Nickel-catalyzed regioselective hydroamination of ynamides with secondary amines

Article abstract of DOI:10.1021/acs.joc.0c02807

The first Ni(OTf)2-catalyzed hydroamination of ynamides 2 was developed by reacting with secondary amines (1 and 4). This protocol features excellent regioselectivity, a broad substrate scope of secondary aryl amines, and good functional group tolerance for ynamides. Using this method, a variety of substituted ethene-1,1- diamine compounds were prepared in moderate to excellent yields with high regioselectivities.

Full text of DOI:10.1021/acs.joc.0c02807

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Article
Nickel-Catalyzed Regioselective Hydroamination of Ynamides with
Secondary Amines
Xiao-Di Nie, Xiao-Li Han, Jian-Ting Sun, Chang-Mei Si,* Bang-Guo Wei,* and Guo-Qiang Lin
Cite This: J. Org. Chem. 2021, 86, 3433−3443
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ABSTRACT: The first Ni(OTf)2-catalyzed hydroamination of yna-
mides 2 was developed by reacting with secondary amines (1 and 4).
This protocol features excellent regioselectivity, a broad substrate scope
of secondary aryl amines, and good functional group tolerance for
ynamides. Using this method, a variety of substituted ethene-1,1-
diamine compounds were prepared in moderate to excellent yields with
high regioselectivities.
INTRODUCTION
■
The development of efficient synthetic methodologies has
always been important and attractive to organic chemists,1 due
to their potential use in syntheses of natural products and
pharmaceutical drugs.2 In particular, hydroamination has
attracted significant interest because of its utilization in the
preparation of heterocyclic compounds,3 including depsipep-
tides,4 pharmaceuticals,5 and important natural products.6
Although hydroamination usually involves the challenging
formation of enamine-containing heterocyclic compounds, the
reaction process can overcome the intriguing selectivity of
inter/intramolecular nucleophilic attack and demonstrate
exceptional ability to activate π-conjugated systems. In the
past few decades, numerous precious metals, lanthanides, and
alkaline earth metals have been widely used to catalyze
hydroamination of alkynes.7 Moreover, base-mediated hydro-
amination reactions have also been reported in recent years.8
However, the application of cheap metal Lewis acid remains to
be explored for the catalysis of the hydroamination process.
Hydroamination of alkynes mostly used indole or sub-
stituted indoles as amine partners (Figure 1a),8b,c,9 and this
strategy was further developed to a cascade process to form
some valuable heterocyclic skeletons (Figure 1b).10 Another
important type of hydroamination is the reaction of alkynes
with amides, leading to an isoquinolin-1(2H)-one framework
(Figure 1c).11 Very recently, Esteruelas and co-workers
established Ruthenium-catalyzed oxidative amidation of
terminal alkynes with primary and secondary amines to afford
the corresponding amides (Figure 1d).7c
Figure 1. Hydroamination of amines with alkynes.
enamides.21 In addition, ynamide was studied for the
hydroamination reaction, in which noble metal Au was used
to catalyze the addition of primary amines to ynamides to
Ynamides, known as nitrogen-substituted alkynes with an
electron-withdrawing group at the nitrogen atom, have
undoubtedly become one of the most popular synthons due
to their high reactivity and high regio- and stereoselectivity.12
In the past decade, ynamides were successfully applied in the
syntheses of many important versatile skeletons, including
functional indoles,13 quinolines,14 pyridines,15 pyrroles,16
oxazoles,17 benzofurans,18 carbolines,19 amidines,20 and
Received: November 24, 2020
Published: February 3, 2021
https://dx.doi.org/10.1021/acs.joc.0c02807
© 2021 American Chemical Society
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afford enamines (Figure 2a).22 Later on, transition-metal-free
hydroamination was developed, and indole substrates could
Table 1. Optimization of Reaction Conditions
a
b
c
entry
catalyst
Na2CO3
K3PO4
NaOtBu
KOH
AuCl3
solvent
yield (%)
E/Z
d
1
DMF
DMF
DMF
DMF
NR
NR
NR
NR
complex
complex
56
58
46
66
53
45
trace
92
NR
NR
NR
43
91
NR
68
NR
NR
86
d
2
d
3
d
4
5
6
7
8
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
PPh3AuCl/AgSbF6
[Ph3C][B(C6F5)4]
BF3·Et2O
TMSOTf
Sc(OTf)3
Cu(OTf)2
Er(OTf)3
La(OTf)3
Ni(OTf)2
NiBr2
Ni(acac)2
(Ph3P)2NiCl2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
10:1
>20:1
>20:1
10:1
>20:1
>20:1
9
10
11
12
13
14
15
16
17
Figure 2. Hydroamination of amines with ynamides.
>20:1
undergo the addition to ynamides, producing (Z)-N-(2-
aminovinyl)-sulfonamide with excellent regioselectivity (Figure
2b).23 To our best knowledge, such hydroamination with
secondary amines other than indole and its analogues has not
been reported. On the basis of our continuous efforts in Lewis
acid-catalyzed chemical transformations of ynamides,24 we
envisioned the addition of amines to ynamides could occur
under Lewis acid conditions. Herein we present our work on
the first Ni(OTf)2-catalyzed regioselective hydroamination of
secondary amines with ynamides (Figure 2c).
e
18
19
20
>20:1
>20:1
f
e
21
22
23
DCE
DMF
MeCN
toluene
>20:1
>20:1
g
24
a
The reactions were performed with 1a (0.4 mmol), 2a (0.6 mmol),
and the catalyst (0.04 mmol) in dry solvent (2 mL) at 80 °C for 15
RESULTS AND DISCUSSION
■
b
c
Our investigation started with the reaction of N-methylaniline
1a with ynamide 2a. First, various inorganic bases including
Na2CO3, K3PO4,25 NaOtBu,23 and KOH8b,c failed to promote
min to 1 h. Isolated yield. NR = no reaction. E/Z was determined
d
e
by 1H NMR and HPLC. 0.8 mmol of the base was used. The
f
reaction temperature was 60 °C. The reaction temperature was 110
g
the reaction (Table 1, entries 1−4). Then AuCl3 and
PPh3AuCl/AgSbF6
°C. The reaction was performed with 1a (2.8 mmol), 2a (4.2 mmol),
24b
and Ni(OTf)2 (0.28 mmol) in anhydrous toluene (14 mL) at 80 °C
were examined, and both reactions
for 1h.
were messy (Table 1, entries 5 and 6). Fortunately,
[Ph3C][B(C6F5)4]26 could lead to the desired product 3aa in
56% yield with moderate regioselectivity (E/Z = 10:1, Table 1,
entry 7). BF3·Et2O24e and TMSOTf24a could effectively
improve the regioselectivity (E/Z > 20:1), but the yields
were still unsatisfactory (Table 1, entries 8 and 9). Next, a
variety of Lewis acids, including a catalytic amount of
Sc(OTf)3, Cu(OTf)2,24b Er(OTf)3, and La(OTf)3, were
examined. Although most of them could maintain or enhance
E/Z selectivities, they failed to improve the yields of the
desired product 3aa, and La(OTf)3 could not catalyze this
reaction at all (Table 1, entries 10−13). Fortunately, Ni(OTf)2
could effectively catalyze this hydroamination reaction, and the
desired product 3aa was obtained in 92% yield with excellent
regioselectivity (E/Z > 20:1, Table 1, entry 14). It is worth
noting that other nickel salts, NiBr2, Ni(acac)2, and
(Ph3P)2NiCl2, could not catalyze this reaction (Table 1,
entries 15−17). The evaluation of reaction temperatures and
solvents led to the best outcome when the reaction was
conducted in toluene at 80 °C (Table 1, entries 18−23).
Although the reaction could work in a halogenated solvent like
DCE, the yield was reduced. Polar solvents, such as THF,
DMF, and MeCN, were unsuitable for this hydroamination
reaction. Notably, a gram-scale reaction was performed under
optimal reaction conditions, and the desired product 3aa was
obtained in 86% yield with excellent regioselectivity (E/Z >
20:1, Table 1, entry 24).
Next, we turned to investigate the scope and limitation of
such hydroamination of secondary amines 1a−1x with
ynamides 2 (Scheme 1). First, the reactions of TsNBn-type
ynamides with N-substituted (alkyl, allyl, and benzyl) anilines
1a−1f were surveyed under the optimized conditions, and the
results were summarized in Scheme 1. N-Methyl- and N-ethyl-
substituted anilines 1a and 1b could smoothly react with
ynamide 2a, producing the desired products 3aa−3ba in
excellent yields with high regioselectivities. N-Allyl and N-
benzyl-substituted anilines could give corresponding products
3ca and 3da in moderate yields, together with excellent
regioselectivities. Larger substitutions like N-cyclopropyl and
N-cyclohexyl groups were also tolerated, albeit with a slight
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obtained in moderate yields with excellent regioselectivities.
The reaction of N-methylaniline 1a with the ynamide
containing m-trifluoromethyl 2l is complex. We also tried the
reaction of N-Methylaniline 1a and ynamides containing
terminal alkyne 2m, but the result was complex. In addition,
the replacement of the Ts group in ynamides with p-
chlorobenzenesulfonyl or oxazolidin-2-one also gave positive
results under the optimized conditions, and the desired
products 3ab and 3ak were obtained in moderate yields with
satisfactory regioselectivities. It is worth noting that non-
aromatic secondary amines such as N-methylpentane-1-amine
and pyrrolidine were not suitable for this hydroamination
reaction. The chemical structures of 3aa−3ak, 3ba−3xa were
unambiguously confirmed by the result of X-ray crystallo-
graphic analysis of compound 3ua (see the Supporting
Information).
