolidin-2-one (1j)
Following the general procedure 1: white solid, mp:
129.8e130.8 ꢀC, 68%; Rf ¼ 0.6 (30% EtOAc/Petroleum Ether); 1H
4.2.17. N-(3,3-dimethylbut-1-yn-1-yl)-4-methyl-N-
phenylbenzenesulf-onamide (1q)
NMR (500 MHz, CDCl3)
d 7.44e7.43 (m, 1H), 7.33e7.31 (m, 1H),
7.30e7.23 (m, 2H), 4.51 (t, J ¼ 8.0 Hz, 2H), 4.02 (t, J ¼ 8.0 Hz, 2H); 13
C
Following the general procedure 2: white solid, mp: 94e95 ꢀC,
43%; Rf ¼ 0.6 (30% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
NMR (125 MHz, CDCl3)
d 155.64, 134.12, 131.22, 129.51, 128.37,
123.95, 80.07, 70.15, 63.06, 46.92; mass spectrum (ESI): m/e (%
CDCl3)
d
7.55 (d, J ¼ 8.0 Hz, 2H), 7.33e7.24 (m, 7H), 2.44 (s, 3H), 1.24
relative intensity) 244.0 (100) (MþNa)þ.
(s, 9H); 13C NMR (125 MHz, CDCl3)
d 144.56, 139.47, 132.70, 129.14,
128.82, 128.37, 127.72, 125.92, 78.46, 73.06, 31.00, 27.51, 21.66; mass
4.2.11. (S)-4-benzyl-3-(phenylethynyl)oxazolidin-2-one (1k)
Following the general procedure 1: white solid, mp: 96e98 ꢀC,
63%; Rf ¼ 0.35 (30% EtOAc/Petroleum Ether); 1H NMR (600 MHz,
spectrum (ESI): m/e (% relative intensity) 350.1 (100) (MþNa)þ;
4.2.18. N-methyl-N-(phenylethynyl)methanesulfonamide (1r)
Following the general procedure 1: white solid, mp: 58e60 ꢀC,
61%; Rf ¼ 0.45 (30% EtOAc/Petroleum Ether); 1H NMR (600 MHz,
CDCl3)
d 7.51e7.43 (m, 2H), 7.40e7.27 (m, 6H), 7.27e7.23 (m, 2H),
4.42e4.33 (m, 2H), 4.21e4.14 (m, 1H), 3.30 (d, J ¼ 13.8 Hz, 1H),
3.06e2.98 (m, 1H); 13C NMR (150 MHz, CDCl3)
d
155.49, 134.19,
CDCl3)
d 7.42e7.41 (m, 2H), 7.31e7.30 (m, 3H), 3.30 (s, 3H), 3.13 (s,
131.67, 129.42, 129.09, 128.33, 128.29, 127.58, 122.17, 77.89, 73.32,
67.48, 58.53, 38.04; mass spectrum (ESI): m/e (% relative intensity)
300.1 (100) (MþNa)þ.
3H); 13C NMR (150 MHz, CDCl3)
d 131.54, 128.34, 128.12, 122.33,
82.98, 69.46, 39.26, 36.78; mass spectrum (ESI): m/e (% relative
intensity) 232.0 (100) (MþNa)þ.
4.2.12. (S)-4-isopropyl-3-(phenylethynyl)oxazolidin-2-one (1l)
Following the general procedure 1: white solid, mp: 83e84 ꢀC,
49%; Rf ¼ 0.6 (30% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
4.3. Experimental characterization data for 2a-2r, 3a, 3b, 4ae4c,
5a, 5b, 5c, 6a, 6b, 7a, 7b
CDCl3)
d
7.45e7.42 (m, 2H), 7.31e7.29 (m, 3H), 4.43 (t, J ¼ 8.5, 1H),
4.3.1. General procedure A for TfOH-mediated reaction of ynamides
with acetonitrile (2ae2r)
To a suspension of ynamide (0.15 mmol, 1.0 equiv) and H2O
(0.3 mmol, 2.0 equiv) in dry acetonitrile (2.00 mL) was added TfOH
4.42e4.19 (m, 1H), 4.07e4.03 (m, 1H), 2.33e2.26 (m, 1H), 1.04 (d,
J ¼ 3.5, 3H),1.03 (d, J ¼ 3.5, 3H); 13C NMR (150 MHz, CDCl3)
d
155.95,
131.47, 128.26, 128.08, 122.35, 72.32, 64.85, 62.08, 29.32, 17.25,
15.28; mass spectrum (ESI): m/e (% relative intensity) 252.0 (100)
(M þ Na)þ.
dropwise (13.0
mL, 0.15 mmol, 1.0 equiv) via a syringe pump
at ꢁ40 ꢀC under nitrogen atmosphere. The reaction was monitored
by TLC. When progress appeared to be completed after about
0.5 h at the same temperature, the saturated sodium bicarbonate
solution was added to the mixture and the resulting mixture was
4.2.13. (S)-4-phenyl-3-(phenylethynyl)oxazolidin-2-one (1m)
Following the general procedure 1: white solid, mp: 144e146 ꢀC,
Please cite this article in press as: Wang W-S, et al., Regioselective TfOH-mediated hydroamidation of ynamides with nitriles, Tetrahedron
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6
W.-S. Wang et al. / Tetrahedron xxx (2017) 1e9
extracted with EtOAc. The organic layers were washed with sat aq
NaCl and dried over Na2SO4. Filtration and concentration of the
mixture in vacuo afforded the crude product that was purified by
flash silica gel column chromatography [gradient eluent: EtOAc/
petroleum ether] to obtain the corresponding products.
