AgOTf-catalyzed reaction of sulfonyl hydrazones with ynamides led to stereoselective synthesis of α-amino alkenyl-substituted hydrazone derivatives

Article abstract of DOI:10.1016/j.tet.2019.130534

A novel method for the synthesis of α-amino alkenyl-substituted hydrazone derivatives was disclosed through silver-catalyzed reaction of sulfonyl hydrazones with ynamides. The present method features mild conditions, high stereoselectivity and good yields. The proposed mechanism involves silver-mediated generation of a keteniminium ion intermediate to facilitate the stereoselective addition of hydrazones in the presence of K₂CO₃, while pyrazole ring could not be constructed under the current conditions.

Full text of DOI:10.1016/j.tet.2019.130534

Tetrahedron 75 (2019) 130534
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AgOTf-catalyzed reaction of sulfonyl hydrazones with ynamides led to
stereoselective synthesis of
derivatives
a-amino alkenyl-substituted hydrazone
a
,
b
,
*
, Shikun Yan , Changyin Zhao , Xuejun Sun , Laijin Tian b, Xin Meng a
a
a
a
a
,
, **
Ziping Cao
a
School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, PR China
Shandong Key Laboratory of Life-Organic Analysis, Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, Qufu 273165, PR
b
China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 June 2019
Received in revised form
A novel method for the synthesis of a-amino alkenyl-substituted hydrazone derivatives was disclosed
through silver-catalyzed reaction of sulfonyl hydrazones with ynamides. The present method features
mild conditions, high stereoselectivity and good yields. The proposed mechanism involves silver-
mediated generation of a keteniminium ion intermediate to facilitate the stereoselective addition of
13 August 2019
Accepted 16 August 2019
Available online 21 August 2019
hydrazones in the presence of K
conditions.
2
CO
3
, while pyrazole ring could not be constructed under the current
©
2019 Elsevier Ltd. All rights reserved.
Keywords:
Hydrazone
Ynamide
Enamide
Silver catalysis
Alkenylation
1
. Introduction
diaryliodonium salts or arylboronic acids with hydrazones could
lead to N-arylation products [7,8]. By contrast, the N-alkenylation of
hydrazones were rarely reported. One of major reasons responsible
for this fact is that hydrazones are readily converted into diazo
intermediate under base conditions. Recently, Shi and Hashemi
independently reported the aza-Michael addition reactions of
hydrazones with propiolate derivatives in the presence of DABCO
N-Tosylhydrazones are
a
class of important organic in-
termediates, and have been utilized in a large number of organic
transformations [1]. For example, N-tosylhydrazones can act as
efficient diazo precursors for various carbene or carbenoid-
participated reactions like the cyclopropanation of alkenes and
alkylation of XeH bonds (Scheme 1a) [2,3]. The in-situ generated
diazo compounds was also frequently used as good 1,3-dipolars in
cycloaddition or related reactions (Scheme 1b) [4]. However, the
utilization of N-tosylhydrazones has not yet been fully explored,
especially for the applications as nucleophiles or electrophiles. Our
research interest is in the NeH functionalization of hydrazones as
nucleophiles (Scheme 1c). In this respect, the alkylation of NeH
bonds of hydrazones was readily achieved through substitution
reaction and addition reaction [5,6]. Copper-catalyzed reactions of
3
and PPh respectively, achieving the synthesis of N-alkenylation
derivatives [9]. Even so, the development of new reactions to build
the N-alkenylation products is still meaningful to expand hydra-
zone chemistry. In addition, as a class of structurally new sulfon-
amide products, they possess potential applications in
pharmaceuticals [10], bioactive compounds [11], dyes and herbi-
cides [12].
Ynamides are also a class of useful building blocks for various
organic transformations [13,14]. The addition to alkyne motif is one
of the most important transformations of ynamides, and is an
efficient method for introducing
a-amino alkenyl groups (Scheme
2
). In this context, various nucleophilic substrates were examined
*
Corresponding author. School of Chemistry and Chemical Engineering, Qufu
for achieving such a type of reactions [15e17]. For example, free
amines or protected amides have been used for providing a variety
of interesting products under metal-catalyzed or metal-free con-
ditions (Scheme 2(a,b)) [18e20]. Recently, our group reported the
Normal University, Qufu 273165, PR China.
** Corresponding author.
E-mail addresses: caozp_qfnu@163.com (Z. Cao), mengxin1108@163.com
(
X. Meng).
https://doi.org/10.1016/j.tet.2019.130534
040-4020/© 2019 Elsevier Ltd. All rights reserved.
0

2
Z. Cao et al. / Tetrahedron 75 (2019) 130534
a condition.
Next, a series of metal catalysts were screened to improve the
yield of 3aa (Table 1, entries 2e11). Other silver salts such as AgNO
and AgNTf also leaded to the formation of product 3aa but with
3
2
lower yields (Table 1, entries 2e6). The addition of 4 Å molecular
sieves lowered the yield of 3aa to only 13% (Table 1, entry 7). Among
other metal catalysts examined, CuOTfꢁC
AgOTf and afforded the adduct 3aa in 50% yield, whereas FeCl
In(OTf) and AuCl did not work for the addition reaction (Table 1,
6 6
H was less reactive than
3
,
3
3
entries 8e11). Subsequently, the examination of solvents indicated
that no better yield of product was obtained (Table 1, entries
Scheme 1. The reactivities of N-tosylhydrazones for various organic transformations.
2 3 2 3
12e16). Various carbonates as the bases such as Na CO and Cs CO
were proven to be suitable to current reaction albeit with low ef-
t
ficiencies, whereas the stronger bases (KO Bu) were inefficient for
the formation of 3aa (Table 1, entries 17e20). The utility of several
organic bases (Et N, DIPEA, DABCO and DBU) cannot afford the
3
adduct 3aa in better yields (Table 1, entries 21e24). Furthermore,
temperature effects were rapidly tested, and the product 3aa could
be obtained in 56 and 75% yields at the temperatures of 25 and
ꢀ
6
0 C, respectively (Table 1, entries 25e26). Finally, the optimal
reaction conditions were established involving with the use of
ꢀ
AgOTf and K
2
CO
3
in DCE at 40 C (Table 1, entry 2).
With the optimized conditions in hand, the scope of ynamide
substrates was firstly investigated and summarized in Table 2. It
could be found that the substrates 2b-d containing an electron-
donor or electron-deficient group on phenyl of aryl ynamides
with hydrazone 1a could be readily converted into the desired
adducts 3 ab-ad in 36e74% yields. The meta-substituted aryl yna-
mide 2e was also a good substrate to form the product 3ae. Alkyl
substituted ynamides such as 2f could lead to the formation of 3af
in 73% yield. In particular, the reaction of the bulky tert-butyl-
substituted ynamide 2g with 1a could proceed efficiently to give
the a-amino alkenyl-substituted hydrazone 3 ag in moderate yield.
Scheme 2. The reactions of N-containing nucleophiles with ynamides.
In addition, the nitrogen substituents of ynamides were examined
as well. The results showed that ynamide 2h bearing with a linear
alkyl group was reactive under current conditions, leading to syn-
thesis of 3ah in 64% yield, whereas the larger isopropyl substituent
could not be suitable. The protected sulfonyl of ynamides could be
replaced with para- or ortho-nitrobenzenesulfonyl (p-Ns or o-Ns,
reactions of nitrogen-containing heterocycles (2H-tetrazole) with
ynamides in the absence of any catalyst [21], which facilitates the
chemical modification of tetrazole drugs (Scheme 2(c)). Following
our ongoing interests in the alkyne chemistry [22], we envisage
that the reaction of N-tosylhydrazones with ynamides can realize
the alkenylation of the NeH bond of hydrazones (Scheme 2(d)).
3ai-aj), or alkylsulfonyl (3ak) groups. However, the oxazolidin-2-
one derived ynamides such as 2l could be not good substrate for
current reaction, affording an inseparable mixture. In addition, the
Herein we reported the synthesis of a-amino alkenyl-substituted
terminal
ynamides
such
as
N-ethynyl-N,4-
hydrazone derivatives by silver catalysis. The mechanism was
proposed to involve the nucleophilic addition to the keteniminium
intermediates in situ generated from ynamides by silver catalysis.
