Regioselective N-Addition/Substitution Reaction of α-Alkylidene Pyrazolinones with Propargyl Sulfonium Salts to Construct Allylthio-Containing Pyrazolones

Article abstract of DOI:10.1021/acs.joc.9b02029

The regioselective N-addition/substitution reaction between α-alkylidene pyrazolinones and propargyl sulfonium salts has been developed to construct functionalized allylthio-containing pyrazolones with moderate to excellent yields. α-Alkylidene pyrazolinones act as N-nucleophilic agents which are distinguished from reported C-nucleophilic reactions. Excellent regioselectivity, readily available starting materials, the broad range of substrates, gram-scale synthesis, and simple operation illustrate the synthetic advantages of this new reaction pathway.

Full text of DOI:10.1021/acs.joc.9b02029

Subscriber access provided by LUNDS UNIV
Article
Regioselective N-Addition/Substitution Reaction of #-Alkylidene Pyrazolinones
with Propargyl Sulfonium Salts to Construct Allylthio-Containing Pyrazolones
Shou-Jie Shen, Xiao-Li Du, Xiao-Li Xu, Ming-Gang Zhao, and Jin-Yan Liang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02029 • Publication Date (Web): 09 Sep 2019
Downloaded from pubs.acs.org on September 9, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 15
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Regioselective N-Addition/Substitution Reaction of α-Alkylidene
Pyrazolinones with Propargyl Sulfonium Salts to Construct Allylthio-
Containing Pyrazolones
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Shou-Jie Shen,*,† Xiao-Li Du,† Xiao-Li Xu,‡ Ming-Gang Zhao,† and Jin-Yan Liang*,‡
†Key Laboratory of Magnetic Molecules, Magnetic Information Materials Ministry of Education, The School of
Chemical and Material Science, Shanxi Normal University, Linfen, 041004, China
‡College of Life Science, Shanxi Normal University, Linfen, 041004, China
Email: shoujie_shen@outlook.com; jinyan_liang@outlook.com
Supporting Information
O
Ar1
O
Ar1
N
N
NaOAc•3H2O
CH3CN
Ar
SMe
N
+
Ar
Me
SMe2Br
N
R
R
. Excellent regioselectivity
. Mild conditions
. Broad substrate scope
. 39 examples and 38-91% yields
ABSTRACT: The regioselective N-addition/substitution reaction between α-alkylidene pyrazolinones and propargyl
sulfonium salts has been developed to construct functionalized allylthio-containing pyrazolones with moderate to excellent
yields. α-Alkylidene pyrazolinones act as N-nucleophilic agents which is distinguished from reported C-nucleophilic
reactions. Excellent regioselectivity, readily available starting materials, the broad range of substrates, gram-scale synthesis
and simple operation illustrate the synthetic advantages of this new reaction pathway.
pyrazolones bearing a γ-H have recently been used as 1,3-
■INTRODUCTION
binuclophiles (initiated by γ-C and subsequent C-4) in the
asymmetric [3 + 2] or [3 + 3] annulation for preparing
Pyrazolones constitute a class of privileged heterocycles
spiro-pyrazolones.6 Despite these excellent work, the N-2
that extensively exist in bioactive natural alkaloids and
initiating nucleophilic reaction of α, β-unsaturated
pyrazolones has been underexplored. Therefore,
exploration of diverse reaction pathways of α, β-
unsaturated pyrazolones, especially N-2 addition reaction,
pharmaceuticals.1 Accordingly, a variety of organo- or
metal catalyzed methods based on the multiple reactive
sites located on pyrazolones have been developed to
provide structurally versatile pyrazolones during the past
and development of an efficient protocol to construct
decades, especially in an asymmetric fashion to access
functionalized pyrazolone frameworks are challenging yet
pyrazolone candidates with medicinal value.2 In general,
highly desirable.
two major forms are frequently utilized in these
O
O
R3
1
R3
1
transformations (Figure 1). The first form is pyrazolin-5-
ones with C-4, O (connected to C-5) or N-2 as nucleophilic
sites (I). A vast of addition and cascade reactions initiated
from C-4 position have been reported to access diverse C4-
substituted, fused and spiro-pyrazolones efficiently while
O-atom often acts as the second nucleophilic site to furnish
fused ring-closure reactions.3 In contrast, N-2 initiating
reactions of pyrazolones were less explored and only
several examples have been reported.4 The other form is α,
β-unsaturated pyrazolones which unveil multidentate
nucleophilic species based on possible resonating forms,
including C-4, O (connected to C-5), γ-C and N-2
nucleophilic sites (II).5 In particular, α, β-unsaturated
5
5
R1
4
N
N
4
R1

N
N
H
3
3
2
2
R2
R2
less explored
under-explored
I
II
Figure 1. N-2 Initiating Reactions of Pyrazolones
Sulfur ylides are valuable synthons and have wide
applications in a variety of transformations such as
olefination, cyclopropanation, epoxidation, aziridination
and rearrangement reactions.7,8 Particularly, propargyl
sulfonium salts are a kind of versatile building blocks that
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 15
are easily accessible and convenient to access functional equivalent of the base was sufficient to furnish the reaction.
1
cyclic skeletons due to the multiple reaction centers.
Generally, propargyl sulfonium salts can tautomerize to
allenic sulfonium salts under basic conditions, including
three reactive sites of α-carbon, β-carbon and α´-carbon
(Scheme 1). As C2 synthons, Kanematsu’s,9 Huang’s10a,b and
our group11 reported propargyl sulfonium salts involved [3
+ 2] cascade annulation reactions to obtain related
annulation products (structures A, B, C and D in Scheme
1). Propargyl sulfonium salts could react as a C1 synthon
via [5 + 1] annulation or both as a C1 and C2 synthon via [4
+ 1]/[3 + 2] annulation process to construct more complex
scaffolds (structures E and F in Scheme 1).10c,12 All the
above reported processes are concentrated on cascade
annulation reactions while a non-cyclic procedure has not
been involved. Based on our continuing interests on
constructing functionalized pyrazolones and exploring the
diverse reactive pathway of propargyl sulfonium salts,11,13
we intend to explore the possibility whether α, β-
unsaturated pyrazolones bearing a γ-H could generate
active N-2 nucleophilic intermediate under basic
conditions that are captured by β-carbon of active allenic
sulfonium salts to afford a new non-cyclic process. We
herein report the realization of such a regioselective
NaOAc·3H2O-promoted N-addition/substitution reaction
between α-alkylidene pyrazolinones and propargyl
sulfonium salts (Scheme 1).
Next, the reaction was an obvious stepwise process and α-
alkylidene pyrazolinone 1a was consumed completely
within 5 minutes at 22 °C while the amount of product 3a
was trace (monitored by TLC). It indicated that the
nucleophilic N-addition of α-alkylidene pyrazolinone to
propargyl sulfonium salt was fast. In contrast, the
subsequent substitution reaction was sluggish at 22 °C and
required nearly 20 h at 50 °C to finish thoroughly. The
direct operation of reaction at 50 °C showed negative
effect in yield (entries 4 vs 6 in Table 1). Temperature
affected the substitution reaction greatly and 50 °C was
optimal (entries 4 vs 1–3 and 6 in Table). As to solvent,
CH3CN gave relatively best result (entries 4 vs 7–10).
Evaluation of different inorganic base was conducted and
NaOAc·3H2O afforded the highest yield (entries 4 vs 11–
15). Anhydrous NaOAc gave a slight decrease of 79% yield
(entries 4 vs 16). The quantity of base also influenced the
reaction and 0.5 equivalent was optimal while 0.25 and 1.0
equivalent led to a decrease in yields (entries 17–18 in
Table 1). The nucleophilic γ-carbon addition products of
1a were not observed due to the stronger nucleophilicity
of nitrogen than γ-carbon under the current reaction
conditions.
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Optimization of the Reaction Conditionsa
Ph
O
O
Ph
SMe
N
N
Ph
Ph
Me
conditions
N
N
+
SMe2Br
2a
Scheme 1. Reactions of Propargyl Sulfonium Salts
Acting as C1 and C2 Synthons
Ph
Ph
3a
1a
Entry
Base
Solvent
T (C)
Yield (%)b
Reported annulation process:
Me
S
Me
1
2
3
NaOAc•3H2O
NaOAc•3H2O
NaOAc•3H2O
CH3CN
CH3CN
CH3CN
22
28
47
71
base
30
40
H
[4 + 1]/[3 + 2]
annulation
CO2Et
CO2Et
[5 + 1]
annulation
N


•
CH3
'
S


N

N
Me
O
SMe
Me
4
NaOAc•3H2O
CH3CN
50
83
PG
[3 + 2]
F
E
annulation
5
NaOAc•3H2O
CH3CN
60
76
R1
SMe
Me
N
PG
O
Me
Ar
O
6c
7
NaOAc•3H2O
NaOAc•3H2O
CH3CN
CHCl3
50
50
70
75
Me
O

N
N
OR
O

n( )
N
O
R
B
R2
A
D
C
8
NaOAc•3H2O
NaOAc•3H2O
NaOAc•3H2O
Li2CO3
DCE
50
50
50
50
72
9
This work: Regioselective N-Addition/Substitution Reaction
Ar1
9
THF
Ar1
O
SMe
O
Ar1
N
SMe2Br
N
base
Ar
N
Ar
N
10
11
toluene
CH3CN
35
23
+
SMe2Br
Ar
Me
N
N
CH3CN
R
R
R
12
13
14
Na2CO3
K2CO3
CH3CN
CH3CN
CH3CN
50
50
50
70
73
31
■ RESULTS AND DISCUSSION
Cs2CO3
We initiated our study by selecting α-alkylidene
pyrazolinone 1a and propargyl sulfonium salt 2a as model
substrates (Table 1). Extensive exploration of a range of
bases, solvents and temperature revealed that
NaOAc·3H2O (0.5 equiv) effectively promoted the desired
N-addition/substitution reaction of 1a and 2a in CH3CN,
providing functionalized allylthio-containing pyrazolone
3a with 83% isolated yield (entry 4 in Table 1). Several key
observations should be noted. First, compared to the
stoichiometric quantity of base (2.0 or 3.0 equiv) in
previous reports of propargyl sulfonium salts,8-11 0.5
15
tBuOK
CH3CN
CH3CN
CH3CN
CH3CN
50
50
50
50
35
79
68
70
16
NaOAc
17d
NaOAc•3H2O
18e
NaOAc•3H2O
aUnless otherwise noted, the reactions were performed under
air and α-alkylidene pyrazolinone 1a (0.2 mmol, 1.0 equiv),
propargyl sulfonium salt 2a (0.24 mmol, 1.2 equiv) and base
(0.1 mmol, 0.5 equiv) in solvent (2.0 mL) were mixed, stirred
o
at 22 C until starting material 1a disappeared (monitored by
TLC), and heated at related temperature for 20 h. bIsolated
ACS Paragon Plus Environment

