2-Pyridyl Sulfoxide Directed Pd(II)-Catalyzed C-H Olefination of Arenes with Molecular Oxygen as the Sole Oxidant

Article abstract of DOI:10.1055/a-1385-6119

Pd(II)-catalyzed C-H olefination of aryl 2-pyridyl sulfoxides with unactivated and activated olefins has been demonstrated. We employed environmentally benign and inexpensive molecular oxygen as the sole oxidant. The versatile nature of the 2-pyridyl sulf

Full text of DOI:10.1055/a-1385-6119

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–H
paper
A
en
M. Yadav et al.
Paper
Synthesis
2-Pyridyl Sulfoxide Directed Pd(II)-Catalyzed C–H Olefination of
Arenes with Molecular Oxygen as the Sole Oxidant
Mamta Yadav
Ram Singh Jat
Bibek Sarma
O
S
O
S
R
Pd(OAc)2
N
N
R
M. Bhanuchandra*
DMF, 80 °C, 13 h
O2
Department of Chemistry, School of Chemical Sciences and
Pharmacy, Central University of Rajasthan, Bandarsindri,
Rajasthan-305817, India
20 examples
yield up to 87%
economical & clean oxidant
mallibhanuchandra@curaj.ac.in
eMDMe.pBaaihClraotmmnrraueelclnshipbtaohonnafddnCriuahnceghmAainusdtrhryao,@rSccuhroaoj.laocf.iCnhemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Rajasthan-305817, India
Received: 28.01.2021
Accepted after revision: 08.02.2021
Published online: 08.02.2021
try. A few such directing groups are 8-aminoquinoline, pi-
colinamide, sulfoximine,7 pyridyldiisopropylsilyl (PyDipSi),8
N-(2-pyridyl)sulfonyl,9 and carboxylate.10 Despite their la-
bile oxido-redox nature and strong coordination ability to-
wards transition metals, sulfur-containing directing groups
have recently been used for o-C–H functionalization reac-
tions.1f,11 This is due to organosulfur compounds being
widely found in biologically active molecules, natural prod-
ucts,12 and smart materials.13 Often, these motifs are used
as building blocks, reagents, and chiral ligands14 in organic
synthesis. Of note, sulfoxide-directed C–H olefination al-
lows installation of an alkene unit in the final product
which then could be transformed to sulfur heterocy-
cles.11e,15 In particular, the versatile and removable 2-pyr-
idyl sulfoxide group was proven to be efficient with Pd(II)
catalysis in o-C–H functionalization reactions.11a,b,16 For ex-
ample, the Zhang11a group demonstrated efficient direct
alkenylation of arenes with various acrylates and styrenes.
With the same directing group, mono- and di-ortho-olefi-
nated arenes were successfully synthesized by Arrayás, Car-
retero, and co-workers16b (Scheme 1). However, stoichio-
metric amounts of oxidants such as K2S2O8 (2 equiv) and
AgOAc (5 equiv) were employed in those reactions to com-
plete the catalytic cycle. These oxidants ultimately produce
undesired waste which may have ramifications on the envi-
ronment. Considering the importance of the direct C–H ole-
fination of arenes and vast applications of the sulfur moi-
ety, we took the opportunity to develop a greener approach
for the oxidative olefination of arenes with the 2-pyridyl
sulfoxide directing group. We knew that molecular oxygen
as oxidant would be the ultimate choice,17 as it is rich in
availability, nature-friendly, and inexpensive. Further, the
sole byproduct produced in a molecular oxygen mediated
C–H olefination reaction is H2O.18
DOI: 10.1055/a-1385-6119; Art ID: ss-2021-f0033-op
Abstract Pd(II)-catalyzed C–H olefination of aryl 2-pyridyl sulfoxides
with unactivated and activated olefins has been demonstrated. We em-
ployed environmentally benign and inexpensive molecular oxygen as
the sole oxidant. The versatile nature of the 2-pyridyl sulfoxide directing
group has been proven by its transformation to the sulfone functional-
ity. Deuterium scrambling experiments and intramolecular kinetic iso-
topic studies were carried out to gain insights into the reaction path-
way.
Key words C–H olefination, 2-pyridyl sulfoxides, molecular oxygen,
palladium(II) catalysis
Transition-metal-catalyzed oxidative olefination of aryl
C–H bonds with olefins has been considered as one of the
straightforward methods to access functional materials.1
The Fujiwara–Moritani reaction, which represents the
oxidative cross-coupling of arene C–H bonds with alkenes
under palladium catalysis, is an attractive method in terms
of the step economy feature.2 Later on, numerous methods
have been developed to tackle the regioselective issues in
the oxidative olefination of aromatic C–H bonds with
alkenes.3 Cognizing the fact that the directing group can be
an ultimate choice in controlling the regioselectivity of C–H
olefination,4 nitrogen-5 and oxygen-based3b,6 moieties have
often been used as chelating groups for transition metals in
C–H functionalization reactions. Even though excellent re-
activity and regioselectivity have been achieved by intro-
ducing directing groups on arenes, removal of the chelating
group from the final product is rather challenging.
In this regard, many research groups came up with the
concept of removable and modifiable directing groups for
the C(sp2)–H bond functionalization of arenes, as this opens
a plethora of synthetic applications in academia and indus-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
M. Yadav et al.
Paper
Synthesis
Polar aprotic solvents, such as THF, 1,4-dioxane, and
DMSO, were found to be inferior in this olefination reaction
(entries 3–5). To our delight, the o-C–H olefination reaction
worked well in DMF solvent to deliver 3ad in 52% yield (en-
try 6). The reaction was completely turned off in protic
MeOH (entry 7). The yield of 3ad improved to 65% when the
temperature was decreased from 110 °C to 80 °C in DMF
(entry 8). The effect of the palladium catalyst was next ex-
amined in the o-C–H olefination reaction. Using
Pd(PPh3)2Cl2 gave trace amounts of the product (entry 9).