Scheme 1. Reactions of Secondary Amines with
Ynamides
a b c
, ,
Next, we turned our attention to investigate the hydro-
amination of bicyclic secondary amines 4 with ynamides 2
(Scheme 2). When indolines 4a and 4b were applied, the
desired products 5ah and 5bl were obtained in moderate yields
with 10:1 E/Z selectivities (Scheme 2). Other ynamides 2g, 2i,
and 2f also led to similar results. Notably, both 1H-indole and
Scheme 2. Reactions of Indolines and Tetrahydroquinoline
a b c
, ,
with Ynamides
a
The reaction was performed with 1 (0.4 mmol), 2 (0.6 mmol), and
Ni(OTf)2 (0.04 mmol) in anhydrous toluene (2 mL) for 15 min to 1
b
c
1
h at 80 °C. Isolated yield. E/Z was determined by H NMR and
HPLC.
decrease in regioselectivity for 3fa. Then, various substitutions
at the phenyl ring of N-methylaniline were investigated under
the optimized conditions. The results showed that all these
substituted N-methyl anilines 1g−1s could react with ynamide
2a, affording the desired products 3ga−3sa in excellent
regioselectivities. The para-electron-withdrawing substitutions
(1p−1s) generally led to slightly decreased yields. Diaryl-
amines 1t−1x were also examined, and the desired products
3ta−3xa were produced in moderate yields with excellent
regioselectivities. Finally, different substituted ynamides 2c−2j
were evaluated, and the desired products 3ac−3aj were
a
The reaction was performed with 4 (0.4 mmol), 2 (0.6 mmol), and
Ni(OTf)2 (0.04 mmol) in anhydrous toluene (2 mL) for 15 min to 1
h at 80 °C. Isolated yield. E/Z was determined by H NMR and
HPLC.
b
c
1
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1,4-dihydroquinoline failed to obtain the desired products due
to the complex reaction system. When tetrahydroquinoline 4c
was used, the desired 5ca−5cf were obtained in moderate
yields and mostly with 10:1 E/Z selectivities. We think that
steric hindrance and ring tension of bicyclic secondary amines
have a significant effect on stereoselectivity. According to the
experimental X-ray crystallographic analysis of compound 5bl,
the chemical structures of 5ah−5cf were unambiguously
determined (see the Supporting Information).
To verify this process, 2a was subjected to the standard
reaction conditions with deuterated N-methylaniline 1a-D,27
and the desired isotope-substituted product 3aa-D was isolated
(Scheme 3). This showed that the proton for hydroamination
came from secondary amines (see the Supporting Informa-
tion).
CONCLUSIONS
■
In summary, a new method for the hydroamination of
ynamides 2 with secondary amines (1 and 4) has been
developed through the catalysis of Lewis acid Ni(OTf)2. This
facile and convenient process could afford substituted ethene-
1,1-diamine compounds 3aa−3ak, 3ba−3xa, and 5ah−5cf in
moderate to excellent yields with high regioselectivities.
EXPERIMENTAL SECTION
■
General. Toluene was dried with calcium chloride and distilled.
THF was treated with sodium metal. All reactions were monitored by
thin-layer chromatography (TLC). IR spectra were recorded using
film on a Fourier transform infrared spectrometer. NMR spectra were
tested at 400 or 600 MHz, and chemical shifts are reported in δ
(ppm) referenced to the appropriate residual solvent peaks unless
otherwise noted. HRMS were measured on an LTQ-Orbitrap-XL
apparatus. The heat source was an oil bath. The secondary amines
1a−1x and 4a−4c, conventional solvents, and reagents are
commercially available.
a
Scheme 3. Deuterium Labeling Experiment
General Procedure for the Synthesis of Ynamides 2..24e,28
A
solution of an amide (2 mmol), K3PO4 (4 mmol), CuSO4·5H2O (0.2
mmol), and 1,10-phenanthroline (0.4 mmol) in dry toluene was
added 1-bromoalkyne (2.2 mmol in toluene) under a nitrogen
atmosphere. The reaction was stirred at 75 °C for 24 h. The heat
source was an oil bath. The reaction mixture was cooled to room
temperature, diluted with EtOAc, and filtered through a pad of Celite,
and the filtrate was concentrated under reduced pressure. The crude
products were purified by using column chromatography on silica gel
to afford the desired ynamide.
General Procedure for the Synthesis of 3 and 5. To a
solution of Ni(OTf)2 (0.04 mmol) and ynamides 2 (0.6 mmol) in
anhydrous toluene (2 mL) under a N2 atmosphere was added
secondary amines 1 or 4 (0.4 mmol) at 80 °C. The heat source was an
oil bath. After stirring for 15 min to 1 h, the reaction was quenched by
aqueous NaHCO3 and then extracted with EtOAc (10 mL × 3). The
combined organic layers were washed with brine, dried over MgSO4,
filtered, and concentrated under reduced pressure, and the residue
was purified by using column chromatography on silica gel to give the
desired products 3 or 5.
a
The reaction was performed with 1a-D (0.4 mmol), 2a (0.6 mmol),
and Ni(OTf)2 (0.04 mmol) in anhydrous toluene (2 mL) for 1 h at
80 °C, 26% for 3aa-D, 66% for 3aa, E/Z > 20:1.
As shown in Figure 3, a plausible mechanism was proposed
for this Ni(OTf)2-catalyzed transformation based on the above
Procedure for Synthesis of 3aa (Gram Scale). To a solution of
Ni(OTf)2 (0.28 mmol, 100 mg) and ynamide 2a (4.2 mmol, 1.5 g) in
anhydrous toluene (14 mL) under a N2 atmosphere was added
secondary amine 1a (2.8 mmol, 0.30 mL) at 80 °C. The heat source
was an oil bath. After stirring for 1 h, the reaction was quenched by
aqueous NaHCO3, extracted with EtOAc (20 mL × 3), and washed
with brine. The combined organic layers were dried over MgSO4,
filtered, and concentrated under reduced pressure, and the residue
was purified by using column chromatography on silica gel to give the
desired products 3aa (1.13 g, 86%, E/Z > 20:1, PE/EA = 15:1)
(E)-N-Benzyl-4-methyl-N-(1-(methyl(phenyl)amino)-2-
phenylvinyl)benzenesulfonamide (3aa): colorless oil (172 mg, 92%,
PE/EA = 15:1); IR (film) vmax 3449, 2925, 1634, 1496, 1346, 1161,
1
696 cm−1; H NMR (400 MHz, DMSO-d6) δ 7.77−7.72 (m, 2H),
7.44−7.40 (m, 2H), 7.32−7.27 (m, 3H), 7.23−7.20 (m, 2H), 7.13−
7.09 (m, 2H), 7.07−7.03 (m, 1H), 7.01−6.96 (m, 4H), 6.71−6.66
(m, 1H), 6.64−6.59 (m, 2H), 6.03 (s, 1H), 4.61−4.56 (m, 2H), 2.59
(s, 3H), 2.43 (s, 3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ
144.6, 143.8, 129.7, 128.2, 128.1, 128.0, 127.4, 127.1, 119.1, 116.1,
115.4, 51.2, 36.4, 21.0 ppm; HRMS (ESI-Orbitrap) m/z [M + H]+
calcd for C29H29N2O2S+ 469.1944, found 469.1947.
(E)-N-Benzyl-4-methyl-N-(1-(methyl(phenyl)amino)-2-
phenylvinyl)benzenesulfonamide (3aa-D). To a solution of Ni-
(OTf)2 (0.04 mmol) and ynamide 2a (0.6 mmol) in anhydrous
toluene (2 mL) under a N2 atmosphere was added secondary amine
1a-D (0.4 mmol) at 80 °C. After stirring for 1 h, the reaction mixture
was quenched with aqueous NaHCO3 and extracted with EtOAc (10
mL × 3), and the combined organic layers were washed with brine.
Dried, filtered, and concentrated, the residue was purified by flash
Figure 3. Proposed reaction mechanism.
experimental results and the known ynamide chemistry.12,24 In
brief, the activation of the alkyne bond in 2 led to a vinyl
Ni(II) intermediate int-1, which was further attacked by
secondary amines from the less steric side to give int-2. The
subsequent protonation could readily afford the desired
product, along with the release of Ni(OTf)2 into the catalytic
cycle.
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chromatography on silica gel to give the desired product 3aa-D (28%
D): colorless oil (48 mg, 26%, PE/EA = 15:1); 1H NMR (400 MHz,
DMSO-d6) δ 7.76−7.70 (m, 2H), 7.43−7.39 (m, 2H), 7.31−7.25 (m,
3H), 7.22−7.18 (m, 2H), 7.13−7.07 (m, 2H), 7.07−7.01 (m, 1H),
7.00−6.94 (m, 4H), 6.69−6.66 (m, 1H), 6.63−6.57 (m, 2H), 6.01 (s,
0.72H), 4.60−4.56 (m, 2H), 2.57 (s, 3H), 2.42 (s, 3H) ppm; HRMS
(ESI-Orbitrap) m/z [M + Na]+ calcd for C29H27DN2O2SNa+
492.1827, found 492.1812.
0.3H, minor), 2.42 (s, 3H, major), 2.38 (s, 0.9H, minor), 1.58−1.45
(m, 4H, major), 1.44−1.41 (m, 1.2H, minor), 1.38−1.33 (m, 2H,
major), 1.32−1.28 (m, 0.6H, minor), 1.13−1.07 (m, 0.9H, minor),
1.00−0.90 (m, 3H, major), 0.82−0.78 (m, 0.3H, minor), 0.77−0.67
(m, 1H, major) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 145.0
(minor), 143.8 (major), 143.7 (major), 143.6 (minor), 142.1
(minor), 138.3 (major),137.6 (minor), 137.0 (major), 136.2
(major), 136.1 (minor), 135.5 (minor), 135.0 (major), 130.0
(minor), 129.7 (major), 129.5 (minor), 128.7 (minor), 128.4
(major), 128.2 (minor), 128.1 (major), 127.9 (major), 127.7
(minor), 127.5 (major), 127.4 (major), 127.3 (minor), 127.1
(minor), 126.1 (major), 126.7, 124.6, 121.7 (major), 121.0
(minor), 57.6 (major), 57.1 (minor), 51.9 (minor), 51.4 (major),
30.8 (major), 25.9 (major), 25.7 (minor),, 25.2 (minor), 25.0
(major), 21.0 (major), 20.9 (minor) ppm; HRMS (ESI-Orbitrap) m/
z [M + Na]+ calcd for C34H36N2O2SNa+ 559.2390, found 559.2395.