This process is different from the well-known cycloaddition route
of alkynes and hydrazones to give the pyrazole product [23]. To the
best of our knowledge, this reactivity of N-tosylhydrazones with
ynamides has not yet been reported.
dimethylbenzenesulfonamide were incompatible for this reaction,
leading to the formation of hydrolytic amides.
Next, various arylaldehyde-derived hydrazones were examined
(Table 2). The substrate 1b with a methoxyl group can react with
ynamide 2a to produce -amino alkenyl-substituted hydrazone 3ba
a
efficiently. Somewhat surprisingly, the addition of p-tolylaldehyde-
derived hydrozone 1c with 2a could not proceed under the opti-
mized conditions. This limitation in reactivity could be overcome
by changing the protecting group (Ts-) of hydrazones for para-
nitrobenzenesulfonyl. Thus, the reaction of hydrazone 1d with 2a
could proceed smoothly, affording the desired product 3da in good
efficiency. This change was also required for other hydrazones for
achieving the present transformations efficiently. As exemplified,
p-Ns-protecting hydrazones 1e-f bearing with electron-deficient
halo-substituents were tolerated to form the addition product
3ea and 3fa in 79% and 59% yields, respectively. m-Tolylaldehyde-
derived hydrozone 1g was suitable for this reaction, leading to the
formation of 3ga in 69% yield. It should be noted that the addition
reaction could be also readily achieved in good yields with the
utilization of hydrozones 1h and 1i that have a sterically hindered
ortho-substituent. In addition, a heteroarene-substituted hydro-
2
. Results and discussion
Initial experiments were carried out with sulfonyl hydrazone 1a
(
0.39 mmol, 1.3 equiv) and ynamide 2a (0.3 mmol, 1.0 equiv) as the
substrates, using AgOTf (0.2 equiv) as a catalyst and NaH (2.0 equiv)
ꢀ
as a base in 1,2-dichloroethane (DCE, 0.5 mL) at 40 C for providing
the aminocyclopropene product 5 [2b]. However, no reaction
occurred (Table 1, entry 1). By replacing NaH with K CO , to our
2 3
delight, a new product can be obtained in 81% yield and charac-
terized as a simple adduct 3aa possessing an E-type alkene motif,
along with a small amount of hydrolytic by-product 4 (Table 1,
entry 2). Notably, the addition reaction can proceed in a highly
stereoselective manner. It should be also mentioned that neither
cyclopropene nor pyrazole products could be observed under such
zone 1j was compatible to current reaction, and the desired
a-

Z. Cao et al. / Tetrahedron 75 (2019) 130534
3
Table 1
a
The optimization of reaction conditions.
Entry
Cata.(0.2 equiv)
Base (2.0 equiv)
NaH
Solvent (0.5 mL)
Time (h)
Yield 3aa (%)b
1
2
3
4
5
6
AgOTf
AgOTf
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
12
4
12
24
12
5
24
12
12
4
12
12
12
12
12
4
4
4
4
12
12
12
12
12
2.5
6
0
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
2
K CO
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
81
62
54
64
45
13
0
0
50
0
0
0
15
0
80
40
45
72
0
16
20
0
AgNO
AgNTf
AgSbF
3
2
6
AgBF
AgOTf
FeCl
In(OTf)
CuOTfꢁC
AuCl
4
c
7
8
9
3
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
H
6 6
3
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
CH
3
CN
THF
toluene
DMFd
DCM
DCE
DCE
DCE
DCE
DCE
DCE
DCE
Cs
Na
KHCO
2
CO
3
2
CO
3
3
t
KO Bu
Et
DIPEA
3
N
DABCO
DBU
DCE
DCE
DCE
0
75
56
e
f
K
K
2
CO
CO
3
3
2
a
All the reactions were carried out with hydrazone 1a (120.4 mg, 0.39 mmol, 1.3 equiv), ynamide 2a (85.6 mg, 0.3 mmol, 1.0 equiv), Base (2.0 equiv) with catalyst (0.2 equiv)
in the indicated solvent (0.5 mL), unless otherwise noted.
b
Yield of isolated product 3aa; The amide 4 of less than 10% were observed for all of reactions.
c
4
Å MS (30 mg) was added.
d
e
f
Dry DMF was used.
ꢀ
At 60 C.
ꢀ
At 25 C.
amino alkenyl-substituted hydrazone 3ja can be provided in 70%
yield. The structure of 3ja was also confirmed by X-ray crystal
analysis (Fig. 1, left part), indicating the syn-addition of hydro-
zone1j to ynamide 2a to afford the E-type product. [24] The use of
3. Conclusion
In summary, we have developed a silver-catalyzed stereo-
selective addition reaction of sulfonyl hydrazones with ynamides to
prepare functionalized a-amino alkenyl-substituted hydrazone
1
NOESY H NMR data (3ja) allowed for further confirmation of the
assigned alkenyl-hydrozone geometry (Fig. 1, right part). The con-
figurations of alkene unit of other products (Table 2) were tenta-
tively assigned by analogy with that of 3ja.
products in good yields. Compared with the previously-reported
reactions of hydrazones with alkynes, the present reaction pro-
ceeds without the generation of diazo intermediate or silver car-
bene. This reaction was proposed to involve the silver-mediated
generation of keteniminium intermediate and base-promoted for-
mation of hydrazone anion, which may be often ignored as basic
processes towards for the NeH functionalization of hydrazones.
Further works will focus on the investigation of detailed mecha-
nism and the bioactivity studies of these sulfonamide products.
The proposed mechanism for silver-catalyzed synthesis of 3aa is
outlined in Scheme 3 [13,21]. On the one hand, the base-mediated
deprotonation of sulfonyl hydrazone 1a can afford anion A (or
0
expressed as the resonance structure A ). On the other hand, the
coordination of alkyne motif of 2a to silver cation can form complex
B which is in equilibrium with the reactive keteniminium ion in-
termediate C. Subsequently, the addition of nitrogen anion A to C
and the protodemetalation afford the desired
a-amino alkenyl-
substituted hydrazone 3aa. Notably, the formation of neither
diazo nor silver carbene intermediates were observed, presumably
because the highly reactive ynamides can rapidly capture the ni-
trogen anion A, thus preventing the further transformation of A to
4. Experimental section
4.1. General methods
0
All reactions were carried out under air atmosphere, unless
otherwise indicated. All reagents were purchased from commercial
sources and used without further purification. H and C NMR
diazo intermediate (via A ). The addition of A to keteniminium C
prefers the orientation a rather than the orientation b due to the
greater steric effect of phenyl relative to [Ag], and thus leads to the
formation of syn-adduct 3aa (Scheme 3).
1
13
1
spectra were recorded on a Bruker Avance III HD 500 (500.1 MHz, H;
13
1
25.8 MHz, C) instrument operating at the denoted spectrometer

4
Z. Cao et al. / Tetrahedron 75 (2019) 130534
Table 2
The scope of ynamide 2 and hydrazone 1 substratesa,b.
Scheme 3. The proposed mechanism for the formation of 3aa by silver catalysis.
NMR spectra and calibrated against the solvent residual peak.
Multiplicities are reported as follows: b ¼ broad, s ¼ singlet,
d ¼ doublet, t ¼ triplet, q ¼ quartet, m ¼ multiplet, or as combina-
tion of them. Coupling constants J are given in Hertz (Hz). Melting
points were measured with an X-4 microscope apparatus and were
uncorrected. High-resolution mass spectrometry with electrospray
ionization (ESI-HRMS) was recorded on a Bruke P-SIMS-Gly FT-ICR
mass spectrometer.
4.2. General experimental procedure for synthesis of hydrazones
1a-j
A round-bottom flask charged with a stirring bar, aldehyde
(
10 mmol, 1.0 equiv) and sulfonyl hydrazide [25] (10 mmol, 1.0
ꢀ
equiv) in EtOH (10 mL) was placed into a bath oil of 70 C for 2e3 h.