4.3.1.6. (Z)-N-(2-(4-fluorophenyl)-1-(2-oxooxazolidin-3-yl)vinyl)
acetam-ide (2f). Following the general procedure A: white solid,
mp: 47e49 ꢀC, 87%; Rf ¼ 0.2 (50% EtOAc/Petroleum Ether); NOE see
SI (S 60) 1H NMR (500 MHz, DMSOed6)
d 9.64 (s, 1H), 7.35e7.32 (m,
2H), 7.16e7.12 (m, 2H), 6.58 (s, 1H), 4.37e4.34 (m, 2H), 3.65e3.62
(m, 2H), 1.96 (s, 3H); 13C NMR (125 MHz, DMSOed6)
d
169.30,
4.3.1.1. (Z)-N-(1-(2-oxooxazolidin-3-yl)-2-phenylvinyl)acetamide
(2a). Following the general procedure A: white solid, mp:
32e33 ꢀC, 86%; Rf ¼ 0.2 (50% EtOAc/Petroleum Ether); 1H NMR
162.25e160.30 (d, J ¼ 243.75 Hz), 155.90, 131.42e131.39 (d,
J ¼ 3.75 Hz),130.04e129.98 (d, J ¼ 7.5 Hz),129.07,,115.95e115.78 (d,
J ¼ 21.25 Hz), 113.12, 63.04, 44.69, 23.89; 19F NMR (470 MHz,
(500 MHz, DMSOed6)
d
9.63 (s, 1H), 7.33e7.28 (m, 4H), 7.20e7.17
DMSOed6)
d
ꢁ115.04 (s, 1F); mass spectrum (ESI): m/e (% relative
(m, 1H), 6.58 (s, 1H), 4.34 (t, J ¼ 8.0 Hz, 2H), 3.63 (t, J ¼ 8.0 Hz, 2H),
intensity) 287.0 (100) (MþH)þ; HRMS calcd for C13H13FN2O3Naþ
1.96 (s, 3H),; 13C NMR (125 MHz, DMSOed6)
d
169.28, 155.90,
(MþNa)þ287.0802 found 287.0783.
134.91, 129.20, 129.03, 128.08, 127.24, 114.11, 63.03, 44.73, 23.93;
mass spectrum (ESI): m/e (% relative intensity) 269.0 (100)
(MþNa)þ; HRMS calcd for C13H14N2O3Naþ (MþNa)þ 269.0902,
found 269.0897.
4.3.1.7. (Z)-N-(2-(4-chlorophenyl)-1-(2-oxooxazolidin-3-yl)vinyl)
acetam-ide (2g). Following the general procedure A: white solid,
mp: 135e136 ꢀC, 76%; Rf ¼ 0.2 (30% EtOAc/Petroleum Ether); 1H
NMR (500 MHz, DMSOed6)
d
9.68 (s, 1H), 7.36 (d, J ¼ 9.0 Hz, 2H),
4. 3.1. 2. (Z)-N-(2-cyclopropyl-1-(4-methyl-N-phenyl-
phenylsulfonamido)-vinyl)acetamide (2b). Following the general
procedure A: colorless oil, 92%; Rf ¼ 0.2 (50% EtOAc/Petroleum
7.31 (d, J ¼ 9.0, Hz, 2H), 6.58 (s, 1H), 4.36 (t, J ¼ 8.0 Hz, 2H), 3.65 (t,
J ¼ 8.0 Hz, 2H),1.96 (s, 3H); 13C NMR (125 MHz, DMSOed6)
d 169.36,
155.79, 133.99, 131.45, 129.81, 129.77, 128.99, 112.71, 63.07, 44.72,
23.94; mass spectrum (ESI): m/e (% relative intensity) 302.9 (100)
(MþNa)þ; HRMS calcd for C13H13ClN2O3Naþ (MþNa)þ303.0512
found 303.0507.
Ether); 1H NMR (500 MHz, DMSOed6)
d 9.61 (s, 1H), 7.18 (d,
J ¼ 8.0 Hz, 2H), 7.13 (d, J ¼ 8.0 Hz, 2H), 6.53 (s, 1H), 4.36e4.33 (m,
2H), 3.64e3.61 (m, 2H), 2.27 (s, 3H), 1.95 (s, 3H); 13C NMR
(125 MHz, DMSOed6)
d 169.19, 155.92, 136.56, 131.95, 129.64,
128.57, 128.00, 114.22, 63.01, 44.68, 23.88, 21.21; mass spectrum
(ESI): m/e (% relative intensity) 283.0 (100) (MþNa)þ; HRMS calcd
for C14H16N2O3Naþ (MþNa)þ 283.1059, found 283.1054.
4.3.1.8. (Z)-N-(2-(4-bromophenyl)-1-(2-oxooxazolidin-3-yl)vinyl)
acetam-ide (2h). Following the general procedure A: white solid,
mp: 135e137 ꢀC, 61%; Rf ¼ 0.2 (30% EtOAc/Petroleum Ether); 1H
NMR (500 MHz, DMSOed6)
d
9.68 (s,1H), 7.5 (d, J ¼ 8.5 Hz, 2H), 7.24
4.3.1.3. (Z)-N-(2-(4-methoxyphenyl)-1-(2-oxooxazolidin-3-yl)vinyl)
aceta-mide (2c). Following the general procedure A: white solid,
mp: 111e113 ꢀC, 66%; Rf ¼ 0.2 (30% EtOAc/Petroleum Ether); 1H
(d, J ¼ 8.5, Hz, 2H), 6.56 (s, 1H), 4.36 (t, J ¼ 8.0 Hz, 2H), 3.65 (t,
J ¼ 8.0 Hz, 2H),1.96 (s, 3H); 13C NMR (125 MHz, DMSOed6)
d 169.36,
155.77, 134.37, 131.90, 130.08, 129.87, 119.99, 112.73, 63.08, 44.73,
23.95; mass spectrum (ESI): m/e (% relative intensity) 346.9 (100)
(MþNa)þ; HRMS calcd for C13H13BrN2O3Naþ (MþNa)þ347.0007
found 347.0000.
NMR (500 MHz, DMSOed6)
d
9.57 (s, 1H), 7.24 (d, J ¼ 8.5 Hz, 2H),
6.89 (d, J ¼ 8.5 Hz, 2H), 6.50 (s, 1H), 4.35 (t, J ¼ 8.0 Hz, 2H),
d 3.74 (s,
3H), 3.62 (t, J ¼ 8.0 Hz, 2H), 1.94 (s, 3H); 13C NMR (125 MHz,
DMSOed6)
d 169.10, 158.57, 155.98, 129.40, 127.58, 127.13, 114.52,
114.27, 63.00, 55.49, 44.63, 23.84; mass spectrum (ESI): m/e (%
4.3.1.9. N-(2-(2-chlorophenyl)-1-(2-oxooxazolidin-3-yl)vinyl)acet-
amide (2i). Following the general procedure A: colorless oil, 67%;
Rf ¼ 0.3 (30% EtOAc/Petroleum Ether); NOE see SI (S 68) (Z) 1H NMR
relative intensity) 299.1 (100) (MþNa)þ; HRMS calcd for
C
14H16N2O4Naþ (MþNa)þ299.1008 found 299.1003.