(E)-N-Benzyl-N-(1-((3,4-dichlorophenyl)(methyl)amino)-2-phe-
nylvinyl)-4-methylbenzenesulfonamide (3ga): colorless oil (154 mg,
72%, PE/EA = 15:1); IR (film) vmax 3287, 2092, 1635, 1480, 1348,
(E)-N-Benzyl-N-(1-(ethyl(phenyl)amino)-2-phenylvinyl)-4-meth-
ylbenzenesulfonamide (3ba): colorless oil (150 mg, 78%, PE/EA =
1
15:1); IR (film) vmax 3442, 2090, 1597, 1480, 1136, 696 cm−1; H
NMR (400 MHz, DMSO-d6) δ 7.75 (d, J = 8.4 Hz, 2H), 7.45 (d, J =
8.0 Hz, 2H), 7.32−7.26 (m, 3H), 7.25−7.21 (m, 2H), 7.07−7.02 (m,
2H), 7.02−6.96 (m, 3H), 6.94−6.88 (m, 2H), 6.63−6.53 (m, 3H),
6.02 (s, 1H), 4.65−4.55 (m, 2H), 3.27−3.15 (m, 2H), 2.43 (s, 3H),
0.80 (t, J = 7.0 Hz, 3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6)
δ 144.0, 143.9, 136.6, 136.2, 135.2, 134.1, 129.8, 128.4, 128.3, 128.3,
127.8, 127.6, 127.5, 127.4, 126.6, 119.0, 117.5, 115.4, 51.2, 42.5, 21.0,
12.9 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C30H30N2O2SNa+ 505.1920, found 505.1925.
1
1161, 697 cm−1; H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J = 8.4
Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.31−7.26 (m, 3H), 7.24−7.21 (m,
2H), 7.16−7.09 (m, 3H), 7.08−7.06 (m, 1H), 6.90 (d, J = 7.2 Hz,
2H), 6.57 (d, J = 2.8 Hz, 1H), 6.45 (dd, J = 8.8, 2.8 Hz, 1H), 6.08 (s,
1H), 4.70−4.65 (m, 2H), 2.62 (s, 3H), 2.42 (s, 3H) ppm; 13C{1H}
NMR (100 MHz, DMSO-d6) δ 144.6, 144.0, 136.3, 136.2, 136.1,
133.9, 130.8, 129.8, 129.7, 128.3, 127.7, 127.3, 127.2, 127.2, 120.1,
117.7, 116.4, 115.0, 51.8, 35.9, 21.1 ppm; HRMS (ESI-Orbitrap) m/z
[M + Na]+ calcd for C29H26Cl2N2O2SNa+ 559.0984, found 559.0985.
(E)-N-Benzyl-N-(1-((2-bromophenyl)(methyl)amino)-2-phenyl-
vinyl)-4-methylbenzenesulfonamide (3ha): colorless oil (201 mg,
92%, PE/EA = 15:1), E/Z = 83:17 in a mixture. The major peak in
HPLC report (Supporting Information) is the stereochemistry of E:
(E)-N-(1-(Allyl(phenyl)amino)-2-phenylvinyl)-N-benzyl-4-methyl-
benzenesulfonamide (3ca): colorless oil (107 mg, 54%, PE/EA =
15:1); IR (film) vmax 3372, 2084, 1637, 1495, 1347, 1160, 749, 695
1
cm−1; H NMR (400 MHz, DMSO-d6) δ 7.74 (d, J = 8.0 Hz, 2H),
7.44 (d, J = 8.4 Hz, 2H), 7.31−7.26(m, 3H), 7.25−7.21 (m, 2H),
7.07−7.00 (m, 3H), 6.97−6.88 (m, 4H), 6.66−6.57 (m, 3H), 5.96 (s,
1H), 5.50−5.38 (m, 1H), 5.12 (dd, J = 17.4, 1.4 Hz, 1H), 5.02 (dd, J
= 10.4, 1.2 Hz, 1H), 4.65−4.56 (m, 2H), 3.79 (d, J = 6.0 Hz, 2H),
2.43 (s, 3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 144.1,
143.9, 136.4, 136.1, 135.9, 134.5, 134.1, 129.8, 128.4, 128.3, 128.2,
127.8, 127.6, 127.5, 126.7, 119.4, 117.5, 117.1, 116.2, 51.5, 51.0, 21.0
ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C31H30N2O2SNa+ 517.1920, found 517.1923.
1
IR (film) vmax 3396, 2082, 1638, 1476, 1347, 750 cm−1; H NMR
(400 MHz, CDCl3) δ 7.71−7.66 (m, 0.4H, minor), 7.65−7.62 (m,
2H, major), 7.49−7.46 (m, 1H, minor), 7.40−7.37 (m, 1H, minor),
7.32−7.27 (m, 5H, major), 7.25−7.21 (m, 5H, major), 7.20−7.19 (m,
2H, major), 7.18−7.17 (m, 0.4H, minor), 7.15−7.14 (m, 0.2H,
minor), 7.12−7.07 (m, 2H, major), 6.95−6.89 (m, 1H, major), 6.83−
6.80 (m, 0.4H, minor), 5.66 (s, 0.2H, minor), 5.35 (s, 1H, major),
4.63−4.61 (m, 2H, major), 3.09 (s, 3H, major), 2.90 (s, 0.6H, minor),
2.49 (s, 3H, major), 2.41 (s, 0.6H, minor) ppm; 13C{1H} NMR (100
MHz, CDCl3) δ 145.7 (minor), 145.3 (major), 143.8 (major), 143.4
(minor), 140.9 (major), 139.8 (minor), 137.4 (minor), 136.6
(major), 136.3 (minor), 135.7 (minor), 135.5 (major), 135.5
(major), 134.0 (minor), 134.0 (major), 130.5 (major), 129.7
(minor), 129.3 (major), 129.3 (minor), 129.0 (minor), 128.7
(major), 128.5 (major), 128.4 (minor), 128.2 (major), 128.2
(minor), 128.1 (major), 127.8 (major), 127.6 (minor), 127.5
(major), 126.2 (major), 125.7 (minor), 125.6 (major), 121.7
(minor), 119.7 (major), 112.2 (major), 111.9 (minor), 54.1
(major), 51.1 (minor), 40.5 (major), 40.0 (minor), 21.7 (major),
21.6 (minor) ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C29H27BrN2O2SNa+ 569.0869, found 569.0869.
(E)-N-Benzyl-N-(1-((2-methoxyphenyl)(methyl)amino)-2-phenyl-
vinyl)-4-methylbenzenesulfonamide (3ia): colorless oil (185 mg,
93%, PE/EA = 15:1), E/Z = 90:10 in a mixture. The major peak in
HPLC report (Supporting Information) is the stereochemistry of E:
IR (film) vmax 3395, 2957, 2076, 1627, 1499, 1346, 1161, 749 cm−1;
1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.0 Hz, 2H, major),
7.39−7.34 (m, 0.2H, minor), 7.27−7.24 (m, 0.5H, minor), 7.22−7.19
(m, 5H, major), 7.19−7.16 (m, 2H, major), 7.15−7.14 (m, 0.2H,
minor), 7.14−7.06 (m, 5H, major), 7.06−7.04 (m, 0.5H, minor),
7.04−7.00 (m, 1H, major), 7.00−6.99 (m, 0.1H, minor), 6.99−6.98
(m, 0.1H, minor), 6.96−6.93 (m, 1H, major), 6.93−6.90 (m, 0.1H,
minor), 6.90−6.87 (m, 0.1H, minor), 6.81−6.76 (m, 1H, major), 6.66
(dd, J = 8.0, 1.2 Hz, 1H, major), 5.47 (s, 0.1H, minor), 5.43 (s, 1H,
major), 4.55−4.52 (m, 2H, major), 3.81 (s, 0.3H, minor), 3.57 (s, 3H,
major), 2.87 (s, 3H, major), 2.69 (s, 0.3H, minor), 2.41 (s, 3H,
major), 2.33 (s, 0.3H, minor) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 154.3 (minor), 153.1 (major), 143.5 (major), 143.0
(E)-N-Benzyl-N-(1-(benzyl(phenyl)amino)-2-phenylvinyl)-4-
methylbenzenesulfonamide (3da): colorless oil (148 mg, 68%, PE/
EA = 10:1); IR (film) vmax 3442, 2089, 1631, 1495, 1347, 1159, 695
cm−1; 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.0 Hz, 2H), 7.25−
7.21 (m, 5H), 7.19−7.17 (m, 2H), 7.16−7.13 (m, 5H), 7.01−6.97
(m, 3H), 6.96−6.92 (m, 2H), 6.92−6.88 (m, 2H), 6.69 (d, J = 8.0 Hz,
2H), 6.63 (dd, J = 8.0, 7.6 Hz, 1H), 5.97 (s, 1H), 4.65−4.62 (m, 2H),
4.54−4.51 (m, 2H), 2.39 (s, 3H) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 145.2, 143.9, 139.1, 137.1, 136.6, 136.5, 134.0, 129.6, 129.0,
128.8, 128.6, 128.5, 128.4, 128.2, 127.8, 127.5, 127.0, 126.9, 120.2,
117.8, 116.9, 52.8, 52.3, 21.7 ppm; HRMS (ESI-Orbitrap) m/z [M +
Na]+ calcd for C35H32N2O2SNa+ 567.2077, found 567.2077.
(E)-N-Benzyl-N-(1-(cyclopropyl(phenyl)amino)-2-phenylvinyl)-4-
methylbenzenesulfonamide (3ea). colorless oil (170 mg, 86%, PE/
EA = 15:1); IR (film) vmax 3443, 2089, 1639, 1480, 1159, 694 cm−1;
1H NMR (400 MHz, DMSO-d6) δ 7.73 (d, J = 8.0 Hz, 2H), 7.38 (d, J
= 8.0 Hz, 2H), 7.18−7.14 (m, 5H), 7.13−7.08 (m, 2H), 7.07−7.01
(m, 5H), 6.83 (d, J = 7.6 Hz, 2H), 6.78−6.72 (m, 1H), 6.40 (s, 1H),
4.59−4.51 (m, 2H), 2.40 (s, 3H), 2.36−2.31 (m, 1H), 0.56−0.48 (m,
2H), 0.36−0.29 (m, 2H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6)
δ 144.6, 143.7, 136.7, 136.7, 134.3, 134.3, 129.6, 128.5, 128.3, 128.0,
127.7, 127.5, 127.2, 127.0, 120.9, 119.6, 115.4, 50.6, 30.1, 21.0, 8.8
ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C31H30N2O2SNa+ 517.1920, found 517.1921.