Page 3 of 15
The Journal of Organic Chemistry
c
O
Ph
O
Ph
yield. α-Alkylidene pyrazolinone 1a (0.2 mmol, 1.0 equiv),
propargyl sulfonium salt 2a (0.24 mmol, 1.2 equiv) and base
(0.1 mmol, 0.5 equiv) in solvent (2.0 mL) were mixed and
heated at 50 oC for 20 h. d0.25 equiv of NaOAc·3H2O was used.
e1.0 equiv of NaOAc·3H2O was used.
SMe
N
N
NaOAc•3H2O (50 mol %)
Ar/Me
1
2
3
4
5
6
7
8
Ar/Me
R1
+
N
SMe2Br
2a
N
CH3CN, c = 0.1 M
22 oC for 520 min
Alkyl
Ph
Ph
then 50 o
C
1
3
Alkyl = Me, R1 = H:
b
3a
3b
3c
3d
3e
, R = H: 83%
, R = Me: 68%
Having discovered the optimal conditions (Table 1, entry
4), we began to explore the substrate scope of the reaction
(Scheme 2). Generally, the existence of methyl group at β-
position of alkylidene pyrazolinones was crucial for the
success of the reaction. When methyl and aromatic groups
were involved in disubstituted alkylidene pyrazolinones 1,
a broad range of phenyl substituted substrates 1, including
methyl, methoxy, chloro-, bromo-, iodo-, nitro- and cyano-
groups on ortho-, meta- or para-positions of aromatic
group, could react smoothly with propargyl sulfonium salt
2a to generate the corresponding allylthio-containing
pyrazolones in 68−91% yields (3a−3n in Scheme 2). α-
Alkylidene pyrazolinones with electron-withdrawing
groups gave relatively higher yields than electron-donating
substrates (3b−3c vs 3d−3h). Naphthyl-substituted α-
alkylidene pyrazolinones worked well to afford 3o, 3p and
3q in 70, 75 and 74% yields, respectively. Hetero aromatic
unsaturated pyrazolinones containing thiophene and
pyrrole groups could also be employed in this N-
R
, R = OMe: 74%
, R = Cl: 86%
, R = Br: 78%
, R = I: 91%
Ph
O
SMe
N
N
3f
Ph
9
3g
3h
, R = NO2: 90%
, R = CN: 88%
Crystal structure of compound 3a
Ph Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ph
N
N
O
O
O
SMe
SMe
SMe
N
N
N
R
N
R
Ph
Ph
, R = Me: 74%
Ph
3i
3j
3k
3l
3m
3n
3o
, R = Me: 70%
, R = OMe: 73%
, R = Cl: 82%
, 70%
, R = OMe: 72%
, R = Cl: 90%
R
Ph
N
Ph
O
O
Ph
O
SMe
SMe
N
SMe
N
N
S
N
N
N
Me
Ph
Ph
Ph
, R = H: 75%
, R = OMe: 74%
3p
3q
3r
3s
, 69%
, 63%
R1 = Me:
R1 = Ph:
Ph
O
Ph
N
N
Ph
N
N
O
O
SMe
N
SMe
SMe
Me
Ph
Ph
N
addition/substitution
reaction,
providing
the
Ph
, 72%
Me
Ph
3u
Ph
corresponding allylthio-containing pyrazolones 3r and 3s
with 63% and 69% yields. Double methyl substituted
unsaturated pyrazolinone could also participate in the
reaction and offer access to 3t with 72% yield. In addition,
the structure of allylthio-containing pyrazolone derivative
3a was assigned by single crystal X-ray analysis.14 In
contrast, when methyl group was replaced by other alkyl
groups such as ethyl and benzyl, disubstituted alkylidene
pyrazolinones 1 was inactive and did not engage in the
reaction and a large amount of unsaturated pyrazolinones
was recovered with related 82% and 78% yields (3u and
3v in Scheme 2). The unsuccessful preparation of 3u and
3v partially attributed to the weak basicity of NaOAc·3H2O
which are not beneficial to the enolization of substrates.
Ph
3v
, 0%
c
d
3t
, 0%
aUnless otherwise noted, the reactions were performed under
air and α-alkylidene pyrazolinones 1 (0.2 mmol, 1.0 equiv),
propargyl sulfonium salt 2a (0.24 mmol, 1.2 equiv) and
NaOAc·3H2O (0.1 mmol, 0.5 equiv) in CH3CN (2.0 mL) were
mixed, stirred for several minutes at 22 oC until starting
material 1 disappeared (monitored by TLC), and heated at 50
oC for 20−36 h. bIsolated yield. cNo desired products were
obtained and 82% of 1u was recovered. dNo desired products
were obtained and 78% of 1v was recovered.
Subsequently, we investigated the influence of different
substituents on pyrazolinone ring (Scheme 3). To our
delight, unsaturated pyrazolinones 1 with 4-methyl, 4-
methoxy, 4-fluoro-, 4-bromo-, and 4-nitro- substituents on
Ar2 reacted with propargyl sulfonium salt 2a efficiently,
delivering the corresponding products with 65−81% yields
(3aa−3ae in Scheme 3). In contrast, ortho- or meta-
positions of substituents on Ar2 gave reduced yields of
38−47% partially due to the instability of relative
unsaturated pyrazolinones (3af−3ah in Scheme 3). It is
noteworthy that the substrate having electron-
withdrawing group C6F5- afforded the desired product
with a moderate yield of 59% (3ai). Aromatic substituents
of R1 such as 4-fluoro-, 4-methoxy and 4-bromo phenyl
groups provided tolerance in the constructing related
allylthio-containing pyrazolones and furnished 3 in 70, 87
and 83% yields, respectively (3aj−3al in Scheme 3). When
R1 was alkyl groups such as methyl, the reaction could also
proceed to afford 3am with 74% yield.
Scheme 2. Scope of Disubstituted α-Alkylidene
Pyrazolinonesa
Scheme 3. Scope of α-Alkylidene Pyrazolinones on
Pyrazolinone Ringa
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 15
Ar2
O
Ar2
O
Ph
O
Ph
O
SEt
SEt
NaOAc•3H2O
(50 mol %)
N
N
N
N
NaOAc•3H2O (50 mol %)
Ar1
Me
Ar1
+
Ph
1
2
3
4
5
6
7
8
Ph
SMe
N
N
SMe2Br
2a
N
N
CH3CN, c = 0.1 M
22 oC for 520 min
1a
1a
+
+
Br
SEt2
2b
R1
R1
3
CH3CN, c = 0.1 M
Me
Ph
Ph
22 oC for 15 min
then 50 o
C
1
b
b
4
5
, 25%
, 56%
then 50 o
C
Ar2 = aryl:
F
R
F
O
Ph
Br
R
F
N
Br
F
NaOAc•3H2O (50 mol %)
Ph
Ph
+
O
O
O
O
N
Br
S
N
N
N
N
N
N
CH3CN, c = 0.1 M
F
Ph
Ph
Ph
Ph
SMe
SMe
SMe
SMe
N
N
22 oC for 15 min
2c
Ph
, 42%
6
then 50 o
C
Ph
Ph
3af
3ag
Ph
Ph
3ai
b
3ah
, 39%
, R = Et: 38%
, 59%
3aa
3ab
3ac
3ad
3ae
, R = Me: 65%
, R =OMe: 76%
, R = F: 75%
O
Ph
, R = F: 47%
SMe
Ph
9
N
NaOAc•3H2O (50 mol %)
Br
+
+
SMe2
SMe2
1a
1a
1a
Ph
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CH3CN, c = 0.1 M
, R = Br: 81%
, R = NO2: 79%
R1 = aryl or alkyl:
2d
2e
22 oC for 1 h
Ph
then 50 o
C
7
, E: Z = 1.5: 1, 88%
Me
Me
NaOAc•3H2O (50 mol %)
Br
3a
TMS
Br
CH3CN, c = 0.1 M
O
N
O
O
22 oC for 5 min
N
N
N
72%
Ph
N
Ph
Ph
SMe
SMe
SMe
N
then 50 o
C
O
SMe
N
NaOAc•3H2O (50 mol %)
N
+
3a
SMe2Br
2a
CH3CN, c = 0.1 M
22 oC for 10 min
then 50 oC for 20 h
Me
F
OMe
Br
Cl
3.2 mmol
1.08 g
1.09 g, 81% yield
3aj
, 70%
3ak
3al
3am
, 74%
, 87%
, 83%
aUnless otherwise noted, the reactions were performed under
air and α-alkylidene pyrazolinones 1 (0.2 mmol, 1.0 equiv),
propargyl sulfonium salt 2a (0.24 mmol, 1.2 equiv) and
NaOAc·3H2O (0.1 mmol, 0.5 equiv) in CH3CN (2.0 mL) were
mixed, stirred for several minutes at 22 oC until starting
material 1a disappeared (monitored by TLC), and heated at
50 oC for 20−36 h. bIsolated yield.
aThe reactions were performed under air and α-alkylidene
pyrazolinone 1a (0.2 mmol, 1.0 equiv), sulfonium salts 2b, 2c,
2d or 2e (0.24 mmol, 1.2 equiv) and NaOAc·3H2O (0.1 mmol,
0.5 equiv) in CH3CN (2.0 mL) were mixed, stirred for several
minutes at 22 oC until starting material 1a disappeared
(monitored by TLC), and heated at 50 oC for 20 h. bIsolated
yield.
To further broaden the scope of the reaction, other
The synthetic efficiency of this NaOAc·3H2O promoted
method has inspired us to probe for its mechanistic details
with a series of control experiments. Deuterium labeling
experiment provided 22% of γ-position deuteriation
product 8 with the isomerization of C=C double bond (Z: E
= 2.7: 1),16 which suggests that NaOAc·3H2O is likely acting
as a base and initiates the reaction through deprotonation
to form active N-nucleophilic intermediate. The influence
of possible byproduct of MeBr is also investigated by
introducing iodomethane in the reaction instead of
propargyl sulfonium salt 2a under standard condition
(Scheme 5, b), and N-methylation product 9 was separated
with 21% yield, together with recovery of 1a in 69% yield.
In contrast, when iodomethane was added to the reaction
under standard condition (Scheme 5, c), 81% of desired
product 3a and only 5% of N-methylation product 9 were
obtained. These results support that the byproduct of
MeBr has little interference on the reaction.
representative
propargyl
sulfonium
salts
were
investigated the adaptability to this transformation
(Scheme 4). Propargyl sulfonium salt 2b was compatible
and gave the predicted allylthio-containing pyrazolone 4 in
25% yield, together with additional isomerization product
5 in 56% yield. When propargyl sulfonium salt 2c was
utilized in the reaction, the allyl bromide product 6 was
received with 42% yield and an inseparable complex
mixture was also obtained. The structure of 6 was assigned
by single crystal X-ray analysis (see SI for details).15 Phenyl
substituted propargyl sulfonium salt 2d was also
adaptable to afford desired product 7 with total yield of
88% (E: Z = 1.5: 1). Trimethylsilyl-containing propargyl
sulfonium salt 2e can also be applied to the reaction but
the removal of trimethylsilyl group was affected and
product 3a was obtained. We also carried out the reaction
on a large-scale using α-alkylidene pyrazolinone 1a (1.08
g, 3.2 mmol) and propargyl sulfonium salt 2a (1.2 equiv) as
the representative substrates under the optimal reaction
conditions, affording the corresponding product 3a in 81%
yield. These results suggest the broad substrate
adaptability and the synthetic utility of this new reaction
pathway.
Scheme 5. Control Experiments for Mechanistic Insight
Scheme 4. Scope of Propargyl Sulfonium Salts and
Scale-up Operationa
ACS Paragon Plus Environment

Page 5 of 15
1
2
3
The Journal of Organic Chemistry
O
Ph
O
Ph
N
(a) NaOAc (50 mol %)
N
Ph
Ph
Me
N
+
D2O
10 equiv
N
■ EXPERIMENTAL SECTION

CH3CN, c = 0.1 M
22% CH/D3Ph
50 o
C
Ph
1a
General Information. All reactions were performed in
oven-dried or flame-dried round-bottom flasks and vials.
Stainless steel syringes and cannula were used to transfer
air- and moisture-sensitive liquids. Flash chromatography
was performed using silica gel 60 (230−400 mesh) from
Aladdin. Commercial reagents were purchased from
Aladdin, J&K, Macklin and Meryer and used as received. All
solvents were used after being freshly distilled unless
otherwise noted. Proton nuclear magnetic resonance (1H
NMR) spectra and carbon nuclear magnetic resonance (13C
NMR) spectra were recorded on Bruker UltraShield600
(600 MHz). The mass spectroscopic data were obtained
8
(Z: E = 2.7: 1)
4
5
6
7
8
9
O
Ph
O
O
Ph
N
(b) NaOAc•3H2O (50 mol %)
N
Ph
N
Ph
Me
Me
+ 1a
+
MeI
N
CH3CN, c = 0.1 M
Ph
50 o
C
Ph
1a
2.0 equiv
69%
9
, 21%
O
Ph
Ph
(c) NaOAc•3H2O (50 mol %)
2a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
N
(1.2 equiv)
Ph
N
Ph
Me
+
MeI
3a
Me +
N
CH3CN, c = 0.1 M
Ph
22 oC for 5 min
Ph
1a
2.0 equiv
81%
9
, 5%
then 50 o
C
using
a Micromass Platform II single quadrupole
According to the control experiments and previous
reports on α-alkylidene pyrazolinones and propargyl
sulfonium salts, a possible mechanism is proposed in
Scheme 6. Under the activation of inorganic base
NaOAc·3H2O, the α-alkylidene pyrazolone 1 could undergo
deprotonation to form intermediate I and propargyl
sulfonium salt 2a can isomerize to allenic sulfonium salts