The reactions with other palladium complexes, such as
Pd(PPh3)4, Pd(dba)2, PdCl2, and PdCl2(C6H5CN)2, were found
to be inefficient and the desired product was obtained in
moderate yields (entries 10–13). Based on the above re-
sults, the optimized conditions for the o-C–H olefination
reaction comprised Pd(OAc)2 (10 mol%) in DMF at 80 °C un-
der oxygen atmosphere. Under these conditions, we
O
S
O
S
Pd(OAc)2
R
+
N
R
N
oxidant
Oxidant: AgOAc
ref. 11a
ref. 16b
this work
K2S2O8 or PhI(OAc)2
O2
Scheme 1 Palladium-catalyzed o-C–H olefination of 2-pyridyl sulfoxides
Herein, we disclose our findings on the direct C–H olefi-
nation of arenes with unactivated and activated olefins us-
ing molecular oxygen as the sole oxidant.
We commenced our study by reacting 2-pyridyl sulfox-
ide 1a with 4-acetoxystyrene (2d) using Pd(OAc)2 (10 mol%)
under oxygen atmosphere at 110 °C. At first, we screened
the solvent in the olefination reaction and the results are
summarized in Table 1. As per literature reports, DCE and
MeCN proved to be effective solvents for C–H olefination of
the 2-pyridyl sulfoxide.11a,16b However, the reactions in
those solvents (DCE and MeCN) were not efficient and pro-
vided moderate yields of the desired product 3ad (Table 1,
entries 1 and 2).
screened
a few representative sulfur-based directing
groups in the alkenylation reaction (Figure 1). The reaction
did not proceed with the highly electron-withdrawing 2-
pyridyl sulfone directing group. Reactions with diphenyl
sulfoxide, methyl phenyl sulfoxide, and phenyl 2-pyridyl
sulfide were found to be ineffective. Based on these results,
we decided to choose 2-pyridyl sulfoxide as directing group
to explore the scope of the olefination reaction.
Table 1 Optimization of the Reaction Conditionsa
O
O
S
O
S
O
O
S
O
S
catalyst (10 mol%)
S
+
S
N
Me
solvent, temp, 13 h
O2
N
N
N
OAc
Figure 1 Directing groups that fail to provide o-C–H olefination product
3ad
1a
2d
OAc
Entry Catalyst
Solvent
Temp (°C) Yield (%)b
At first, we investigated the scope of the o-C–H olefina-
tion reaction with unactivated styrene derivatives and the
results are shown in Scheme 2. The reaction of styrene with
1a afforded a mixture of mono- and di-ortho-alkenylated
product in 68% and 10% yield, respectively. Substituents
such as methyl and acetoxy at the meta- or para-position of
the phenyl ring of styrene furnished the corresponding
products 3ab–ad in acceptable yields. Halo substituents
such as fluoro and chloro were compatible under the opti-
mized reaction conditions, delivering the o-alkenylated (ar-
ylsulfinyl)pyridines 3ae–ag in good yields. Product 3ah was
obtained in lower yield due to steric factors. The presence of
versatile halo substituents in the final C–H olefinated prod-
ucts may provide an opportunity to employ such products
as starting materials in various cross-coupling reactions to
synthesize complex molecules. The -extended o-alkenylat-
ed (phenylsulfinyl)pyridine 3ai was isolated, albeit in poor
yield. Our efforts to obtain o-C–H olefinated products with
heteroaryl substrates such as 4-vinylpyridine and 1-vinyl-
1H-imidazole were unsuccessful.
1
2
Pd(OAc)2
DCE
110
110
110
110
110
110
110
80
26
45
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
MeCN
THF
3
15
4
1,4-dioxane
29
5
DMSO
DMF
MeOH
DMF
DMF
DMF
DMF
DMF
DMF
18
6
52
7
NRc
65
8
9
Pd(PPh3)2Cl2
Pd(PPh3)4
Pd(dba)2
80
trace
57
10
11
12
13
80
80
40
PdCl2
80
54
PdCl2(C6H5CN)2
80
40
a Reaction conditions: 1a (0.25 mmol), 2d (0.5 mmol), solvent (2.5 mL),
13 h, O2 atmosphere.
b Isolated yield.
c NR = no reaction.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H

C
M. Yadav et al.
Paper
Synthesis
O
S
O
S
O
O
S
CO2R1
4
S
Pd(OAc)2 10 mol%
Pd(OAc)2 (10 mol%)
Ar
+
R
R
N
N
N
N
N
DMF, 80 °C, 13 h
O2
DMF, 80 °C, 13 h
O2
1a
2
3
1
5
CO2R1
Ar
O
S
O
O
S
CO2Et
3aa, R = H, 68%a
3ae, R = p-F, 80%
3af, R = p-Cl, 62%
3ag, R = m-Cl, 50%
3ah, R = o-Cl, 30%
3ai, R = p-Ph, 14%
S
O
3ab, R = p-Me, 81%
3ac, R = m-Me, 47%
3ad, R = p-OAc, 65%
N
N
S
R
N
CO2R1
CO2Et
R
5ba, R, R1 = Me, 64%
5db
5db'
5bb, R = Me, R1 = Et, 84%
5ca, R = tBu, R1 = Me, 45%
5cb, R = tBu, R1 = Et, 54%
(5db/5db' = 1:0.6)a; 75%
Scheme 2 Substrate scope of unactivated alkenes. Reagents and condi-
tions: 1a (0.25 mmol), 2 (0.5 mmol), DMF (2.5 mL), 13 h, O2 atmosphere;
isolated yields. a Di-ortho-olefination product 3aa′ was obtained in 10%
yield.