(E)-N-Benzyl-N-(1-(cyclohexyl(phenyl)amino)-2-phenylvinyl)-4-
methylbenzenesulfonamide (3fa): colorless oil (161 mg, 75%, PE/
EA = 15:1). E/Z = 76:24 in a mixture. The major peak in HPLC
report (Supporting Information) is the stereochemistry of E: IR (film)
1
vmax 3418, 2083, 1633, 1346, 1160, 697 cm−1; H NMR (400 MHz,
DMSO-d6) δ 7.72 (d, J = 8.4 Hz, 2H, major), 7.57 (d, J = 8.0 Hz,
0.6H, minor), 7.43 (d, J = 8.0 Hz, 2H, major), 7.36−7.34 (m, 0.6H,
minor), 7.34−7.28 (m, 5H, major), 7.25−7.22 (m, 1.5H, minor),
7.19−7.18 (m, 0.3H, minor), 7.18−7.16 (m, 1H, major), 7.13−7.07
(m, 1.2H, minor), 7.05−6.99 (m, 4H, major), 6.99−6.96 (m, 1.2H,
minor), 6.95−6.93 (m, 0.3H, minor), 6.92−6.81 (m, 4H, major),
6.67−6.60 (m, 1H, major), 5.79 (s, 1H, major), 5.39 (s, 0.3H, minor),
4.62−4.58 (m, 2H, major), 3.49−3.40 (m, 1H, major), 3.05−2.99 (m,
3437
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The Journal of Organic Chemistry
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Article
(minor), 141.5 (major), 141.5 (minor), 137.9 (minor), 137.7
(major), 137.3 (minor), 136.8 (major), 136.3 (major), 136.0
(minor), 135.0 (major), 130.6 (minor), 129.2 (major), 129.1
(minor), 128.4 (major), 128.4 (major), 128.2 (major), 128.1
(minor), 128.1 (minor), 128.0 (minor), 127.8 (major), 127.8
(major), 127.2 (major), 126.9 (minor), 126.1 (minor), 125.6
(major), 125.5 (minor), 125.3 (major), 124.5 (major), 121.4
(minor), 120.9 (major), 112.1 (minor), 111.4 (major), 110.5
(major), 110.3 (minor), 55.5 (minor), 54.9 (major), 52.6 (major),
52.0 (minor), 39.9 (major), 39.0 (minor), 22.7 (minor), 21.7 (major)
ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C30H30N2O3SNa+ 521.1869, found 521.1868.
3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 153.4, 144.6,
143.8, 137.5, 137.4, 136.5, 136.5, 134.6, 129.7, 128.3, 128.2, 128.1,
127.9, 127.4, 127.1, 126.6, 120.2, 116.1, 112.6, 51.1, 36.6, 21.2, 21.0
ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C30H30N2O2SNa+ 505.1920, found 505.1921.
(E)-N-Benzyl-N-(1-((4-bromophenyl)(methyl)amino)-2-phenyl-
vinyl)-4-methylbenzenesulfonamide (3oa): colorless oil (181 mg,
83%, PE/EA = 15:1); IR (film) vmax 3419, 2102, 1635, 1491, 1161,
1
698 cm−1; H NMR (400 MHz, DMSO-d6) δ 7.74 (d, J = 8.0 Hz,
2H), 7.41 (d, J = 8.4 Hz, 2H), 7.30−7.25 (m, 3H), 7.24−7.21 (m,
2H), 7.14−7.05 (m, 5H), 6.05−6.90 (m, 2H), 6.48 (dd, J = 7.2, 2.0
Hz, 2H), 6.04 (s, 1H), 4.66−4.58 (m, 2H), 2.57 (s, 3H), 2.42 (s, 3H)
ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 144.0, 143.9, 136.7,
136.3, 136.3, 134.2, 130.8, 129.8, 128.2, 128.2, 128.1, 127.5, 127.3,
127.1, 126.9, 117.1, 116.8, 110.5, 51.6, 36.1, 21.0 ppm; HRMS (ESI-
Orbitrap) m/z [M + Na]+ calcd for C29H27BrN2O2SNa+ 569.0869,
found 569.0867.
(E)-N-Benzyl-N-(1-((2-chlorophenyl)(methyl)amino)-2-phenyl-
vinyl)-4-methylbenzenesulfonamide (3ka): colorless oil (140 mg,
70%, PE/EA = 15:1). E/Z = 83:17 in a mixture. The major peak in
HPLC report (Supporting Information) is the stereochemistry of E:
1
IR (film) vmax 3442, 2090, 1629, 1480, 1348, 1162, 698 cm−1; H
NMR (400 MHz, DMSO-d6) δ 7.68−7.62 (m, 2H, major), 7.48−7.45
(m, 0.4H, minor), 7.44−7.41 (m, 2H, major), 7.41−7.39 (m, 0.4H,
minor), 7.37−7.29 (m, 1H, minor), 7.29−7.21 (m, 5H, major), 7.19−
7.17 (m, 1H, minor), 7.16−7.12 (m, 5H, major), 7.07−7.05 (m, 0.6H,
minor), 7.05−7.00 (m, 3H, major), 6.99−6.94 (m, 1H, major), 6.92−
6.90 (m, 0.2H, minor), 5.46 (s, 0.2H, minor), 5.33 (s, 1H, major),
4.57−4.50 (m, 2H, major), 2.87 (s, 3H, major), 2.57 (s, 0.6H, minor),
2.43 (s, 3H, major), 2.36 (s, 0.6H, minor) ppm; 13C{1H} NMR (100
MHz, DMSO-d6) δ 144.0 (major), 143.8 (minor), 143.4 (minor),
143.3 (major), 140.2 (major), 139.5 (minor), 136.9 (major), 135.7
(minor), 135.3 (minor), 134.8 (major),134.5 (major), 130.6 (minor),
130.4 (major), 130.2 (minor), 130.0 (major), 129.5 (major), 128.5
(minor), 128.4 (minor), 128.2 (minor), 128.0 (major), 127.9
(major), 127.7 (major), 127.6 (minor), 127.5 (major), 127.5
(major), 127.3 (minor), 127.2 (minor), 127.1 (major), 126.1
(major), 126.0 (minor), 125.7 (minor), 124.8 (major),111.9
(major), 110.9 (minor), 53.1 (major), 50.7 (minor), 26.3 (minor),
21.1 (major) ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C29H27ClN2O2SNa+ 525.1374, found 525.1378.
(E)-N-Benzyl-N-(1-((4-fluorophenyl)(methyl)amino)-2-phenylvin-
yl)-4-methylbenzenesulfonamide (3pa): colorless oil (136 mg, 70%,
PE/EA = 15:1); IR (film) vmax 3442, 2084, 1633, 1508, 1346, 1161,
1
665 cm−1; H NMR (400 MHz, DMSO-d6) δ 7.75 (d, J = 8.0 Hz,
2H), 7.41 (d, J = 8.0 Hz, 2H), 7.32−7.25 (m, 3H), 7.24−7.20 (m,
2H), 7.14−7.07 (m, 2H), 7.05−6.99 (m, 1H), 6.93 (d, J = 7.2 Hz,
2H), 6.83−6.74 (m, 2H), 6.62−6.54 (m, 2H), 5.97 (s, 1H), 4.65−
4.57 (m, 2H), 2.58 (s, 3H), 2.41 (s, 3H) ppm; 13C{1H} NMR (100
1
MHz, DMSO-d6) δ 156.0 (C−F, JC−F = 234.7 Hz), 143.8, 141.2,
137.5, 136.4 (C−F, 4JC−F = 4.1 Hz), 134.4, 129.7, 128.2, 128.1, 127.5,
127.4, 127.1, 126.6, 117.0 (C−F, 3JC−F = 7.5 Hz), 115.6, 114.7 (C−F,
2JC−F = 22.1 Hz), 51.5, 36.6, 21.0 ppm; 19F NMR (376 MHz, CDCl3)
δ −125.0 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C29H27FN2O2SNa+ 509.1670, found 509.1672.
(E)-N-Benzyl-4-methyl-N-(1-(methyl(4-(trifluoromethyl)phenyl)-
amino)-2-phenylvinyl)benzenesulfonamide (3qa): colorless oil (139
mg, 65%, PE/EA = 15:1); IR (film) vmax 3561, 2084, 1634, 1495,
1352, 1161, 665 cm−1; 1H NMR (400 MHz, DMSO-d6) δ 7.75 (d, J =
8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.31−7.24 (m, 5H), 7.24−7.20
(m, 2H), 7.15−7.04 (m, 3H), 6.94 (d, J = 7.6 Hz, 2H), 6.63 (d, J =
8.4 Hz, 2H), 6.16 (s, 1H), 4.72−4.65 (m, 2H), 2.66 (s, 3H), 2.40 (s,
3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 147.7, 143.9,
136.3 (C−F, 3JC−F = 2.0 Hz), 133.9, 129.7, 128.7, 128.2, 128.2, 127.5,
(E)-N-Benzyl-4-methyl-N-(1-(methyl(3-(trifluoromethyl)phenyl)-
amino)-2-phenylvinyl)benzenesulfonamide (3la): colorless oil (159
mg, 74%, PE/EA = 15:1); IR (film) vmax 3442, 2083, 1636, 1339,
1162, 663 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.0 Hz,
2H), 7.27−7.23 (m, 5H), 7.22−7.18 (m, 2H), 7.06−6.98 (m, 4H),
6.90−6.85 (m, 3H), 6.72−6.64 (m, 2H), 6.00 (s, 1H), 4.67−4.63 (m,
2H), 2.72 (s, 3H), 2.43 (s, 3H) ppm; 13C{1H} NMR (100 MHz,
2
127.3, 127.2, 127.1, 125.4 (C−F, 3JC−F = 2.0 Hz), 124.7 (C−F, JC−F
= 268.9 Hz), 118.8 (C−F, 1JC−F = 31.9 Hz), 118.1, 114.5, 51.9, 36.1,
20.9 ppm; 19F NMR (376 MHz, CDCl3) δ −59.7 ppm; HRMS (ESI-
Orbitrap) m/z [M + Na]+ calcd for C30H27F3N2O2SNa+ 559.1638,
found 559.1639.