(500 MHz, DMSOed6)
d 9.75 (s, 1H), 7.45e7.42 (m, 2H), 7.30e7.27
4.3.1.4. (Z)-N-(2-(4-ethylphenyl)-1-(2-oxooxazolidin-3-yl)vinyl)
acetam-ide (2d). Following the general procedure A: white solid,
mp: 99e102 ꢀC, 83%; Rf ¼ 0.3 (50% EtOAc/Petroleum Ether); 1H
(m, 1H), 7.25e7.21 (m, 1H), 6.77 (s, 1H), 3.60 (t, J ¼ 8.0 Hz, 2H), 3.44
(t, J ¼ 8.0 Hz, 2H), 1.97 (s, 3H); 13C NMR (125 MHz, DMSOed6)
d
169.51, 154.99, 133.38, 132.60, 131.03, 129.76, 129.06, 128.85,
NMR (500 MHz, DMSOed6)
d
9.77 (s, 1H), 7.65 (d, J ¼ 8.5 Hz, 2H),
127.73, 109.67, 64.58, 45.04, 22.91; (E) 1H NMR (500 MHz,
DMSOed6) 9.66 (s, 1H), 7.50e7.48 (m, 1H), 7.45e7.42 (m, 1H),
7.51 (d, J ¼ 8.5 Hz, 2H), 6.68 (s, 1H), 4.40e4.37 (m, 2H), 3.70e3.67
d
(m, 2H), 1.99 (s, 3H); 13C NMR (125 MHz, DMSOed6)
d
169.53,
7.31e7.27 (m, 1H), 7.25e7.21 (m, 1H), 6.30 (s, 1H), 4.32 (t, J ¼ 8.0 Hz,
155.69, 139.55, 131.16, 128.58, 127.47e126.71 (q, J ¼ 31.25 Hz),
2H), 3.82 (t, J ¼ 8.0 Hz, 2H), 1.90 (s, 3H); 13C NMR (125 MHz,
125.83e125.74 (q, J ¼ 3.75 Hz), 123.65, 112.16, 63.11, 44.80, 23.99;
DMSOed6)
d 170.08, 155.63, 133.48, 132.69, 131.43, 129.70, 129.52,
19F NMR (470 MHz, DMSOed6)
d
ꢁ61.00 (s, 3F); mass spectrum
128.75, 127.49, 109.25, 63.00, 45.48, 24.04; mass spectrum (ESI): m/
(ESI): m/e (% relative intensity) 337.0 (100) (MþNa)þ; HRMS calcd
for C14H13F3N2O3Naþ (MþNa)þ 337.0776, found 337.0770.
e (% relative intensity) 303.0 (100) (MþNa)þ; HRMS calcd for
C
13H13ClN2O3Naþ (MþNa)þ303.0512 found 303.0511.
4.3.1.5. N-(2-(4-bromophenyl)-1-(2-oxooxazolidin-3-yl)vinyl)acet-
amide (2e). Following the general procedure A: yellow solid, mp:
211e213 ꢀC, 71%; Rf ¼ 0.3 (30% EtOAc/Petroleum Ether); NOE see SI
4.3.1.10. (Z)-N-(2-(3-chlorophenyl)-1-(2-oxooxazolidin-3-yl)vinyl)
acetam-ide(2j). Following the general procedure A: colorless oil,
81%; Rf ¼ 0.3 (50% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
(S 58) (E) 1H NMR (500 MHz, DMSOed6)
d
9.85 (s, 1H), 8.16 (d,
DMSOed6) d 9.71 (s, 1H), 7.35e7.30 (m, 2H), 7.28e7.24 (m, 2H), 6.58
J ¼ 8.5 Hz, 2H), 7.60 (d, J ¼ 8.5, Hz, 2H), 6.26 (s, 1H), 4.34 (t,
(s,1H), 4.36 (t, J ¼ 8.0 Hz, 2H), 3.67 (t, J ¼ 7.5 Hz, 2H),1.97 (s, 3H); 13
C
J ¼ 8.0 Hz, 2H), 3.86 (t, J ¼ 8.0 Hz, 2H), 1.99 (s, 3H); 13C NMR
NMR (125 MHz, DMSOed6)
d 169.42, 155.72, 137.39, 133.61, 130.81,
(125 MHz, DMSOed6)
d
169.86, 154.67, 145.50, 143.13, 133.02,
130.37, 127.73, 126.90, 126.44, 112.43, 63.12, 44.78, 23.96; mass
128.99, 124.04, 110.40, 62.14, 45.63, 23.23; (Z) 1H NMR (500 MHz,
DMSOed6)
9.85 (s, 1H), 8.15 (d, J ¼ 9.0 Hz, 2H), 7.54 (d, J ¼ 9.0, Hz,
2H), 6.71 (s, 1H), 4.42 (t, J ¼ 8.0 Hz, 2H), 3.72 (t, J ¼ 8.0 Hz, 2H), 2.00
(s, 3H); 13C NMR (125 MHz, DMSOed6)
169.70, 155.54, 145.71,
spectrum (ESI): m/e (% relative intensity) 303.0 (100) (MþNa)þ;
d
HRMS calcd for
303.0514.
C
13H13N2O3ClNaþ (MþNa)þ 303.0512, found
d
142.76, 132.36, 128.88, 124.25, 111.41, 63.18, 44.84, 24.07; mass
spectrum (ESI): m/e (% relative intensity) 314.0 (100) (MþNa)þ;
HRMS calcd for C13H13N3O5Naþ (MþNa)þ314.0753 found 314.0747.