O
O
S
Cl
S
+
N
N
Cl
CO2R1
5ea/5eb
CO2R1
We next turned our attention to examining the scope of
the reaction with respect to activated olefins (Scheme 3).
Acrylate derivatives such as methyl, ethyl, and isobutyl ac-
rylate effectively participated in the o-C–H alkenylation re-
action to afford the desired products 5aa–ac in moderate to
good yields. Interestingly, (vinylsulfonyl)benzene (4d) also
participated in the reaction, providing 5ad in 22% yield.
5ea'/5eb'
R1 = Me, 5ea = 21%; 5ea' = 29%
R1 = Et, 5eb = 26%; 5eb' = 25%
Scheme 4 Substrate scope of 2-pyridyl sulfoxides. Reagents and condi-
tions: 1 (0.25 mmol), 4 (0.5 mmol), DMF (2.5 mL), 13 h, O2 atmosphere;
isolated yields. a Calculated by 1H NMR.
O
S
O
S
these cases, both regioisomers were isolated in pure form
through column chromatography.
Pd(OAc)2 (10 mol%)
R
+
N
R
N
DMF, 80 °C, 13 h
O2
We conducted a few experiments to outline the plausi-
ble reaction mechanism for this o-C–H olefination reaction.
Treatment of 1a with Pd(OAc)2 (1 equiv) in DMF at 80 °C
provided the six-membered cyclopalladated complex 6 in
60% yield (Scheme 5).11b,20 The formation of complex 6 was
realized through coordination of the Pd(II) species to the ni-
trogen atom of the (arylsulfinyl)pyridine directing group
and subsequent deprotonation, with Pd–C bond formation.
Next, we subjected complex 6 to the C–H olefination reac-
tion with 2d in DMF at 80 °C in the presence of oxygen at-
mosphere. Finally, we were able to isolate the desired prod-
uct 3ad in 83% yield. This result indicates the involvement
of a palladacycle in the o-C–H alkenylation reaction.
1a
4
5
O
S
O
S
O
S
O
S
N
N
N
N
i
CO2Me
CO2Et
5ab, 87%
CO2 Bu
SO2Ph
5aa, 57%
5ac, 85%
5ad, 22%
Scheme 3 Substrate scope of activated alkenes. Reagents and condi-
tions: 1a (0.25 mmol), 4 (0.5 mmol), DMF (2.5 mL), 13 h, O2 atmosphere;
isolated yields.
To study the scope of the sulfoxide, we prepared a few
(arylsulfinyl)pyridine derivatives 1b–e and subjected them
to the optimized o-C–H olefination reaction conditions
(Scheme 4). The reaction of 2-(p-tolylsulfinyl)pyridine (1b)
individually with methyl acrylate (4a) as well as with ethyl
acrylate (4b) provided 5ba and 5bb in good yields. (Aryl-
sulfinyl)pyridine 1c with a tert-butyl substituent at the
para-position of the aromatic ring underwent the reaction
with 4a to give 5ca in 45% yield and similarly reacted with
4b to provide 5cb in 54% yield. An inseparable mixture of
regioisomers 5db/5db′ was isolated when 2-(naphthalen-
2-ylsulfinyl)pyridine (1d) reacted with acrylate 4b.19 As an-
ticipated, meta-chloro-substituted 2-pyridyl sulfoxide 1e
gave the two regioisomeric products 5ea and 5ea′ in 21%
and 29% yield, respectively, upon reaction with 4a. A similar
trend was observed for the C–H olefination of 1e with 4b to
deliver the products 5eb and 5eb′ in 51% combined yield. In
O
S
Pd(OAc)2 (1 equiv)
2d (4 equiv)
1a
3ad
N
DMF, 80 °C, 1 h
60%
DMF, 80 °C
13 h, O2, 83%
Pd
O
O
6
2
Scheme 5 Synthesis of palladacycle 6 and o-olefinated sulfoxide
To gain further insight into the reaction mechanism, we
performed deuterium scrambling experiments with D2O.
The reaction of 1a with 10 equivalents of D2O in the pres-
ence of 10 mol% Pd(OAc)2 and DMF at 80 °C for 13 hours un-
der O2 atmosphere did not deliver deuterium incorporated
product,21 suggesting C–H bond palladation to be irrevers-
ible in nature. An intramolecular kinetic isotopic effect
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H

D
M. Yadav et al.
Paper
Synthesis
kH/kD = 1.4 was observed for the reaction of 1a-d with 2d,
implying that o-C–H bond breakage is most likely not in-
volved in the rate-determining step (Scheme 6).
Low cost and environmentally benign molecular oxygen
was used as the sole oxidant in this process. A wide range of
o-olefinated aryl 2-pyridyl sulfoxides was obtained in ap-
preciable yields. Oxidation of the 2-pyridyl sulfoxide unit
was efficient in providing the corresponding sulfone. Cur-
rent efforts are focused on the carbon–heteroatom bond-
formation reaction with the versatile 2-pyridyl sulfoxide di-
recting group.
(73% D)
H/D
(43% D)
H/D
O
S
O
S
2d (2 equiv)
optimized conditions
N
N
kH/kD = 1.4
H
1a-d
3ad (3ad-d)
61% yield
OAc
Scheme 6 Kinetic isotopic effect
1H NMR (500 MHz) and 13C NMR (125 MHz) spectra were taken on a
Bruker Avance 500 MHz NMR spectrometer. Chemical shifts () are
reported in parts per million, relative to chloroform at 7.26 ppm for
1H and relative to CDCl3 at 77.0 ppm for 13C in CDCl3. Data for 1H NMR
are reported as follows: chemical shift (ppm), multiplicity (s = singlet,
bs = broad singlet, d = doublet, bd = broad doublet, t = triplet, bt =
broad triplet, q = quartet, m = multiplet), coupling constants, J (in Hz),
and integration. Data for 13C NMR are reported in terms of chemical
shift (ppm). High-resolution mass spectra were obtained using a TOF
analyzer in ESI mode. TLC analysis was performed on commercial alu-
minum TLC plates, silica gel coated with fluorescent indicator F254.