1
CDCl3) δ 137.4, 137.2, 136.3, 134.5, 131.0 (C−F, JC−F = 31.0 Hz),
129.7, 129.0, 128.6, 128.3, 128.0, 127.8, 127.6, 127.2, 124.2 (C−F,
3
2JC−F = 271.0 Hz), 118.6, 117.8, 115.9 (C−F, JC−F = 3.0 Hz), 112.0
(E)-N-Benzyl-N-(1-((4-cyanophenyl)(methyl)amino)-2-phenylvin-
yl)-4-methylbenzenesulfonamide (3ra): colorless oil (122 mg, 62%,
PE/EA = 15:1); IR (film) vmax 3350, 2215, 1644, 1346, 1161, 699
2
(C−F, JC−F = 3.0 Hz), 52.7, 36.5, 21.7 ppm; 19F NMR (376 MHz,
CDCl3) δ −60.9 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd
for C30H27F3N2O2SNa+ 559.1638, found 559.1635.
1
cm−1; H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J = 8.4 Hz, 2H),
(E)-N-Benzyl-N-(1-((3-bromophenyl)(methyl)amino)-2-phenyl-
vinyl)-4-methylbenzenesulfonamide (3ma): colorless oil (207 mg,
95%, PE/EA = 15:1); IR (film) vmax 3442, 2924, 2105, 1635, 1481,
7.44 (d, J = 8.0 Hz, 2H), 7.33−7.27 (m, 5H), 7.25−7.21 (m, 2H),
7.14−7.05 (m, 3H), 6.94−6.87 (m, 2H), 6.57 (d, J = 9.2 Hz, 2H),
6.19 (s, 1H), 4.72−4.64 (m, 2H), 2.65 (s, 3H), 2.43 (s, 3H) ppm;
13C{1H} NMR (100 MHz, DMSO-d6) δ 148.2, 144.0, 136.1, 136.1,
135.5, 133.7, 132.5, 129.9, 128.4, 128.3, 128.3, 127.7, 127.3, 127.3,
119.6, 118.9, 114.8, 99.7, 51.8, 35.7, 21.0 ppm; HRMS (ESI-Orbitrap)
m/z [M + Na]+ calcd for C30H27N3O2SNa+ 516.1716, found
516.1717.
1
1347, 698 cm−1; H NMR (400 MHz, DMSO-d6) δ 7.75 (d, J = 8.4
Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.31−7.25 (m, 3H), 7.24−7.19 (m,
2H), 7.14−7.08 (m, 2H), 7.07−7.01 (m, 1H), 6.96−6.91 (m, 2H),
6.90−6.84 (m, 1H), 6.80−6.75 (m, 1H),6.68−6.64 (m, 1H), 6.52
(dd, J = 8.4, 1.6 Hz, 1H), 6.06 (s, 1H), 4.71−4.58 (m, 2H), 2.60 (s,
3H), 2.42 (s, 3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ
146.1, 143.9, 136.4, 136.3, 136.2, 134.1, 129.9, 129.8, 128.2, 128.1,
127.6, 127.3, 127.1, 127.0, 121.8, 121.5, 117.6, 117.4, 113.9, 51.6,
36.0, 21.1 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C29H27BrN2O2SNa+ 569.0869, found 569.0871.
Methyl-(E)-4-((1-((N-benzyl-4-methylphenyl)sulfonamido)-2-
phenylvinyl)(methyl)amino)benzoate (3sa): colorless oil (151 mg,
72%, PE/EA = 8:1); IR (film) vmax 3442, 2084, 1637, 1433, 1278, 664
1
cm−1; H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J = 8.0 Hz, 2H),
7.50 (d, J = 8.8 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.30−7.24 (m,
5H), 7.11−7.06 (m, 2H), 7.05−7.01 (m, 1H), 6.95−6.90 (m, 2H),
6.55 (d, J = 9.2 Hz, 2H), 6.17 (s, 1H), 4.73−4.61 (m, 2H), 3.72 (s,
3H), 2.66 (s, 3H), 2.40 (s, 3H) ppm; 13C{1H} NMR (100 MHz,
DMSO-d6) δ 165.9, 148.7, 143.9, 136.3, 136.2, 136.0, 129.9, 129.8,
128.3, 128.2, 128.2, 127.6, 127.3, 127.2, 127.2, 119.4, 118.4, 114.1,
51.7, 51.4, 35.8, 21.0 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+
calcd for C31H30N2O4SNa+ 549.1819, found 549.1822.
(E)-N-Benzyl-4-methyl-N-(1-(methyl(m-tolyl)amino)-2-
phenylvinyl)benzenesulfonamide (3na): colorless oil (158 mg, 82%,
PE/EA = 15:1); IR (film) vmax 3652, 3341, 2105, 1493, 1346, 1160,
1
697 cm−1; H NMR (400 MHz, DMSO-d6) δ 7.73 (d, J = 8.0 Hz,
2H), 7.41 (d, J = 8.0 Hz, 2H), 7.33−7.25 (m, 3H), 7.19−7.16 (m,
2H), 7.14−7.09 (m, 2H), 7.05−7.01 (m, 1H), 6.98−6.94 (m, 2H),
6.90−6.85 (m, 1H), 6.50 (d, J = 7.6 Hz, 1H), 6.44−6.33 (m, 2H),
5.99 (s, 1H), 4.60−4.51 (m, 2H), 2.58 (s, 3H), 2.41 (s, 3H), 2.05 (s,
3438
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J. Org. Chem. 2021, 86, 3433−3443

The Journal of Organic Chemistry
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Article
(E)-N-Benzyl-N-(1-(diphenylamino)-2-phenylvinyl)-4-methylben-
zenesulfonamide (3ta): white solid (159 mg, 75%, PE/EA = 10:1);
mp 127−128 °C; IR (film) vmax 3321, 2959, 1739, 1689, 1525, 1367,
1179, 833 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.4 Hz,
2H), 7.35−7.32 (m, 3H), 7.32−7.27 (m, 2H), 7.24 (d, J = 8.0 Hz,
2H), 7.13−7.09 (m, 2H), 7.08−7.02 (m, 5H), 7.02−6.97 (m, 2H),
6.95−6.89 (m, 2H), 6.87−6.82 (m, 4H), 6.27 (s, 1H), 4.63−4.58 (m,
2H), 2.48 (s, 3H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 144.1,
143.7, 137.0, 136.9, 136.1, 134.3, 129.4, 128.8, 128.6, 128.4, 128.3,
127.6, 127.6, 127.5, 126.6, 123.2, 123.1, 117.1, 51.5, 21.6 ppm;
HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for C34H30N2O2SNa+
553.1920, found 553.1920.
7.26−7.22 (m, 2H), 7.13−7.09 (m, 2H), 7.06−6.94 (m, 5H), 6.72−
6.65 (m, 1H), 6.59 (d, J = 8.0 Hz, 2H), 6.02 (s, 1H), 4.72−4.61 (m,
2H), 2.61 (s, 3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ
144.6, 138.2, 138.1, 137.4, 136.3, 134.3, 129.4, 129.3, 129.1, 129.0,
128.5, 128.3, 128.1, 127.6, 127.4, 127.1, 126.8, 126.3, 119.4, 116.4,
115.4, 51.8, 36.7 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd
for C28H25ClN2O2SNa+ 511.1218, found 511.1217.
(E)-N-Benzyl-N-(2-(4-fluorophenyl)-1-(methyl(phenyl)amino)-
vinyl)-4-methylbenzenesulfonamide (3ac): white solid (140 mg,
72%, PE/EA = 15:1); mp 113−114 °C; IR (film) vmax 3442, 2922,
1
2104, 1632, 1347, 1160, 698 cm−1; H NMR (400 MHz, DMSO-d6)
δ 7.73 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.31−7.25 (m,
3H), 7.22−7.17 (m, 2H), 7.01−6.97 (m, 3H), 6.96−6.89 (m, 3H),
6.71−6.63 (m, 1H), 6.57 (d, J = 8.0 Hz, 2H), 6.01 (s, 1H), 4.60−4.52
(m, 2H), 2.57 (s, 3H), 2.42 (s, 3H) ppm; 13C{1H} NMR (100 MHz,
(E)-N-Benzyl-N-(1-((4-bromophenyl)(phenyl)amino)-2-phenyl-
vinyl)-4-methylbenzenesulfonamide (3ua): white solid (163 mg,
67%, PE/EA = 15:1); mp 121−122 °C; IR (film) vmax 3448, 2089,
1
1636, 1487, 990, 696 cm−1; H NMR (400 MHz, DMSO-d6) δ 7.59
1
DMSO-d6) δ 160.7 (C−F, JC−F = 242.9 Hz), 144.6, 143.8, 137.0,
3
136.5, 136.4, 131.0 (C−F, 4JC−F = 3.0 Hz), 129.8, 129.0 (C−F, JC−F
(d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.31−7.26 (m, 3H),
7.21−7.16 (m, 2H), 7.11−7.08 (m, 3H), 7.08−7.04 (m, 3H), 7.03−
6.94 (m, 4H), 6.79 (d, J = 8.0 Hz, 2H), 6.55 (d, J = 9.2 Hz, 2H), 6.18
(s, 1H), 4.55−4.48 (m, 2H), 2.42 (s, 3H) ppm; 13C{1H} NMR (100
MHz, DMSO-d6) δ 143.8, 143.1, 142.8, 136.5, 136.0, 134.9, 133.5,
131.3, 129.7, 129.0, 128.3, 128.0, 127.7, 127.6, 127.5, 127.0, 126.9,
123.8, 123.7, 123.0, 117.5, 114.3, 51.2, 21.0 ppm; HRMS (ESI-
Orbitrap) m/z [M + Na]+ calcd for C34H29BrN2O2SNa+ 631.1025,
found 631.1024.
= 8.0 Hz), 128.4, 128.2, 128.1, 127.5, 127.4, 119.4, 115.4, 115.0 (C−
2
F, JC−F = 21.2 Hz), 114.9, 51.1, 36.1, 21.0 ppm; 19F NMR (376
MHz, CDCl3) δ −114.9 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+
calcd for C29H27FN2O2SNa+ 509.1670, found 509.1671.