4.3.1.11. (Z)-N-(1-(4-benzyl-2-oxooxazolidin-3-yl)-2-phenylvinyl)
acetam-ide (2k). Following the general procedure A: colorless oil,
80%; Rf ¼ 0.3 (50% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
Please cite this article in press as: Wang W-S, et al., Regioselective TfOH-mediated hydroamidation of ynamides with nitriles, Tetrahedron
(2017), http://dx.doi.org/10.1016/j.tet.2017.03.060

W.-S. Wang et al. / Tetrahedron xxx (2017) 1e9
7
DMSOed6)
d
9.58 (s, 1H), 7.35e7.31 (m, 4H), 7.24e7.20 (m, 4H), 7.02
4.3.1.16. (Z)-N-(1-(N-benzyl-4-methylphenylsulfonamido)-2-
phenylvinyl)-acetamide (2p). Following the general procedure A:
white solid, mp: 138e140 ꢀC, 66%; Rf ¼ 0.2 (10% EtOAc/Petroleum
(d, J ¼ 6.0 Hz, 2H), 6.78 (s, 1H), 4.27 (t, J ¼ 8.0 Hz, 1H), 4.15 (t,
J ¼ 8.0 Hz,1H), 4.08e4.05 (m,1H), 2.90e2.86 (m,1H), 2.72e2.66 (m,
1H), 2.00 (s, 3H); 13C NMR (125 MHz, DMSOed6)
d
169.28, 155.71,
Ether); 1H NMR (500 MHz, DMSOed6)
d 8.73 (s, 1H), 7.66 (d,
136.42, 135.09, 129.16, 129.06, 129.00, 128.93, 128.37, 127.47, 127.32,
127.18, 68.30, 56.90, 38.44, 24.06; mass spectrum (ESI): m/e (%
relative intensity) 359.0 (100) (MþNa)þ; HRMS calcd for
J ¼ 8.0 Hz, 2H), 7.37 (d, J ¼ 8.0 Hz, 2H), 7.12e7.06 (m, 10H), 6.57 (s,
1H), 4.47 (s, 2H), 2.40 (s, 3H), 1.83 (s, 3H); 13C NMR (125 MHz,
DMSOed6)
d 169.13, 144.08, 136.71, 135.09, 134.32, 130.07, 130.00,
C
20H20N2O3Naþ (MþNa)þ 359.1372, found 359.1366.
128.61, 128.24, 128.10, 128.06, 127.53, 127.34, 122.75, 52.04, 23.80,
21.51; mass spectrum (ESI): m/e (% relative intensity) 443.1 (100)
(MþNa)þ; HRMS calcd for C24H24N2O3SNaþ (MþNa)þ 443.1405,
found 443.1401.
4.3.1.12. (S,Z)-N-(1-(4-isopropyl-2-oxooxazolidin-3-yl)-2-
phenylvinyl)ace-tamide(2l). Following the general procedure A:
colorless oil, 85%; Rf ¼ 0.4 (50% EtOAc/Petroleum Ether); 1H NMR
4. 3.1.17. (Z)-N -(3, 3-dimethyl-1-(4-methyl-N-phenyl-
phenylsulfonamido)-but-1-en-1-yl)acetamide (2q). Following the
general procedure A: white solid, mp: 157e159 ꢀC, 78%; Rf ¼ 0.25
(500 MHz, DMSOed6)
d 9.57 (s, 1H), 7.30e7.20 (m, 4H), 7.20e7.17
(m, 1H), 6.69 (s, 1H), 4.33 (t, J ¼ 8.5 Hz, 1H), 4.07 (t, J ¼ 8.5 Hz, 1H),
3.77e3.73 (m, 1H), 1.97 (s, 3H), 1.75e1.68 (m, 1H), 0.75 (d, J ¼ 7.0 Hz,
3H), 0.64 (d, J ¼ 7.0 Hz, 3H),; 13C NMR (125 MHz, DMSOed6)
(30% EtOAc/Petroleum Ether); 1H NMR (500 MHz, DMSOed6)
d 8.66
(s, 1H), 7.59 (d, J ¼ 8.0 Hz, 2H), 7.50 (d, J ¼ 8.0 Hz, 2H), 7.34 (d,
J ¼ 8.0 Hz, 2H), 7.31e7.28 (m, 2H), 7.12e7.10 (m, 1H), 5.74 (s, 1H),
2.34 (s, 3H),1.87 (s, 3H), 0.96 (s, 9H); 13C NMR (125 MHz, DMSOed6)
d
169.42, 156.80, 135.09, 128.83, 128.67, 127.37, 115.88, 65.55, 60.84,
30.57, 24.05, 18.65, 17.04; mass spectrum (ESI): m/e (% relative in-
tensity)311.1 (100) (MþNa)þ; HRMS calcd for C16H20N2O3Naþ
(MþNa)þ 311.1372, found 311.1367.
d
168.79, 144.33, 141.21, 136.58, 135.84, 129.98, 129.25, 128.11,
126.17, 125.20, 122.35, 32.58, 30.01, 23.72, 21.43; mass spectrum
(ESI): m/e (% relative intensity) 409.2 (100) (MþNa)þ; HRMS calcd
for C21H26N2O3SNaþ (MþNa)þ 409.1556, found 409.1540.
4.3.1.13. (R,Z)-N-(1-(2-oxo-4-phenyloxazolidin-3-yl)-2-phenylvinyl)
aceta-mide (2m). Following the general procedure A: colorless oil,
73%; Rf ¼ 0.2 (20% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
4.3.1.18. (Z)-N-(1-(N-methylmethylsulfonamido)-2-phenylvinyl)acet-
amide (2r). Following the general procedure A: white solid, mp:
111e113 ꢀC, 41%; Rf ¼ 0.2 (30% EtOAc/Petroleum Ether); 1H NMR
DMSOed6)
d
9.54 (s, 1H), 7.31 (t, J ¼ 7.5 Hz, 2H), 7.26e7.18 (m, 8H),
6.45 (s, 1H), 4.94e4.90 (m, 1H), 4.71e4.67 (m, 1H), 4.23e4.19 (m,
1H), 1.94 (s, 3H); 13C NMR (125 MHz, DMSOed6)
d
169.28, 155.81,
(500 MHz, DMSOed6)
d
9.54 (s, 1H), 7.47 (d, J ¼ 8.0 Hz, 2H), 7.34 (t,
136.59, 134.90, 129.11, 128.92, 128.76, 128.52, 128.37, 127.74, 127.24,
115.04, 70.02, 60.25, 23.86; mass spectrum (ESI): m/e (% relative
intensity) 361.0 (100) (MþK)þ; HRMS calcd for C19H18N2O3Naþ
(MþNa)þ 345.1215, found 345.1212.