Silica gel (Merk 100–200 mesh and 230–400 mesh) was used for col-
umn chromatography. Unless otherwise noted, materials obtained
from commercial suppliers were used without further purification.
Thiophenols, 2-bromopyridine, and alkenes were purchased from
Sigma-Aldrich, India. N,N-Dimethylformamide (DMF) was distilled
under reduced pressure and stored under nitrogen. All reactions were
performed in oven-dried glass reaction tubes. Compounds 1a,16b
1b,16c 1d,16c 1e,16b 3aa,11a 3aa′,16b 3ad,11a 3ae,11a 5aa,11a 5ab,11a 5ad,16b
and 5ba11a are previously reported and showed the identical spectra
according to the literature.
On the basis of our findings and literature re-
ports,5e,11a,b,17c,d a plausible reaction mechanism is proposed
and depicted in Scheme 7. Initially, the Pd(II) species reacts
with 1a to form palladacycle 6. Then, ligand exchange and
alkene insertion probably leads to the generation of species
8. Finally, -hydride elimination from 8 provides the o-alke-
nylation product along with Pd(0). Molecular oxygen oxi-
dizes Pd(0) to the Pd(II) active catalyst for completion of the
catalytic cycle.
H2O
1a
Pd(OAc)2
O2
O
S
AcOH
Pd(0)
cyclo-
palladation
N
R
AcOH
O
S
β-H elimination
II
Pd
N
R
O
S
O
2-((4-tert-Butylphenyl)sulfinyl)pyridine (1c); Typical Procedure
for 2-(Arylsulfinyl)pyridines 1
N
R
2
O
6
ligand
exchange
O
S
Pd
4-tert-Butylbenzenethiol (500 mg, 3 mmol), 2-bromopyridine (470
mg, 3 mmol, 1 equiv), K2CO3 (830 mg, 6 mmol, 2 equiv), and DMSO (4
mL) were placed in an oven-dried round-bottom flask. The resulting
solution was stirred at 110 °C for 20 h. The reaction mixture was
quenched with H2O and extracted with CH2Cl2 (3 × 20 mL). The organ-
ic layer was separated, dried over Na2SO4, and concentrated under
vacuum. The crude residue was purified using column chromatogra-
phy on silica gel (hexane/EtOAc, 9:1) to provide 2-((4-tert-butylphe-
nyl)thio)pyridine. The thiol (710 mg, 3.0 mmol) was transferred to a
100 mL flask, CH2Cl2 (10 mL) was added, and the mixture was cooled
to 0 °C. The subsequent oxidation was carried out by slow addition of
mCPBA (510 mg, 3.0 mmol, 1 equiv) and stirring for 3–4 h at 0 °C to
room temperature. Then, saturated aqueous NaHCO3 solution was
added and the mixture was stirred for 30 min, then extracted with
CH2Cl2 (3 × 20 mL). The organic layer was separated, dried over
Na2SO4, and concentrated under vacuum. The crude residue was puri-
fied using column chromatography on silica gel (hexane/EtOAc, 7:3)
to provide 1c as a white solid; yield: 553 mg (71%); mp 111–112 °C.
OAc
8
alkene
insertion
N
Pd
OAc
7
R
Scheme 7 Plausible catalytic cycle of the o-C–H olefination
Next, we envisioned demonstrating the synthetic versa-
tility of the 2-pyridyl sulfoxide directing group. Oxidation
of o-alkenylated 2-pyridyl sulfoxide 5aa to the correspond-
ing sulfone with mCPBA was efficient and provided 9 in 92%
yield (Scheme 8).
O
O
S
O
S
mCPBA (2 equiv)
N
CH2Cl2, 0 °C to rt
3 h
N
1H NMR (CDCl3, 500 MHz):  = 8.57–8.56 (m, 1 H), 8.08–8.06 (m, 1 H),
7.90–7.87 (m, 1 H), 7.71–7.69 (m, 2 H), 7.48–7.46 (m, 2 H), 7.32–7.29
(m, 1 H), 1.29 (s, 9 H).
CO2Me
9, 92%
CO2Me
5aa
Scheme 8 Transformation of the directing group
13C NMR (CDCl3, 125 MHz):  = 166.80, 154.59, 149.63, 140.70,
137.96, 126.18, 124.79, 124.47, 118.40, 34.56, 30.80.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H18NOS+: 260.1104; found:
260.1103.
In conclusion, we have developed an efficient method
for the o-C–H olefination of arenes with the aid of the 2-
pyridyl sulfoxide directing group under palladium catalysis.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H

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M. Yadav et al.
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Synthesis
(E)-4-(2-(Pyridin-2-ylsulfinyl)styryl)phenyl Acetate (3ad); Typical
Procedure for 2-Pyridyl Sulfoxide Directed Pd(II)-Catalyzed C–H
Olefination of Arenes
1H NMR (CDCl3, 500 MHz):  = 8.50 (d, J = 5.0 Hz, 1 H), 8.04 (d, J = 8.0
Hz, 1 H), 7.95 (d, J = 16.5 Hz, 1 H), 7.90 (d, J = 7.5 Hz, 1 H), 7.86 (t, J =
8.0 Hz, 1 H), 7.68 (d, J = 7.5 Hz, 1 H), 7.55 (s, 1 H), 7.47–7.41 (m, 3 H),
7.33 (t, J = 7.5 Hz, 1 H), 7.29–7.26 (m, 2 H), 6.99 (d, J = 16.0 Hz, 1 H).