(E)-N-Benzyl-N-(2-(4-methoxyphenyl)-1-(methyl(phenyl)amino)-
vinyl)-4-methylbenzenesulfonamide (3ad): yellow oil (155 mg,
78%, PE/EA = 15:1); IR (film) vmax 3441, 2090, 1637, 1245, 1025,
1
990, 663 cm−1; H NMR (400 MHz, DMSO-d6) δ 7.71 (d, J = 8.4
Hz, 2H), 7.39 (d, J = 8.0 Hz, 2H), 7.31−7.24 (m, 3H), 7.21−7.16 (m,
2H), 7.02−6.95 (m, 2H), 6.93 (d, J = 8.8 Hz, 2H), 6.72−6.65 (m,
3H), 6.58 (d, J = 8.0 Hz, 2H), 6.01 (s, 1H), 4.58−4.51 (m, 2H), 3.64
(s, 3H), 2.59 (s, 3H), 2.41 (s, 3H) ppm; 13C{1H} NMR (100 MHz,
DMSO-d6) δ 158.1, 144.7, 143.7, 136.6, 135.5, 135.1, 129.7, 128.6,
128.4, 128.2, 128.0, 127.4, 126.8, 118.9, 116.9, 114.9, 113.7 ppm;
HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for C30H30N2O3SNa+
521.1869, found 521.1872.
(E)-N-Benzyl-4-methyl-N-(1-(methyl(phenyl)amino)-2-(p-tolyl)-
vinyl)benzenesulfonamide (3ae): white solid (160 mg, 83%, PE/EA
= 15:1); mp 105−106 °C; IR (film) vmax 3374, 1633, 1510, 1347,
1161, 748, 698 cm−1; 1H NMR (400 MHz, DMSO-d6) δ 7.71 (d, J =
8.4 Hz, 2H), 7.42−7.38 (m, 2H), 7.29−7.25 (m, 3H), 7.20−7.16 (m,
2H), 7.00−6.96 (m, 2H), 6.94−6.90 (m, 2H), 6.88−6.84 (m, 2H),
6.67 (dd, J = 7.6, 6.8 Hz, 2H), 6.58 (d, J = 8.0 Hz, 2H), 5.99 (s, 1H),
4.57−4.53 (m, 2H), 2.57 (s, 3H), 2.42 (s, 3H), 2.16 (s, 3H) ppm;
13C{1H} NMR (100 MHz, DMSO-d6) δ 144.7, 143.8, 136.6, 136.5,
(E)-N-Be nzyl-4-meth yl- N- (2-phe nyl-1-(ph enyl(3-
(trifluoromethyl)phenyl)amino)vinyl)benzenesulfonamide (3va):
white solid (155 mg, 65%, PE/EA = 15:1); mp 119−120 °C; IR
1
(film) vmax 3417, 2106, 1632, 1493, 1333, 1162, 696 cm−1; H NMR
(400 MHz, DMSO-d6) δ 7.61 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.0 Hz,
2H), 7.28−7.23 (m, 5H), 7.18−7.12 (m, 3H), 7.09−7.03 (m, 2H),
7.02−6.96 (m, 5H), 6.95−6.92 (m, 2H), 6.66 (d, J = 8.4 Hz, 1H),
6.63−6.59 (m, 1H), 6.17 (s, 1H), 4.57−4.44 (m, 2H), 2.42 (s, 3H)
ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 144.9, 144.0, 142.0,
1
136.1, 135.9, 135.0, 133.5, 129.8, 129.5, 129.3, 129.1 (C−F, JC−F
=
31.4 Hz), 128.3, 128.0, 127.7, 127.6, 126.9, 125.2, 124.6, 123.8, 123.7
(C−F, 2JC−F = 271.1 Hz), 117.8 (C−F, 3JC−F = 3.8 Hz), 117.5, 116.7
(C−F, 3JC−F = 3.8 Hz), 51.2, 21.0 ppm; 19F NMR (376 MHz, CDCl3)
δ −56.9 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C35H29F3N2O2SNa+ 621.1794, found 621.1795.
(E)-N-(1-([1,1′-Biphenyl]-4-yl(phenyl)amino)-2-phenylvinyl)-N-
benzyl-4-methylbenzenesulfonamide (3wa): colorless oil (201 mg,
83%, PE/EA = 15:1); IR (film) vmax 3425, 2920, 2082, 1632, 1488,
1160, 749 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.4 Hz,
2H), 7.49−7.44 (m, 2H), 7.41−7.35 (m, 2H), 7.31−7.27 (m, 3H),
7.27−7.23 (m, 3H), 7.23−7.19 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H),
7.08−7.05 (m, 2H), 7.04−6.99 (m, 2H), 6.98−6.87 (m, 4H), 6.85−
6.79 (m, 4H), 6.24 (s, 1H), 4.60−4.55 (m, 2H), 2.38 (s, 3H) ppm;
13C{1H} NMR (100 MHz, CDCl3) δ 144.1, 143.8, 143.5, 140.6,
137.0, 137.0, 136.0, 135.9, 134.3, 129.5, 128.9, 128.8, 128.7, 128.5,
128.3, 127.7, 127.6, 127.4, 127.0, 126.8, 126.7, 123.4, 123.3, 117.6,
51.7, 21.6 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C40H34N2O2SNa+ 629.2233, found 629.2231.
136.3, 136.0, 131.5, 129.7, 128.8, 128.4, 128.2, 128.0, 127.4, 127.4,
127.1, 119.1, 116.6, 115.1, 51.1, 36.2, 21.0, 20.7 ppm; HRMS (ESI-
Orbitrap) m/z [M + Na]+ calcd for C30H30N2O2SNa+ 505.1920,
found 505.1923.
(E)-N-Benzyl-N-(2-(4-bromophenyl)-1-(methyl(phenyl)amino)-
vinyl)-4-methylbenzenesulfonamide (3af): white solid (159 mg,
73%, PE/EA = 15:1); mp 96−97 °C; IR (film) vmax 3442, 2085, 1633,
1495, 1090, 593 cm−1; 1H NMR (400 MHz, DMSO-d6) δ 7.73 (d, J =
8.4 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.29−7.25 (m, 5H), 7.21−7.19
(m, 2H), 6.98 (dd, J = 8.4, 7.2 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H),
6.72−6.65 (m, 1H), 6.59 (d, J = 8.0 Hz, 2H), 5.97 (s, 1H), 4.59−4.52
(m, 2H), 2.57 (s, 3H), 2.41 (s, 3H) ppm; 13C{1H} NMR (100 MHz,
DMSO-d6) δ 144.5, 143.9, 137.9, 136.4, 136.2, 133.9, 131.0, 129.8,
129.0, 128.5, 128.2, 128.1, 127.5, 127.4, 119.6, 119.2, 115.7, 114.3,
51.3, 36.3, 21.0 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C29H27BrN2O2SNa+ 569.0869, found 569.0873.
(E)-4-Methyl-N-(1-(methyl(phenyl)amino)-2-phenylvinyl)-N-phe-
nylbenzenesulfonamide (3ag): colorless oil (156 mg, 86%, PE/EA =
15:1), E/Z = 91:9 in a mixture. The major peak in the HPLC report
(Supporting Information) is the stereochemistry of E: IR (film) vmax
3367, 2922, 2091, 1642, 1354, 1206, 696 cm−1; 1H NMR (400 MHz,
DMSO-d6) δ 7.53 (d, J = 8.4 Hz, 2H, major), 7.48−7.46 (m, 0.12H,
minor), 7.43−7.39 (m, 2H, major), 7.36−7.35 (m, 0.12H, minor),
7.32−7.28 (m, 3H, major), 7.27−7.26 (m, 0.18H, minor), 7.24−7.23
(m, 0.12H, minor), 7.20 (d, J = 7.6 Hz, 2H, major), 7.18−7.17 (m,
0.18H, minor), 7.16−7.09 (m, 5H, major), 7.09−7.07 (m, 0.3H,
minor), 7.06−7.00 (m, 2H, major), 6.95−6.89 (m, 0.12H, minor),
6.78−6.71 (m, 3H, major), 6.13 (s, 1H, major), 5.93 (s, 0.06H,
(E)-N-Benzyl-N-(1-((4-methoxyphenyl)(phenyl)amino)-2-phenyl-
vinyl)-4-methylbenzenesulfonamide (3xa): colorless oil (190 mg,
85%, PE/EA = 15:1); IR (film) vmax 3396, 3063, 2047, 1630, 1348,
1
747 cm−1; H NMR (400 MHz, DMSO-d6) δ 7.54 (d, J = 8.0 Hz,
2H), 7.35−7.26 (m, 5H), 7.23−7.17(m, 2H), 7.09−7.03 (m, 2H),
7.02−6.92 (m, 3H), 6.90−6.80 (m, 4H), 6.74−6.63 (m, 3H), 6.47 (d,
J = 7.6 Hz, 2H), 6.08 (s, 1H), 4.56−4.45 (m, 2H), 3.72 (s, 3H), 2.41
(s, 3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 156.3, 144.7,
143.7, 136.7, 136.1, 135.6, 135.3, 133.8, 129.6, 128.3, 128.3, 127.9,
127.6, 127.6, 127.4, 127.0, 126.6, 125.9, 121.3, 119.9, 116.6, 114.4,
55.2, 51.0, 21.0 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C35H32N2O3SNa+ 583.2026, found 583.2026.