J ¼ 8.0 Hz, 2H), 7.24 (t, J ¼ 7.5 Hz, 1H), 6.51 (s, 1H), 2.97 (s, 3H), 2.90
(s, 3H),1.99 (s, 3H).; 13C NMR (125 MHz, DMSOed6)
d
169.78,134.51,
131.76, 128.94, 128.46, 127.76, 118.54, 39.76, 36.21, 23.69; mass
spectrum (ESI): m/e (% relative intensity) 291.1 (100) (MþNa)þ;
HRMS calcd for
291.0772.
C
12H16N2O3SNaþ (MþNa)þ 291.0779, found
4.3.1.14. (R)-N-(1-(2-oxo-4-phenyloxazolidin-3-yl)hex-1-en-1-yl)
acetam-ide (2n). Following the general procedure A: NOE see SI (S
80) (Z): colorless oil, 35%; Rf ¼ 0.3 (30% EtOAc/Petroleum Ether); 1H
4.3.2. General procedure B for TfOH-mediated amidation of ynamides
with other nitriles (3a, 3b)
To a stirring suspension of ynamide (0.15 mmol, 1.0 equiv), ni-
triles (0.3 mmol, 2.0 equiv) and H2O (0.3 mmol, 2.0 equiv) in dry
NMR (500 MHz, DMSOed6)
d 9.03 (s, 1H), 7.37e7.33 (m, 5H),
5.27e5.24 (m,1H), 4.94e4.90 (m,1H), 4.68e4.64 (m, 1H), 4.23e4.17
(m, 1H), 1.95e1.87 (m, 1H), 1.86 (s, 3H), 1.84e1.80 (m, 1H), 1.23e1.13
(m, 4H), 0.80 (t, J ¼ 6.0 Hz, 3H); 13C NMR (125 MHz, DMSOed6)
dichloromethane (2.00 mL) was added TfOH dropwise (26.0
mL,
0.3 mmol) via a syringe pump at ꢁ40 ꢀC under nitrogen atmo-
sphere. The reaction was monitored by TLC. When progress
appeared to be completed after about 0.5 h at the same tempera-
ture, the saturated sodium bicarbonate solution was added to the
mixture and the resulting mixture was extracted with EtOAc. The
organic layers were washed with sat aq NaCl and dried over
Na2SO4. Filtration and concentration of the mixture in vacuo
afforded the crude product that was purified by flash silica gel
column chromatography [gradient eluent: EtOAc/petroleum ether]
to obtain corresponding products.
d
168.86,155.50,138.00,129.06,129.01,128.20,126.47,117.55, 69.66,
59.48, 31.39, 26.33, 23.45, 22.34, 14.27; mass spectrum (ESI): m/e (%
relative intensity) 325.2 (100) (MþNa)þ; HRMS calcd for
C
17H22N2O3Naþ (MþNa)þ325.1528, found 325.1510. (E) colorless
oil, 36%; Rf ¼ 0.2 (30% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
DMSOed6)
d
9.20 (s, 1H), 7.39e7.30 (m, 5H), 4.99 (t, J ¼ 8.0 Hz, 1H),
4.89e4.86 (m, 1H), 4.63e4.60 (m, 1H), 3.97e3.93 (m, 1H), 1.86 (s,
3H),1.85e1.82 (m, 2H),1.16e1.07 (m, 4H), 0.75 (t, J ¼ 7.5 Hz, 3H); 13
C
NMR (125 MHz, DMSOed6)
d 168.83, 156.50, 139.18, 131.96, 129.14,
128.70, 127.66, 127.01, 69.80, 59.82, 31.13, 25.99, 22.97, 21.73, 14.16;
mass spectrum (ESI): m/e (% relative intensity) 325.1 (100)
(MþNa)þ; HRMS calcd for C17H22N2O3Naþ (MþNa)þ325.1528,
found 325.1512.
4.3.2.1. (Z)-N-(1-(2-oxooxazolidin-3-yl)-2-phenylvinyl)pentanami-
de(3a). Following the general procedure B: colorless oil, 91%;
Rf ¼ 0.6 (50% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
DMSOed6) d 9.59 (s, 1H), 7.33e7.29 (m, 4H), 7.21e7.18 (m, 1H), 6.57
4.3.1.15. (Z)-N-(1-(4-methyl-N-phenylphenylsulfonamido)-2-
phenylvinyl)-acetamide (2o). Following the general procedure A:
white solid, mp: 163e164 ꢀC, 50%; Rf ¼ 0.2 (30% EtOAc/Petroleum
(s, 1H), 4.35 (t, J ¼ 8.0 Hz, 2H), 3.64 (t, J ¼ 8.0 Hz, 2H), 2.21 (t,
J ¼ 7.5 Hz, 2H), 1.55e1.49 (m, 2H), 1.35e1.25 (m, 2H), 0.88 (t,
J ¼ 7.5 Hz, 3H); 13C NMR (125 MHz, DMSOed6)
d 172.27, 155.86,
Ether); 1H NMR (500 MHz, DMSOed6)
d
9.17 (s, 1H), 7.53 (d,
134.95, 129.20,129.03, 128.06, 127.21, 114.06, 63.02, 44.73, 36.12,
27.56, 22.22, 14.18; mass spectrum (ESI): m/e (% relative intensity)
311.2 (100) (MþNa)þ; HRMS calcd for C16H20N2O3Naþ (MþNa)þ
311.1366, found 311.1348.
J ¼ 8.0 Hz, 2H), 7.36e7.30 (m, 6H), 7.24e7.08 (m, 6H), 6.77 (s, 1H),
2.34 (s, 3H), 1.96 (s, 3H); 13C NMR (125 MHz, DMSOed6)
d
169.31,
144.47, 139.97, 136.98, 134.09, 130.11, 129.97, 129.17, 128.71, 128.61,
128.02, 127.81, 126.35, 124.39, 121.60, 24.01, 21.53; mass spectrum
(ESI): m/e (% relative intensity) 429.2 (100) (MþNa)þ; HRMS calcd
for C23H22N2O3SNaþ (MþNa)þ 429.1243, found 429.1224.