After completion detected by TLC analysis, with cooling, white
precipitate was formed, and then filtered and washed by cold
alcohol for 3e5 times to afford pure hydrazone product in usually
>80% yield.
4.3. General experimental procedure for synthesis of ynamides 2a-l
A Schlenk flask charged with a stirring bar, sulfonamide
(
(
12 mmol, 1.2 equiv), K
1.0 mmol, 10 mol%), and 1,10-phenanthroline (2.0 mmol, 20 mol%)
, repeatedly for 3 times, and
2 3 4 2
CO (20 mmol, 2.0 equiv), CuSO ‧5H O
frequency given in mega Hertz (MHz) for the specified nucleus.
was vacuumed and backfilled with N
2
Chemical shifts are given in parts per million (ppm) relative to
then a solution of alkynyl bromide [26] (10 mmol, 1.0 equiv) in
toluene (10 mL, 1 M) was added to the mixture by a syringe. The
1
13
tetramethylsilane (TMS) as an external standard for H and
C
Fig. 1. X-ray structure of product 3ja (left) and confirmation of geometry through NOESY 1H NMR analysis (right).

Z. Cao et al. / Tetrahedron 75 (2019) 130534
5
ꢀ
resulting mixture was heated to 60 C for 24e48 h. After comple-
tion, the mixture was filtered through celite pad, and the filtrate
was concentrated under reduced pressure. The residue was sub-
jected to column chromatography on silica gel (PE/EtOAc ¼ 20/1e5/
C
13
H
11ClN
3
O
4
S (M þ H) 340.0153, found340.0157.
(E)-N'-(2-bromobenzylidene)-4-nitrobenzenesulfonohydrazide
ꢀ
(1i): Yellow solid, m.p. 180.1e180.9 C, yield 85%; R
f
¼ 0.19 (PE/
1
EtOAc ¼ 5/1); H NMR (DMSO‑d
6
, 500 MHz):
d
12.18 (b, 1H), 8.44
1
) to give the ynamide product.
(ddd, J ¼ 9.0, 2.4, 2.0 Hz, 2H), 8.26 (s, 1H), 8.14 (ddd, J ¼ 8.9, 2.4,
2
.0 Hz, 2H), 7.76 (dd, J ¼ 7.8, 1.7 Hz, 1H), 7.65 (dd, J ¼ 8.0, 1.1 Hz, 1H),
13
4
.4. Typical experimental procedure for synthesis of 3aa
7.41 (dd, J ¼ 7.5, 7.2 Hz, 1H), 7.34 (ddd, J ¼ 7.9, 7.5, 1.8 Hz, 1H);
C
6
NMR (DMSO‑d , 125.8 MHz): d 150.0, 146.2, 144.1, 133.1, 132.1, 132.0,
An oven-dried Schlenk tube charged with a magnetic stirred bar,
128.8, 128.2, 127.1, 124.7, 123.3. HRMS (ESI) m/z calcd for
þ
sulfonyl hydrazones 1a (120.4 mg, 0.39 mmol, 1.3 equiv), ynamide
a (85.6 mg, 0.3 mmol, 1.0 equiv), K CO (82.8 mg, 0.6 mmol, 2.0
equiv) and AgOTf (15.4 mg, 0.06 mmol, 0.2 equiv) was sealed with a
stopper, then vacuumed and filled with N repeatedly for three
C
13
H
11BrN
3
O
4
S (M þ H) 383.9648, found 383.9651.
2
2
3
(E)-4-Nitro-N'-(thiophen-2-ylmethylene)benzenesulfonohy-
ꢀ
drazide (1j): yellow solid, m.p. 152.1e153.0 C, yield 92%; R
f
¼ 0.17
1
2
(PE/EtOAc ¼ 5/1); H NMR (DMSO‑d
6
, 500 MHz):
d
11.80 (b, 1H),
times. Subsequently, DCE (0.5 mL) was added by a syringe, followed
8.44 (ddd, J ¼ 9.0, 2.4, 2.1 Hz, 2H), 8.14 (s, 1H), 8.09 (d, J ¼ 8.9 Hz,
by the mixture was stirred and placed into a preheated oil bath of
2H), 7.62 (d, J ¼ 5.0 Hz, 1H), 7.39 (dd, J ¼ 3.6, 1.0 Hz, 1H), 7.07 (dd,
ꢀ
13
4
0 C for about 4 h after the completion, the resulting mixture was
J ¼ 5.0, 3.7 Hz, 1H); C NMR (DMSO‑d
6
, 125.8 MHz): d 150.0, 144.1,
quenched with water (2 mL), and extracted with DCM (5 mL) for
three times. The combined organic phase was washed with brine
143.5, 137.8, 131.3, 129.1, 128.8, 127.9, 124.6. HRMS (ESI) m/z calcd
þ
for C11
H
10
N
3
O
4
S
2
(M þ H) 312.0107, found 312.0104.
and dried over anhydrous MgSO
4
. After the filtration of desiccant,
N-methyl-N-(phenylethynyl)ethanesulfonamide (2k): white solid,
ꢀ
1
the solution was condensed by a rotary evaporator. The residue was
suffered to column chromatography to give the addition product
aa.
m.p. 59.8e60.5 C, yield 51%; R
(CDCl , 500 MHz):
f
¼ 0.38 (PE/EtOAc ¼ 5/1); H NMR
3
d
7.40-7.35 (m, 2H), 7.30-7.23 (m, 3H), 3.33-3.27
1
3
3
(m, 5H),1.44 (t, J ¼ 6.7 Hz, 3H); C NMR (CDCl
3
, 125.8 MHz): d 131.3,
128.2, 127.9, 122.5, 83.3, 69.0, 45.6, 39.4, 7.9. HRMS (ESI) m/z calcd
þ
4
.5. Analytical data for all new compounds [27]
for C11
H14NO
2
S (M þ H) 224.0740, found 224.0735.
N-((E)-1-(2-((E)-4-chlorobenzylidene)-1-tosylhydrazinyl)-2-
(
E)-N'-(4-methylbenzylidene)-4-nitrobenzenesulfonohydrazide
phenylvinyl)-N,4-dimethylbenzenesulfonamide (3aa): white solid,
ꢀ
ꢀ
(
1d): yellow solid, m.p. 147.4e148.2 C, yield 83%; R
f
¼ 0.60 (PE/
11.76 (b, 1H), 8.43
ddd, J ¼ 9.0, 2.4, 2.0 Hz, 2H), 8.13 (ddd, J ¼ 9.0, 2.1, 2.0 Hz, 2H), 7.92
s, 1H), 7.47 (d, J ¼ 8.2 Hz, 2H), 7.20 (d, J ¼ 8.0 Hz, 2H), 2.30 (s, 3H);
m.p. 88.3e89.1 C, yield 144.2 mg, 80.9%; R
f
¼ 0.58 (PE/EtOAc ¼ 5/
1
1
EtOAc ¼ 3/1); H NMR (DMSO‑d
6
, 500 MHz):
d
1); H NMR (CDCl
3
, 500 MHz):
d
8.41 (s, 1H), 7.82 (d, J ¼ 8.3 Hz, 2H),
(
(
7.77 (d, J ¼ 8.2 Hz, 2H), 7.63 (d, J ¼ 8.5 Hz, 2H), 7.43-7.39 (m, 4H),
7.38-7.30 (m, 7H), 5.34 (s, 1H), 3.07 (s, 3H), 2.47 (s, 3H), 2.44 (s, 3H);
1
3
13
C NMR (DMSO‑d
6
, 125.8 Hz):
d
149.9, 148.4, 144.3, 140.2, 130.7,
3
C NMR (CDCl , 125.8 MHz): d 148.2, 144.8, 144.0, 136.2, 135.5,
1
C
29.4, 128.8, 126.9, 124.6, 21.0. HRMS (ESI) m/z calcd for
135.0, 132.5, 132.3, 132.0.129.6, 129.3, 129.2, 128.94, 128.93, 128.88,
þ
14
H
14
N
3
O
4
S (M þ H) 320.0700, found 320.0698.