13C NMR (CDCl3, 125 MHz):  = 165.89, 149.58, 142.11, 138.76,
137.98, 136.66, 134.67, 131.35, 130.57, 129.94, 128.71, 128.05,
126.92, 126.02, 125.46, 125.23, 125.05, 124.57, 119.14.
An oven-dried glass reaction tube with a septum was charged with 2-
(phenylsulfinyl)pyridine (1a; 51 mg, 0.25 mmol) and Pd(OAc)2 (6 mg,
0.025 mmol, 0.1 equiv). The mixture was degassed with three vacu-
um–oxygen cycles before DMF (2.5 mL) and olefin 2d (81 mg, 0.5
mmol, 2 equiv) were added at room temperature. Then the reaction
mixture was purged with O2 using a balloon and the reaction tube
was closed with a screw cap. Finally, the mixture was stirred on a pre-
heated heating block at 80 °C for 13 h. The reaction mixture was
quenched with H2O and extracted with ethyl acetate (3 × 10 mL). The
organic layer was separated, dried over Na2SO4, and concentrated un-
der vacuum. The crude residue was purified using column chroma-
tography on silica gel (hexane/EtOAc, 4:1) to provide 3ad as a yellow
solid; yield: 59 mg (65%).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H15ClNOS+: 340.0557;
found: 340.0556.
(E)-2-((2-(2-Chlorostyryl)phenyl)sulfinyl)pyridine (3ah)
Yellow solid; yield: 26 mg (30%); mp 123–124 °C.
1H NMR (CDCl3, 500 MHz):  = 8.49 (d, J = 4.0 Hz, 1 H), 8.02 (d, J = 8.0
Hz, 1 H), 7.95–7.91 (m, 2 H), 7.86–7.84 (m, 2 H), 7.76 (d, J = 7.0 Hz, 1
H), 7.49–7.40 (m, 4 H), 7.34 (t, J = 7.0 Hz, 1 H), 7.28–7.24 (m, 2 H).
13C NMR (CDCl3, 125 MHz):  = 166.01, 149.67, 142.19, 138.08,
136.98, 135.10, 133.73, 131.50, 129.88, 129.19, 128.85, 128.10,
127.20 (2 C), 126.62, 126.47, 125.12, 124.67, 119.21.
(E)-2-((2-(4-Methylstyryl)phenyl)sulfinyl)pyridine (3ab)
Light green solid; yield: 64 mg (81%); mp 88–89 °C.
1H NMR (CDCl3, 500 MHz):  = 8.49 (d, J = 4.0 Hz, 1 H), 8.02 (d, J = 8.0
Hz, 1 H), 7.89 (dd, J = 11.5, 6.0 Hz, 2 H), 7.83 (t, J = 9.0 Hz, 1 H), 7.69 (d,
J = 7.5 Hz, 1 H), 7.48 (d, J = 8.5 Hz, 2 H), 7.44 (t, J = 7.0 Hz, 1 H), 7.38 (t,
J = 6.5 Hz, 1 H), 7.26–7.24 (m, 1 H), 7.21 (d, J = 8.0 Hz, 2 H), 7.04 (d, J =
16.0 Hz, 1 H), 2.39 (s, 3 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H15ClNOS+: 340.0557;
found: 340.0556.
(E)-2-((2-(2-([1,1′-Biphenyl]-4-yl)vinyl)phenyl)sulfinyl)pyridine
(3ai)
13C NMR (CDCl3, 125 MHz):  = 165.90, 149.58, 141.63, 138.21,
137.88, 137.34, 134.06, 132.06, 131.27, 129.43, 128.11, 126.90,
125.79, 125.13, 124.49, 122.80, 119.21, 21.30.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H18NOS+: 320.1104; found:
320.1105.
Yellow solid; yield: 14 mg (14%); mp 157–158 °C.
1H NMR (CDCl3, 500 MHz):  = 8.51 (d, J = 4.0 Hz, 1 H), 8.04 (d, J = 8.0
Hz, 1 H), 8.00 (d, J = 16.0 Hz, 1 H), 7.91 (d, J = 8.0 Hz, 1 H), 7.85 (t, J =
7.5 Hz, 1 H), 7.73 (d, J = 7.5 Hz, 1 H), 7.68–7.64 (m, 6 H), 7.49–7.36 (m,
5 H), 7.28–7.25 (m, 1 H), 7.12 (d, J = 16.5 Hz, 1 H).
13C NMR (CDCl3, 125 MHz):  = 165.95, 149.61, 141.85, 140.90,
140.51, 137.95, 137.17, 135.90, 131.59, 131.32, 128.83, 128.36,
127.45, 127.44, 127.40, 126.93, 125.89, 125.17, 124.55, 123.91,
119.20.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C25H20NOS+: 382.1260; found:
382.1261.
(E)-2-((2-(3-Methylstyryl)phenyl)sulfinyl)pyridine (3ac)
Colorless solid; yield: 38 mg (47%); mp 136–137 °C.
1H NMR (CDCl3, 500 MHz):  = 8.50 (d, J = 3.5 Hz, 1 H), 8.04 (d, J = 8.0
Hz, 1 H), 7.90 (d, J = 8.0 Hz, 1 H), 7.86–7.79 (m, 2 H), 7.71 (t, J = 7.5 Hz,
2 H), 7.46 (t, J = 7.0 Hz, 1 H), 7.41 (t, J = 7.5 Hz, 1 H), 7.32 (d, J = 15.5
Hz, 1 H), 7.29–7.20 (m, 4 H), 2.44 (s, 3 H).
13C NMR (CDCl3, 125 MHz):  = 166.00, 149.57, 142.97, 137.91,
137.60, 136.04, 135.94, 131.28, 130.41, 130.30, 128.31, 128.07,
126.33, 126.23, 125.95, 125.30, 125.08, 124.47, 119.16, 19.91.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H18NOS+: 320.1104; found:
320.1105.