4.3.2.2. (Z)-2-(4-methoxyphenyl)-N-(1-(2-oxooxazolidin-3-yl)-2-
phenylvi-nyl) acetamide (3b). Following the general procedure B:
Please cite this article in press as: Wang W-S, et al., Regioselective TfOH-mediated hydroamidation of ynamides with nitriles, Tetrahedron
(2017), http://dx.doi.org/10.1016/j.tet.2017.03.060

8
W.-S. Wang et al. / Tetrahedron xxx (2017) 1e9
white solid, mp: 147e148 ꢀC, 83%; Rf ¼ 0.2 (30% EtOAc/Petroleum
solution was allowed to warm to ambient temperature for 5 min
before the reaction vessel was placed into a preheated oil bath at
45 ꢀC and maintained at that temperature. After 2 h, the reaction
mixture was allowed to cool to ambient temperature and aqueous
sodium hydroxide solution (1 mL, 1 N) was introduced to neutralize
the trifluoromethanesulfonate salts. Ethyl acetate (5 mL) was added
to dilute the mixture and the layers were separated. The organic
layer was washed with brine (2 mL), was dried over anhydrous
sodium sulfate, and was filtered. The volatiles were removed under
reduced pressure and the residue was purified by flash column
chromatography to give the product.
Ether); 1H NMR (500 MHz, DMSOed6)
d 9.83 (s, 1H), 7.33e7.28 (m,
4H), 7.22e7.18 (m, 3H), 6.88 (d, J ¼ 8.6 Hz, 2H), 6.60 (s, 1H),
4.37e4.34 (t, J ¼ 8.0 Hz, 2H), 3.73 (s, 3H), 3.63 (t, J ¼ 8.0 Hz, 2H), 3.48
(s, 2H); 13C NMR (125 MHz, DMSOed6)
d 170.42, 158.50, 155.86,
134.84, 130.59, 129.09, 129.04, 128.09, 127.96, 127.30, 114.49, 114.18,
63.03, 55.49, 44.69, 42.37; mass spectrum (ESI): m/e (% relative
intensity) 375.2 (100) (MþNa)þ; HRMS calcd for C20H20N2O4Naþ
(MþNa)þ 375.1315, found 375.1295.
4.3.3. General procedure C for TfOH-mediated reaction of ynamides
with other nitriles (4ae4c)
To a stirring suspension of ynamide (0.15 mmol, 1.0 equiv), ni-
triles (0.3 mmol, 2.0 equiv) and H2O (0.3 mmol, 2.0 equiv) in dry
4.3.4.1. 3-(2,6-dimethyl-5-phenylpyrimidin-4-yl)oxazolidin-2-
one(5a). Following the general procedure D: white solid, 39%; mp:
119e121 ꢀC. Rf ¼ 0.5 (50% EtOAc/Petroleum Ether); 1H NMR
dichloromethane (2.00 mL) was added TfOH dropwise (26.0
mL,
0.3 mmol, 2.0 equiv) via a syringe pump at ꢁ40 ꢀC under nitrogen
atmosphere. The reaction was monitored by TLC. When progress
appeared to be completed after about 3 h at the same temperature,
the saturated sodium bicarbonate solution was added to the
mixture and the resulting mixture was extracted with EtOAc. The
organic layers were washed with sat aq NaCl and dried over
Na2SO4. Filtration and concentration of the mixture in vacuo
afforded the crude product that was purified by flash silica gel
column chromatography [gradient eluent: EtOAc/petroleum ether]
to obtain corresponding products.
(500 MHz, CDCl3) d7.44e7.41 (m, 2H), 7.38e7.35 (m, 1H), 7.27e7.24
(m, 2H), 4.29 (t, J ¼ 7.5 Hz, 2H), 3.93 (t, J ¼ 7.5 Hz, 2H), 2.70 (s, 3H),
2.36 (s, 3H); 13C NMR (125 MHz, CDCl3)
d
167.87, 166.26, 155.82,
154.55, 134.46, 129.29, 128.48, 128.01, 126.52, 62.59, 45.62, 25.60,
23.09; mass spectrum (ESI): m/e (% relative intensity) 292.1 (100)
(MþNa)þ; HRMS calcd for C15H15N3O2Naþ (MþNa)þ 292.1062,
found 292.1058.
4.3.4.2. 3-(6-butyl-2-methyl-5-phenylpyrimidin-4-yl)oxazolidin-2-
one (5b). Following the general procedure D: colorless oil, 40%;
Rf ¼ 0.5 (30% EtOAc/Petroleum Ether); 1H NMR (500 MHz, CDCl3)
4.3.3.1. N-(2-phenylacetyl)benzamide (4a). Following the general
procedure C: white solid, mp: 122e124 ꢀC, 28%; Rf ¼ 0.7 (30%
d
7.44e7.36 (m, 3H), 7.27e7.24 (m, 2H), 4.28 (t, J ¼ 8.0, 2H), 3.89 (t,
J ¼ 8.0 Hz, 2H), 2.73 (s, 3H), 2.61 (t, J ¼ 8.0 Hz, 2H), 1.58e1.52 (m,
EtOAc/Petroleum Ether); 1H NMR (500 MHz, CDCl3)
d 8.82 (s, 1H),
2H), 1.26e1.20 (m, 2H), 0.78 (t, J ¼ 7.5 Hz, 3H); 13C NMR (125 MHz,
7.84 (d, J ¼ 6.3 Hz, 2H), 7.63e7.58 (m, 1H), 7.49e7.46 (m, 2H),
CDCl3) d 171.62, 166.55,156.02, 154.74, 134.19, 129.51, 128.37, 128.01,
7.39e7.34 (m, 4H), 7.33e7.28 (m, 1H), 4.34 (s, 2H); 13C NMR
126.60, 62.58, 45.73, 34.92, 31.31, 25.68, 22.56, 13.67; mass spec-
trum (ESI): m/e (% relative intensity) 312.1 (100) (MþH)þ; HRMS
calcd for C18H21N3O2Naþ (MþNa)þ 334.1531, found 334.1532.