128.6, 128.0, 127.6, 37.0, 21.71, 21.67. HRMS (ESI) m/z calcd for
þ
(
E)-N'-(4-fluorobenzylidene)-4-nitrobenzenesulfonohydrazide
C
30
H29ClN
3
O
S
4 2
(M þ H) 594.1283, found 594.1286.
ꢀ
(
1e): yellow solid, m.p. 149.5e150.4 C, yield 87%; R
f
¼ 0.21 (PE/
11.87 (b, 1H), 8.43
ddd, J ¼ 8.9, 2.5, 2.0 Hz, 2H), 8.14 (ddd, J ¼ 9.0, 2.4, 2.0 Hz, 2H), 7.97
N-((E)-1-(2-((E)-4-chlorobenzylidene)-1-tosylhydrazinyl)-2-(4-
1
EtOAc ¼ 3/1); H NMR (DMSO‑d
6
, 500 MHz):
d
methoxyphenyl)vinyl)-N,4-dimethylbenzenesulfonamide
(3 ab):
¼ 0.49
ꢀ
(
(
(
white solid, m.p. 110.1e112.2 C, yield 137.8 mg, 73.6%; R
f
13
1
s, 1H), 7.69-7.59 (m, 2H), 7.23 (dd, J ¼ 8.9, 8.9 Hz, 2H); C NMR
DMSO‑d , 125.8 MHz):
163.2 (d, J ¼ 248.2 Hz), 150.0, 147.2, 144.2,
(PE/EtOAc ¼ 3/1); H NMR (CDCl
3
, 500 MHz): d 8.39 (s, 1H), 7.79 (d,
6
d
J ¼ 8.3 Hz, 2H), 7.75 (d, J ¼ 8.3 Hz, 2H), 7.62 (d, J ¼ 8.5 Hz, 2H), 7.41
1
30.0 (d, J ¼ 3.2 Hz), 129.2 (d, J ¼ 8.5 Hz), 128.8, 124.6, 115.9 (d,
(d, J ¼ 8.8 Hz, 2H), 7.38-7.29 (m, 6H), 6.93 (d, J ¼ 8.8 Hz, 2H), 5.33 (s,
S (M þ H)þ
1H), 3.84 (s, 3H), 3.11 (s, 3H), 2.46 (s, 3H), 2.43 (s, 3H); C NMR
13
J ¼ 21.9 Hz). HRMS (ESI) m/z calcd for C13
H11FN
3
O
4
3
24.0449, found 324.0445.
3
(CDCl , 125.8 MHz): d 160.4, 147.4, 144.7, 143.9, 136.1, 135.5, 132.6,
(
E)-N'-(4-bromobenzylidene)-4-nitrobenzenesulfonohydrazide
132.2, 130.3, 129.6, 129.24, 129.17, 128.90, 128.86, 128.3, 127.9, 124.4,
ꢀ
(
1f): yellow solid, m.p. 181.3e182.1 C, yield 83%; R
f
¼ 0.22 (PE/
11.96 (b, 1H), 8.42 (d,
J ¼ 8.9 Hz, 2H), 8.13 (d, J ¼ 8.8 Hz, 2H), 7.95 (s,1H), 7.63-7.56 (m, 2H),
114.4, 55.4, 36.8, 21.69, 21.65. HRMS (ESI) m/z calcd for
1
(M þ H)þ 624.1388, found 624.1385.
EtOAc ¼ 3/1); H NMR (DMSO‑d
6
, 500 MHz):
d
31 3 5 2
C H31ClN O S
N-((E)-1-(2-((E)-4-chlorobenzylidene)-1-tosylhydrazinyl)-2-(4-
13
7
1
.53 (d, J ¼ 8.6 Hz, 2H); C NMR (DMSO‑d
6
, 125.8 MHz):
d
150.0,
chlorophenyl)vinyl)-N,4-dimethylbenzenesulfonamide (3ac): white
ꢀ
47.1, 144.2, 132.6, 131.8, 128.8, 124.6, 123.6. HRMS (ESI) m/z calcd
solid, m.p. 92.6e93.2 C, yield 124.5 mg, 66.1%; R
f
¼ 0.57 (PE/
þ
1
for C13
H11BrN
3
O
4
S (M þ H) 383.9648, found 383.9653.
EtOAc ¼ 5/1); H NMR (CDCl
3
, 500 MHz): d 8.30 (s, 1H), 7.69 (d,
(
E)-N'-(3-methylbenzylidene)-4-nitrobenzenesulfonohydrazide
J ¼ 8.3 Hz, 2H), 7.65 (d, J ¼ 8.3 Hz, 2H), 7.52 (d, J ¼ 8.5 Hz, 2H), 7.30-
ꢀ
(
1g): yellow solid, m.p. 147.9e148.5 C, yield 85%; R
f
¼ 0.14 (PE/
11.84 (b, 1H), 8.43 (d,
J ¼ 8.8 Hz, 2H), 8.14 (d, J ¼ 8.9 Hz, 2H), 7.93 (s, 1H), 7.38 (s, 1H), 7.37
d, J ¼ 7.8 Hz,1H), 7.27 (dd, J ¼ 7.6, 7.6 Hz,1H), 7.21 (d, J ¼ 7.5 Hz,1H),
.30 (s, 3H); 13C NMR (DMSO‑d
, 125.8 MHz): 149.9, 148.4, 144.3,
7.19 (m, 8H), 7.16 (s, 2H), 5.23 (s, 1H), 2.96 (s, 3H), 2.36 (s, 3H), 2.34
1
13
EtOAc ¼ 5/1); H NMR (DMSO‑d
6
, 500 MHz):
d
(s, 3H); C NMR (CDCl
3
, 125.8 MHz):
d
148.6, 144.9, 144.2, 136.4,
135.5, 135.3, 135.1, 132.4, 132.3, 130.6, 129.8, 129.6, 129.29, 129.23,
(
2
1
129.18, 129.0, 128.9, 128.0, 126.4, 36.9, 21.71, 21.67. HRMS (ESI) m/z
þ
6
d
calcd for C30
H28Cl
2
N
3
O
4
S
2
(M þ H) 628.0893, found 628.0894.
38.1, 133.3, 131.1, 128.8, 128.7, 127.3, 124.6, 124.2, 20.8. HRMS (ESI)
m/z calcd for C14
N-((E)-2-(4-bromophenyl)-1-(2-((E)-4-chlorobenzylidene)-1-
þ
14
H N
3
O
4
S (M þ H) 320.0700, found 320.0695.
tosylhydrazinyl)vinyl)-N,4-dimethylbenzenesulfonamide
(3ad):
¼ 0.38
ꢀ
(
E)-N'-(2-chlorobenzylidene)-4-nitrobenzenesulfonohydrazide
white solid, m.p. 103.5e104.7 C, yield 145.2 mg, 72.0%; R
f
ꢀ
1
(
1h): yellow solid, m.p. 166.6e167.2 C, yield 90%; R
f
¼ 0.23 (PE/
12.17 (b, 1H), 8.43
ddd, J ¼ 8.9, 2.4, 1.9 Hz, 2H), 8.30 (s, 1H), 8.14 (ddd, J ¼ 8.9, 2.4,
(PE/EtOAc ¼ 10/1); H NMR (CDCl
3
, 500 MHz): d 8.40 (s,1H), 7.79 (d,
1
EtOAc ¼ 5/1); H NMR (DMSO‑d
6
, 500 MHz):
d
J ¼ 8.2 Hz, 2H), 7.75 (d, J ¼ 8.2 Hz, 2H), 7.62 (d, J ¼ 8.4 Hz, 2H), 7.52
(
1
7
(d, J ¼ 8.4 Hz, 2H), 7.39-7.31 (m, 6H), 7.29 (d, J ¼ 8.4 Hz, 2H), 5.31 (s,
13
.8 Hz, 2H), 7.78 (dd, J ¼ 7.7, 1.6 Hz, 1H), 7.47 (dd, J ¼ 8.0, 1.1 Hz, 1H),
3
1H), 3.06 (s, 3H), 2.46 (s, 3H), 2.44 (s, 3H); C NMR (CDCl ,
13
.42 (ddd, J ¼ 7.9, 7.3, 1.7 Hz, 1H), 7.37 (dd, J ¼ 7.6, 7.5 Hz, 1H);
C
125.8 MHz): d 148.6, 144.9, 144.2, 136.4, 135.7, 135.3, 132.4, 132.2,
132.1, 131.0, 130.0, 129.6, 129.3, 129.2, 129.0, 128.9, 128.0, 126.4,
NMR (DMSO‑d
6
, 125.8 MHz):
d
150.0,144.1,143.9,133.0,131.8,130.5,
129.9, 128.8, 127.7, 126.7, 124.7. HRMS (ESI) m/z calcd for
123.3, 36.9, 21.70, 21.66. HRMS (ESI) m/z calcd for

6
Z. Cao et al. / Tetrahedron 75 (2019) 130534
C
30
H
28BrClN
3
O
4
S
2
(M þ H)þ 672.0388, found 672.0385.