(E)-N-Benzyl-4-chloro-N-(1-(methyl(phenyl)amino)-2-
phenylvinyl)benzenesulfonamide (3ab): white solid (174 mg, 89%,
PE/EA = 15:1); mp 116−117 °C; IR (film) vmax 3442, 2090, 1634,
1496, 1350, 1162, 695 cm−1; 1H NMR (400 MHz, DMSO-d6) δ 7.81
(d, J = 8.4 Hz, 2H), 7.63 (d, J = 8.4 Hz, 2H), 7.33−7.27 (m, 3H),
3439
https://dx.doi.org/10.1021/acs.joc.0c02807
J. Org. Chem. 2021, 86, 3433−3443

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
minor), 2.70 (s, 3H, major), 2.59 (s, 0.18H, minor), 2.40 (s, 3H,
major), 2.34 (s, 0.18H, minor) ppm; 13C{1H} NMR (100 MHz,
DMSO-d6) δ 154.3 (minor), 145.0 (major), 144.5 (major), 139.6
(major), 138.3 (major), 136.9 (major), 134.8 (major), 130.3 (major),
130.1 (minor), 129.8 (major), 129.3 (major), 129.0 (major), 128.9
(major), 128.1 (major), 127.9 (minor), 127.7 (major), 127.5 (major),
126.6 (minor), 124.0 (minor), 119.9 (major), 119.1 (major), 115.7
(major), 115.5 (major), 38.3 (major), 26.8 (minor), 21.5 (major)
EA = 15:1); IR (film) vmax 3442, 2083, 1635, 1485, 1165, 695 cm−1;
1H NMR (400 MHz, DMSO-d6) δ 7.54 (d, J = 8.4 Hz, 2H), 7.43 (d, J
= 8.0 Hz, 2H), 7.32−7.29 (m, 4H), 7.28−7.25 (m, 1H), 7.21−7.17
(m, 2H), 7.11−7.07 (m, 3H), 6.96 (d, J = 7.2 Hz, 1H), 6.78 (dd, J =
7.8, 7.0 Hz, 1H), 6.59−6.53 (m, 1H), 6.21 (d, J = 8.0 Hz, 1H), 5.92
(s, 1H), 3.61 (dd, J = 9.0, 8.2 Hz, 2H), 2.82 (dd, J = 9.0, 8.2 Hz, 2H),
2.42 (s, 3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 144.6,
144.1, 138.5, 136.7, 134.5, 134.4, 130.0, 129.9, 129.0, 128.2, 127.9,
127.8, 127.7, 127.4, 126.5, 126.4, 124.4, 119.2, 114.0, 109.7, 50.1,
27.4, 21.1 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C29H26N2O2SNa+ 489.1607, found 489.1609.
(E)-N-Allyl-N-(1-(indolin-1-yl)-2-phenylvinyl)-4-methylbenzene-
sulfonamide (5ai): colorless oil (124 mg, 72%, E/Z = 10:1, PE/EA =
15:1); IR (film) vmax 3456, 2923, 2109, 1633, 1484, 1398, 748 cm−1;
1H NMR (400 MHz, DMSO-d6) δ 7.73 (d, J = 8.0 Hz, 2H), 7.45 (d, J
ppm; HRMS (ESI-Orbitrap) m/z [M
+
H]+ calcd for
C29H27FN2O2SNa+, 509.1669, found 509.1672; HRMS (ESI-Orbi-
trap) m/z [M + Na]+ calcd for C28H26N2O2SNa+ 477.1607, found
477.1609.
(E)-N,4-Dimethyl-N-(1-(methyl(phenyl)amino)-2-phenylvinyl)-
benzenesulfonamide (3ah): colorless oil (117 mg, 75%, PE/EA =
1
15:1); IR (film) vmax 3442, 2090, 1635, 1349, 1164, 666 cm−1; H
NMR (400 MHz, DMSO-d6) δ 7.59 (d, J = 8.4 Hz, 2H), 7.37(d, J =
8.0 Hz, 2H), 7.22−7.14 (m, 4H), 7.13−7.05 (m, 3H), 6.81−6.77 (m,
2H), 6.77−6.75 (m, 1H), 5.67 (s, 1H), 3.04 (s, 3H), 2.94 (s, 3H),
2.40 (s, 3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 145.1,
143.6, 140.8, 134.6, 129.6, 128.7, 128.3, 127.2, 127.0, 126.8, 119.1,
115.3, 114.9, 37.8, 37.5, 21.0 ppm; HRMS (ESI-Orbitrap) m/z [M +
Na]+ calcd for C23H24N2O2SNa+ 415.1451, found 415.1450.
= 8.0 Hz, 2H), 7.18−7.11 (m, 2H), 7.09−6.99 (m, 4H), 6.80−6.73
(m, 1H), 6.64−6.57 (m, 1H), 6.04 (d, J = 8.0 Hz, 1H), 5.87−5.72 (m,
1H), 5.61 (s, 1H), 5.15−5.05 (m, 2H), 3.99 (d, J = 6.4 Hz, 2H), 3.62
(dd, J = 9.4, 8.4 Hz, 2H), 3.03 (dd, J = 9.0, 8.2 Hz, 2H), 2.43 (s, 3H)
ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 144.6, 143.8, 136.0,
134.6, 132.8, 130.0, 129.7, 128.1, 127.7, 127.4, 126.4, 126.3, 124.5,
119.3, 118.9, 115.1, 109.5, 51.5, 49.3, 27.4, 21.1 ppm; HRMS (ESI-
Orbitrap) m/z [M + Na]+ calcd for C26H26N2O2SNa+ 453.1607,
found 453.1604.
(E)-N-Allyl-4-methyl-N-(1-(methyl(phenyl)amino)-2-
phenylvinyl)benzenesulfonamide (3ai): colorless oil (130 mg, 78%,
PE/EA = 15:1); IR (film) vmax 3443, 2082, 1635, 1347, 1161, 695
(E)-N-Benzyl-N-(1-(5-methylindolin-1-yl)-2-phenylvinyl)-
methanesulfonamide (5bl): white solid (115 mg, 69%, E/Z = 10:1,
PE/EA = 15:1); mp 129−130 °C.IR (film) vmax 3443, 2085, 1632,
1
cm−1; H NMR (400 MHz, DMSO-d6) δ 7.71 (d, J = 8.0 Hz, 2H),
7.38 (d, J = 8.0 Hz, 2H), 7.18−7.13 (m, 2H), 7.12−7.03 (m, 5H),
6.82 (d, J = 8.0 Hz, 2H), 6.76−6.69 (m, 1H), 5.95 (s, 1H), 5.87−5.72
(m, 1H), 5.22−5.11 (m, 2H), 4.01 (d, J = 6.0 Hz, 2H), 2.85 (s, 3H),
2.39 (s, 3H) ppm; 13C{1H} NMR (100 MHz, DMSO-d6) δ 144.8,
143.6, 137.8, 136.5, 134.4, 133.7, 129.6, 128.5, 128.2, 127.3, 127.1,
126.7, 119.3, 118.4, 116.1, 115.4, 50.7, 36.9, 21.0 ppm; HRMS (ESI-
Orbitrap) m/z [M + Na]+ calcd for C25H26N2O2SNa+ 441.1607,
found 441.1609.
1
1493, 1339, 1149, 698 cm−1; H NMR (400 MHz, CDCl3) δ 7.36−
7.29 (m, 5H), 7.19−7.13 (m, 2H), 7.12−7.02 (m, 3H), 6.95−6.89
(m, 1H), 6.68 (dd, J = 8.0, 0.4 Hz, 1H), 6.13 (d, J = 8.0 Hz, 1H), 5.77
(s, 1H), 4.52−4.48 (m, 2H), 3.67 (dd, J = 9.0, 8.2 Hz, 2H), 3.04 (dd,
J = 9.0, 8.2 Hz, 2H), 2.91 (s, 3H), 2.21 (s, 3H) ppm; 13C{1H} NMR
(100 MHz, CDCl3) δ 142.6, 135.9, 135.0, 134.1, 130.5, 129.3, 129.1,
128.7, 128.2, 127.4, 126.4, 125.6, 113.5, 110.3, 52.1, 50.5, 42.0, 28.1,
20.8 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for
C25H26N2O2SNa+ 441.1607, found 441.1606.
(E)-N-butyl-4-Methyl-N-(1-(methyl(phenyl)amino)-2-
phenylvinyl)benzenesulfonamide (3aj). colorless oil (123 mg, 71%,
PE/EA = 15:1); IR (film) vmax 3442, 2995, 2089, 1769, 1635, 1376,
(E)-N-Benzyl-N-(2-(4-bromophenyl)-1-(indolin-1-yl)vinyl)-4-
methylbenzenesulfonamide (5af): colorless oil (143 mg, 64%, E/Z =
12:1, PE/EA = 15:1); IR (film) vmax 3443, 2089, 1631, 1485, 1161,
1
1056, 628 cm−1; H NMR (400 MHz, DMSO-d6) δ 7.73 (d, J = 8.4
Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.18−7.13 (m, 2H), 7.12−7.04 (m,
5H), 6.83 (d, J = 7.6 Hz, 2H), 6.75−6.67 (m, 1H), 5.95 (s, 1H), 3.28
(dd, J = 8.2, 7.4 Hz, 2H), 2.87 (s, 3H), 2.41 (s, 3H), 1.57−1.45 (m,
2H), 1.23−1.14 (m, 2H), 0.78 (t, J = 7.4 Hz, 3H) ppm; 13C{1H}
NMR (100 MHz, DMSO-d6) δ 144.8, 143.7, 137.2, 136.5, 134.5,
129.7, 128.6, 128.2, 127.4, 127.2, 126.8, 119.3, 116.1, 115.3, 47.5,
36.6, 30.5, 21.0, 19.3, 13.5 ppm; HRMS (ESI-Orbitrap) m/z [M +
Na]+ calcd for C26H30N2O2SNa+ 457.1920, found 457.1921.
1
702 cm−1; H NMR (400 MHz, DMSO-d6) δ 7.73 (d, J = 8.4 Hz,
2H), 7.47 (d, J = 8.0 Hz, 2H), 7.31−7.29 (m, 1H), 7.28−7.25 (m,
4H), 7.21−7.17 (m, 2H), 7.04 (d, J = 7.2 Hz, 1H), 6.84 (d, J = 8.4
Hz, 2H), 6.72 (dd, J = 8.0, 7.2 Hz, 1H), 6.58 (dd, J = 7.8, 7.0 Hz,
1H), 5.75 (d, J = 8.0 Hz, 1H), 5.63 (s, 1H), 4.56−4.52 (m, 2H),
3.31−3.26 (m, 2H), 2.91 (dd, J = 8.8, 8.0 Hz, 2H), 2.45 (s, 3H) ppm;
13C{1H} NMR (100 MHz, DMSO-d6) δ 144.4, 136.4, 136.1, 134.5,
(E)-3-(1-(Methyl(phenyl)amino)-2-phenylvinyl)oxazolidin-2-one
134.0, 131.5, 130.6, 130.3, 130.0, 129.5, 128.7, 128.3, 128.0, 126.7,
125.0, 119.6, 119.3, 113.9, 110.0, 53.0, 49.5, 27.7, 21.6 ppm; HRMS
(ESI-Orbitrap) m/z [M + Na]+ calcd for C30H27BrN2O2SNa+
581.0869, found 581.0872.