II. The N-nucleophilic attack of I to II initiates the reaction
and gives intermediate III. Subsequently, protonation of
the species III to form IV and release of MeBr provide the
desired product 3.
instrument. Infrared (IR) spectra were obtained using a
Perkin Elmer Spectrum 100 FT-IR spectrometer.
General Procedure for the Synthesis of α-Alkylidene
Pyrazolinones (1):
α-Alkylidene pyrazolinones 1a-1v, 1aa-1am were
3c,6b,17
prepared through a known procedure:
Aryl formyl
acetate (5.5 mmol, 1.1 equiv) was slowly added to the
mixture of the corresponding hydrazine (5 mmol, 1.0
equiv) in glacial acetic acid (2 ml). The mixture was stirred
at room temperature for 24 h. NEt3 (5 mmol, 1.0 equiv)
was added to neutralize the hydrochloride while
phenylhydrazine hydrochloride was used. After the
reaction was completed, ethyl (50 mL) was added. The
precipitate was filtered and washed with 5 mL of ether
(three times). The corresponding pyrozolone products
were obtained as solid and used in the following step.
Under nitrogen atmosphere, a mixture of pyrazolone (5
mmol, 1.0 equiv), acetophenone (6 mmol, 1.2 equiv) and
pyridine (0.8 mL, 10 mmol) in THF (10 mL) was stirred for
10 min followed by slow addition (30 min) of Titanium
isopropoxide (4.3 mL, 15 mmol). The mixture was stirred
at room temperature for 24 h. The resulting reaction
mixture was diluted with EtOAc (100 mL) and washed
with 1 N aqueous HCl, saturated aqueous solution of
NaHCO3 and brine. The organic layer was dried over
Na2SO4, concentrated, and purified by column
chromatography to provide α-alkylidene pyrazolinone
derivatives 1. If the products are mixed with excess liquid
acetophenes, they can be further purified by washed with
petroleum ether.
Scheme 6. Plausible Reaction Mechanism
O
O
Ar
Ar
Ar1
Ar1
Base
N
H
N
N
deprotonation
N
R
R
1
I
Ar1
O
N
N
Ar
isomerization
SMe2Br
SMe2Br
•
SMe2Br
2
II
R
III
protonation
Ar1
O
Ar1
O
N
N
N
N
MeBr
Ar
SMe2Br
SMe
Ar
R
IV
R
3
■ CONCLUSIONS
α-Alkylidene pyrazolinones 1f, 1i, 1j, 1n, 1o, 1q, 1s, 1af,
1ag, 1ak, 1al and 1am were not reported before and we
In summary, we have developed a regioselective N-
addition/substitution reaction between α-alkylidene
pyrazolinones and propargyl sulfonium salts for the first
time, affording potentially bioactive allylthio-containing
pyrazolones in moderate to excellent yields. In this
reaction, α-alkylidene pyrazolinones act as N-nucleophilic
agents which are distinguished from reported C-
nucleophilic reactions. Meanwhile, the sulfur group was
retained to access organosulfur compounds. The proposed
mechanism is also discussed. Excellent regioselectivity,
readily available starting materials, the broad range of
substrates, gram-scale synthesis and simple operation
illustrate the synthetic advantages of this reaction
pathway.
gave
Characterization
the
corresponding
of the
characterization
remaining α-alkylidene
data.
pyrazolinones was consistent with what was previously
reported.6b
(Z)-4-(1-(4-iodophenyl)ethylidene)-2,5-diphenyl-2,4-
dihydro-3H-pyrazol-3-one (1f): red solid (1.67 g, 72%
yield). m. p. 167.3–168.3 °C. IR νmax (neat)/cm-1: 3055,
2981, 1707, 1580, 1462, 1368, 1321, 1293, 1207, 1163,
1068, 853, 775; 1H NMR (600 MHz, CDCl3): δ 8.07 (d, J = 8.4
Hz, 2H), 7.46 (t, J = 7.8 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.24
(t, J = 7.2 Hz, 1H), 7.19 (t, J = 7.2 Hz, 1H), 7.05 (t, J = 7.2 Hz,
2H), 6.97 (d, J = 7.8 Hz, 2H), 6.75 (d, J = 7.8 Hz, 2H), 2.96 (s,
3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.5, 163.7, 150.7,
139.4, 138.3, 136.7, 132.6, 130.0, 128.7, 128.1, 127.8,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 15
127.7, 125.0, 124.5, 119.2, 96.1, 22.2. HRMS (ESI-TOF,
7.05 (dd, J = 2.4, 8.4 Hz, 1H), 7.01 (d, J = 2.4 Hz, 1H), 6.98
m/z): calcd for C23H18IN2O+, [M + H]+, 465.0458, found
465.0456.
(d, J = 1.8 Hz, 1H), 6.80–6.78 (m, 3H), 3.92 (s, 3H), 3.09 (s,
3H); 13C{1H} NMR (150 MHz, CDCl3): δ 166.7, 164.2, 158.9,
151.3, 138.6, 135.0, 135.0, 133.0, 130.0, 128.7, 127.9,
127.5, 127.3, 126.3, 125.9, 124.9, 123.9, 119.3, 119.1,
105.4, 55.3, 22.4. HRMS (ESI-TOF, m/z): calcd for
C28H22N2O2Na+, [M + Na]+, 441.1573, found 441.1570.
(Z)-4-(1-(1-methyl-1H-pyrrol-2-yl)ethylidene)-2,5-
diphenyl-2,4-dihydro-3H-pyrazol-3-one (1s, Z:E 6:1): red
solid (1.04 g, 61% yield). m. p. 167.4–168.4 °C. IR νmax
(neat)/cm-1: 3028, 2937, 1695, 1529, 1500, 1310, 1252,
1129, 1064, 959, 775; 1H NMR (600 MHz, CDCl3): δ 8.12 (d,
J = 7.8 Hz, 2H), 7.46 (t, J = 7.8 Hz, 3H), 7.24–7.16 (m, 6H),
6.60 (s, 1H), 6.30 (s, 1H), 6.13 (s, 1H), 3.19 (s, 3H), 2.97 (s,
3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.5, 154.1, 150.7,
138.8, 134.7, 132.5, 130.1, 128.7, 127.8, 127.6, 126.9,
124.7, 120.7, 119.1, 117.6, 110.5, 34.9, 23.0. HRMS (ESI-
TOF, m/z): calcd for C22H20N3O+, [M + H]+, 342.1601, found
342.1605.
1
2
3
4
5
6
7
8
(Z)-2,5-diphenyl-4-(1-(o-tolyl)ethylidene)-2,4-dihydro-3H-
pyrazol-3-one (1i): red solid (1.02 g, 58% yield). m. p.
166.5–167.5 °C. IR νmax (neat)/cm-1: 3092, 2991, 1698,
1
1622, 1584, 1468, 1391, 1307, 1263, 1119, 944, 754; H
NMR (600 MHz, CDCl3): δ 8.09 (d, J = 7.8 Hz, 2H), 7.47 (t, J =
7.8 Hz, 2H), 7.24 (t, J = 7.2 Hz, 1H), 7.10–7.07 (m, 1H),
7.01–6.97 (m, 5H), 6.92 (t, J = 7.2 Hz, 1H), 6.85 (t, J = 6.6 Hz,
2H), 2.92 (s, 3H), 2.15 (s, 3H); 13C{1H} NMR (150 MHz,
CDCl3): δ 166.6, 163.7, 151.2, 140.5, 138.4, 133.4, 132.2,
130.0, 128.7, 128.6, 128.0, 127.9, 127.5, 127.2, 125.3,
125.2, 124.9, 119.1, 23.5.1, 19.7. HRMS (ESI-TOF, m/z):
calcd for C24H21N2O+, [M + H]+, 353.1648, found 353.1649.
(Z)-4-(1-(3-methoxyphenyl)ethylidene)-2,5-diphenyl-2,4-
dihydro-3H-pyrazol-3-one (1j): red solid (1.38 g, 75%
yield). m. p. 168.7–169.7 °C. IR νmax (neat)/cm-1: 3032,
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
2879, 1682, 1590, 1485, 1338, 1193, 1031, 976, 787; H
NMR (600 MHz, CDCl3): δ 8.09 (d, J = 7.8 Hz, 2H), 7.47 (t, J =
7.8 Hz, 2H), 7.24 (t, J = 7.2 Hz, 1H), 7.12 (dt, J = 1.8, 4.8 Hz,
1H), 7.07–7.01 (m, 5H), 6.75 (d, J = 7.8 Hz, 1H), 6.68 (dd, J
= 1.8, 7.8 Hz, 1H), 6.51 (t, J = 1.8 Hz, 1H), 3.59 (s, 3H), 3.00
(s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 166.2, 164.1,
158.8, 150.9, 141.4, 138.4, 133.1, 128.9, 128.7, 127.8,
124.9, 124.1, 120.9, 119.2, 115.7, 114.3, 55.1, 22.6. HRMS
(Z)-2-(2-ethylphenyl)-5-phenyl-4-(1-phenylethylidene)-
2,4-dihydro-3H-pyrazol-3-one (1af): red solid (622 mg,
34% yield). m. p. 167.6–168.6 °C. IR νmax (neat)/cm-1: 3067,
1
2892, 1689, 1489, 1318, 1167, 1040, 907, 694; H NMR
(600 MHz, CDCl3): δ 7.44–7.36 (m, 3H), 7.19 (dt, J = 1.8, 7.8
Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 7.13 (d, J = 1.2 Hz, 2H),
7.12–6.97 (m, 7H), 3.01 (s, 3H), 2.79 (q, J = 7.8 Hz, 2H),
1.29 (t, J = 7.8 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ
166.3, 165.0, 150.7, 141.4, 140.2, 135.9, 133.0, 129.6,
129.2, 128.7, 128.0, 127.6, 127.5, 127.4, 126.4, 123.1, 24.7,
22.5, 14.3. HRMS (ESI-TOF, m/z): calcd for C25H23N2O+, [M
+ H]+, 367.1805, found 367.1806.
+
(ESI-TOF, m/z): calcd for C24H21N2O2 , [M + H]+, 369.1598,
found 369.1602.
(Z)-4-(1-(2-chlorophenyl)ethylidene)-2,5-diphenyl-2,4-
dihydro-3H-pyrazol-3-one (1n): red solid (967 mg, 52%
yield). m. p. 167.4–168.4 °C. IR νmax (neat)/cm-1: 3036,
1
2979, 1689, 1595, 1489, 1319, 1118, 944, 771; H NMR
(Z)-2-(2-fluorophenyl)-5-phenyl-4-(1-phenylethylidene)-
2,4-dihydro-3H-pyrazol-3-one (1ag): yellow solid (765 mg,
43% yield). m. p. 164.2–165.5 °C. IR νmax (neat)/cm-1: 3053,
(600 MHz, CDCl3): δ 8.07 (d, J = 7.8 Hz, 2H), 7.46 (t, J = 7.8
Hz, 2H), 7.24 (t, J = 7.8 Hz, 1H), 7.14 (d, J = 7.8 Hz, 1H), 7.08
(dd, J = 2.4, 7.2 Hz, 3H), 7.04–6.99 (m, 3H), 6.87 (dt, J = 0.6,
7.8 Hz, 1H), 6.81 (dd, J = 1.8, 7.8 Hz, 1H), 2.92 (s, 3H);
13C{1H} NMR (150 MHz, CDCl3): δ 163.6, 162.9, 150.9,
139.3, 138.3, 132.2, 131.1, 129.8, 129.5, 129.3, 128.7,
128.1, 128.1, 127.4, 126.1, 126.0, 125.0, 119.1, 22.4. HRMS
(ESI-TOF, m/z): calcd for C23H18ClN2O+, [M + H]+, 373.1102,
found 373.1107.
(Z)-4-(1-(naphthalen-1-yl)ethylidene)-2,5-diphenyl-2,4-
dihydro-3H-pyrazol-3-one (1o): red solid (1.24 g, 64%
yield). m. p. 167.8–168.8 °C. IR νmax (neat)/cm-1: 3058,
2957, 1690, 1594, 1490, 1321, 1164, 1030, 903, 853, 775;
1H NMR (600 MHz, CDCl3): δ 8.12 (d, J = 7.8 Hz, 2H), 7.73
(d, J = 8.4 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.4
Hz, 1H), 7.53–7.46 (m, 4H), 7.26 (t, J = 7.8 Hz, 1H), 7.11 (t, J
= 7.2 Hz, 1H), 7.01 (d, J = 6.6 Hz, 1H), 6.85 (t, J = 7.2 Hz,
1H), 6.71 (d, J = 7.2 Hz, 1H), 6.65 (t, J = 7.2 Hz, 2H), 3.10 (s,
3H); 13C{1H} NMR (150 MHz, CDCl3): δ 165.6, 163.7, 151.4,
138.4, 138.3, 133.2, 132.2, 130.1, 129.1, 128.7, 128.3,
127.7, 127.4, 126.8, 126.7, 126.4, 126.0, 125.5, 125.0,
124.8, 124.4, 119.1, 23.9. HRMS (ESI-TOF, m/z): calcd for
C27H20N2ONa+, [M + Na]+, 411.1468, found 411.1473.
(Z)-4-(1-(6-methoxynaphthalen-2-yl)ethylidene)-2,5-
1
2981, 1672, 1569, 1421, 1368, 1212, 1063, 923, 758; H
NMR (600 MHz, CDCl3): δ 7.61 (t, J = 7.8 Hz, 1H), 7.59–7.35
(m, 1H), 7.27–7.25 (m, 2H), 7.14 (t, J = 7.2 Hz, 1H), 7.12–
7.06 (m, 3H), 7.04–6.99 (m, 6H), 3.00 (s, 3H); 13C{1H} NMR
(150 MHz, CDCl3): δ 166.7, 164.6, 157.9, 156.2, 151.8,
140.3, 133.0, 129.7, 129.1, 129.0, 128.7, 128.2, 127.8,
127.7, 127.6, 127.5, 125.7, 125.6, 124.3, 123.1, 116.8,
116.7, 22.6. 19F NMR (600 MHz, CDCl3): δ -118.56. HRMS
(ESI-TOF, m/z): calcd for C23H17FN2ONa+, [M + Na]+,
379.1217, found 379.1213.
(Z)-5-(4-methoxyphenyl)-4-(1-phenylethylidene)-2-(p-
tolyl)-2,4-dihydro-3H-pyrazol-3-one (1ak): red solid (898
mg, 47% yield). m. p. 169.3–170.3 °C. IR νmax (neat)/cm-1:
3037, 1696, 1535, 1437, 1330, 1249, 1161, 1027, 915, 797;
1H NMR (600 MHz, CDCl3): δ 7.96 (d, J = 9.0 Hz, 2H), 7.26
(d, J = 8.4 Hz, 2H), 7.16–7.14 (m, 1H), 7.07–7.03 (m, 4H),
6.94 (dd, J = 1.8, 6.6 Hz, 2H), 6.52 (dd, J = 1.8, 6.6 Hz, 2H),
3.71 (s, 3H), 2.99 (s, 3H), 2.40 (s, 3H); 13C{1H} NMR (150
MHz, CDCl3): δ 165.9, 163.9, 159.2, 150.5, 140.2, 136.0,
134.4, 129.4, 129.3, 129.2, 128.7, 127.6, 125.4, 124.3,
119.2, 113.1, 55.1, 22.6, 20.9. HRMS (ESI-TOF, m/z): calcd
for C25H22N2O2Na+, [M + Na]+, 405.1573, found 405.1576.
(Z)-5-(4-bromophenyl)-4-(1-phenylethylidene)-2-(p-
diphenyl-2,4-dihydro-3H-pyrazol-3-one (1q): red solid (1.65
g, 79% yield). m. p. 168.9–169.9 °C. IR νmax (neat)/cm-1:
3059, 2993, 2838, 1691, 1594, 1500, 1388, 1271, 1209,
1123, 1064, 902, 810; 1H NMR (600 MHz, CDCl3): δ 8.12 (d,
J = 7.8 Hz, 2H), 7.47 (t, J = 7.8 Hz, 2H), 7.44 (d, J = 9.0 Hz,
2H), 7.25 (t, J = 7.8 Hz, 1H), 7.21 (dd, J = 1.8, 8.4 Hz, 1H),
tolyl)-2,4-dihydro-3H-pyrazol-3-one (1al): red solid (838
mg, 39% yield). m. p. 170.2–171.2 °C. IR νmax (neat)/cm-1:
3072, 2939, 1697, 1588, 1379, 1271, 1123, 1027, 902, 886;
1H NMR (600 MHz, CDCl3): δ 7.90 (d, J = 8.4 Hz, 2H), 7.25 (t,
J = 7.8 Hz, 3H), 7.21 (dt, J = 1.8, 6.0 Hz, 1H), 7.12 (d, J = 8.4
ACS Paragon Plus Environment