131.5, 131.0, 129.7, 129.4, 129.3, 129.05, 128.98, 128.94, 128.6, 128.5,
N-((E)-1-(2-((E)-4-chlorobenzylidene)-1-tosylhydrazinyl)-2-(3-
123.9, 37.5, 21.7. HRMS (ESI) m/z calcd for C29
H26ClN
4
O
6
S
2
(M þ H)þ
chlorophenyl)vinyl)-N,4-dimethylbenzenesulfonamide (3ae): white
solid, m.p. 78.1e79.0 C, yield 119.7 mg, 63.5%; R
625.0977, found 625.0975.
N-((E)-1-(2-((E)-4-chlorobenzylidene)-1-tosylhydrazinyl)-2-
phenylvinyl)-N-methylethanesulfonamide (3ak): white solid, m.p.
ꢀ
f
¼ 0.59 (PE/
1
EtOAc ¼ 5/1); H NMR (CDCl
3
, 500 MHz):
d
8.40 (s, 1H), 7.81 (d,
ꢀ
1
J ¼ 8.3 Hz, 2H), 7.76 (d, J ¼ 8.3 Hz, 2H), 7.63 (d, J ¼ 8.3 Hz, 2H), 7.45
79.4e80.3 C, yield 55.6 mg, 34.8%; R
NMR (CDCl , 500 MHz):
f
¼ 0.63 (PE/EtOAc ¼ 3/1);
H
(
3
d, J ¼ 7.7 Hz, 1H), 7.39-7.29 (m, 9H), 5.31 (s, 1H), 3.06 (s, 3H), 2.47 (s,
3
d
8.32 (s, 1H), 7.90 (d, J ¼ 8.3 Hz, 2H), 7.58
1
3
H), 2.44 (s, 3H); C NMR (CDCl
3
, 125.8 MHz):
d
148.9, 145.0, 144.2,
(d, J ¼ 8.6 Hz, 2H), 7.41 (d, J ¼ 8.1 Hz, 2H), 7.37 (d, J ¼ 7.3 Hz, 2H),
136.5, 136.4, 135.2, 134.8, 134.0, 132.3, 132.2, 130.3, 129.7, 129.3,
7.36-7.30 (m, 5H), 5.28 (s, 1H), 3.40 (q, J ¼ 7.45 Hz, 2H), 3.14 (s, 3H),
1
3
129.2, 129.1, 129.0, 128.9, 128.6, 128.0, 126.3, 125.8, 37.0, 21.71, 21.67.
2.50 (s, 3H), 1.51 (t, J ¼ 7.45 Hz, 3H); C NMR (CDCl
3
, 125.8 MHz):
HRMS (ESI) m/z calcd for C30
found 628.0898.
H28Cl
2
N
3
O
4
S
2
(M þ H)þ 628.0893,
d 149.2, 145.2, 136.4, 135.5, 132.3, 132.0, 131.8, 129.4, 129.2, 129.0,
128.92, 128.89, 128.4, 126.3, 48.5, 37.3, 21.8, 7.7. HRMS (ESI) m/z
þ
N-((E)-1-(2-((E)-4-chlorobenzylidene)-1-tosylhydrazinyl)hex-1-
calcd for C25
H27ClN
3
O
4
S
2
(M þ H) 532.1126, found 532.1125.
en-1-yl)-N,4-dimethylbenzenesulfonamide (3af): white solid, m.p.
N-((E)-1-(2-((E)-4-methoxybenzylidene)-1-tosylhydrazinyl)-2-
ꢀ
1
72.4e73.1 C, yield 125.1 mg, 72.6%; R
f
¼ 0.51 (PE/EtOAc ¼ 5/1); H
phenylvinyl)-N,4-dimethylbenzenesulfonamide (3ba): white solid,
ꢀ
NMR (CDCl , 500 MHz):
3
d
8.23 (s, 1H), 7.74 (d, J ¼ 8.3 Hz, 2H), 7.66
m.p. 112.1e112.7 C, yield 119.2 mg, 67.3%; R
f
¼ 0.41 (PE/EtOAc ¼ 5/
1
(
7
3
1
d, J ¼ 8.3 Hz, 2H), 7.58 (d, J ¼ 8.5 Hz, 2H), 7.35 (d, J ¼ 8.5 Hz, 2H),
1); H NMR (CDCl
3
, 500 MHz):
d
8.46 (s, 1H), 7.84 (d, J ¼ 8.3 Hz, 2H),
.28 (d, J ¼ 8.2 Hz, 2H), 7.23 (d, J ¼ 8.2 Hz, 2H), 5.04 (t, J ¼ 7.5 Hz,1H),
7.77 (d, J ¼ 8.3 Hz, 2H), 7.64 (d, J ¼ 8.8 Hz, 2H), 7.42-7.32 (m, 9H),
.18 (s, 3H), 2.42 (s, 3H), 2.39 (s, 3H), 2.32 (q, J ¼ 7.2 Hz, 2H), 1.42-
6.90 (d, J ¼ 8.8 Hz, 2H), 5.32 (s, 1H), 3.83 (s, 3H), 3.08 (s, 3H), 2.46 (s,
13
13
.30 (m, 4H), 0.92 (t, J ¼ 7.1 Hz, 3H); C NMR (CDCl
3
, 125.8 MHz):
3H), 2.44 (s, 3H); C NMR (CDCl
3
, 125.8 MHz):
d
161.5, 150.7, 144.6,
d
146.3, 144.4, 143.8, 136.9, 136.0, 135.7, 133.5, 132.5, 129.6, 129.3,
143.9, 135.9, 135.7, 132.3, 132.1, 129.6, 129.5, 129.4, 129.1, 129.0,
1
28.9, 128.8, 128.7, 127.6, 37.5, 30.3, 27.8, 22.4, 21.6, 21.5, 13.8. HRMS
128.9, 128.5, 128.1, 127.0, 126.7, 114.0, 55.4, 37.0, 21.69, 21.67. HRMS
(
ESI) m/z calcd for C28
H33ClN
3
O
4
S
2
(M þ H)þ 574.1596, found
(ESI) m/z calcd for C31
H
32
N
3
O
S
5 2
(M þ H)þ 590.1778, found
574.1593.
590.1775.