(125 MHz, CDCl3)
d 173.84, 165.48, 133.65, 133.25, 132.63, 129.78,
128.97, 128.61, 127.69, 127.22, 43.91; mass spectrum (ESI): m/e (%
relative intensity) 262.1 (100) (MþNa)þ; HRMS calcd for
C
15H13NO2Naþ (MþNa)þ 262.0838, found 262.0828.
4.3.4.3. 3-(5-(4-bromophenyl)-2,6-dimethylpyrimidin-4-yl)oxazoli-
din-2-one (5c). Following the general procedure D: yellow oil, 42%;
Rf ¼ 0.4 (50% EtOAc/Petroleum Ether); 1H NMR (500 MHz, CDCl3)
4.3.3.2. 4-Chloro-N-(2-phenylacetyl)benzamide (4b). Following the
general procedure C: white solid, mp: 166e169 ꢀC, 37%; Rf ¼ 0.8
d
7.55 (d, J ¼ 8.0 Hz, 2H), 7.55 (d, J ¼ 8.0 Hz, 2H), 4.36 (t, J ¼ 8.0 Hz,
(30% EtOAc/Petroleum Ether); 1H NMR (500 MHz, CDCl3)
d
8.91 (s,
2H), 4.06 (t, J ¼ 8.0 Hz, 2H), 2.70 (s, 3H), 2.35 (s, 3H); 13C NMR
1H), 7.78 (d, J ¼ 8.0 Hz, 2H), 7.43 (d, J ¼ 8.0 Hz, 2H), 7.39e7.35 (m,
(125 MHz, CDCl3) d 167.61, 166.45, 155.74, 154.32, 133.61, 131.68,
2H), 7.35e7.30 (m, 3H), 4.32 (s, 2H); 13C NMR (125 MHz, CDCl3)
131.08, 125.26, 122.22, 62.65, 45.48, 25.57, 23.07; mass spectrum
(ESI): m/e (% relative intensity) 347.9 (100) (MþNa)þ; HRMS calcd
for C15H15N3O2Naþ (MþNa)þ 348.0348, found 348.0346.
d
173.88, 164.54, 139.78., 133.49, 130.95, 129.77, 129.27, 129.16,
128.64, 127.31, 43.95; mass spectrum (ESI): m/e (% relative in-
tensity) 296.0 (100)(MþNa)þ; HRMS calcd for C15H12ClNO2Naþ
(MþNa)þ 296.0454, found 296.0457.
4.3.4.4. 3-(6-methyl-3,4-diphenylpyridin-2-yl)oxazolidin-2-one(6a).
Following the general procedure D: white solid, 33%; mp:
166e168 ꢀC. Rf ¼ 0.5 (50% EtOAc/Petroleum Ether); 1H NMR
4.3.3.3. N-(2-phenylacetyl)cinnamamide (4c). Following the gen-
eral procedure C: white solid, 47%; mp: 122e124 ꢀC Rf ¼ 0.6 (30%
(500 MHz, CDCl3) d7.25e7.19 (m, 7H), 7.13e7.12 (m, 2H), 7.05e7.03
EtOAc/Petroleum Ether); 1H NMR (500 MHz, CDCl3)
d
8.60 (s, 1H),
(m, 2H), 4.23 (t, J ¼ 7.5 Hz, 2H), 3.72 (t, J ¼ 7.5 Hz, 2H), 2.63 (s, 3H);
7.83 (d, J ¼ 15.5 Hz, 1H), 7.58e7.56 (m, 2H), 7.42e7.37 (m, 5H),
13C NMR (125 MHz, CDCl3)
d
157.55, 156.72, 152.05, 148.35, 138.38,
7.34e7.31 (m, 3H), 7.22 (d, J ¼ 15.5 Hz, 1H), 4.00 (s, 2H); 13C NMR
135.42, 131.16, 130.01, 129.14, 128.04, 127.96, 127.69, 127.42, 124.63,
62.53, 46.28, 23.98; mass spectrum (ESI): m/e (% relative intensity)
353.0 (100) (MþNa)þ; HRMS calcd for C21H18N2O2Naþ (MþNa)þ
353.1266, found 353.1262.
(125 MHz, CDCl3)
d 172.23, 166.02, 146.30, 134.24, 133.30, 130.77,
129.61, 128.92, 128.52, 127.56, 119.21, 44.43; mass spectrum (ESI):
m/e (% relative intensity) 288.0 (100) (MþNa)þ; HRMS calcd for
C
17H15NO2Naþ (MþNa)þ 288.0968, found 288.0978.
4.3.4.5. 3-(3-(4-bromophenyl)-6-methyl-4-phenylpyridin-2-yl)oxa-
zolidin-2-one (6b). Following the general procedure D: yellow oil,
35%; Rf ¼ 0.5 (50% EtOAc/Petroleum Ether); 1H NMR (500 MHz,
4.3.4. General procedure D for reaction of amides with other nitriles
or phenylacetylene. (5a, 5b, 5c, 6a, 6b)12
Trifluoromethanesulfonic anhydride (60
mL, 0.40 mmol, 2.0
CDCl3) d7.37e7.35 (m, 2H), 7.25e7.19 (m, 4H), 7.03e6.99 (m, 3H),
equiv) was added via syringe over 1 min to a stirred mixture of
amide 2a (50 mg, 0.20 mmol, 1.0 equiv) and 2-chloropyridine
4.31 (t, J ¼ 7.5 Hz, 2H), 3.85 (t, J ¼ 7.5 Hz, 2H), 2.61 (s, 3H); 13C NMR
(125 MHz, CDCl3) d 157.77, 156.50, 152.04, 148.24, 138.09, 134.54,
(23
m
L, 0.24 mmol, 1.2 equiv) in dichloromethane (2 mL)
131.73, 131.22, 129.58, 129.07, 128.15, 127.88, 124.58, 121.68, 62.58,
46.28, 23.96; mass spectrum (ESI): m/e (% relative intensity) 430.9
(100) (MþNa)þ; HRMS calcd for C21H18BrN2O2þ (MþH)þ 409.0552,
found 409.0548.
at ꢁ78 ꢀC. After 5 min, the reaction mixture was placed in an ice-
water bath and warmed to 0 ꢀC, the nitrile or phenylacetylene
(0.22 mmol, 1.1 equiv) was added via syringe, and the resulting
Please cite this article in press as: Wang W-S, et al., Regioselective TfOH-mediated hydroamidation of ynamides with nitriles, Tetrahedron
(2017), http://dx.doi.org/10.1016/j.tet.2017.03.060

W.-S. Wang et al. / Tetrahedron xxx (2017) 1e9
9
4.3.5. General procedure E for the preparation of 7a, 7b12
Trifluoromethanesulfonic anhydride (60 L, 0.40 mmol, 2.0
equiv) was added via syringe over 1 min to a stirred mixture of
1997;62:8968;
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amide 2a (50 mg, 0.20 mmol, 1.0 equiv) and 2-chloropyridine
(23
m
L, 0.24 mmol, 1.2 equiv) in dichloroethane (2 mL) at ꢁ30 ꢀC.