Page 7 of 15
The Journal of Organic Chemistry
Hz, 2H), 7.09–7.05 (m, 4H), 6.87 (d, J = 8.4 Hz, 2H), 3.00 (s,
113.9, 35.3, 21.0, 15.1. HRMS (ESI-TOF, m/z): calcd for
3H), 2.40 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 166.4,
163.8, 149.7, 140.2, 135.9, 134.8, 132.0, 130.7, 129.8,
129.6, 129.3, 128.7, 127.9, 124.1, 122.0, 119.4, 22.6, 20.9.
HRMS (ESI-TOF, m/z): calcd for C24H19BrN2ONa+, [M + Na]+,
453.0573, found 453.0578.
C28H27N2OS+, [M + H]+, 439.1839, found 439.1841.
1
2
3
4
5
6
7
8
4-(1-(4-Methoxyphenyl)vinyl)-1-(3-(methylthio)prop-1-
en-2-yl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one
(3c):
The reaction was carried out on a 0.2 mmol scale following
the General Procedure. The product 3c was purified
through column chromatography (PE/EtOAc: from 8:1 to
6:1) as foam solid (67 mg, 74% yield). IR νmax (neat)/cm-1:
3063, 2930, 1681, 1582, 1487, 1332, 1285, 1169, 1032,
932, 817; 1H NMR (600 MHz, CDCl3): δ 7.63 (dd, J = 1.2, 8.4
Hz, 2H), 7.45 (t, J = 8.4 Hz, 4H), 7.37 (d, J = 9.0 Hz, 2H),
7.31–7.27 (m, 4H), 6.77 (d, J = 9.0 Hz, 2H), 5.56 (d, J = 1.2
Hz, 1H), 5.52 (s, 1H), 5.31 (d, J = 1.2 Hz, 1H), 5.20 (s, 1H),
3.78 (s, 3H), 2.85 (s, 2H), 1.43 (s, 3H); 13C{1H} NMR (150
MHz, CDCl3): δ 164.6, 159.1, 156.3, 141.3, 137.7, 135.9,
132.8, 130.5, 129.5, 128.9, 128.7, 127.9, 127.7, 126.2,
123.8, 123.4, 118.7, 116.8, 113.6, 55.2, 35.4, 15.1. HRMS
(ESI-TOF, m/z): calcd for C28H26NaN2O2S+, [M + Na]+,
477.1607, found 477.1603.
(Z)-2-(4-bromophenyl)-4-(1-(2-chlorophenyl)ethylidene)-
5-methyl-2,4-dihydro-3H-pyrazol-3-one (1am): red solid
(1.03 g, 53% yield). m. p. 178.2–179.1 °C. IR νmax
(neat)/cm-1: 3089, 2972, 1678, 1533, 1326, 1283, 1147,
1037, 953, 826; 1H NMR (600 MHz, CDCl3): δ 7.91 (d, J = 9.0
Hz, 2H), 7.53–7.50 (m, 3H), 7.42–7.38 (m, 2H), 7.18–7.16
(m, 1H), 2.83 (s, 3H), 1.55 (s, 3H); 13C{1H} NMR (150 MHz,
CDCl3): δ 163.5, 161.2, 148.5, 139.9, 137.5, 131.8, 130.8,
130.2, 130.1, 127.9, 127.1, 120.2, 117.6, 21.7, 16.1. HRMS
(ESI-TOF, m/z): calcd for C18H14BrClN2ONa+, [M + Na]+,
410.9870, found 410.9870.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Propargyl Sulfonium Salts (2a, 2b, 2c, 2d and 2e) were
prepared through a known procedure.18
General Procedure for the Reaction of α-Alkylidene
Pyrazolinones 1 with Propargyl Sulfonium Salts 2: To a
flame-dried sealable 2-dram vial equipped with a stir bar
was added unsaturated pyrazolones 1 (0.2 mmol, 1.0
equiv), NaOAc·3H2O (0.1 mmol, 0.5 equiv) and 2 (0.24
mmol, 1.2 equiv) under air. Subsequently CH3CN (2 mL, c =
0.1 M) was added to vial via syringe. The reaction mixture
was kept stirring for 5–20 min at 22 °C until α-alkylidene
pyrazolinone 1 was fully consumed (monitored by TLC).
Then the reaction was heated to 50 °C for 20 to 36 h. The
organic solvent was removed under reduced pressure and
purified through column chromatography (eluent:
petroleum ether and EtOAc) to afford the desired products
3.
4-(1-(4-Chlorophenyl)vinyl)-1-(3-(methylthio)prop-1-en-
2-yl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3d): The
reaction was carried out on a 0.2 mmol scale following the
General Procedure. The product 3d was purified through
column chromatography (PE/EtOAc: from 8:1 to 6:1) as
foam solid (79 mg, 86% yield). IR νmax (neat)/cm-1: 3058,
1
2989, 1675, 1570, 1484, 1308, 1073, 906, 753; H NMR
(600 MHz, CDCl3): δ 7.62 (dd, J = 1.2, 8.4 Hz, 2H), 7.46 (t, J =
8.4 Hz, 2H), 7.41 (dd, J = 1.8, 8.4 Hz, 2H), 7.32–7.26 (m,
6H), 7.16 (d, J = 8.4 Hz, 2H), 5.61 (d, J = 0.6 Hz, 1H), 5.51 (d,
J = 0.6 Hz, 1H), 5.49 (s, 1H), 5.18 (s, 1H), 2.85 (s, 2H), 1.44
(s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.2, 156.5,
140.6, 138.6, 137.1, 135.5, 133.0, 130.5, 129.6, 128.8,
128.6, 128.1, 127.8, 126.4, 123.7, 119.2, 118.9, 112.6, 35.6,
15.0. HRMS (ESI-TOF, m/z): calcd for C27H24ClN2OS+, [M +
H]+, 459.1292, found 459.1298.
1-(3-(Methylthio)prop-1-en-2-yl)-2,5-diphenyl-4-(1-
phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one
(3a):
The
reaction was carried out on a 0.2 mmol scale following the
General Procedure. The product 3a was purified through
column chromatography (PE/EtOAc: from 6:1 to 4:1) as
white solid (70 mg, 83% yield). m. p. 182.7–183.7 °C. IR
νmax (neat)/cm-1: 3055, 1675, 1486, 1321, 1157, 1061, 907,
4-(1-(4-Bromophenyl)vinyl)-1-(3-(methylthio)prop-1-en-
2-yl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3e): The
reaction was carried out on a 0.2 mmol scale following the
General Procedure. The product 3e was purified through
column chromatography (PE/EtOAc: from 6:1 to 4:1) as
foam solid (78 mg, 78% yield). IR νmax (neat)/cm-1: 3039,
1
773; H NMR (600 MHz, CDCl3): δ 7.64 (d, J = 7.8 Hz, 2H),
1
7.48–7.43 (m, 4H), 7.41 (d, J = 7.2 Hz, 2H), 7.28–7.16 (m,
7H), 5.66 (s, 1H), 5.52 (s, 1H), 5.51 (s, 1H), 5.20 (s, 1H),
2.85 (s, 2H), 1.43 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ
164.4, 156.4, 140.9, 140.0, 138.1, 135.6, 130.5, 129.5,
128.7, 128.0, 127.7, 127.3, 127.0, 126.8, 126.2, 123.8,
119.1, 118.5, 113.2, 35.4, 15.0. HRMS (ESI-TOF, m/z): calcd
for C27H25N2OS+, [M + H]+, 425.1682, found 425.1680.
1-(3-(Methylthio)prop-1-en-2-yl)-2,5-diphenyl-4-(1-(p-
2976, 1677, 1562, 1473, 1390, 1124, 973, 837; H NMR
(600 MHz, CDCl3): δ 7.62 (dd, J = 1.2, 8.4 Hz, 2H), 7.46 (dd, J
= 7.8, 8.4 Hz, 2H), 7.41 (dd, J = 1.2, 8.4 Hz, 2H), 7.33–7.30
(m, 3H), 7.29–7.25 (m, 5H), 5.62 (d, J = 0.6 Hz, 1H), 5.51 (d,
J = 0.6 Hz, 1H), 5.50 (s, 1H), 5.18 (s, 1H), 2.85 (s, 2H), 1.44
(s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.4, 156.3,
141.1, 139.3, 137.4, 135.8, 131.1, 130.5, 129.7, 128.8,
128.6, 127.8, 126.4, 123.9, 121.3, 119.0, 118.7, 112.8, 35.7,
15.2. HRMS (ESI-TOF, m/z): calcd for C27H24BrN2OS+, [M +
H]+, 503.0787, found 503.0784.
tolyl)vinyl)-1,2-dihydro-3H-pyrazol-3-one
(3b):
The
reaction was carried out on a 0.2 mmol scale following the
General Procedure. The product 3b was purified through
column chromatography (PE/EtOAc: from 8:1 to 6:1) as
foam solid (59 mg, 68% yield). IR νmax (neat)/cm-1: 3025,
4-(1-(4-Iodophenyl)vinyl)-1-(3-(methylthio)prop-1-en-2-
yl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3f): The
reaction was carried out on a 0.2 mmol scale following the
General Procedure. The product 3f was purified through
column chromatography (PE/EtOAc: from 5:1 to 4:1) as
foam solid (100 mg, 91% yield). IR νmax (neat)/cm-1: 3027,
1
2851, 1648, 1444, 1285, 1061, 968, 806; H NMR (600
MHz, CDCl3): δ 7.64 (d, J = 7.8 Hz, 2H), 7.64–7.44 (m, 4H),
7.34 (d, J = 7.8 Hz, 2H), 7.31–7.26 (m, 4H), 7.05 (d, J = 7.8
Hz, 2H), 5.61 (d, J = 1.2 Hz, 1H), 5.52 (s, 1H), 5.36 (d, J = 1.2
Hz, 1H), 5.21 (s, 1H), 2.86 (s, 2H), 2.30 (s, 3H), 1.46 (s, 3H);
13C{1H} NMR (150 MHz, CDCl3): δ 164.6, 156.3, 141.4,
138.2, 137.3, 137.0, 136.0, 130.5, 129.4, 129.0, 128.7,
128.7, 127.8, 127.7, 126.7, 126.2, 123.8, 118.6, 117.6,
1
2917, 1673, 1510, 1445, 1307, 1011, 904, 816; H NMR
(600 MHz, CDCl3): δ 7.62 (d, J = 7.2 Hz, 2H), 7.53 (d, J = 6.6
Hz, 2H), 7.46 (t, J = 8.4 Hz, 2H), 7.41 (dd, J = 1.2, 8.4 Hz,
2H), 7.34–7.26 (m, 4H), 7.14 (d, J = 8.4 Hz, 2H), 5.62 (d, J =
0.6 Hz, 1H), 5.49 (d, J = 2.4 Hz, 2H), 5.18 (s, 1H), 2.85 (s,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 15
2H), 1.45 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.3,
(m, 4H), 7.29–7.24 (m, 4H), 7.13 (t, J = 7.8 Hz, 1H), 7.02 (d,
1
2
3
4
5
6
7
8
156.4, 141.1, 139.9, 137.5, 137.3, 137.1, 135.8, 130.5,
129.6, 128.8, 128.8, 127.8, 126.4, 123.9, 119.0, 118.7,
112.7, 35.7, 15.2. HRMS (ESI-TOF, m/z): calcd for
C27H23IN2NaOS+, [M + Na]+, 573.0468, found 573.0466.
1-(3-(Methylthio)prop-1-en-2-yl)-4-(1-(4-
J = 7.8 Hz, 1H), 6.92 (dd, J = 1.8, 4.2 Hz, 1H), 6.73 (dd, J =
2.4, 7.8 Hz, 1H), 5.65 (d, J = 1.2 Hz, 1H), 5.51 (s, 1H), 5.50
(d, J = 1.2 Hz, 1H), 5.20 (s, 1H), 3.77 (s, 3H), 2.85 (s, 2H),
1.44 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.4, 159.2,
156.4, 141.6, 140.9, 138.1, 135.6, 130.5, 129.5, 129.0,
128.8, 128.7, 127.7, 126.2, 123.7, 119.6, 119.1, 118.7,
113.2, 113.1, 112.4, 55.2, 35.4, 15.0. HRMS (ESI-TOF, m/z):
calcd for C28H26N2NaO2S+, [M + Na]+, 477.1607, found
477.1609.
nitrophenyl)vinyl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-
one (3g): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3g was
purified through column chromatography (PE/EtOAc:
from 5:1 to 3:1) as foam solid (84 mg, 90% yield). IR νmax
(neat)/cm-1: 3032, 2987, 1681, 1527, 1397, 1262, 1098,
1002, 935, 882; 1H NMR (600 MHz, CDCl3): δ 8.03 (d, J = 9.0
Hz, 2H), 7.61 (d, J = 7.2 Hz, 2H), 7.50–7.45 (m, 4H), 7.39
(dd, J = 1.8, 8.4 Hz, 2H), 7.31–7.24 (m, 4H), 5.74 (s, 1H),
5.73 (s, 1H), 5.49 (s, 1H), 5.17 (s, 1H), 2.86 (s, 2H), 1.44 (s,
3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.1, 156.4, 147.1,
147.0, 140.8, 137.0, 135.6, 130.5, 129.9, 128.9, 128.6,
128.1, 128.0, 127.7, 126.6, 123.9, 123.2, 121.6, 118.9,
111.7, 36.0, 15.2. HRMS (ESI-TOF, m/z): calcd for
C27H24N3O3S+, [M + H]+, 470.1533, found 470.1533.
9
4-(1-(3-Chlorophenyl)vinyl)-1-(3-(methylthio)prop-1-en-
2-yl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3k): The
reaction was carried out on a 0.2 mmol scale following the
General Procedure. The product 3k was purified through
column chromatography (PE/EtOAc: from 6:1 to 4:1) as
foam solid (75 mg, 82% yield). IR νmax (neat)/cm-1: 3071,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
2878, 1677, 1592, 1469, 1322, 1179, 1025, 966, 892; H
NMR (600 MHz, CDCl3): δ 7.63 (dd, J = 1.2, 8.4 Hz, 2H), 7.47
(t, J = 8.4 Hz, 2H), 7.40 (dd, J = 1.8, 8.4 Hz, 2H), 7.32–7.24
(m, 6H), 7.10–7.09 (m, 2H), 5.64 (d, J = 1.2 Hz, 1H), 5.63 (s,
1H), 5.49 (s, 1H), 5.18 (s, 1H), 2.85 (s, 2H), 1.45 (s, 3H);
13C{1H} NMR (150 MHz, CDCl3): δ 164.2, 156.4, 142.0,
140.7, 137.1, 135.5, 133.8, 130.5, 129.6, 129.2, 128.8,
128.6, 127.7, 127.2, 127.1, 126.4, 125.1, 123.8, 119.5,
119.1, 112.2, 35.7, 15.1. HRMS (ESI-TOF, m/z): calcd for
C27H23ClN2NaOS+, [M + Na]+, 481.1112, found 481.1113.
1-(3-(Methylthio)prop-1-en-2-yl)-2,5-diphenyl-4-(1-(o-
tolyl)vinyl)-1,2-dihydro-3H-pyrazol-3-one (3l): The reaction
was carried out on a 0.2 mmol scale following the General
Procedure. The product 3l was purified through column
chromatography (PE/EtOAc: from 6:1 to 4:1) as foam solid
(65 mg, 74% yield). IR νmax (neat)/cm-1: 3051, 2982, 1672,
4-(1-(1-(3-(Methylthio)prop-1-en-2-yl)-3-oxo-2,5-
diphenyl-2,3-dihydro-1H-pyrazol-4-yl)vinyl)benzonitrile
(3h): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3h was
purified through column chromatography (PE/EtOAc:
from 5:1 to 3:1) as foam solid (79 mg, 88% yield). IR νmax
(neat)/cm-1: 3072, 2976, 1672, 1476, 1331, 1229, 1152,
1034, 913, 826; 1H NMR (600 MHz, CDCl3): δ 7.60 (d, J = 8.4
Hz, 2H), 7.47–7.43 (m, 6H), 7.38 (d, J = 7.8 Hz, 2H), 7.29 (d,
J = 7.2 Hz, 2H), 7.24 (t, J = 7.2 Hz, 2H), 5.69 (s, 1H), 5.68 (s,
1H), 5.48 (s, 1H), 5.17 (s, 1H), 2.85 (s, 2H), 1.43 (s, 3H);
13C{1H} NMR (150 MHz, CDCl3): δ 164.1, 156.4, 145.0,
140.8, 137.2, 135.6, 131.7, 130.5, 129.8, 129.0, 128.8,
128.7, 128.0, 127.9, 127.6, 126.5, 123.9, 118.8, 111.7,
110.8, 35.9, 15.1. HRMS (ESI-TOF, m/z): calcd for
C28H24N3OS+, [M + H]+, 450.1635, found 450.1637.
1
1568, 2448, 1379, 1253, 1062, 937, 784; H NMR (600
MHz, CDCl3): δ 7.61 (d, J = 7.8 Hz, 2H), 7.47 (t, J = 7.8 Hz,
2H), 7.29 (t, J = 7.2 Hz, 1H), 7.19–7.17 (m, 3H), 7.11 (t, J =
7.8 Hz, 2H), 6.97 (d, J = 7.2 Hz, 1H), 6.91 (dt, J = 1.2, 7.2 Hz,
1H), 6.86 (t, J = 7.2 Hz, 1H), 6.83 (d, J = 7.2 Hz, 1H), 6.18 (d,
J = 1.8 Hz, 1H), 5.35 (d, J = 1.8 Hz, 1H), 5.29 (s, 1H), 5.09 (s,
1H), 2.77 (s, 2H), 2.12 (s, 3H), 1.47 (s, 3H); 13C{1H} NMR
(150 MHz, CDCl3): δ 164.4, 154.9, 141.2, 138.3, 136.0,
135.0, 130.3, 129.7, 129.6, 129.1, 128.8, 127.3, 126.7,
126.4, 125.0, 124.0, 120.2, 117.7, 112.5, 35.7, 20.1, 15.3.
HRMS (ESI-TOF, m/z): calcd for C28H27N2OS+, [M + H]+,
439.1839, found 439.1834.
4-(1-(2-Methoxyphenyl)vinyl)-1-(3-(methylthio)prop-1-
en-2-yl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3m):
The reaction was carried out on a 0.2 mmol scale following
the General Procedure. The product 3m was purified
through column chromatography (PE/EtOAc: from 6:1 to
4:1) as foam solid (65 mg, 72% yield). IR νmax (neat)/cm-1:
3022, 2918, 1672, 1580, 1397, 1301, 1189, 1011, 934, 781;
1H NMR (600 MHz, CDCl3): δ 7.61 (d, J = 7.8 Hz, 2H), 7.45 (t,
J = 7.8 Hz, 2H), 7.31–7.26 (m, 3H), 7.19–7.18 (m, 1H), 7.15–
7.13 (m, 3H), 7.01 (t, J = 7.8 Hz, 1H), 6.75 (t, J = 7.8 Hz, 1H),
6.51 (t, J = 7.8 Hz, 1H), 6.06 (d, J = 1.8 Hz, 1H), 5.47 (d, J =
1.8 Hz, 1H), 5.40 (s, 1H), 5.19 (s, 1H), 3.66 (s, 3H), 2.76 (s,
2H), 1.44 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.5,
156.1, 154.7, 141.2, 136.0, 135.8, 130.6, 130.5, 130.1,
129.0, 128.9, 128.7, 128.4, 127.1, 126.2, 123.9, 120.3,
120.1, 118.6, 112.8, 110.2, 55.1, 34.9, 15.0. HRMS (ESI-TOF,
m/z): calcd for C28H27N2O2S+, [M + H]+, 455.1788, found
455.1782.
1-(3-(Methylthio)prop-1-en-2-yl)-2,5-diphenyl-4-(1-(m-
tolyl)vinyl)-1,2-dihydro-3H-pyrazol-3-one (3i): The reaction
was carried out on a 0.2 mmol scale following the General
Procedure. The product 3i was purified through column
chromatography (PE/EtOAc: from 6:1 to 4:1) as foam solid
(61 mg, 70% yield). IR νmax (neat)/cm-1: 3066, 2971, 1662,
1
1571, 1484, 1270, 1068, 955, 803; H NMR (600 MHz,
CDCl3): δ 7. 65 (d, J = 7.8 Hz, 2H), 7.47–7.43 (m, 4H), 7.30–
7.25 (m, 4H), 7.24–7.19 (m, 2H), 7.11 (t, J = 7.8 Hz, 1H),
6.98 (d, J = 7.8 Hz, 1H), 5.63 (d, J = 1.2 Hz, 1H), 5.52 (s, 1H),
5.49 (d, J = 1.2 Hz, 1H), 5.20 (s, 1H), 2.86 (s, 2H), 2.28 (s,
3H), 1.45 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.6,
156.2, 141.4, 140.2, 138.4, 137.2, 136.0, 130.5, 129.4,
129.1, 128.7, 128.0, 127.9, 127.7, 127.6, 126.2, 124.1,
123.9, 118.7, 118.3, 113.7, 35.4, 21.3, 15.1. HRMS (ESI-TOF,
m/z): calcd for C28H27N2OS+, [M + H]+, 439.1839, found
439.1835.
4-(1-(3-Methoxyphenyl)vinyl)-1-(3-(methylthio)prop-1-
en-2-yl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one
(3j):
The reaction was carried out on a 0.2 mmol scale following
the General Procedure. The product 3j was purified
through column chromatography (PE/EtOAc: from 6:1 to
4:1) as foam solid (66 mg, 73% yield). IR νmax (neat)/cm-1:
1
3031, 2980, 1679, 1580, 1501, 1323, 1181, 928, 826; H
NMR (600 MHz, CDCl3): δ 7.64 (d, J = 0.6 Hz, 2H), 7.62–7.44
ACS Paragon Plus Environment