N-((E)-1-(2-((E)-4-chlorobenzylidene)-1-tosylhydrazinyl)-3,3-
N,4-dimethyl-N-((E)-1-(2-((E)-4-methylbenzylidene)-1-((4-
dimethylbut-1-en-1-yl)-N,4-dimethylbenzenesulfonamide
(3 ag):
¼ 0.51 (PE/
nitrophenyl)sulfonyl)hydrazinyl)-2-phenylvinyl)benzenesulfonamide
ꢀ
ꢀ
white solid, m.p. 127.5e128.3 C, yield 78.9 mg, 45.8%; R
f
(3da): yellow solid, m.p. 108.9e110.2 C, yield 119.5 mg, 65.8%;
1
1
EtOAc ¼ 5/1); H NMR (CDCl
3
, 500 MHz):
d
8.27 (s, 1H), 7.68 (d,
R
f
¼ 0.75 (PE/EtOAc ¼ 3/1); H NMR (CDCl
3
, 500 MHz): d 8.50 (s,
J ¼ 8.3 Hz, 2H), 7.61 (d, J ¼ 8.2 Hz, 2H), 7.60 (d, J ¼ 8.3 Hz, 2H), 7.37
1H), 8.38 (d, J ¼ 8.8 Hz, 2H), 8.08 (d, J ¼ 8.8 Hz, 2H), 7.79 (d,
J ¼ 8.3 Hz, 2H), 7.57 (d, J ¼ 8.0 Hz, 2H), 7.46-7.35 (m, 5H), 7.33 (d,
J ¼ 8.1 Hz, 2H), 7.21 (d, J ¼ 7.9 Hz, 2H), 5.46 (s, 1H), 3.11 (s, 3H), 2.45
(
d, J ¼ 8.5 Hz, 2H), 7.26 (d, J ¼ 8.1 Hz, 2H), 7.21 (d, J ¼ 8.1 Hz, 2H),
13
4
.73 (s, 1H), 3.24 (s, 3H), 2.41 (s, 3H), 2.39 (s, 3H), 1.19 (s, 9H);
C
13
NMR (CDCl
3
, 125.8 MHz): 146.9, 145.9, 144.4, 143.7, 136.0, 135.2,
d
3
(s, 3H), 2.38 (s, 3H); C NMR (CDCl , 125.8 MHz): d 151.4, 150.6,
133.0, 132.6, 130.4, 129.5, 129.2, 128.97, 128.96, 128.7, 127.6, 40.1,
144.2, 141.4, 141.1, 135.6, 134.3, 131.7, 130.6, 130.5, 129.7, 129.6, 129.5,
3
3.9, 29.1, 21.62, 21.56. HRMS (ESI) m/z calcd for C28
H
33ClN
3
O
S
4 2
129.0, 128.6, 128.1, 127.89, 127.87, 123.7, 37.0, 21.6, 21.5. HRMS (ESI)
þ
þ
(
M þ H) 574.1596, found 574.1599.
m/z calcd for C30
H
29
N
4
O
6
S
2
(M þ H) 605.1523, found 605.1527.
N-benzyl-N-((E)-1-(2-((E)-4-chlorobenzylidene)-1-
N-((E)-1-(2-((E)-4-fluorobenzylidene)-1-((4-nitrophenyl)sulfonyl)
tosylhydrazinyl)-2-phenylvinyl)-4-methylbenzenesulfonamide (3ah):
hydrazinyl)-2-phenylvinyl)-N,4-dimethylbenzenesulfonamide (3ea):
ꢀ
ꢀ
white solid, m.p. 107.6e109.1 C, yield 128.1 mg, 63.7%; R
f
¼ 0.35
8.38 (s,1H), 7.87 (d,
J ¼ 8.2 Hz, 2H), 7.58 (d, J ¼ 8.5 Hz, 2H), 7.42 (d, J ¼ 8.3 Hz, 2H), 7.39-
.33 (m, 8H), 7.30-7.27 (m, 3H), 7.09 (d, J ¼ 8.1 Hz, 2H), 7.06 (d,
J ¼ 7.4 Hz, 1H), 7.00 (dd, J ¼ 7.6, 7.2 Hz, 2H), 5.83 (s, 1H), 4.62 (s, 2H),
yellow solid, m.p. 127.7e128.4 C, yield 143.6 mg, 78.6%; R
f
¼ 0.40
1
1
(
PE/EtOAc ¼ 10/1); H NMR (CDCl
3
, 500 MHz):
d
(PE/EtOAc ¼ 5/1); H NMR (CDCl
3
, 500 MHz): d 8.49 (s, 1H), 8.40 (d,
J ¼ 8.8 Hz, 2H), 8.08 (d, J ¼ 8.7 Hz, 2H), 7.78 (d, J ¼ 8.3 Hz, 2H), 7.71-
7.64 (m, 2H), 7.47-7.35 (m, 5H), 7.33 (d, J ¼ 8.2 Hz, 1H), 7.10 (dd,
7
13
J ¼ 8.6, 8.6 Hz, 3H), 5.48 (s, 1H), 3.11 (s, 3H), 2.45 (s, 3H); C NMR
13
2
.47 (s, 3H), 2.36 (s, 3H); C NMR (CDCl
3
, 125.8 MHz):
d
146.8,
(CDCl
3
, 125.8 MHz):
d
164.3 (d, J ¼ 252.2 Hz), 150.6, 149.8, 144.3,
144.8, 143.4, 137.1, 136.1, 134.1, 133.8, 133.2,132.5, 132.3, 131.8, 130.9,
141.1, 135.5, 134.0, 131.5, 130.4, 129.8 (d, J ¼ 8.9 Hz), 129.7, 129.6 (d,
1
5
6
29.3, 129.2, 129.1, 128.89, 128.85, 128.81, 128.5, 127.7, 127.6, 127.5,
J ¼ 3.3 Hz), 129.1, 128.7, 128.4, 127.9, 123.8, 116.0 (d, J ¼ 22.2 Hz),
4.5, 21.7, 21.5. HRMS (ESI) m/z calcd for C36
H
33ClN
3
O
S
4 2
(M þ H)þ
115.9, 37.0, 21.6. HRMS (ESI) m/z calcd for C29
H26FN
4
O
6
S
2
(M þ H)þ
70.1596, found 670.1594.
609.1272, found 609.1278.
N-((E)-1-(2-((E)-4-chlorobenzylidene)-1-tosylhydrazinyl)-2-
phenylvinyl)-N-methyl-4-nitrobenzenesulfonamide (3ai): white
N-((E)-1-(2-((E)-4-bromobenzylidene)-1-((4-nitrophenyl)sulfo-
nyl)hydrazinyl)-2-phenylvinyl)-N,4-dimethylbenzenesulfonamide
ꢀ
ꢀ
solid, m.p. 77.1e78.0 C, yield 85.8 mg, 49.8%; R
f
¼ 0.61 (PE/
8.40-8.36 (m, 3H), 8.08
ddd, J ¼ 8.9, 2.3, 2.0 Hz, 2H), 7.73 (d, J ¼ 8.3 Hz, 2H), 7.64 (d,
J ¼ 8.6 Hz, 2H), 7.46-7.32 (m, 9H), 5.36 (s, 1H), 3.16 (s, 3H), 2.47 (s,
(3fa): yellow solid, m.p. 122.7e123.5 C, yield 118.2 mg, 58.9%;
1
1
EtOAc ¼ 5/1); H NMR (CDCl
3
, 500 MHz):
d
R
f
¼ 0.47 (PE/EtOAc ¼ 5/1); H NMR (CDCl
3
, 500 MHz): d 8.44 (s,
(
1H), 8.40 (ddd, J ¼ 8.9, 2.2, 1.8 Hz, 2H), 8.07 (ddd, J ¼ 8.9, 2.2, 1.9 Hz,
2H), 7.76 (d, J ¼ 8.3 Hz, 2H), 7.54 (b, 4H), 7.47-7.35 (m, 5H), 7.33 (d,
13
13
3
1
H); C NMR (CDCl
3
, 125.8 MHz):
d
150.4, 148.2, 145.3, 144.1, 136.6,
J ¼ 8.2 Hz, 2H), 5.49 (s, 1H), 3.10 (s, 3H), 2.45 (s, 3H); C NMR
34.2, 132.2, 131.8, 131.6, 129.6, 129.4, 129.19, 129.17, 129.1, 129.02,
3
(CDCl , 125.8 MHz): d 150.7, 149.2, 144.3, 141.2, 135.4, 133.6, 132.3,
1
C
28.98, 128.5, 127.7, 124.3, 37.4, 21.7. HRMS (ESI) m/z calcd for
132.1, 131.5, 130.3, 129.8, 129.7, 129.2, 129.1, 128.70, 128.65, 127.8,
þ
31
H
32
N
3
O
4
S
2
(M þ H) 574.1829, found 574.1833.