Isobutyl (E)-3-(2-(Pyridin-2-ylsulfinyl)phenyl)acrylate (5ac)
Yellow oil; yield: 70 mg (85%).
1H NMR (CDCl3, 500 MHz):  = 8.53–8.47 (m, 2 H), 8.06 (d, J = 8.0 Hz, 1
H), 7.92–7.86 (m, 2 H), 7.66 (d, J = 7.5 Hz, 1 H), 7.51–7.45 (m, 2 H),
7.28–7.26 (m, 1 H), 6.54 (d, J = 16.0 Hz, 1 H), 4.07–4.00 (m, 2 H), 2.08–
2.0 (m, 1 H), 1.01 (d, J = 7.0 Hz, 6 H).
13C NMR (CDCl3, 125 MHz):  = 166.25, 165.36, 149.75, 143.69,
139.61, 137.95, 134.19, 131.35, 130.64, 126.90, 125.28, 124.50,
121.53, 118.98, 70.78, 27.78, 19.08.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H20NO3S+: 330.1158;
found: 330.1157.
(E)-2-((2-(4-Chlorostyryl)phenyl)sulfinyl)pyridine (3af)
Yellow solid; yield: 53 mg (62%); mp 124–125 °C.
1H NMR (CDCl3, 500 MHz):  = 8.48 (d, J = 4.0 Hz, 1 H), 8.03 (d, J = 8.0
Hz, 1 H), 7.95–7.89 (m, 2 H), 7.85 (t, J = 7.0 Hz, 1 H), 7.69 (d, J = 7.5 Hz,
1 H), 7.51 (d, J = 8.5 Hz, 2 H), 7.47–7.40 (m, 2 H), 7.37 (d, J = 8.5 Hz, 2
H), 7.27–7.25 (m, 1 H), 7.01 (d, J = 16.0 Hz, 1 H).
13C NMR (CDCl3, 125 MHz):  = 165.90, 149.54, 141.93, 137.97,
136.82, 135.35, 133.81, 131.34, 130.69, 128.91, 128.54, 128.13,
125.90, 125.19, 124.55, 119.13.
Ethyl (E)-3-(5-Methyl-2-(pyridin-2-ylsulfinyl)phenyl)acrylate
(5bb)
Yellow liquid; yield: 66 mg (84%).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H15ClNOS+: 340.0557;
found: 340.0555.
1H NMR (CDCl3, 500 MHz):  = 8.47–8.42 (m, 2 H), 8.05 (d, J = 8.0 Hz, 1
H), 7.86 (t, J = 7.5 Hz, 1 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.44 (s, 1 H), 7.29–
7.24 (m, 2 H), 6.41 (d, J = 16.0 Hz, 1 H), 4.28 (q, J = 7.0 Hz, 2 H), 2.36 (s,
3 H), 1.35 (t, J = 7.5 Hz, 3 H).
(E)-2-((2-(3-Chlorostyryl)phenyl)sulfinyl)pyridine (3ag)
Yellow solid; yield: 43 mg (50%); mp 89–90 °C.
13C NMR (CDCl3, 125 MHz):  = 166.35, 165.65, 149.92, 142.07,
140.80, 139.84, 138.00, 134.34, 131.66, 127.67, 125.92, 124.51,
121.57, 119.18, 60.77, 21.48, 14.10.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H

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M. Yadav et al.
Paper
Synthesis
HRMS (ESI-TOF): m/z [M + H]+ calcd for C17H18NO3S+: 316.1002;
found: 316.1003.
Methyl (E)-3-(2-Chloro-6-(pyridin-2-ylsulfinyl)phenyl)acrylate
(5ea′)
Brown solid; yield: 23 mg (29%); mp 104–105 °C.
Methyl (E)-3-(5-tert-Butyl-2-(pyridin-2-ylsulfinyl)phenyl)acrylate
(5ca)
1H NMR (CDCl3, 500 MHz):  = 8.52 (d, J = 4.0 Hz, 1 H), 8.10 (d, J = 8.0
Hz, 1 H), 7.99–7.92 (m, 2 H), 7.76 (d, J = 7.5 Hz, 1 H), 7.51 (d, J = 7.0 Hz,
1 H), 7.39 (t, J = 8.0 Hz, 1 H), 7.34–7.31 (m, 1 H), 6.84 (d, J = 16.0 Hz, 1
H), 3.86 (s, 3 H).
13C NMR (CDCl3, 125 MHz):  = 166.17, 165.66, 149.84, 146.27,
138.20, 137.64, 134.33, 133.99, 132.31, 130.31, 128.63, 124.64,
124.42, 119.32, 52.03.
Yellow solid; yield: 38 mg (45%); mp 144–145 °C.
1H NMR (CDCl3, 500 MHz):  = 8.51–8.47 (m, 2 H), 8.08 (d, J = 8.0 Hz, 1
H), 7.89 (t, J = 8.0 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7.63 (s, 1 H), 7.51
(d, J = 8.5 Hz, 1 H), 7.28–7.26 (m, 1 H), 6.47 (d, J = 16.0 Hz, 1 H), 3.85 (s,
3 H), 1.31 (s, 9 H).
13C NMR (CDCl3, 125 MHz):  = 166.74, 165.57, 154.97, 149.81,
140.75, 140.52, 137.91, 133.91, 128.29, 125.58, 124.41, 124.01,
120.97, 119.09, 51.89, 35.02, 31.00.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H13ClNO3S+: 322.0299;
found: 322.0293.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H22NO3S+: 344.1315;
Ethyl (E)-3-(4-Chloro-2-(pyridin-2-ylsulfinyl)phenyl)acrylate
found: 344.1310.
(5eb)
Yellow solid; yield: 22 mg (26%); mp 107–108 °C.