Page 9 of 15
The Journal of Organic Chemistry
4-(1-(2-Chlorophenyl)vinyl)-1-(3-(methylthio)prop-1-en-
1H), 7.69–7.67 (m, 3H), 7.60 (d, J = 8.4 Hz, 1H), 7.57 (d, J =
1.8 Hz, 1H), 7.48–7.46 (m, 4H), 7.29–7.28 (m, 1H), 7.20–
7.19 (m, 3H), 7.11 (dd, J = 1.8, 9.0 Hz, 1H), 7.07 (d, J = 1.8
Hz, 1H), 5.77 (d, J = 0.6 Hz, 1H), 5.53 (s, 1H), 5.49 (s, 1H),
5.19 (s, 1H), 3.91 (s, 3H), 2.90 (s, 2H), 1.47 (s, 3H); 13C{1H}
NMR (150 MHz, CDCl3): δ 164.6, 157.7, 156.4, 141.3, 138.2,
136.0, 135.5, 134.0, 130.4, 129.7, 129.4, 128.9, 128.7,
127.8, 127.6, 126.4, 126.2, 125.9, 125.4, 123.8, 118.7,
118.4, 118.1, 113.8, 105.8, 55.2, 35.5, 15.1. HRMS (ESI-TOF,
m/z): calcd for C32H29N2O2S+, [M + H]+, 505.1944, found
505.1946.
1
2
3
4
5
6
2-yl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3n): The
reaction was carried out on a 0.2 mmol scale following the
General Procedure. The product 3n was purified through
column chromatography (PE/EtOAc: from 6:1 to 4:1) as
foam solid (82 mg, 90% yield). IR νmax (neat)/cm-1: 3030,
1
2944, 1677, 1589, 1491, 1270, 1086, 933, 812; H NMR
(600 MHz, CDCl3): δ 7.60 (d, J = 7.2 Hz, 2H), 7.46 (t, J = 7.8
Hz, 2H), 7.29 (dd, J = 2.4, 7.2 Hz, 3H), 7.17 (d, J = 7.2 Hz,
1H), 7.13 (t, J = 7.8 Hz, 2H), 7.08 (dd, J = 1.8, 7.2 Hz, 1H),
7.01 (d, J = 1.8 Hz, 1H), 6.94 (dt, J = 2.4, 7.2 Hz, 2H), 6.24 (d,
J = 1.2 Hz, 1H), 5.43 (d, J = 1.8 Hz, 1H), 5.34 (s, 1H), 5.14 (s,
1H), 2.77 (s, 2H), 1.46 (s, 3H); 13C{1H} NMR (150 MHz,
CDCl3): δ 164.2, 154.7, 140.7, 139.8, 136.4, 135.6, 132.2,
131.4, 130.5, 129.2, 129.1, 128.8, 128.6, 128.0, 127.3,
126.4, 126.0, 124.0, 121.3, 118.4, 111.3, 35.5, 15.1. HRMS
(ESI-TOF, m/z): calcd for C27H24ClN2OS+, [M + H]+,
459.1292, found 459.1295.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-(3-(Methylthio)prop-1-en-2-yl)-2,5-diphenyl-4-(1-
(thiophen-2-yl)vinyl)-1,2-dihydro-3H-pyrazol-3-one
(3r):
The reaction was carried out on a 0.2 mmol scale following
the General Procedure. The product 3r was purified
through column chromatography (PE/EtOAc: from 6:1 to
4:1) as colorless oil (54 mg, 63% yield). IR νmax (neat)/cm-
1: 3035, 2918, 1674, 1647, 1582, 1488, 1322, 1147, 1061,
972, 833; 1H NMR (600 MHz, CDCl3): δ 7.63 (dd, J = 0.6, 7.8
Hz, 2H), 7.52 (dd, J = 1.2, 7.8 Hz, 2H), 7.47 (t, J = 7.8 Hz,
2H), 7.33–7.28 (m, 4H), 7.10 (dd, J = 0.6, 5.4 Hz, 1H), 7.03
(dd, J = 1.2, 3.6 Hz, 1H), 6.87 (dd, J = 3.6, 4.8 Hz, 1H), 5.69
(s, 1H), 5.55 (s, 1H), 5.24 (s, 1H), 5.23 (s, 1H), 2.05 (s, 2H),
1.43 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.1, 156.5,
143.9, 140.9, 135.6, 131.8, 130.4, 129.7, 128.8, 128.7,
127.9, 127.2, 126.3, 125.5, 124.5, 123.8, 119.3, 117.2,
113.1, 35.4, 15.0. HRMS (ESI-TOF, m/z): calcd for
1-(3-(Methylthio)prop-1-en-2-yl)-4-(1-(naphthalen-1-
yl)vinyl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3o):
The reaction was carried out on a 0.2 mmol scale following
the General Procedure. The product 3o was purified
through column chromatography (PE/EtOAc: from 6:1 to
4:1) as foam solid (66 mg, 70% yield). IR νmax (neat)/cm-1:
3037. 2975, 1658, 1589, 1452, 1358, 1284, 1031, 980, 814;
1H NMR (600 MHz, CDCl3): δ 7.90–7.88 (m, 1H), 7.64–7.61
(m, 3H), 7.50–7.44 (m, 3H), 7.37–7.31 (m, 2H), 7.30 (t, J =
1.2 Hz, 1H), 7.15 (d, J = 1.2 Hz, 1H), 7.14 (t, J = 1.8 Hz, 1H),
7.11–6.94 (m, 1H), 6.82–6.78 (m, 4H), 6.56 (d, J = 2.4 Hz,
1H), 5.56 (d, J = 1.8 Hz, 1H), 5.14 (s, 1H), 5.00 (s, 1H), 2.73
(s, 2H), 1.44 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ
164.2, 155.2, 140.3, 139.3, 137.2, 135.6, 133.2, 131.2,
129.9, 128.8, 128.6, 128.3, 127.8, 127.2, 127.0, 126.6,
126.5, 126.0, 125.4, 125.1, 124.8, 123.9, 120.7, 117.8,
112.0, 35.8, 15.2. HRMS (ESI-TOF, m/z): calcd for
C31H27N2OS+, [M + H]+, 475.1839, found 475.1836.
1-(3-(Methylthio)prop-1-en-2-yl)-4-(1-(naphthalen-2-
yl)vinyl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3p):
The reaction was carried out on a 0.2 mmol scale following
the General Procedure. The product 3p was purified
through column chromatography (PE/EtOAc: from 10:1 to
4:1) as colorless oil (71 mg, 75% yield). IR νmax (neat)/cm-
1: 3033, 2989, 1668, 1565, 1487, 1312, 1220, 1101, 979,
856; 1H NMR (600 MHz, CDCl3): δ 7.91 (s, 1H), 7.78 (dd, J =
7.2, 16.8 Hz, 2H), 7.71–7.67 (m, 3H), 7.59 (dd, J = 1.8, 8.4
Hz, 1H), 7.49–7.47 (m, 4H), 7.43 (dt, J = 4.8, 7.2 Hz, 2H),
7.31–7.28 (m, 1H), 7.20–7.19 (m, 3H), 5.81 (s, 1H), 5.57 (s,
1H), 5.53 (s, 1H), 5.19 (s, 1H), 2.91 (s, 2H), 1.48 (s, 3H);
13C{1H} NMR (150 MHz, CDCl3): δ 164.6, 156.5, 141.3,
138.3, 137.7, 136.0, 133.3, 132.9, 130.4, 129.4, 128.9,
128.7, 128.2, 127.8, 127.7, 127.5, 127.4, 126.3, 126.1,
125.7, 125.6, 125.0, 123.8, 123.4, 118.9, 118.6, 113.7, 35.6,
15.2. HRMS (ESI-TOF, m/z): calcd for C31H27N2OS+, [M +
H]+, 475.1839, found 475.1840.
+
C25H23N2OS2 , [M + H]+, 431.1246, found 431.1247.
4-(1-(1-Methyl-1H-pyrrol-2-yl)vinyl)-1-(3-
(methylthio)prop-1-en-2-yl)-2,5-diphenyl-1,2-dihydro-3H-
pyrazol-3-one (3s): The reaction was carried out on a 0.2
mmol scale following the General Procedure. The product
3s was purified through column chromatography
(PE/EtOAc: from 6:1 to 4:1) as colorless oil (59 mg, 69%
yield). IR νmax (neat)/cm-1: 3055, 2977, 1670, 1594, 1447,
1
1382, 1201, 1166, 1027, 951, 853; H NMR (600 MHz,
CDCl3): δ 7.60 (dd, J = 0.6, 7.8 Hz, 2H), 7.46 (t, J = 7.8 Hz,
2H), 7.40 (dd, J = 1.8, 8.4 Hz, 2H), 7.31–7.27 (m, 4H), 6.34
(t, J = 2.4 Hz, 1H), 5.98 (dd, J = 1.8, 3.0 Hz, 1H), 5.88 (dd, J =
2.4, 9.0 Hz, 1H), 5.71 (d, J = 1.8 Hz, 1H), 5.45 (s, 1H), 5.39
(d, J = 1.8 Hz, 1H), 5.18 (s, 1H), 3.47 (s, 3H), 2.80 (s, 2H),
1.44 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.2, 155.6,
140.8, 135.6, 133.1, 130.2, 129.6, 129.4, 128.7, 128.4,
127.5, 126.3, 123.8, 123.0, 119.0, 118.9, 113.1, 109.9,
107.1, 35.3, 34.8, 15.0. HRMS (ESI-TOF, m/z): calcd for
C26H26N3OS+, [M + H]+, 428.1791, found 428.1795.
1-(3-(Methylthio)prop-1-en-2-yl)-2,5-diphenyl-4-(prop-1-
en-2-yl)-1,2-dihydro-3H-pyrazol-3-one (3t): The reaction
was carried out on a 0.2 mmol scale following the General
Procedure. The product 3t was purified through column
chromatography (PE/EtOAc: from 6:1 to 4:1) as colorless
oil (52 mg, 72% yield). IR νmax (neat)/cm-1: 3062, 2983,
1
1668, 1549, 1433, 1327, 1252, 1098, 972, 819; H NMR
(600 MHz, CDCl3): δ 7.58 (d, J = 7.8 Hz, 2H), 7.53 (dd, J =
1.2, 7.8 Hz, 2H), 7.46–7.43 (m, 5H), 7.29–7.26 (m, 1H), 5.41
(s, 1H), 5.38 (s, 1H), 5.18 (s, 1H), 5.14 (s, 1H), 2.76 (s, 2H),
1.79 (s, 3H), 1.49 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ
164.5, 154.1, 141.6, 136.1, 134.0, 130.7, 130.5, 130.1,
129.6, 129.8, 128.8, 128.1, 126.4, 124.2, 124.1, 118.0,
117.4, 114.4, 35.4, 22.6, 15.3. HRMS (ESI-TOF, m/z): calcd
for C22H23N2OS+, [M + H]+, 363.1526, found 363.1528.
4-(1-(6-Methoxynaphthalen-2-yl)vinyl)-1-(3-
(methylthio)prop-1-en-2-yl)-2,5-diphenyl-1,2-dihydro-3H-
pyrazol-3-one (3q): The reaction was carried out on a 0.2
mmol scale following the General Procedure. The product
3q was purified through column chromatography
(PE/EtOAc: from 10:1 to 4:1) as colorless oil (75 mg, 74%
yield). IR νmax (neat)/cm-1: 3038, 2933, 1681, 157, 1392,
1267, 1083, 912, 808; 1H NMR (600 MHz, CDCl3): δ 7.83 (s,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 15
1-(3-(Methylthio)prop-1-en-2-yl)-5-phenyl-4-(1- 164.5, 156.9, 141.4, 140.1, 138.2, 135.1, 132.1, 131.9,
1
2
3
4
5
6
7
8
phenylvinyl)-2-(p-tolyl)-1,2-dihydro-3H-pyrazol-3-one
(3aa): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3aa was
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (57 mg, 65% yield). IR νmax
(neat)/cm-1: 3045, 2922, 1677, 1559, 1482, 1298, 1120,
1087, 914, 872; 1H NMR (600 MHz, CDCl3): δ 7.51 (d, J = 7.8
Hz, 2H), 7.43 (d, J = 6.6 Hz, 2H), 7.40 (d, J = 7.2 Hz, 2H),
7.27–7.15 (m, 8H), 5.65 (s, 1H), 5.51 (s, 1H), 5.50 (s, 1H),
5.20 (s, 1H), 2.85 (s, 2H), 2.39 (s, 3H), 1.44 (s, 3H); 13C{1H}
NMR (150 MHz, CDCl3): δ 164.6, 155.8, 141.4, 140.3, 138.4,
136.2, 133.4, 130.5, 129.4, 129.3, 129.1, 127.9, 127.7,
127.2, 126.9, 124.0, 118.7, 118.5, 113.5, 35.4, 20.9, 15.1.
HRMS (ESI-TOF, m/z): calcd for C28H26N2NaOS+, [M + Na]+,
461.1658, found 461.1655.
2-(4-Methoxyphenyl)-1-(3-(methylthio)prop-1-en-2-yl)-5-
phenyl-4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one
(3ab): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3ab was
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (69 mg, 76% yield). IR νmax
(neat)/cm-1: 3066, 2952, 1561, 1445, 1270, 1184, 1077,
977, 835; 1H NMR (600 MHz, CDCl3): δ 7.42 (dd, J = 2.4, 7.2
Hz, 2H), 7.30 (d, J = 6.6 Hz, 2H), 7.29 (d, J = 6.6 Hz, 2H),
7.18–7.04 (m, 6H), 6.87 (dd, J = 1.2, 7.2 Hz, 2H), 5.51 (d, J =
1.2 Hz, 1H), 5.42 (d, J = 1.2 Hz, 1H), 5.38 (s, 1H), 5.11 (s,
1H), 3.73 (s, 3H), 2.73 (s, 2H), 1.32 (s, 3H); 13C{1H} NMR
(150 MHz, CDCl3): δ 164.5, 158.1, 155.4, 140.8, 140.1,
138.2, 130.4, 129.3, 128.8, 128.5, 127.9, 127.6, 127.2,
126.8, 125.8, 119.3, 118.4, 114.0, 112.9, 55.4, 35.3, 15.0.
HRMS (ESI-TOF, m/z): calcd for C28H26N2NaO2S+, [M + Na]+,
477.1607, found 477.1609.
130.5, 129.7, 128.8, 127.8, 127.3, 126.8, 125.1, 124.7,
119.6, 118.8, 118.7, 113.8, 35.4, 15.2. HRMS (ESI-TOF,
m/z): calcd for C27H24BrN2OS+, [M + H]+, 503.0787, found
503.0788.
1-(3-(Methylthio)prop-1-en-2-yl)-2-(4-nitrophenyl)-5-
phenyl-4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one
(3ae): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3ae was
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (66 mg, 79% yield). IR νmax
(neat)/cm-1: 3055, 2923, 1673, 1588, 1479, 1334, 1278,
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
1032, 953, 874; H NMR (600 MHz, CDCl3): δ 8.34 (dd, J =
2.4, 7.2 Hz, 2H), 7.89 (dd, J = 1.8, 7.2 Hz, 2H), 7.46 (d, J = 7.2
Hz, 2H), 7.40 (d, J = 7.2 Hz, 2H), 7.34–7.32 (m, 1H), 7.30–
7.28 (m, 2H), 7.25–7.20 (m, 3H), 5.67 (d, J = 1.2 Hz, 1H),
5.57 (s, 1H), 5.42 (d, J = 0.6 Hz, 1H), 5.24 (s, 1H), 2.84 (s,
2H), 1.49 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.7,
158.6, 145.1, 141.4, 139.8, 137.9, 130.5, 130.1, 128.5,
128.1, 128.0, 127.6, 126.8, 124.5, 122.4, 119.0, 114.4, 35.2,
15.4. HRMS (ESI-TOF, m/z): calcd for C27H24N3O3S+, [M +
H]+, 470.1533, found 470.1536.
2-(2-Ethylphenyl)-1-(3-(methylthio)prop-1-en-2-yl)-5-
phenyl-4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one
(3af): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3af was
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (34 mg, 38% yield). IR νmax
(neat)/cm-1: 3036, 2942, 1670, 1589, 1433, 1362, 1098,
1
937, 828; H NMR (600 MHz, CDCl3): δ 7.43 (d, J = 7.2 Hz,
1H), 7.39–7.37 (m, 4H), 7.33 (d, J = 7.2 Hz, 2H), 7.30–7.28
(m, 1H), 7.24 (d, J = 7.2 Hz, 1H), 7.20 (t, J = 7.2 Hz, 2H), 7.16
(t, J = 7.2 Hz, 2H), 7.12 (d, J = 7.2 Hz, 1H), 5.69 (d, J = 1.2
Hz, 1H), 5.65 (s, 1H), 5.31 (s, 1H), 5.22 (s, 1H), 2.93–2.88
(m, 1H), 2.86 (d, J = 3.0 Hz, 2H), 2.73–2.69 (m, 1H), 1.47 (s,
3H), 1.35 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3):
δ 165.5, 154.7, 142.5, 141.2, 140.5, 138.5, 134.4, 130.2,
129.4, 129.2, 129.0, 128.8, 127.9, 127.8, 127.1, 127.0,
126.2, 119.0, 118.7, 112.6, 36.0, 23.9, 15.0, 14.0. HRMS
(ESI-TOF, m/z): calcd for C29H29N2OS+, [M + H]+, 453.1995,
found 453.1995.
2-(4-Fluorophenyl)-1-(3-(methylthio)prop-1-en-2-yl)-5-
phenyl-4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one
(3ac): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3ac was
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (66 mg, 75% yield). IR νmax
(neat)/cm-1: 3029, 1672, 1510, 1397, 1181, 1012, 959,
1
816; H NMR (600 MHz, CDCl3): δ 7.61–7.59 (m, 2H), 7.42
(d, J = 7.8 Hz, 2H), 7.38 (d, J = 7.8 Hz, 2H), 7.28–7.19 (m,
3H), 7.17–7.14 (m, 5H), 5.65 (d, J = 0.6 Hz, 1H), 5.49 (s, 2H),
5.22 (s, 1H), 2.84 (s, 2H), 1.46 (s, 3H); 13C{1H} NMR (150
MHz, CDCl3): δ 164.8, 161.8, 160.3, 156.3, 141.5, 140.2,
138.3, 132.0, 130.5, 129.6, 129.0, 128.0, 127.8, 127.3,
126.9, 125.9, 125.8, 118.9, 118.7, 115.8, 115.6, 113.7, 35.4,
15.2. 19F NMR (600 MHz, CDCl3): δ -115.28. HRMS (ESI-
TOF, m/z): calcd for C27H24FN2OS+, [M + H]+, 443.1588,
found 443.1585.
2-(4-Bromophenyl)-1-(3-(methylthio)prop-1-en-2-yl)-5-
phenyl-4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one
(3ad): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3ad was
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (81 mg, 81% yield). IR νmax
(neat)/cm-1: 3039, 2962, 1670, 1527, 1363, 1299, 1108,
1036, 898, 801; 1H NMR (600 MHz, CDCl3): δ 7.59 (d, J = 7.8
Hz, 2H), 7.56 (d, J = 7.8 Hz, 2H), 7.43 (d, J = 7.2 Hz, 2H),
7.40 (d, J = 7.2 Hz, 1H), 7.30–7.17 (m, 6H), 5.65 (d, J = 0.6
Hz, 1H), 5.51 (s, 1H), 5.45 (d, J = 1.2 Hz, 1H), 5.21 (s, 1H),
2.83 (s, 2H), 1.45 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ
2-(2-Fluorophenyl)-1-(3-(methylthio)prop-1-en-2-yl)-5-
phenyl-4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one
(3ag): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3ag was
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (41 mg, 47% yield). IR νmax
(neat)/cm-1: 3052, 2989, 1671, 1489, 1345, 1287, 1176,
1044, 929, 817; 1H NMR (600 MHz, CDCl3): δ 7.42 (t, J = 6.6
Hz, 1H), 7.30 (d, J = 5.4 Hz, 2H), 7.28 (d, J = 7.8 Hz, 2H),
7.18–7.11 (m, 4H), 7.10–7.02 (m, 5H), 5.58 (d, J = 1.2 Hz,
1H), 5.55 (d, J = 0.6 Hz, 1H), 5.43 (s, 1H), 5.19 (s, 1H), 2.77
(s, 2H), 1.31 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ
164.9, 158.4, 156.7, 155.8, 140.7, 140.0, 138.0, 130.3,
130.0, 129.9, 129.5, 129.3, 128.7, 127.9, 127.7, 127.2,
126.9, 124.3, 124.3, 123.3, 123.2, 120.1, 118.8, 116.9,
116.8, 112.2, 35.0, 14.7. 19F NMR (600 MHz, CDCl3): δ -
118.91. HRMS (ESI-TOF, m/z): calcd for C27H24FN2OS+, [M +
H]+, 443.1588, found 443.1587.
2-(3-Bromophenyl)-1-(3-(methylthio)prop-1-en-2-yl)-5-
phenyl-4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one
(3ah): The reaction was carried out on a 0.2 mmol scale
ACS Paragon Plus Environment