125.2, 123.8, 37.0, 21.7. HRMS (ESI) m/z calcd for C29
H
26BrN
4
O
6
S
2
þ
N-((E)-1-(2-((E)-4-chlorobenzylidene)-1-tosylhydrazinyl)-2-
(M þ H) 669.0472, found 669.0475.
phenylvinyl)-N-methyl-2-nitrobenzenesulfonamide (3aj): white
solid, m.p. 116.4e117.8 C, yield 128.9 mg, 68.7%; R
N,4-dimethyl-N-((E)-1-(2-((E)-3-methylbenzylidene)-1-((4-
ꢀ
f
¼ 0.49 (PE/
nitrophenyl)sulfonyl)hydrazinyl)-2-phenylvinyl)benzenesulfonamide
1
ꢀ
EtOAc ¼ 5/1); H NMR (CDCl
3
, 500 MHz):
d
8.36 (s, 1H), 8.21 (dd,
(3ga): yellow solid, m.p. 145.3e146.2 C, yield 124.7 mg, 68.7%;
1
J ¼ 7.8, 1.8 Hz, 1H), 7.82 (d, J ¼ 8.3 Hz, 2H), 7.78-7.68 (m, 2H), 7.65
R
f
¼ 0.55 (PE/EtOAc ¼ 5/1); H NMR (CDCl
3
, 500 MHz): d 8.49 (s,
(
5
d
dd, J ¼ 7.8, 1.7 Hz, 1H), 7.60 (d, J ¼ 8.6 Hz, 2H), 7.43-7.32 (m, 9H),
1H), 8.39 (ddd, J ¼ 8.9, 2.2, 1.8 Hz, 2H), 8.09 (ddd, J ¼ 8.8, 2.2, 1.9 Hz,
2H), 7.79 (d, J ¼ 8.3 Hz, 2H), 7.50 (d, J ¼ 7.7 Hz, 1H), 7.47 (s, 1H), 7.45-
7.39 (m, 4H), 7.39-7.34 (m, 1H), 7.33 (d, J ¼ 8.2 Hz, 2H), 7.30 (dd,
13
.44 (s, 1H), 3.25 (s, 3H), 2.48 (s, 3H); C NMR (CDCl
3
, 125.8 MHz):
148.71, 148.68, 145.2, 136.5, 134.2, 133.9, 132.3, 132.2, 132.1, 131.9,

Z. Cao et al. / Tetrahedron 75 (2019) 130534
7
f) J. Barluenga, C. Vald
g) J.R. Fulton, V.K. Aggarwal, J. de Vicente, Eur. J. Org. Chem. 2005 (2005)
479e1492.
eꢀ s, Angew. Chem. Int. Ed. 50 (2011) 7486e7500;
J ¼ 7.7, 7.6 Hz, 1H), 7.23 (d, J ¼ 7.6 Hz, 1H), 5.46 (s, 1H), 3.12 (s, 3H),
13
2
.45 (s, 3H), 2.38 (s, 3H); C NMR (CDCl
3
, 125.8 MHz): d 151.3,150.6,
1
144.2, 141.2, 138.5, 135.6, 134.1, 133.3, 131.7, 131.6, 130.4, 129.7, 129.6,
[
2] For selected recent examples, see: a) M. Ni, J. Zhang, X. Liang, Y. Jiang, T.-
P. Loh, Chem. Commun. 53 (2017) 12286e12289;
b) Z. Liu, Q. Li, P. Liao, X. Bi, Chem. Eur J. 23 (2017) 4756e4760.
3] For selected recent examples, see: a) Z. Liu, J. Huo, T. Fu, H. Tan, F. Ye,
M.L. Hossain, J. Wang, Chem. Commun. 54 (2018) 11419e11422;
b) P.-X. Zhou, Y. Zhang, C. Ge, Y.-M. Liang, C. Li, J. Org. Chem. 83 (2018)
1
29.1, 128.8, 128.69, 128.65, 128.3.127.9, 124.9, 123.7, 37.1, 21.7, 21.3.
(M þ H)þ 605.1523, found
HRMS (ESI) m/z calcd for C30
05.1525.
29 4 6 2
H N O S
[
6
N-((E)-1-(2-((E)-2-chlorobenzylidene)-1-((4-nitrophenyl)sulfo-
nyl)hydrazinyl)-2-phenylvinyl)-N,4-dimethylbenzenesulfonamide
4762e4768;
c) N. Su, T. Deng, D.J. Wink, T.G. Driver, Org. Lett. 19 (2017) 3990e3993.
4] For selected examples, see: a) R. Barroso, M. Escribano, M.-P. Cabal, C. Vald eꢀ s,
ꢀ
(
R
1
7
3ha): yellow solid, m.p. 123.8e124.6 C, yield 117.8 mg, 62.8%;
[
1
f
¼ 0.43 (PE/EtOAc ¼ 5/1); H NMR (CDCl
3
, 500 M Hz):
d
8.91 (s,
Eur. J. Org. Chem. 2014 (2014) 1672e1683;
b) D.F. Taber, P. Guo, J. Org. Chem. 73 (2008) 9479e9481;
c) N. Su, J.A. Theorell, D.J. Wink, T.G. Driver, Angew. Chem. Int. Ed. 54 (2015)
H), 8.40 (ddd, J ¼ 8.9, 2.1, 1.9 Hz, 2H), 8.11 (d, J ¼ 8.9 Hz, 2H), 7.95-
.89 (m, 1H), 7.77 (d, J ¼ 8.3 Hz, 2H), 7.41-7.38 (m, 4H), 7.38-7.30 (m,
1
2942e12946.
[5] For selected examples, see: a) L. Yao, C.-J. Wang, Adv. Synth. Catal. 357 (2015)
84e388;
b) Y. Kong, W. Zhang, M. Tang, H. Wang, Tetrahedron 69 (2013) 7487e7491;
c) Ch.R. Reddy, E. Jithender, Tetrahedron Lett. 50 (2009) 5633e5635;
d) J.M. Keith, L. Gomez, J. Org. Chem. 71 (2006) 7113e7116.
[6] For selected examples, see: a) L. Crespin, L. Biancalana, T. Morack,
D.C. Blakemore, S.V. Ley, Org. Lett. 19 (2017) 1084e1087;
b) M. Movassaghi, O.K. Ahmad, Angew. Chem. Int. Ed. 47 (2008) 8909e8912;
c) G.-L. Zhao, M. Shi, Tetrahedron 61 (2005) 7277e7288.
[7] a) H. Zhang, K.-H. Wang, J. Wang, Y. Su, D. Huang, Y. Hu, Org. Biomol. Chem. 17
(2019) 2940e2947;
b) X. Wu, L. Li, W. Jiang, L. Zhou, Q. Zeng, Appl. Organomet. Chem. 32 (2018)
e4483.
[8] a) T. Asano, H. Yamazaki, C. Kasahara, H. Kubota, T. Kontani, Y. Harayama,
K. Ohno, H. Mizuhara, M. Yokomoto, K. Misumi, T. Kinoshita, M. Ohta,
M. Takeuchi, J. Med. Chem. 55 (2012) 7772e7785;
13
7
H), 5.62 (s, 1H), 3.09 (s, 3H), 2.44 (s, 3H); C NMR (CDCl
3
,
3
1
25.8 MHz): 150.6, 147.0, 144.2, 141.4, 135.6, 135.2, 133.5, 131.6,
d
1
31.1, 130.4, 130.1, 129.7, 129.6, 129.1, 128.9, 128.6, 127.8, 127.3, 127.0,
123.8, 37.2, 21.6. HRMS (ESI) m/z calcd for C29
H26ClN
4
O
6
S
2
(M þ H)þ
6
25.0977, found 625.0980.
