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Synthesis 2021; 53(13): 2269-2276
DOI: 10.1055/a-1385-6119
paper

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
,
M. Bhanuchandra∗

This work was supported by the Department of Science and Technology, 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 Improvement 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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Abstract

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 sulfoxide directing group has been proven by its transformation to the sulfone functionality. Deuterium scrambling experiments and intramolecular kinetic isotopic studies were carried out to gain insights into the reaction pathway.


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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-based[3b] [6] moieties have often been used as chelating groups for transition metals in C–H functionalization reactions. Even though excellent reactivity and regioselectivity have been achieved by introducing 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 industry. A few such directing groups are 8-aminoquinoline, picolinamide, sulfoximine,[7] pyridyldiisopropylsilyl (PyDipSi),[8] N-(2-pyridyl)sulfonyl,[9] and carboxylate.[10] Despite their labile oxido-redox nature and strong coordination ability towards transition metals, sulfur-containing directing groups have recently been used for o-C–H functionalization reactions.[1f] [11] This is due to organosulfur compounds being widely found in biologically active molecules, natural products,[12] and smart materials.[13] Often, these motifs are used as building blocks, reagents, and chiral ligands[14] in organic synthesis. Of note, sulfoxide-directed C–H olefination allows installation of an alkene unit in the final product which then could be transformed to sulfur heterocycles.[11e] [15] In particular, the versatile and removable 2-pyridyl sulfoxide group was proven to be efficient with Pd(II) catalysis in o-C–H functionalization reactions.[11a] [b] [16] For example, the Zhang[11a] group demonstrated efficient direct alkenylation of arenes with various acrylates and styrenes. With the same directing group, mono- and di-ortho-olefinated arenes were successfully synthesized by Arrayás, Carretero, and co-workers[16b] (Scheme [1]). However, stoichiometric amounts of oxidants such as K2S2O8 (2 equiv) and AgOAc (5 equiv) were employed in those reactions to complete the catalytic cycle. These oxidants ultimately produce undesired waste which may have ramifications on the environment. Considering the importance of the direct C–H olefination of arenes and vast applications of the sulfur moiety, 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]

Zoom Image
Scheme 1 Palladium-catalyzed o-C–H olefination of 2-pyridyl sulfoxides

Herein, we disclose our findings on the direct C–H olefination of arenes with unactivated and activated olefins using molecular oxygen as the sole oxidant.

We commenced our study by reacting 2-pyridyl sulfoxide 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 provided moderate yields of the desired product 3ad (Table [1], entries 1 and 2).

Table 1 Optimization of the Reaction Conditionsa

Entry

Catalyst

Solvent

Temp (°C)

Yield (%)b

 1

Pd(OAc)2

DCE

110

26

 2

Pd(OAc)2

MeCN

110

45

 3

Pd(OAc)2

THF

110

15

 4

Pd(OAc)2

1,4-dioxane

110

29

 5

Pd(OAc)2

DMSO

110

18

 6

Pd(OAc)2

DMF

110

52

 7

Pd(OAc)2

MeOH

110

NRc

 8

Pd(OAc)2

DMF

 80

65

 9

Pd(PPh3)2Cl2

DMF

 80

trace

10

Pd(PPh3)4

DMF

 80

57

11

Pd(dba)2

DMF

 80

40

12

PdCl2

DMF

 80

54

13

PdCl2(C6H5CN)2

DMF

 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.

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 (entry 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 examined 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 results, the optimized conditions for the o-C–H olefination reaction comprised Pd(OAc)2 (10 mol%) in DMF at 80 °C under oxygen atmosphere. Under these conditions, we 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.

Zoom Image
Figure 1 Directing groups that fail to provide o-C–H olefination product

At first, we investigated the scope of the o-C–H olefination 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 optimized reaction conditions, delivering the o-alkenylated (arylsulfinyl)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 products may provide an opportunity to employ such products as starting materials in various cross-coupling reactions to synthesize complex molecules. The π-extended o-alkenylated (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.

Zoom Image
Scheme 2 Substrate scope of unactivated alkenes. Reagents and conditions: 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.

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 acrylate effectively participated in the o-C–H alkenylation reaction 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.

Zoom Image
Scheme 3 Substrate scope of activated alkenes. Reagents and conditions: 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. (Arylsulfinyl)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 anticipated, 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 these cases, both regioisomers were isolated in pure form through column chromatography.

Zoom Image
Scheme 4 Substrate scope of 2-pyridyl sulfoxides. Reagents and conditions: 1 (0.25 mmol), 4 (0.5 mmol), DMF (2.5 mL), 13 h, O2 atmosphere; isolated yields. a Calculated by 1H NMR.

We conducted a few experiments to outline the plausible 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 nitrogen 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 reaction with 2d in DMF at 80 °C in the presence of oxygen atmosphere. Finally, we were able to isolate the desired product 3ad in 83% yield. This result indicates the involvement of a palladacycle in the o-C–H alkenylation reaction.

Zoom Image
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 presence of 10 mol% Pd(OAc)2 and DMF at 80 °C for 13 hours under O2 atmosphere did not deliver deuterium incorporated product,[21] suggesting C–H bond palladation to be irreversible in nature. An intramolecular kinetic isotopic effect k H/k D = 1.4 was observed for the reaction of 1a-d with 2d, implying that o-C–H bond breakage is most likely not involved in the rate-determining step (Scheme [6]).

Zoom Image
Scheme 6 Kinetic isotopic effect

On the basis of our findings and literature reports,[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, β-hydride elimination from 8 provides the o-alkenylation product along with Pd(0). Molecular oxygen oxidizes Pd(0) to the Pd(II) active catalyst for completion of the catalytic cycle.