Page 11 of 15
The Journal of Organic Chemistry
following the General Procedure. The product 3ah was (d, J = 1.2 Hz, 1H), 5.23 (s, 1H), 3.78 (s, 3H), 2.85 (s, 2H),
2.38 (s, 3H), 1.48 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ
164.8, 160.6, 155.9, 141.8, 140.3, 138.6, 136.1, 133.6,
131.9, 129.3, 127.9, 127.2, 126.9, 124.0, 121.4, 118.8,
118.4, 113.3, 113.1, 55.2, 35.3, 21.0, 15.2. HRMS (ESI-TOF,
m/z): calcd for C29H29N2O2S+, [M + H]+, 469.1944, found
469.1946.
1
2
3
4
5
6
7
8
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (39 mg, 39% yield). IR νmax
(neat)/cm-13027, 2938, 1665, 1579, 1328, 1198, 1150,
1
967, 852; H NMR (600 MHz, CDCl3): δ 7.83 (d, J = 1.8 Hz,
1H), 7.63 (d, J = 7.8 Hz, 1H), 7.44 (d, J = 7.2 Hz, 2H), 7.41 (d,
J = 8.4 Hz, 1H), 7.38 (d, J = 7.2 Hz, 2H), 7.33 (t, J = 7.8 Hz,
2H), 7.30–7.17 (m, 5H), 5.65 (s, 1H), 5.51 (s, 1H), 5.47 (s,
1H), 5.22 (s, 1H), 2.85 (s, 2H), 1.49 (s, 3H); 13C{1H} NMR
(150 MHz, CDCl3): δ 164.7, 157.2, 141.5, 140.1, 138.2,
137.3, 130.5, 130.0, 129.7, 129.2, 128.9, 128.0, 127.8,
127.4, 126.9, 126.3, 122.3, 122.1, 118.8, 118.7, 113.9, 35.4,
15.2. HRMS (ESI-TOF, m/z): calcd for C27H23BrN2NaOS+, [M
+ Na]+, 525.0607, found 525.0603.
1-(3-(Methylthio)prop-1-en-2-yl)-2-(perfluorophenyl)-5-
phenyl-4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one
(3ai): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3ai was
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (61 mg, 59% yield). IR νmax
(neat)/cm-1: 3072, 2916, 1667, 1539, 1420, 1331, 1298,
1032, 919, 827; 1H NMR (600 MHz, CDCl3): δ 7.37 (d, J = 7.2
Hz, 2H), 7.30 (d, J = 7.2 Hz, 2H), 7.27 (d, J = 7.2 Hz, 1H),
7.21 (t, J = 7.2 Hz, 2H), 7.18–7.12 (m, 3H), 5.74 (d, J = 0.6
Hz, 1H), 5.64 (s, 1H), 5.55 (s, 1H), 5.42 (s, 1H), 2.93 (s, 2H),
1.43 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ 166.1, 158.0,
145.8, 144.1, 141.9, 139.8, 138.9, 137.8, 137.1, 130.2,
130.1, 129.8, 128.5, 128.2, 128.0, 127.9, 127.4, 126.9,
120.1, 119.2, 112.6, 111.9, 34.8, 14.9. 19F NMR (600 MHz,
CDCl3): δ -143.12, -143.15, -151.21, -151.25, -151.29, -
160.96, -160.99, -161.00, -161.03. HRMS (ESI-TOF, m/z):
calcd for C27H20F5N2OS+, [M + H]+, 515.1211, found
515.1215.
5-(4-Fluorophenyl)-1-(3-(methylthio)prop-1-en-2-yl)-2-
phenyl-4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one
(3aj): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3aj was
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (62 mg, 70% yield). IR νmax
(neat)/cm-1: 3019, 2926, 1647, 1478, 1405, 1286, 1167,
1051, 968, 831; 1H NMR (600 MHz, CDCl3): δ 7.62 (d, J = 7.8
Hz, 2H), 7.47 (t, J = 7.8 Hz, 2H), 7.41 (dd, J = 5.4, 8.4 Hz,
2H), 7.35 (d, J = 7.2 Hz, 2H), 7.30–7.28 (m, 1H), 7.21–7.16
(m, 3H), 6.93 (t, J = 8.4 Hz, 2H), 5.67 (s, 1H), 5.56 (s, 1H),
5.49 (s, 1H), 5.20 (s, 1H), 2.85(s, 2H), 1.46 (s, 3H); 13C{1H}
NMR (150 MHz, CDCl3): δ 164.4, 164.1, 162.4, 155.1, 141.4,
140.2, 138.2, 135.8, 132.5, 132.5, 128.9, 128.8, 128.0,
127.3, 126.4, 125.1, 123.9, 123.4, 118.9, 118.7, 115.0,
114.8, 113.7, 35.4, 15.2. 19F NMR (600 MHz, CDCl3): δ -
110.27. HRMS (ESI-TOF, m/z): calcd for C27H23FN2NaOS+,
[M + Na]+, 465.1407, found 465.1409.
5-(4-Bromophenyl)-1-(3-(methylthio)prop-1-en-2-yl)-4-
(1-phenylvinyl)-2-(p-tolyl)-1,2-dihydro-3H-pyrazol-3-one
(3al): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3al was
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (86 mg, 83% yield). IR νmax
(neat)/cm-1: 3022, 2971, 1667, 1571, 1423, 1355, 1279,
1158, 1046, 938, 862; 1H NMR (600 MHz, CDCl3): δ 7.48 (d,
J = 8.4 Hz, 2H), 7.36 (t, J = 7.8 Hz, 2H), 7.29–7.25 (m, 4H),
7.22–7.17 (m, 3H), 5.66 (s, 1H), 5.55 (s, 1H), 5.45 (s, 1H),
5.19 (s, 1H), 2.85 (s, 2H), 2.39 (s, 3H), 1.50 (s, 3H); 13C{1H}
NMR (150 MHz, CDCl3): δ 164.3, 154.5, 141.4, 140.2, 138.3,
136.4, 133.3, 132.0, 131.0, 129.4, 128.0, 127.4, 127.0,
124.1, 124.0, 118.9, 118.8, 114.0, 35.5, 21.0, 15.3. HRMS
(ESI-TOF, m/z): calcd for C28H25BrN2NaOS+, [M + Na]+,
539.0763, found 539.0766.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2-(4-Bromophenyl)-4-(1-(2-chlorophenyl)vinyl)-5-methyl-
1-(3-(methylthio)prop-1-en-2-yl)-1,2-dihydro-3H-pyrazol-3-
one (3am): The reaction was carried out on a 0.2 mmol
scale following the General Procedure. The product 3am
was purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (70 mg, 74% yield). IR νmax
(neat)/cm-1 3046, 2982, 1670, 1533, 1478, 1324, 1278,
1
1109, 1082, 952; H NMR (600 MHz, CDCl3): δ 7.53 (d, J =
8.4 Hz, 2H), 7.41 (dd, J = 1.8, 7.2 Hz, 1H), 7.38 (dd, J = 1.8,
7.2 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.29–7.24 (m, 2H), 6.08
(d, J = 1.8 Hz, 1H), 5.47 (d, J = 1.8 Hz, 1H), 5.43 (s, 1H), 5.41
(s, 1H), 2.90 (s, 2H), 1.92 (s, 3H), 1.89 (s, 3H); 13C{1H} NMR
(150 MHz, CDCl3): δ 164.7, 152.3, 141.7, 140.6, 137.1,
135.3, 132.8, 131.9, 131.8, 131.3, 129.6, 128.7, 126.7,
125.4, 125.0, 120.5, 119.6, 116.9, 110.0, 36.2, 16.0, 12.3.
HRMS (ESI-TOF, m/z): calcd for C22H20BrClN2NaOS+, [M +
Na]+, 497.0060, found 497.0063.
Synthesis of Compound 4 and 5: To a flame-dried
sealable 2-dram vial equipped with a stir bar was added
unsaturated pyrazolones 1a (68 mg, 0.2 mmol, 1.0 equiv),
NaOAc·3H2O (13.6 mg, 0.1 mmol, 0.5 equiv) and propargyl
sulfonium salt 2b (50 mg, 0.24 mmol, 1.2 equiv) under air.
Subsequently, treated CH3CN (2 mL, c = 0.1 M) was added
to vial via syringe. The reaction mixture was kept stirring
for 15 min at 22 °C until unsaturated pyrazolones 1a was
fully consumed (monitored by TLC). Then the reaction was
heated to 50 °C for 20 h. The organic solvent was removed
under reduced pressure and purified through column
chromatography (eluent: PE: EtOAc = 6: 1 to 4: 1) to afford
the desired product 4 and 5 with yield of 25% (22 mg) and
56% (49 mg), respectively.
5-(4-Methoxyphenyl)-1-(3-(methylthio)prop-1-en-2-yl)-4-
(1-phenylvinyl)-2-(p-tolyl)-1,2-dihydro-3H-pyrazol-3-one
(3ak): The reaction was carried out on a 0.2 mmol scale
following the General Procedure. The product 3ak was
purified through column chromatography (PE/EtOAc:
from 6:1 to 4:1) as foam solid (81 mg, 87% yield). IR νmax
(neat)/cm-1: 3039, 2956, 1675, 1498, 1276, 1107, 928, 870,
1-(3-(Ethylthio)prop-1-en-2-yl)-2,5-diphenyl-4-(1-
phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (4): IR νmax
(neat)/cm-1: 3077, 2965, 2853, 1765, 1544, 1474, 1275,
1022, 917, 832; 1H NMR (600 MHz, CDCl3): δ 7.63 (d, J = 7.8
Hz, 2H), 7.46 (t, J = 7.8 Hz, 2H), 7.42 (d, J = 7.8 Hz, 2H), 7.40
(d, J = 7.8 Hz, 2H), 7.30–7.27 (m, 2H), 7.24 (t, J = 7.2 Hz,
2H), 7.20 (t, J = 7.2 Hz, 2H), 7.16 (t, J = 7.2 Hz, 1H), 5.65 (d, J
= 1.2 Hz, 1H), 5.50 (d, J = 1.2 Hz, 1H), 5.48 (s, 1H), 5.22 (s,
1
789; H NMR (600 MHz, CDCl3): δ 7.49 (d, J = 8.4 Hz, 2H),
7.41 (d, J = 7.2 Hz, 2H), 7.35 (d, J = 9.0 Hz, 2H), 7.25 (d, J =
8.4 Hz, 2H), 7.22–7.20 (m, 2H), 7.17 (d, J = 6.6 Hz, 1H), 6.75
(d, J = 8.4 Hz, 2H), 5.66 (d, J = 1.2 Hz, 1H), 5.50 (s, 1H), 5.49
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 15
1
1H), 2.89 (s, 2H), 1.87 (q, J = 7.2 Hz, 2H), 0.98 (t, J = 7.2 Hz,
3H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.6, 156.3, 141.9,
140.2, 138.3, 135.9, 130.5, 129.5, 129.1, 128.8, 128.0,
127.9, 127.7, 127.3, 126.9, 126.3, 123.8, 118.7, 118.6,
113.5, 32.8, 25.7, 13.8. HRMS (ESI-TOF, m/z): calcd for
C28H26N2NaOS+, [M + Na]+, 461.1658, found 461.1656.
(E)-1-(1-(Ethylthio)prop-1-en-2-yl)-2,5-diphenyl-4-(1-
phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (5): IR νmax
(neat)/cm-1: 3057, 29735, 2824, 1698, 1572, 1376, 1269,
1263, 1084, 978, 833; H NMR (600 MHz, CDCl3): δ major
(E): 7.71 (d, J = 9.0 Hz, 2H), 7.57 (d, J = 7.2 Hz, 2H), 7.49–
7.45 (m, 4H), 7.30–7.17 (m, 10H), 7.07 (s, 1H), 6.93 (d, J =
7.2 Hz, 2H), 5.67 (s, 1H), 5.50 (s, 1H), 3.13 (s, 2H), 1.61 (s,
3H); minor (Z): 7.70 (d, J = 9.0 Hz, 2H), 7.51 (d, J = 7.2 Hz,
2H), 7.49–7.45 (m, 4H), 7.30–7.17 (m, 10H), 7.11 (d, J = 7.2
Hz, 2H), 7.04 (s, 1H), 5.69 (s, 1H), 5.52 (s, 1H), 3.90 (s, 2H),
1.61 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): δ major (E):
164.5, 156.7, 140.5, 138.6, 136.5, 135.8, 134.1, 134.0,
133.3, 130.9, 129.3, 128.7, 128.5, 128.3, 127.9, 127.7,
127.2, 126.9, 126.3, 123.9, 118.5, 114.2, 32.3, 26.1, 16.4;
minor (Z): 164.5, 156.8, 140.2, 138.4, 136.1, 136.0, 135.0,
134.0, 133.3, 130.6, 129.4, 128.8, 128.6, 128.3, 128.3,
127.8, 127.5, 127.1, 126.9, 126.2, 123.7, 118.2, 113.0, 32.3,
26.1, 16.4. HRMS (ESI-TOF, m/z): calcd for C33H28N2NaOS+,
[M + Na]+, 523.1815, found 523.1813.
1
2
3
4
5
6
7
8
1
1187, 1028, 932; H NMR (600 MHz, CDCl3): δ 7.59 (d, J =
9
7.2 Hz, 2H), 7.46 (t, J = 7.8 Hz, 2H), 7.34–7.30 (m, 5H),
7.27–7.24 (m, 1H), 7.21 (t, J = 7.2 Hz, 2H), 7.17 (t, J = 7.2 Hz,
2H), 7.13 (t, J = 7.2 Hz, 1H), 6.34 (s, 1H), 5.69 (d, J = 1.2 Hz,
1H), 5.67 (d, J = 1.2 Hz, 1H), 2.53 (q, J = 7.2 Hz, 2H), 1.38 (s,
3H), 1.03 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3):
δ 164.3, 155.5, 140.3, 138.5, 135.8, 133.2, 130.5, 129.7,
129.5, 128.7, 127.9, 127.9, 127.2, 127.0, 126.5, 125.0,
124.7, 118.8, 114.8, 28.1, 15.4, 13.4. HRMS (ESI-TOF, m/z):
calcd for C28H26N2NaOS+, [M + Na]+, 461.1658, found
461.1658.
Synthesis of Compound 6: To a flame-dried sealable 2-
dram vial equipped with a stir bar was added unsaturated
pyrazolones 1a (68 mg, 0.2 mmol, 1.0 equiv), NaOAc·3H2O
(13.6 mg, 0.1 mmol, 0.5 equiv) and propargyl sulfonium
salt 2c (50 mg, 0.24 mmol, 1.2 equiv) under air.
Subsequently, treated CH3CN (2 mL, c = 0.1 M) was added
to vial via syringe. The reaction mixture was kept stirring
for 15 min at 22 °C until unsaturated pyrazolones 1a was
fully consumed (monitored by TLC). Then the reaction was
heated to 50 °C for 20 h. The organic solvent was removed
under reduced pressure and purified through column
chromatography (eluent: PE: EtOAc = 6: 1 to 4: 1) to afford
the product 6 with yield of 42% (38 mg).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Reaction of α-Alkylidene Pyrazolinones 1a with
Propargyl Sulfonium Salts 2e: To a flame-dried sealable
2-dram vial equipped with a stir bar was added
unsaturated pyrazolones 1a (68 mg, 0.2 mmol, 1.0 equiv),
NaOAc·3H2O (13.6 mg, 0.1 mmol, 0.5 equiv) and 2e (61 mg,
0.24 mmol, 1.2 equiv) under air. Subsequently, CH3CN (2
mL, c = 0.1 M) was added to vial via syringe. The reaction
mixture was kept stirring for 5 min at 22 °C until α-
alkylidene pyrazolinone 1a was fully consumed
(monitored by TLC). Then the reaction was heated to 50 °C
for 20 h. The organic solvent was removed under reduced
pressure and purified through column chromatography
(eluent: PE: EtOAc = 6:1 to 4:1) to afford the desilylation
product 3a (61 mg, 72% yield).
Control experiment a: To a flame-dried sealable 2-
dram vial equipped with a stir bar was added unsaturated
pyrazolones 1a (34 mg, 0.1 mmol, 1.0 equiv), NaOAc (4.1
mg, 0.05 mmol, 0.5 equiv) under air. Subsequently, treated
CH3CN (1 mL, c = 0.1 M) and D2O (18 l, 10 equiv) were
added to vial via syringe. The reaction mixture was kept
stirring at 50 °C for 20 h. The organic solvent was removed
under reduced pressure and purified through column
chromatography (eluent: PE: EtOAc = 20: 1 to 10: 1) to
afford D-8 (Z: E =2.7: 1) with 22% of -CH3 deuterium (29
mg, 86% overall yield).
1-(3-Bromoprop-1-en-2-yl)-2,5-diphenyl-4-(1-
phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (6): IR νmax
(neat)/cm-1: 3062, 2933, 1668, 1574, 1379, 1259, 1149,
1028, 932, 834; 1H NMR (600 MHz, CDCl3): δ 7.53 (d, J = 7.8
Hz, 2H), 7.36 (t, J = 7.8 Hz, 2H), 7.33 (d, J = 7.2 Hz, 2H), 7.28
(d, J = 6.6 Hz, 2H), 7.20 (t, J = 7.2 Hz, 2H), 7.16 (d, J = 7.8 Hz,
2H), 7.09 (t, J = 7.2 Hz, 2H), 7.05 (t, J = 7.2 Hz, 1H), 5.53 (d, J
= 0.6 Hz, 1H), 5.37 (s, 1H), 5.31 (s, 1H), 5.17 (s, 1H), 3.57 (s,
2H); 13C{1H} NMR (150 MHz, CDCl3): δ 164.6, 156.4, 140.9,
140.0, 138.1, 135.9, 130.5, 129.6, 128.9, 128.8, 127.9,
127.8, 127.3, 126.8, 126.4, 124.0, 119.7, 118.7, 114.0, 29.2.
HRMS (ESI-TOF, m/z): calcd for C26H22BrN2O+, [M + H]+,
457.0910, found 457.0911.
Synthesis of Compound 7: To a flame-dried sealable 2-
dram vial equipped with a stir bar was added unsaturated
pyrazolones 1a (68 mg, 0.2 mmol, 1.0 equiv), NaOAc·3H2O
(13.6 mg, 0.1 mmol, 0.5 equiv) and propargyl sulfonium
salt 2d (62 mg, 0.24 mmol, 1.2 equiv) under air.
Subsequently, treated CH3CN (2 mL, c = 0.1 M) was added
to vial via syringe. The reaction mixture was kept stirring
for 1 h at 22 °C until unsaturated pyrazolones 1a was fully
consumed (monitored by TLC). Then the reaction was
heated to 50 °C for 20 h. The organic solvent was removed
under reduced pressure and purified through column
chromatography (eluent: PE: EtOAc = 6: 1 to 4: 1) to afford
the product 7 with yield of 88% (84 mg, E: Z =1.5: 1).
1-(3-(Methylthio)-1-phenylprop-1-en-2-yl)-2,5-diphenyl-
4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (7): IR νmax
(neat)/cm-1: 3077, 3012, 2945, 1670, 1568, 1426, 1378,
D-(Z)-4-(1-(4-chlorophenyl)ethylidene)-2,5-diphenyl-2,4-
dihydro-3H-pyrazol-3-one (8): H NMR (600 MHz, CDCl3): δ
1
8.09 (d, J = 7.8 Hz, 2H), 7.46 (t, J = 7.8 Hz, 2H), 7.24 (t, J =
7.2 Hz, 1H), 7.13 (t, J = 7.2 Hz, 1H), 7.09–7.06 (m, 3H),
7.03–6.99 (m, 6H), 3.02 (s, 1.7H), E: 2.99 (s, 0.6H); 13C{1H}
NMR (150 MHz, CDCl3): δ 166.2, 164.2, 151.1, 140.3, 138.7,
133.1, 129.6, 128.8, 128.7, 128.2, 127.8, 127.7, 127.6,
125.0, 124.3, 119.3, 119.2, 22.6.
Control experiment b: To a flame-dried sealable 2-
dram vial equipped with a stir bar was added unsaturated
pyrazolones 1a (68 mg, 0.2 mmol, 1.0 equiv), NaOAc·3H2O
(13.6 mg, 0.1mmol, 0.5 equiv) and MeI (25 L, 0.4 mmol,
2.0 equiv) under air. Subsequently, treated CH3CN (2 mL, c
= 0.1 M) was added to vial via syringe. The reaction
mixture was kept stirring at 50 °C for 20 h. The organic
solvent was removed under reduced pressure and purified
through column chromatography (eluent: PE: EtOAc = 10:
1 to 5: 1) to afford the product 9 with yield of 21% (15 mg),
together with a recovery of 1a with 69% yield (47 mg).
1-Methyl-2,5-diphenyl-4-(1-phenylvinyl)-1,2-dihydro-3H-
pyrazol-3-one (9): IR νmax (neat)/cm-1: 3037, 2986, 1672,
ACS Paragon Plus Environment