(3ak): white solid (158 mg, 82%, PE/EA = 4:1); mp 98−99 °C; IR
1
(film) vmax 3562, 2083, 1754, 1645, 1448, 1211, 755 cm−1; H NMR
(400 MHz, DMSO-d6) δ 7.29−7.25 (m, 5H), 7.23−7.22 (m, 1H),
7.18−7.12 (m, 1H), 6.86−6.81 (m, 2H), 6.82−6.79 (m, 1H), 6.20 (s,
1H), 4.25−4.19 (m, 2H), 3.66−3.58 (m, 2H), 3.03 (s, 3H) ppm;
13C{1H} NMR (100 MHz, DMSO-d6) δ 155.4, 145.0, 136.1, 134.5,
129.2, 128.5, 127.1, 126.8, 119.0, 113.9, 113.8, 61.6, 44.2, 37.5 ppm;
HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for C18H18N2O2Na+
317.1261, found 317.1256.
(E)-N-Benzyl-N-(1-(3,4-dihydroquinolin-1(2H)-yl)-2-phenylvinyl)-
4-methylbenzenesulfonamide (5ca): white solid (118 mg, 60%, E/Z
= 10:1, PE/EA = 15:1); mp 137−138 °C; IR (film) vmax 3519, 2083,
1632, 1493, 1159, 696 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.65 (d,
J = 8.0 Hz, 2H), 7.26−7.22 (m, 4H), 7.22−7.19 (m, 3H), 7.13−7.03
(m, 5H), 6.92 (d, J = 7.6 Hz, 1H), 6.75−6.69 (m, 1H), 6.65−6.58 (m,
1H), 6.48 (dd, J = 8.2, 0.6 Hz, 1H), 6.03 (s, 1H), 4.66−4.58 (m, 2H),
3.17−3.03 (m, 2H), 2.66 (dd, J = 6.8, 6.0 Hz, 2H), 2.42 (s, 3H),
1.77−1.70 (m, 2H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 143.7,
140.6, 137.7, 137.2, 136.9, 135.2, 129.5, 129.2, 128.5, 128.4, 128.2,
128.1, 127.8, 127.6, 126.8, 126.7, 124.5, 119.2, 117.2, 116.1, 51.6,
47.8, 27.7, 21.9, 21.7 ppm; HRMS (ESI-Orbitrap) m/z [M + Na]+
calcd for C31H30N2O2SNa+ 517.1920, found 517.1923.
(E)-N-(1-(Indolin-1-yl)-2-phenylvinyl)-N,4-dimethylbenzenesulfo-
namide (5ah): white solid (100 mg, 62%, E/Z = 10:1, PE/EA =
15:1); mp 98−99 °C; IR (film) vmax 3443, 2089, 1632, 1484, 1156,
1
696 cm−1; H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.4 Hz, 2H),
7.28 (d, J = 8.0 Hz, 2H), 7.19−7.14 (m, 2H), 7.12−7.04 (m, 4H),
6.91−6.85 (m, 1H), 6.74−6.67 (m, 1H), 6.22 (d, J = 7.6 Hz, 1H),
5.45 (s, 1H), 3.76 (dd, J = 9.0, 8.2 Hz, 2H), 3.11 (dd, J = 9.0, 8.2 Hz,
2H), 3.07 (s, 3H), 2.44 (s, 3H) ppm; 13C{1H} NMR (100 MHz,
CDCl3) δ 145.5, 143.8, 136.8, 135.2, 130.6, 129.5, 128.3, 128.1, 128.0,
127.0, 126.4, 124.7, 119.5, 113.1, 110.7, 50.5, 37.8, 28.5, 21.7 ppm;
HRMS (ESI-Orbitrap) m/z [M + Na]+ calcd for C24H24N2O2SNa+
427.1451, found 427.1453.
(E)-N-(1-(3,4-Dihydroquinolin-1(2H)-yl)-2-phenylvinyl)-N,4-di-
methylbenzenesulfonamide (5ch): white solid (85 mg, 51%, E/Z =
10:1, PE/EA = 15:1); mp 123−124 °C; IR (film) vmax 3442, 2939,
1
2091, 1631, 1493, 1172, 749 cm−1; H NMR (400 MHz, CDCl3) δ
7.59 (d, J = 8.4 Hz, 2H), 7.22−7.18 (m, 3H), 7.17−7.13 (m, 3H),
7.12−7.07 (m, 1H), 6.99−6.92 (m, 2H), 6.74−6.68 (m, 1H), 6.63
(dd, J = 8.4, 0.8 Hz, 1H), 5.73 (s, 1H), 3.34 (dd, J = 6.2, 5.4 Hz, 2H),
(E)-N-(1-(Indolin-1-yl)-2-phenylvinyl)-4-methyl-N-phenylbenze-
nesulfonamide (5ag): colorless oil (140 mg, 61%, E/Z = 10:1, PE/
3440
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J. Org. Chem. 2021, 86, 3433−3443

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
3.09 (s, 3H), 2.74 (dd, J = 6.8, 6.0 Hz, 2H), 2.40 (s, 3H), 2.06−1.85
(m, 2H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 143.6, 141.0,
140.4, 135.7, 135.3, 129.4, 129.3, 128.4, 127.6, 127.5, 126.9, 126.6,
124.9, 119.2, 116.2, 115.7, 48.9, 37.8, 27.6, 21.9, 21.6 ppm; HRMS
(ESI-Orbitrap) m/z [M + Na]+ calcd for C25H26N2O2SNa+ 441.1607,
found 441.1609.
AUTHOR INFORMATION
Corresponding Authors
■
Chang-Mei Si − School of Pharmacy and Institutes of
Biomedical Sciences, Fudan University, Shanghai 201203,
China; Email: sicm@fudan.edu.cn
Bang-Guo Wei − School of Pharmacy and Institutes of
Biomedical Sciences, Fudan University, Shanghai 201203,
China; orcid.org/0000-0003-3470-6741;
Email: bgwei1974@fudan.edu.cn
(E)-N-Benzyl-N-(1-(3,4-dihydroquinolin-1(2H)-yl)-2-phenylvinyl)-
methanesulfonamide (5cl): white solid (107 mg, 64%, E/Z = 10:1,
PE/EA = 15:1); mp 122−123 °C; IR (film) vmax 3442, 2084, 1633,
1
1493, 1339, 1148, 697 cm−1; H NMR (400 MHz, CDCl3) δ 7.42−
7.38 (m, 2H), 7.37−7.29 (m, 3H), 7.20−7.15 (m, 4H), 7.12−7.07
(m, 1H), 7.03 (d, J = 7.6 Hz, 1H), 7.00−6.94 (m, 1H), 6.82 (d, J =
8.0 Hz, 1H), 6.76−6.70 (m, 1H), 6.01 (s, 1H), 4.65−4.55 (m, 2H),
3.34−3.22 (m, 2H), 2.79−2.76 (m, 2H), 2.76 (s, 3H), 1.96−1.82 (m,
2H) ppm; 13C{1H} NMR (100 MHz, CDCl3) δ 140.9, 138.4, 136.7,
135.0, 129.5, 128.8, 128.6, 128.4, 128.0, 127.7, 127.0, 126.9, 124.8,
119.7, 117.0, 116.3, 51.9, 48.6, 42.1, 27.5, 22.0 ppm; HRMS (ESI-
Orbitrap) m/z [M + Na]+ calcd for C25H26N2O2SNa+ 441.1607,
found 441.1608.
Authors
Xiao-Di Nie − School of Pharmacy and Institutes of
Biomedical Sciences, Fudan University, Shanghai 201203,
China
Xiao-Li Han − School of Pharmacy and Institutes of
Biomedical Sciences, Fudan University, Shanghai 201203,
China
Jian-Ting Sun − School of Pharmacy and Institutes of
Biomedical Sciences, Fudan University, Shanghai 201203,
China
(E)-N-Allyl-N-(1-(3,4-dihydroquinolin-1(2H)-yl)-2-phenylvinyl)-4-
methylbenzenesulfonamide (5ci): white solid (121 mg, 68%, E/Z =
10:1, PE/EA = 15:1); mp 101−102 °C; IR (film) vmax 3442, 2089,
Guo-Qiang Lin − Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
1
1634, 1493, 1346, 1160, 696 cm−1; H NMR (400 MHz, CDCl3) δ
7.74 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.16−7.11 (m,
4H), 7.10−7.03 (m, 1H), 6.95 (d, J = 7.2 Hz, 1H), 6.88−6.82 (m,
1H), 6.76−6.72 (m, 1H), 6.69−6.62 (m, 1H), 6.00 (s, 1H), 5.91−
5.79 (m, 1H), 5.15 (dd, J = 7.6, 1.2 Hz, 1H), 5.13−5.09 (m, 1H), 4.05
(d, J = 6.0 Hz, 2H), 3.28 (dd, J = 6.2, 5.4 Hz, 2H), 2.72 (d, J = 6.8, 6.0
Hz, 2H), 2.41 (s, 3H), 1.94−1.82 (m, 2H) ppm; 13C{1H} NMR (100
MHz, CDCl3) δ 143.7, 140.8, 137.5, 137.4, 135.1, 133.8, 129.5, 129.2,
128.3, 127.9, 127.8, 126.9, 126.6, 124.3, 119.2, 118.3, 117.2, 116.2,
50.9, 48.1, 27.6, 21.9, 21.6 ppm; HRMS (ESI-Orbitrap) m/z [M +
Na]+ calcd for C27H28N2O2SNa+ 467.1764, found 467.1766.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02807
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(21772027 to B.-G.W. and 21702032 to C.-M.S.) for financial
support. The authors also thank Dr. Han-Qing Dong (Arvinas,
Inc.) for helpful suggestions.
(E)-N-Benzyl-N-(2-(4-bromophenyl)-1-(3,4-dihydroquinolin-
1(2H)-yl)vinyl)-4-methylbenzenesulfonamide (5cf): white solid (140
mg, 61%, E/Z = 12:1, PE/EA = 15:1); mp 107−108 °C; IR (film)
1
vmax 3418, 2088, 1631, 1491, 1128, 701 cm−1; H NMR (400 MHz,
REFERENCES
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DMSO-d6) δ 7.74 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.30
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̈
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J. Org. Chem. 2021, 86, 3433−3443