Ethyl (E)-3-(5-tert-Butyl-2-(pyridin-2-ylsulfinyl)phenyl)acrylate
(5cb)
1H NMR (CDCl3, 500 MHz):  = 8.50 (d, J = 4.5 Hz, 1 H), 8.41 (d, J = 15.5
Hz, 1 H), 8.04 (d, J = 8.0 Hz, 1 H), 7.92–7.89 (m, 2 H), 7.59 (d, J = 8.5 Hz,
1 H), 7.41 (d, J = 8.5 Hz, 1 H), 7.32–7.29 (m, 1 H), 6.43 (d, J = 15.5 Hz, 1
H), 4.31 (q, J = 7.0 Hz, 2 H), 1.36 (t, J = 7.0 Hz, 3 H).
13C NMR (CDCl3, 125 MHz):  = 166.07, 164.97, 149.91, 145.62,
138.69, 138.22, 137.07, 132.51, 131.62, 128.19, 124.97, 124.79,
121.85, 119.00, 60.84, 14.29.
Brown solid; yield: 47 mg (54%); mp 107–108 °C.
1H NMR (CDCl3, 500 MHz):  = 8.51–8.46 (m, 2 H), 8.08 (d, J = 8.0 Hz, 1
H), 7.88 (t, J = 6.5 Hz, 1 H), 7.77 (d, J = 8.5 Hz, 1 H), 7.63 (s, 1 H), 7.51
(dd, J = 8.5, 2.0 Hz, 1 H), 7.29–7.26 (m, 1 H), 6.45 (d, J = 16.0 Hz, 1 H),
4.31 (q, J = 7.5 Hz, 2 H), 1.37 (t, J = 7.5 Hz, 3 H), 1.31 (s, 9 H).
13C NMR (CDCl3, 125 MHz):  = 166.30, 165.52, 154.97, 149.82,
140.66, 140.25, 137.88, 133.98, 128.21, 125.69, 124.40, 124.01,
121.39, 119.16, 60.70, 35.01, 31.01, 14.32.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H15ClNO3S+: 336.0456;
found: 336.0446.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H24NO3S+: 358.1471;
found: 358.1466.
Ethyl (E)-3-(2-Chloro-6-(pyridin-2-ylsulfinyl)phenyl)acrylate
(5eb′)
Brown solid; yield: 21 mg (25%); mp 79–80 °C.
Ethyl (E)-3-(3-(Pyridin-2-ylsulfinyl)naphthalen-2-yl)acrylate
(5db) and Ethyl (E)-3-(2-(Pyridin-2-ylsulfinyl)naphthalen-1-yl)ac-
rylate (5db′)
1H NMR (CDCl3, 500 MHz):  = 8.52 (d, J = 3.5 Hz, 1 H), 8.09 (d, J = 8.0
Hz, 1 H), 7.98–7.90 (m, 2 H), 7.76 (d, J = 7.5 Hz, 1 H), 7.51 (d, J = 8.0 Hz,
1 H), 7.38 (t, J = 8.0 Hz, 1 H), 7.33–7.30 (m, 1 H), 6.79 (d, J = 16.0 Hz, 1
H), 4.31 (q, J = 5.5 Hz, 2 H), 1.37 (t, J = 7.5 Hz, 3 H).
Brown solid; yield: 66 mg (75%).
1H NMR (CDCl3, 500 MHz):  = 8.55–8.43 (m, 4 H), 8.21 (d, J = 8.0 Hz, 1
H), 8.14–8.09 (m, 3 H), 7.96–7.86 (m, 6 H), 7.76 (d, J = 9.0 Hz, 1 H),
7.62–7.57 (m, 4 H), 7.30–7.25 (m, 3 H), 6.85 (d, J = 16.0 Hz, 1 H) (5db′),
6.48 (d, J = 15.0 Hz, 1 H) (5db), 4.40–4.30 (m, 4 H), 1.42–1.37 (m, 6 H).
13C NMR (CDCl3, 125 MHz):  = 166.25, 165.88 (3 C), 165.32, 149.97,
149.84, 149.74, 149.61, 140.72, 140.41, 138.70, 138.00, 134.66,
134.22, 134.12 (2 C), 133.22 (2 C), 130.94, 130.74, 129.75, 129.67,
128.66, 128.64, 128.62, 128.29, 127.56, 127.43, 127.02, 126.81,
124.47, 121.30, 121.23, 119.53, 119.38, 60.96, 60.67, 14.39, 14.29.
13C NMR (CDCl3, 125 MHz):  = 165.74, 165.60, 149.86, 146.20,
138.15, 137.34, 134.32, 134.04, 132.33, 130.23, 129.00, 124.64,
124.44, 119.39, 60.93, 14.27.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H15ClNO3S+: 336.0456;
found: 336.0446.
Palladacycle 6
Yellow solid; yield: 655 mg (60%); mp 191–192 °C (dec).
1H NMR (CDCl3, 500 MHz):  = 9.19 (bd, J = 5.5 Hz, 1 H), 8.27 (bd, J =
5.5 Hz, 1 H), 8.08 (bt, J = 9.0 Hz, 1 H), 8.02 (bd, J = 9.0 Hz, 1 H), 7.92 (bt,
J = 9.0 Hz, 1 H), 7.77 (bd, J = 10.5 Hz, 1 H), 7.67 (bs, 1 H), 7.57 (bt, J =
6.5 Hz, 1 H), 7.39 (bd, J = 9.0 Hz, 1 H), 7.26–7.22 (m, 3 H), 7.03 (bt, J =
7.5 Hz, 1 H), 6.71 (bt, J = 6.5 Hz, 1 H), 6.34 (bt, J = 8.0 Hz, 1 H), 6.12 (bs,
J = 9.0 Hz, 1 H), 2.90 (bd, J = 7.5 Hz, 6 H).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H18NO3S+: 352.1002;
found: 352.0997.