Page 13 of 15
The Journal of Organic Chemistry
1
Province. The instruments were performed using the
Analytical Test Center of Shanxi Normal University, Linfen,
China.
1481, 1335, 1292, 1067, 934, 883; H NMR (600 MHz,
CDCl3): δ 7.66 (d, J = 7.8 Hz, 2H), 7. 52 (t, J = 7.8 Hz, 2H),
7.37 (dd, J = 1.2, 7.2 Hz, 2H), 7.33–7.31 (m, 3H), 7.30–7.26
(m, 3H), 7.15 (t, J = 7.2 Hz, 2H), 7.11 (t, J = 7.2 Hz, 1H), 5.70
(d, J = 1.2 Hz, 1H), 5.68 (d, J = 1.2 Hz, 1H), 2.98 (s, 3H);
13C{1H} NMR (150 MHz, CDCl3): δ 164.5, 157.5, 140.4,
138.6, 135.9, 129.7, 129.6, 129.4, 129.1, 128.4, 127.9,
127.2, 127.1, 126.2, 123.5, 118.6, 113.3, 39.3. HRMS (ESI-
TOF, m/z): calcd for C24H20N2NaO+, [M + Na]+, 375.1468,
found 375.1471.
1
2
3
4
5
6
7
8
■ REFERENCES
(1) For an excellent book on pyrazolone chemistry, see: (a)
Varvounis, G. Pyrazol-3-ones. Part IV: Synthesis and Applications.
In Advances in Heterocyclic Chemistry; Katritzky, A. R., Ed.;
Academic Press: New York, 2009; Vol. 98, p 143–224. For related
reviews, see: (b) Ke, B.; Tian, M.; Li, J.; Liu, B.; He, G. Targeting
Programmed Cell Death Using Small-Molecule Compounds to
Improve Potential Cancer Therapy. Med. Res. Rev. 2016, 36, 983–
1035. (c) Kumar, V.; Kaur, K.; Gupta, G. K.; Sharma, A. K. Pyrazole
Containing Natural Products: Synthetic Preview and Biological
Significance. Eur. J. Med. Chem. 2013, 69, 735–753. (d) Fustero, S.;
Sánchez-Roselló, M.; Barrio, P.; Simón-Fuentes, A. From 2000 to
Mid-2010: A Fruitful Decade for the Synthesis of Pyrazoles. Chem.
Rev. 2011, 111, 6984−7034. (e) Schmidt, A.; Dreger, A. Recent
Advances in the Chemistry of Pyrazoles. Properties, Biological
Activities, and Syntheses. Curr. Org. Chem. 2011, 15, 1423−1463.
(f) Sondhi, S. M.; Dinodia, M.; Singh, J.; Rani, R. Heterocyclic
Compounds as Anti-Inflammatory Agents. Curr. Bioact. Compd.
2007, 3, 91−108. (g) Horton, D. A.; Bourne, G. T.; Smythe, M. L.
The Combinatorial Synthesis of Bicyclic Privileged Structures or
Privileged Substructures. Chem. Rev. 2003, 103, 893–930, and the
references therein.
9
Control experiment c: To a flame-dried sealable 2-
dram vial equipped with a stir bar was added unsaturated
pyrazolones 1a (68 mg, 0.2 mmol, 1.0 equiv), propargyl
sulfonium salt 2a (44 mg, 0.24 mmol, 1.2 equiv),
NaOAc·3H2O (13.6 mg, 0.1mmol, 0.5 equiv) and MeI (25
L, 0.4 mmol, 2.0 equiv) under air. Subsequently treated
CH3CN (1 mL, c = 0.1 M) was added to vial via syringe. The
reaction mixture was kept stirring for 15 min at 22 °C until
unsaturated pyrazolones 1a was fully consumed
(monitored by TLC). Then the reaction was heated to 50 °C
for 20 h. The organic solvent was removed under reduced
pressure and purified through column chromatography
(eluent: PE: EtOAc = 6: 1 to 4: 1) to afford the methylation
product 9 with yield of 5% (3.5 mg) and desired 3a with
81% yield (69 mg).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(2) For recent reviews, see: (a) Chauhan, P.; Mahajan, S.;
Enders, D. Asymmetric Synthesis of Pyrazoles and Pyrazolones
Employing the Reactivity of Pyrazolin-5-one Derivatives. Chem.
Commun. 2015, 51, 12890−12907. (b) Liu, S.; Bao, X.; Wang, B.
Gram-scale Synthesis of 3a: To a flame-dried 50 ml
round-bottom-flask with a stir bar was added unsaturated
pyrazolones 1a (1.08 g, 3.2 mmol, 1.0 equiv), NaOAc·3H2O
(217 mg, 1.6 mmol, 0.5 equiv) and 2a (695 mg, 3.84 mmol,
1.2 equiv) under air. Subsequently, treated CH3CN (32 mL,
c = 0.1 M) was added. The reaction mixture was kept
Pyrazolone:
A
Powerful Synthon for Asymmetric Diverse
Derivatizations. Chem. Commun. 2018, 54, 11515–11529. (c) Xie,
X.; Xiang, L.; Peng, C.; Han, B. Catalytic Asymmetric Synthesis of
Spiropyrazolones and their Application in Medicinal Chemistry.
Chem. Rec. 2019, 19, 1–28. (d) Xie, X.; Huang, W.; Peng, C.; Han, B.
Organocatalytic Asymmetric Synthesis of Six-Membered
Carbocycle-Based Spiro Compounds. Adv. Synth. Catal. 2018, 360,
194−228. (e) Rios, R. Enantioselective Methodologies for the
Synthesis of Spiro Compounds. Chem. Soc. Rev. 2012, 41,
1060−1074.
o
stirring at 22 C for 10 min until unsaturated pyrazolones
1a was fully consumed (monitored by TLC). Then the
reaction was heated to 50 °C for 20 h. The organic solvent
was removed under reduced pressure and purified
through column chromatography (eluent: PE: EtOAc = 6: 1
to 4: 1) to afford the desired product 3a with 81% yield
(1.09 g).
(3) For recent selected examples: see: (a) Vetica, F.; Bailey, S.;
Chauhan, P.; Turberg, M.; Ghaur, A.; Raabe, G.; Enders, D.
Desymmetrization of Cyclopentenediones via Organocatalytic
Cross-Dehydrogenative Coupling. Adv. Synth. Catal. 2017, 359,
3729−3734. (b) Li, S.-W.; Wan, Q.; Kang, Q. Chiral-at-Metal Rh(III)
Complex-Catalyzed Michael Addition of Pyrazolones with α,β-
Unsaturated 2-Acyl Imidazoles. Org. Lett. 2018, 20, 1312−1315.
(c) Han, X.; Yao, W.; Wang, T.; Tan, Y. R.; Yan, Z.; Kwiatkowski, J.;
Lu, Y. Asymmetric Synthesis of Spiropyrazolones through
Phosphine-Catalyzed [4+ 1] Annulation. Angew. Chem. Int. Ed.
2014, 53, 5643–5647. (d) Ni, C.; Tong, X. Amine-Catalyzed
Asymmetric (3 + 3) Annulations of β′-Acetoxy Allenoates:
Enantioselective Synthesis of 4H-Pyrans. J. Am. Chem. Soc. 2016,
138, 7872−7875. (e) Bao, X.; Wei, S.; Qu, J.; Wang, B. C6′ Steric
Bulk of Cinchona Alkaloid Enables an Enantioselective Michael
Addition/Annulation Sequence toward Pyranopyrazoles. Chem.
Commun. 2018, 54, 2028−2031. (f) Hack, D.; Dürr, A. B.; Deckers,
K.; Chauhan, P.; Seling, N.; Rübenach, L.; Mertens, L.; Raabe, G.;
Schoenebeck, F.; Enders, D. Asymmetric Synthesis of
Spiropyrazolones by Sequential Organo- and Silver Catalysis.
Angew. Chem., Int. Ed. 2016, 55, 1797−1800. (g) Zheng, J.; Wang,
S.-B.; Zheng, C.; You, S.-L. Asymmetric Synthesis of
■ ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on
the ACS Publications website at DOI: http://pubs.acs.org.
Copies of of 1H, 13C and 19F NMR spectra (PDF)
Crystallographic information of compound 3a and 6 (CIF)
■ AUTHOR INFORMATION
Corresponding Authors
*E-mail: shoujie_shen@outlook.com.
*E-mail: jinyan_liang@outlook.com.
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGMENT
Spiropyrazolones
by
Rhodium-Catalyzed
C(sp2)−H
This work was supported by the research program from
National Natural Science Foundation of China (No. 21805175),
Natural Science Foundation of Shanxi Province (No.
201801D221067 and 201801D121048), the Natural Science
Foundation of Shanxi Normal University (No. 0505/02080160
and 0109/01053018), and the 1331 Engineering of Shanxi
Functionalization/Annulation Reactions. Angew. Chem., Int. Ed.
2017, 56, 4540−4544. (h) Zhao, B.-L.; Du, D.-M. Catalytic
Asymmetric
Mannich/Cyclization
of
2-Isothiocyanato-1-
indanones: An Approach to the Synthesis of Bispirocyclic
Indanone–Thioimidazolidine–Oxindoles. Org. Lett. 2018, 20,
3797−3800. (i) Bao, X.; Wei, S.; Qian, X.; Qu, J.; Wang, B.; Zou, L.;
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 15
Ge, G. Asymmetric Construction of a Multi-Pharmacophore-
Containing Dispirotriheterocyclic Scaffold and Identification of a
7, 3142−3146. (f) Leng, H.-J.; Li, Q.-Z.; Zeng, R.; Dai, Q.-S.; Zhu, H.-
P.; Liu, Y.; Huang, W.; Han, B.; Li, J.-L. Asymmetric Construction of
Spiropyrazolone Skeletons via Amine-Catalyzed [3+3] Annulation.
Adv. Synth. Catal. 2018, 360, 229−234. (g) Zheng, J.; Li, P.; Gu, M.;
Lin, A.; Yao, H. Synthesis of Spiropentadiene Pyrazolones by
Rh(III)-Catalyzed Formal sp3 C–H Activation/Annulation. Org.
Lett. 2017, 19, 2829−2832. (h) Li, H.; Gontla, R.; Flegel, J.; Merten,
C.; Ziegler, S.; Antonchick, A. P.; Waldmann, H. Enantioselective
Formal C(sp3)−H Bond Activation in the Synthesis of Bioactive
1
2
3
4
5
6
7
8
Human Carboxylesterase
1 Inhibitor. Org. Lett. 2018, 20,
3394−3398.
(4) (a) Gould, E.; Walden, D. M.; Kasten, K.; Johnston, R. C.; Wu,
J.; Slawin, A. M. Z.; Mustard, T. J. L.; Johnston, B.; Davies, T.; Ha-
Yeon Cheong, P.; Smith, A. D. Catalyst Selective and
Regiodivergent O- to C- or N-Carboxyl Transfer of Pyrazolyl
Carbonates: Synthetic and Computational Studies. Chem. Sci.
2014, 5, 3651−7989. (b) Gogoi, S.; Zhao, C.-G.; Ding, D.
Enantioselective Synthesis of β-(3-Hydroxypyrazol-1-yl) Ketones
Using an Organocatalyzed Michael Addition Reaction. Org. Lett.
2009, 11, 2249−2252. (c) Siegmund, A.; Retz, D.; Xi, N.; Domi-
nguez, C.; Bürli, R.; Liu. L. Selective β-Hydroxyethylation at the N-1
Position of a Pyrazolone: Synthesis of Benzyl 1-( β-Hydroxyethyl)-
5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylate.
Synlett 2008, 1005−1008. (d) Gomes, M. J. S.; Pinto, L. F. V.; Glória,
P. M. C.; Rzepa, H. S.; Prabhakar, S.; Lobo, A. M.; N-Heteroatom
Substitution Effect in 3-Aza-Cope Rearrangements. Chem. Cent. J.
2013, 7, 94−106. (e) Lu, Z.; Xie, C.; Han, J.; Pan, Y. Tandem 1,5-
Migration/Michael Reactions to Prepare Adducts of Pyrazolone
Derivatives: Protecting Group-Directed Rearrangement. RSC Adv.
2012, 2, 8949−8952. (f) Singh, P.; Paul, K.; Holzer, W. Synthesis of
Pyrazole-Based Hybrid Molecules: Search for Potent Multidrug
Resistance Modulators. Bioorg. Med. Chem. 2006, 14, 5061−5071.
(5) (a) Meninno, S.; Mazzanti, A.; Lattanzi, A. Asymmetric
Synthesis of Pyrazolone Fused Spirocyclohexeneimines via a
Vinylogous Michael/Cyclization Cascade Reaction. Adv. Synth.
Catal. 2019, 361, 79−84. (b) Mondal, B.; Maity, R.; Pan, S. C. Highly
Spiropyrazolone
Derivatives.
Angew.
Chem.
Int.
Ed.
2019, 58, 307−311. (i) Xu, J.; Hu, L.; Hu, H.; Ge, S.; Liu, X.; Feng,
X. Enantioselective Vinylogous Michael–Aldol Reaction to
Synthesize Spirocyclohexene Pyrazolones in Aqueous Media. Org.
Lett. 2019, 21, 1632−1636.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(7) For selected reviews, see: (a) Li, A.-H.; Dai, L.-X.; Aggarwal,
V. K. Asymmetric Ylide Reactions: Epoxidation, Cyclopropanation,
Aziridination, Olefination, and Rearrangement. Chem. Rev. 1997,
97, 2341−2372. (b) Aggarwal, V. K.; Winn, C. L. Catalytic,
Asymmetric Sulfur Ylide-Mediated Epoxidation of Carbonyl
Compounds: Scope, Selectivity, and Applications in Synthesis. Acc.
Chem. Res. 2004, 37, 611−620. (c) McGarrigle, E. M.; Myers, E. L.;
Illa, O.; Shaw, M. A.; Riches, S. L.; Aggarwal, V. K. Chalcogenides as
Organocatalysts. Chem. Rev. 2007, 107, 5841−5883. (d) Sun, X.-L.;
Tang, Y. Ylide-Initiated Michael Addition−Cyclization Reactions
beyond Cyclopropanes. Acc. Chem. Res. 2008, 41, 937−948. (e) Lu,
L.-Q.; Chen, J.-R.; Xiao, W.-J. Development of Cascade Reactions for
the Concise Construction of Diverse Heterocyclic Architectures.
Acc. Chem. Res. 2012, 45, 1278−1293. (f) Lu, L.-Q.; Li, T.-R.; Wang,
Q.; Xiao, W.-J. Beyond Sulfide-Centric Catalysis: Recent Advances
in the Catalytic Cyclization Reactions of Sulfur Ylides. Chem. Soc.
Rev. 2017, 46, 4135–4149. (g) Kaiser, D.; Klose, I.; Oost, R.;
Neuhaus, J.; Maulide, N. Bond-Forming and -Breaking Reactions at
Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate
Salts. Chem. Rev. 2019, DOI: 10.1021/acs.chemrev.9b00111. (h)
Wu, X.-P.; Sun, S.; Yu, J.-T.; Cheng, J. Recent Applications of α-
Carbonyl Sulfoxonium Ylides in Rhodiumand Iridium-Catalyzed
C−H Functionalizations. Synlett 2019, 30, 21–29. (i) Vaitla, J.;
Bayer, A. Sulfoxonium Ylide Derived Metal Carbenoids in Organic
Synthesis. Synthesis 2019, 51, 612–628 and references cited
therein.
(8) For selected examples, see: (a) Zhu, B.-H.; Zhou, R.; Zheng,
J.-C.; Deng, X.-M.; Sun, X.-L.; Shen, Q.; Tang, Y. Highly Selective
Ylide-Initiated Michael Addition/Cyclization Reaction for
Synthesis of Cyclohexadiene Epoxide and Vinylcyclopropane
Derivatives. J. Org. Chem. 2010, 75, 3454−3457. (b) McGarrigle, E.
M.; Fritz, S. P.; Favereau, L.; Yar, M.; Aggarwal, V. K. An Efficient
Synthesis of Imidazolinium Salts using Vinyl Sulfonium Salts. Org.
Lett. 2011, 13, 3060−3063. (c) Chen, J.-R.; Dong, W.-R.; Candy, M.;
Pan, F.-F.; Jorres, M.; Bolm, C. Enantioselective Synthesis of
Dihydropyrazoles by Formal [4+1] Cycloaddition of in Situ-
Derived Azoalkenes and Sulfur Ylides. J. Am. Chem. Soc. 2012, 134,
6924−6927. (d) Li, T.-R.; Tan, F.; Lu, L.-Q.; Wei, Y.; Wang, Y.-N.; Liu,
Y.-Y.; Yang, Q.-Q.; Chen, J.-R.; Shi, D.-Q.; Xiao, W.-J. Asymmetric
Trapping of Zwitterionic Intermediates by Sulphur Ylides in a
Palladium-Catalysed Decarboxylation-Cycloaddition Sequence.
Nat. Commun. 2014, 5, 5500. (e) Wu, B.; Chen, M.-W.; Ye, Z.-S.; Yu,
Diastereo-
tetrahydrofuran-pyrazolones via Organocatalytic Cascade
Reaction between γ-Hydroxyenones and Unsaturated
and
Enantioselective
Synthesis
of
Spiro-
Pyrazolones. J. Org. Chem. 2018, 83, 8645−8654. (c) Kaya, U.;
Chauhan, P.; Mahajan, S.; Deckers, K.; Valkonen, A.; Rissanen, K.;
Enders, D. Squaramide-Catalyzed Asymmetric aza-Friedel-
Crafts/N,O-Acetalization Domino Reactions Between 2-Naphthols
and Pyrazolinone Ketimines. Angew. Chem., Int. Ed. 2017, 56,
15358−15362. (d) Wang, S.; Rodriguez-Escrich, C.; Pericas, M. A.
H-Bond-Directing Organocatalyst for Enantioselective [4 + 2]
Cycloadditions via Dienamine Catalysis. Org. Lett. 2016, 18,
556−559. (e) Chauhan, P.; Mahajan, S.; Loh, C. C. J.; Raabe, G.;
Enders, D. Streocontrolled Construction of Six Vicinal Stereogenic
Centers
on
Spiropyrazolones
via
Organocascade
Michael/Michael/1,2-Addition Reactions. Org. Lett. 2014, 16,
2954−2957. (f) Zhang, J.-X.; Li, N.-K.; Liu, Z.-M.; Huang, X.-F.; Geng,
Z.-C.; Wang, X.-W. Enantioselective Synthesis of Unsymmetrical
Diaryl-Substituted Spirocyclohexanonepyrazolones through
a
Cascade [4+2] Double Michael Addition. Adv. Synth. Catal. 2013,
355, 797−808.
(6) (a) Rassu, G.; Zambrano, V.; Pinna, L.; Curti, C.; Battistini, L.;
Sartori, A.; Pelosi, G.; Casiraghi, G.; Zanardi, F. Direct and
Enantioselective
Vinylogous
Michael
Addition
of
α-
Alkylidenepyrazolinones to Nitroolefins Catalyzed by Dual
Cinchona Alkaloid Thioureas. Adv. Synth. Catal. 2014, 356,
2330−2336. (b) Yetra, S. R.; Mondal, S.; Mukherjee, S.; Gonnade, R.
G.;
Biju,
A.
T.
Enantioselective
Synthesis
of
Spirocyclohexadienones by NHC-Catalyzed Formal [3+3]
Annulation Reaction of Enals. Angew. Chem., Int. Ed. 2016, 55,
268−272. (c) Mondal, S.; Mukherjee, S.; Yetra, S. R.; Gonnade, R. G.;
Biju, A. T. Organocatalytic Enantioselective Vinylogous Michael-
Aldol Cascade for the Synthesis of Spirocyclic Compounds. Org.
Lett. 2017, 19, 4367−4370. (d) Liu, J.-Y.; Zhao, J.; Zhang, J.-L.; Xu,
C.-B.; Zhou, Y.-G.
A
Streamlined Synthesis of 2,3-
Dihydrobenzofurans via the ortho-Quinone Methides Generated
from 2-Alkyl-Substituted Phenols. Adv. Synth. Catal. 2014, 356,
383−387. (f) Zhang, Q.; Liu, X.; Xin, X.; Zhang, R.; Liang, Y.; Dong, D.
Formal [4+2] Annulation of Enaminones and Cyanomethyl Sulfur
Ylide: One-Pot Access to Polysubstituted Pyridin-2(1H)-ones.
Chem. Commun. 2014, 50, 15378−15380. (g) Li, C.; Jiang, K.;
Ouyang, Q.; Liu, T.-Y.; Chen, Y.-C. [3 + 1]-and [3 + 2]-
Cycloadditions of Azaoxyallyl Cations and Sulfur Ylides. Org. Lett.
2016, 18, 2738−2741. (h) Wang, D.; Wang, X.; Zhang, X.-G.; Miao,
Z.-W. Efficient Synthesis of 4,7-Dihydro-1H-oxepino[2,3-
c]pyrazoles by Potassium Carbonate Promoted [4+3] Annulation
P.-F. Quaternary Carbon Center Forming Formal [3
+ 3]
Cycloaddition Reaction via Bifunctional Catalysis: Asymmetric
Synthesis of Spirocyclohexene Pyrazolones. Org. Lett. 2017, 19,
1846−1849. (e) Yang, W.; Sun, W.; Zhang, C.; Wang, Q.; Guo, Z.;
Mao, B.; Liao, J.; Guo, H. Lewis-Base-Catalyzed Asymmetric [3 + 3]
Annulation Reaction of Morita-Baylis-Hillman Carbonates:
Enantioselective Synthesis of Spirocyclohexenes. ACS Catal. 2017,
ACS Paragon Plus Environment