After 5 min, the reaction mixture was placed in an ice-water bath
and warmed to 0 ꢀC, and then the reaction vessel was placed into a
preheated oil bath at 80 ꢀC and maintained at that temperature.
After 2 h, the reaction mixture was allowed to cool to ambient
temperature and aqueous sodium hydroxide solution (1 mL, 1 N)
was introduced to neutralize the trifluoromethanesulfonate salts.
Ethyl acetate (5 mL) was added to dilute the mixture and the layers
were separated. The organic layer was washed with brine (2 mL),
was dried over anhydrous sodium sulfate, and was filtered. The
volatiles were removed under reduced pressure and the residue
was purified by flash column chromatography to give the product.
(e) Feng C, Loh TP. Org Lett. 2014;16:3444.
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4.3.5.1. 3-(1-methylisoquinolin-3-yl)oxazolidin-2-one
(7a).
Following the general procedure E: white solid, 30%; mp:
155e157 ꢀC. Rf ¼ 0.6 (30% EtOAc/Petroleum Ether); 1H NMR
(500 MHz, CDCl3)
d
8.34 (s, 1H), 8.04 (d, J ¼ 8.5 Hz, 1H), 7.82 (d,
J ¼ 8.0 Hz, 1H), 7.63 (t, J ¼ 7.5 Hz, 1H), 7.48 (t, J ¼ 8.0 Hz, 1H),
4.54e4.51 (m, 2H), 4.45e4.41 (m, 2H), 2.92 (s, 3H); 13C NMR
(g) Kozawa Y, Mori M. J Org Chem. 2003;68:3064;
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5. Boeckmann RK, Goldstein SW, Walters MA. J Am Chem Soc. 1988;110:8250.
6. For leading reviews on ynamide chemistry, see: (a) DeKorver KA, Li H,
Lohse AG, et al. Chem Rev. 2010;110:5064;
(b) Wang XN, Yeom HS, Fang LC, et al. Acc Chem Res. 2014;47:560;
(c) Evano G, Coste A, Jouvin K. Angew Chem Int Ed. 2010;49:2840 (For recent
examples, see);
(125 MHz, CDCl3)
d 157.44, 155.26, 144.67, 137.85, 130.24, 127.49,
125.62, 125.38, 124.69, 106.00, 62.08, 44.52, 22.02; mass spectrum
(ESI): m/e (% relative intensity) 251.0 (100) (MþNa)þ; HRMS calcd
for C13H12N2O2Naþ (MþNa)þ 251.0796, found 251.0791.
4.3.5.2. 3-(7-bromo-1-methylisoquinolin-3-yl)oxazolidin-2-one (7b).
Following the general procedure E: white solid, 31%; mp:
176e178 ꢀC. Rf ¼ 0.5 (30% EtOAc/Petroleum Ether); 1H NMR
(d) Jadhav AM, Pagar VV, Huple DB, Liu RS. Angew Chem Int Ed. 2015;54:3812;
(e) Tokimizu Y, Wieteck M, Rudolph M, et al. Org Lett. 2015;17:604;
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(g) Yabuuchi Y, Kuzuguchi T, Yoshimura T, Matsuo JI. Org Lett. 2016;18:4951;
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(c) Walker PR, Campbell CD, Suleman A, Carr G, Anderson EA. Angew Chem Int
Ed. 2013;52:9139;
(500 MHz, CDCl3) d 8.33 (s, 1H), 8.19 (s, 1H), 7.71e7.67 (m, 2H), 4.53
(t, J ¼ 8.0 Hz, 2H), 4.41 (t, J ¼ 8.0 Hz, 2H), 2.87 (s, 3H); 13C NMR
(125 MHz, CDCl3)
d 156.58, 155.17, 145.15, 136.33, 133.59, 129.13,
127.72, 125.60, 118.97, 105.55, 62.10, 44.41, 22.07; mass spectrum
(ESI): m/e (% relative intensity) 328.9 (100) (MþNa)þ; HRMS calcd
for C13H12BrN2Oþ2 (MþH)þ 307.0082, found 307.0074.
(d) Kiruthika SE, Nandakumar A, Perumal PT. Org Lett. 2014;16:4424;
(e) Prabagar B, Nayak S, Prasad R, Sahoo AK. Org Lett. 2016;18:3066;
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(h) Pan F, Shu C, Ye LW. Org Biomol Chem. 2016;14:9456;
Acknowledgments
€
(i) Wezeman T, Zhong S, Nieger M, Brase S. Angew Chem Int Ed. 2016;55:3823;
(j) Duret G, Quinlan R, Martin RE, et al. Org Lett. 2016;18:1610.
8. Hu L, Xu SL, Zhao ZG, et al. J Am Chem Soc. 2016;138:13135.
9. (a) Madelaine C, Valerio V, Maulide N. Chem Asian J. 2011;6:2224;
(b) Lecomte M, Evano G. Angew Chem Int Ed. 2016;55:4547;
We thank Professor Richard P. Hsung [University of Wisconsin at
Madison] for invaluable discussions. Y.T. thanks National Natural
Science Foundation of China [21572154] and the Fundamental
Research Funds for the Central Universities [201612013] for finan-
cial support.
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Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
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Please cite this article in press as: Wang W-S, et al., Regioselective TfOH-mediated hydroamidation of ynamides with nitriles, Tetrahedron
(2017), http://dx.doi.org/10.1016/j.tet.2017.03.060