N-((E)-1-(2-((E)-2-bromobenzylidene)-1-((4-nitrophenyl)sulfo-
nyl)hydrazinyl)-2-phenylvinyl)-N,4-dimethylbenzenesulfonamide
ꢀ
(
R
1
1
7
3
3ia): yellow solid, m.p. 81.2e82.5 C, yield 127.8 mg, 63.7%;
1
f
¼ 0.46 (PE/EtOAc ¼ 5/1); H NMR (CDCl
3
, 500 MHz): d 8.89 (s,
H), 8.39 (d, J ¼ 8.8 Hz, 2H), 8.10 (d, J ¼ 8.9 Hz, 2H), 7.91 (dd, J ¼ 7.9,
.6 Hz, 1H), 7.78 (d, J ¼ 6.1 Hz, 2H), 7.54 (dd, J ¼ 8.0, 0.8 Hz, 1H), 7.43-
.35 (m, 6H), 7.33 (d, J ¼ 8.2 Hz, 2H), 7.28-7.21 (m, 1H), 5.62 (s, 1H),
13
.09 (s, 3H), 2.44 (s, 3H); C NMR (CDCl
3
, 125.8 MHz): d 150.6,
b) S. Yoshida, Y. Hayashi, K. Obitsu, A. Nakamura, T. Kikuchi, T. Sawada,
T. Kimura, T. Takahashi, T. Mukuta, Org. Process Res. Dev. 16 (2012)
149.4, 144.2, 141.4, 135.6, 133.5, 133.3, 132.6, 131.8, 131.6, 130.4,
1818e1826.
1
29.7, 129.6, 129.0, 128.9, 128.5, 127.8, 127.61, 127.59, 125.2, 123.8,
(M þ H)þ
[9] a) S.A. Hashemi, Tetrahedron Lett. 53 (2012) 5141e5143;
b) Z.-L. Yuan, Y. Wei, M. Shi, Eur. J. Org. Chem. 2010 (2010) 4088e4097.
[10] S. He, P. Jeyakkumar, S. Avula, X. Wang, H. Zhang, C. Zhou, Sci. Sin. Chim. 46
2016) 823e847.
11] a) Z. Chohan, M. Youssoufi, A. Jarrahpour, T.B. Hadda, Eur. J. Med. Chem. 45
2010) 1189e1199;
b) M. Banerjee, A. Poddar, G. Mitra, A. Surolia, T. Owa, B. Bhattacharyya, J. Med.
Chem. 48 (2005) 547e555.
12] a) T. Jabusch, R. Tjeerdema, J. Agric. Food Chem. 53 (2005) 7179e7183;
b) S. Zhang, X. Cheng, J. Yang, Dyes Pigments 43 (1999) 167e172.
13] For reviews of ynamides, see: a) G. Evano, C. Theunissen, M. Lecomte, Aldri-
chim Acta 48 (2015) 59e70;
37.2, 21.6. HRMS (ESI) m/z calcd for C29
H26BrN
4
O
6
S
2
6
69.0472, found 668.0474.
(
N,4-dimethyl-N-((E)-1-(1-((4-nitrophenyl)sulfonyl)-2-((E)-thio-
phen-2-ylmethylene)hydrazinyl)-2-phenylvinyl)benzenesulfonamide
[
(
ꢀ
(
R
1
3ja): yellow solid, m.p. 140.6e141.5 C, yield 124.5 mg, 69.5%;
1
f
¼ 0.48 (PE/EtOAc ¼ 5/1); H NMR (CDCl
3
, 500 MHz): d 8.65 (s,
[
H), 8.40 (dd, J ¼ 7.1, 1.8 Hz, 2H), 8.09 (dd, J ¼ 7.1, 1.9 Hz, 2H), 7.81 (d,
J ¼ 8.4 Hz, 2H), 7.46-7.38 (m, 5H), 7.39-7.31 (m, 3H), 7.28 (dd, J ¼ 3.6,
[
0
2
.7 Hz, 1H), 7.04 (dd, J ¼ 5.0, 3.7 Hz, 1H), 5.46 (s, 1H), 3.09 (s, 3H),
.46 (s, 3H); 1 C NMR (CDCl
3
b) X.-N. Wang, H.-S. Yeom, L.-C. Fang, S. He, Z.-X. Ma, B.L. Kedrowski,
R.P. Hsung, Acc. Chem. Res. 47 (2014) 560e578;
c) G. Evano, A. Coste, K. Jouvin, Angew. Chem. Int. Ed. 49 (2010) 2840e2859;
d) K.A. DeKorver, H. Li, A.G. Lohse, R. Hayashi, Z. Lu, Y. Zhang, R.P. Hsung,
Chem. Rev. 110 (2010) 5064e5106;
3
, 125.8 MHz):
d 150.7, 145.9, 144.3,
140.8,138.4,135.5,134.7,132.7,131.9,131.6,130.7,129.7,129.6,129.2,
1
29.1, 128.6, 127.9, 127.8, 123.6, 36.9, 21.7. HRMS (ESI) m/z calcd for
(M þ H)þ 597.0931, found 597.0936.
27 25 4 6 3
C H N O S
e) C.A. Zificsak, J.A. Mulder, R.P. Hsung, C. Rameshkumar, L.L. Wei, Tetrahedron
7 (2001) 7575e7606.
5
Acknowledgements
[14] For selected recent examples, see: a) B. Prabagar, R.K. Mallick, R. Prasad,
V. Gandon, A.K. Sahoo, Angew. Chem. Int. Ed. 58 (2019) 2365e2370;
b) Q. Zhao, D.F.L. Rayo, D. Campeau, M. Daenen, F. Gagosz, Angew. Chem. Int.
Ed. 57 (2018) 13603e13607;
We thank the National Nature Science Foundation of China
(
NSFC, 21402106) and the Project-sponsored by the Scientific
c) X. Zhao, X. Song, H. Jin, Z. Zeng, Q. Wang, M. Rudolph, F. Rominger,
A.S.K. Hashmi, Adv. Synth. Catal. 360 (2018) 2720e2726;
d) S.S. Giria, R.-S. Liu, Chem. Sci. 9 (2018) 2991e2995.
Research Foundation for the Returned Overseas Chinese Scholars,
State Education Ministry (20141685). We also acknowledge the
support provided by Natural Science Foundation of Shandong
[
15] For O-nucleophiles, see: a) L. Hu, Z. Zhao, Y. Yang, Z. Peng, M. Yang, C. Wang,
J. Zhao, J. Am. Chem. Soc. 138 (2016) 13135e13138;
b) S. Xu, J. Liu, D. Hu, X. Bi, Green Chem. 17 (2015) 184e187;
c) K.C.M. Kurtz, M.O. Frederick, R.H. Lambeth, J.A. Mulder, M.R. Tracey,
R.P. Hsung, Tetrahedron 62 (2006) 3928e3938;
(
ZR2018JL013 and ZR2018MB014) and Higher Educational Science
and Technology Program of Shandong (J15LA02). X. Meng ac-
knowledges the support from Qufu Normal University for Research
Start-up Foundation.
d) M.O. Frederick, R.P. Hsung, R.H. Lambeth, J.A. Mulder, M.A. Tracey, Org. Lett.
5
(2003) 2663e2666;
e) J.A. Mulder, R.P. Hsung, M.O. Frederick, M.R. Tracey, C.A. Zificsak, Org. Lett. 4
2002) 1383e1386.
[16] For S-nucleophiles, see: a) H. Yasui, H. Yorimitsu, K. Oshima, Chem. Lett. 37
2008) 40e41;
(
Appendix A. Supplementary data
(
b) S. Kanemura, A. Kondoh, H. Yasui, H. Yorimitsu, K. Oshima, Bull. Chem. Soc.
Jpn. 81 (2008) 506e514.
[17] For electron-rich arenes as the nucleophiles, see: a) Y. Zhang, Tetrahedron 62
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2019.130534.
(2006) 3917e3927;
b) Y. Zhang, Tetrahedron Lett. 46 (2005) 6483e6486;
c) Y. Zhang, R.P. Hsung, X. Zhang, J. Huang, B.W. Slafer, A. Davis, Org. Lett. 7
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2
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13
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