Page 15 of 15
The Journal of Organic Chemistry
of Crotonate- Derived Sulfur Ylides with Benzylidenepyrazolones.
of Azomethine Imines and Propargyl Sulfur Ylide. Org. Biomol.
Chem. 2018, 16, 1068−1072.
(12) Jia, P.; Huang, Y. A Formal [5+1] Annulation Reaction of
Sulfur Ylides and 2-(1H-indol-2-yl)phenols: Access to
Indole-Fused 4H-benzo[e][1,3]oxazines. Adv. Synth. Catal. 2018,
360, 3044−3048.
(13) Liang, J.-Y.; Shen, S.-J.; Chai, X.-Q.; Lv, T. Lewis-Base-
Catalyzed [1 + 2 + 2] Annulation Reaction of Morita–Baylis–
Hillman Carbonates with Unsaturated Pyrazolones: Construction
Synthesis 2019, 51, 2149–2156 and references cited therein.
(9) (a) Aso, M.; Sakamoto, M.; Urakawa, N.; Kanemastsu, K.
Furannulation Strategy. An Efficient Synthesis of Fused 3-
Methylfurans. Heterocycles 1990, 31, 1003−1006. (b) Aso, M.;
Ojida, A.; Yang, G.; Cha, O.-J.; Osawa, E.; Kanematsu, K.
Furannulation Strategy for Synthesis of the Naturally Occurring
Fused 3-Methylfurans: Efficient Synthesis of Evodone and
Menthofuran and Regioselective Synthesis of Maturone via A
Lewis Acid Catalyzed Diels-Alder Reactions. Some Comments for
Its Mechanistic Aspects. J. Org. Chem. 1993, 58, 3960−3968. (c)
Ojida, A.; Tanoue, F.; Kanematsu, K. Total Syntheses of Marine
Furanosesquiterpenoids, Tubipofurans. J. Org. Chem. 1994, 59,
5970−5976.
1
2
3
4
5
6
7
8
of
All-Stereogenic
Carbon
Cyclopentane-Fused
Dispiropyrazolones. J. Org. Chem. 2018, 83, 12744−12752.
(14) Crystallographic data for 3a has been deposited with the
Cambridge Crystallographic Data Centre as deposition number
CCDC 1937495.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(10) (a) Jia, P.; Zhang, Q.; Jin, H.; Huang, Y. [3+ 2]-Annulation of
Prop-2-ynylsulfonium Salts: Access to Hydroindol-5-ones
Containing a Methylthio Group. Org. Lett. 2017, 19, 412−415. (b)
Jia, P.; Zhang, Q.; Zhuge, Y.; Liwei, X.; Huang. Y. One-Pot Synthesis
of Cyclopropanes from Methylene Azabicyclo[3.1.0]hexanes
Obtained by Formal Sequential [1+2]- and [2+3]-Cycloaddition
Reaction of Prop-2-ynylsulfonium Salts and Tosylaminomethyl
Enones. Adv. Synth. Catal. 2018, 360, 438−443. (c) Jia, P.; Zhang,
Q.; Ou, Q.; Huang, Y. Sequential [1+ 4]- and [2+ 3]-Annulation of
Prop-2-ynylsulfonium Salts: Access to Hexahydropyrrolo[3,2-
b]indoles. Org. Lett. 2017, 19, 4664−4667.
(15) Crystallographic data for 6 has been deposited with the
Cambridge Crystallographic Data Centre as deposition number
CCDC 1937494.
(16) For the 1H NMR details, see Supporting Information.
(17) Liu, Y.; Yang, Y.; Huang, Y. Xu, X.-H.; Qing, F.-L. Regio- and
Diastereoselective Vinylogous Mannich Addition of 3-Alkenyl-2-
oxindoles to α-Fluoroalkyl Aldimines. Synlett 2015, 26, 67−72.
(18) Chen, D.-D.; Hou, X-L.; Dai, L.-X. A Facile and Regioselective
Synthesis of 2,5-Disubstituted Pyrroles via Gold-Catalyzed
Cycloisomerization of Acetylenylaziridines. Tetrahedron Lett.
2009, 50, 6944−6946.
(11) Shen, S.; Yang, Y.; Duan, J.; Jia, Z.; Liang, J. Solvent
Incorporated Sequential [3+ 2] Annulation/Substitution Reaction
ACS Paragon Plus Environment