Methyl (E)-3-(4-Chloro-2-(pyridin-2-ylsulfinyl)phenyl)acrylate
(5ea)
White solid; yield: 17 mg (21%); mp 144–145 °C.
13C NMR (CDCl3, 125 MHz):  = 182.43, 182.00, 165.70, 165.43,
153.95, 152.67, 142.76, 142.50, 140.00, 139.91, 135.49, 135.17,
134.70, 134.30, 129.00, 128.90, 126.00, 125.60, 125.46, 124.47,
122.21, 122.12, 121.92, 121.65, 24.36 (2 C).
1H NMR (CDCl3, 500 MHz):  = 8.49 (d, J = 4.0 Hz, 1 H), 8.42 (d, J = 16.0
Hz, 1 H), 8.05 (d, J = 8.0 Hz, 1 H), 7.93–7.89 (m, 2 H), 7.59 (d, J = 8.5 Hz,
1 H), 7.41 (dd, J = 8.5, 2.0 Hz, 1 H), 7.32–7.30 (m, 1 H), 6.45 (d, J = 15.5
Hz, 1 H), 3.85 (s, 3 H).
13C NMR (CDCl3, 125 MHz):  = 166.52, 165.10, 149.91, 145.68,
138.98, 138.25, 137.18, 132.44, 131.63, 128.21, 124.94, 124.80,
121.39, 118.97, 52.00.
Methyl (E)-3-(2-(Pyridin-2-ylsulfonyl)phenyl)acrylate (9)
White solid; yield: 70 mg (92%); mp 141–142 °C.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H13ClNO3S+: 322.0299;
found: 322.0298.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H

G
M. Yadav et al.
Paper
Synthesis
1H NMR (CDCl3, 500 MHz):  = 8.62 (d, J = 6 Hz, 1 H), 8.42 (d, J = 20 Hz,
1 H), 8.36 (d, J = 9.5 Hz, 1 H), 8.31 (d, J = 10 Hz, 1 H), 7.96 (t, J = 10 Hz,
1 H), 7.65–7.59 (m, 3 H), 7.48–7.45 (m, 1 H), 6.15 (d, J = 20.0 Hz, 1 H),
3.79 (s, 3 H).
13C NMR (CDCl3, 125 MHz):  = 166.20, 158.61, 150.37, 140.95,
137.97, 137.19, 134.97, 134.18, 130.78, 129.92, 128.49, 127.12,
122.58, 122.37, 51.91.
Jiao, N. Angew. Chem. Int. Ed. 2009, 48, 4572. (i) Ueda, S.; Okada,
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Angew. Chem. Int. Ed. 2019, 58, 10820.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H14NO4S+: 304.0638;
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J. Am. Chem. Soc. 2010, 132, 468. (c) Graczyk, K.; Ma, W.;
Ackermann, L. Org. Lett. 2012, 14, 4110. (d) Bhanuchandra, M.;
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Commun. 2013, 49, 5225. (e) Liu, H.; Luo, Y.; Zhang, J.; Liu, M.;
Dong, L. Org. Lett. 2020, 22, 4648.
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(b) Yadav, M. R.; Rit, R. K.; Shankar, M.; Sahoo, A. K. J. Org. Chem.
2014, 79, 6123. (c) Rit, R. K.; Yadav, M. R.; Ghosh, K.; Sahoo, A. K.
Tetrahedron 2015, 71, 4450.
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(b) Dudnik, A. S.; Chernyak, N.; Huang, C.; Gevorgyan, V. Angew.
Chem. Int. Ed. 2010, 49, 8729. (c) Chernyak, N.; Dudnik, A. S.;
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found: 304.0630.
Conflict of Interest
The authors declare no conflict of interest.
Funding Information
This work was supported by the Department of Science and Technol-
ogy, Science and Engineering Research Board (DST-SERB, Grant Ref.
No. EEQ/2017/000768) and the University Grants Commission [UGC,
File No. 30-356/2017(BSR)]. M.Y., R.S.J., and B.S. thank the Council of
Scientific and Industrial Research (CSIR), India and the Science and
Engineering Research Board (SERB) for research fellowships. We
thank the Department of Science and Technology, Fund for Improve-
ment of S&T Infrastructure in Higher Educational Institutions [DST-
FIST, Grant No. SR/FST/CSI-257/2014(C)] for a research grant to the
Department of Chemistry, and also thank the Central University of
Rajasthan for support.
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/a-1385-6119. Su
(10) (a) Shi, B.-F.; Zhang, Y.-H.; Lam, J. K.; Wang, D.-H.; Yu, J.-Q. J. Am.
Chem. Soc. 2010, 132, 460. (b) Wei, Y.; Duan, A.; Tang, P.-T.; Li, J.-
W.; Peng, R.-M.; Zhou, Z.-X.; Luo, X.-P.; Kurmoo, M.; Liu, Y.-J.;
Zeng, M.-H. Org. Lett. 2020, 22, 4129.
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(19) The structures of regioisomers were assigned by analogy to
compounds reported in the literature; see ref. 16b.
(20) Pd complex 6 has been synthesized in DCE and the structure
unambiguously determined by X-ray analysis; see ref. 11b. Pd
complex 6 synthesized in DCE and DMF showed identical peaks
in the 1H NMR spectra (see the Supporting Information).
(21) One of the referees suggested the use of 1–2 equivalents of D2O
instead of 10 equivalents of D2O as it is too much for the reac-
tion. However, no deuterium incorporation was found even
with 2 equivalents of D2O. Secondly, to avoid any interference of
D2O in the palladation step, a similar reaction was performed
without D2O and finally the reaction quenched with D2O to
capture deuterated product. But, the 1H NMR data showed that
no deuterated product was formed.
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© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–H