Zoom Image
Scheme 7 Plausible catalytic cycle of the o-C–H olefination

Next, we envisioned demonstrating the synthetic versatility of the 2-pyridyl sulfoxide directing group. Oxidation of o-alkenylated 2-pyridyl sulfoxide 5aa to the corresponding sulfone with mCPBA was efficient and provided 9 in 92% yield (Scheme [8]).

Zoom Image
Scheme 8 Transformation of the directing group

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. 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 appreciable yields. Oxidation of the 2-pyridyl sulfoxide unit was efficient in providing the corresponding sulfone. Current efforts are focused on the carbon–heteroatom bond-formation reaction with the versatile 2-pyridyl sulfoxide directing group.

1H NMR (500 MHz) and 13C NMR (125 MHz) spectra were taken on a Bruker Avance 500 MHz NMR spectrometer. Chemical shifts (δ) 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 aluminum TLC plates, silica gel coated with fluorescent indicator F254. Silica gel (Merk 100–200 mesh and 230–400 mesh) was used for column 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 5ba [11a] are previously reported and showed the identical spectra according to the literature.


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2-((4-tert-Butylphenyl)sulfinyl)pyridine (1c); Typical Procedure for 2-(Arylsulfinyl)pyridines 1

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 organic layer was separated, dried over Na2SO4, and concentrated under vacuum. The crude residue was purified using column chromatography on silica gel (hexane/EtOAc, 9:1) to provide 2-((4-tert-butylphenyl)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 purified 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.

1H NMR (CDCl3, 500 MHz): δ = 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).

13C NMR (CDCl3, 125 MHz): δ = 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.


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(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

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 vacuum–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 preheated 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 under vacuum. The crude residue was purified using column chromatography on silica gel (hexane/EtOAc, 4:1) to provide 3ad as a yellow solid; yield: 59 mg (65%).


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(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): δ = 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).

13C NMR (CDCl3, 125 MHz): δ = 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.


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(E)-2-((2-(3-Methylstyryl)phenyl)sulfinyl)pyridine (3ac)

Colorless solid; yield: 38 mg (47%); mp 136–137 °C.

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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.


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(E)-2-((2-(4-Chlorostyryl)phenyl)sulfinyl)pyridine (3af)

Yellow solid; yield: 53 mg (62%); mp 124–125 °C.

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H15ClNOS+: 340.0557; found: 340.0555.


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(E)-2-((2-(3-Chlorostyryl)phenyl)sulfinyl)pyridine (3ag)

Yellow solid; yield: 43 mg (50%); mp 89–90 °C.

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H15ClNOS+: 340.0557; found: 340.0556.


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(E)-2-((2-(2-Chlorostyryl)phenyl)sulfinyl)pyridine (3ah)

Yellow solid; yield: 26 mg (30%); mp 123–124 °C.

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H15ClNOS+: 340.0557; found: 340.0556.


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(E)-2-((2-(2-([1,1′-Biphenyl]-4-yl)vinyl)phenyl)sulfinyl)pyridine (3ai)

Yellow solid; yield: 14 mg (14%); mp 157–158 °C.

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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.


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Isobutyl (E)-3-(2-(Pyridin-2-ylsulfinyl)phenyl)acrylate (5ac)

Yellow oil; yield: 70 mg (85%).

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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.


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Ethyl (E)-3-(5-Methyl-2-(pyridin-2-ylsulfinyl)phenyl)acrylate (5bb)

Yellow liquid; yield: 66 mg (84%).

1H NMR (CDCl3, 500 MHz): δ = 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).

13C NMR (CDCl3, 125 MHz): δ = 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.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C17H18NO3S+: 316.1002; found: 316.1003.


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Methyl (E)-3-(5-tert-Butyl-2-(pyridin-2-ylsulfinyl)phenyl)acrylate (5ca)

Yellow solid; yield: 38 mg (45%); mp 144–145 °C.

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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 C19H22NO3S+: 344.1315; found: 344.1310.


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Ethyl (E)-3-(5-tert-Butyl-2-(pyridin-2-ylsulfinyl)phenyl)acrylate (5cb)

Brown solid; yield: 47 mg (54%); mp 107–108 °C.

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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 C20H24NO3S+: 358.1471; found: 358.1466.


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Ethyl (E)-3-(3-(Pyridin-2-ylsulfinyl)naphthalen-2-yl)acrylate (5db) and Ethyl (E)-3-(2-(Pyridin-2-ylsulfinyl)naphthalen-1-yl)acrylate (5db′)

Brown solid; yield: 66 mg (75%).

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H18NO3S+: 352.1002; found: 352.0997.


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Methyl (E)-3-(4-Chloro-2-(pyridin-2-ylsulfinyl)phenyl)acrylate (5ea)

White solid; yield: 17 mg (21%); mp 144–145 °C.

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H13ClNO3S+: 322.0299; found: 322.0298.


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Methyl (E)-3-(2-Chloro-6-(pyridin-2-ylsulfinyl)phenyl)acrylate (5ea′)

Brown solid; yield: 23 mg (29%); mp 104–105 °C.

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H13ClNO3S+: 322.0299; found: 322.0293.


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Ethyl (E)-3-(4-Chloro-2-(pyridin-2-ylsulfinyl)phenyl)acrylate (5eb)

Yellow solid; yield: 22 mg (26%); mp 107–108 °C.

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C16H15ClNO3S+: 336.0456; found: 336.0446.


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Ethyl (E)-3-(2-Chloro-6-(pyridin-2-ylsulfinyl)phenyl)acrylate (5eb′)

Brown solid; yield: 21 mg (25%); mp 79–80 °C.

1H NMR (CDCl3, 500 MHz): δ = 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).

13C NMR (CDCl3, 125 MHz): δ = 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.


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Palladacycle 6

Yellow solid; yield: 655 mg (60%); mp 191–192 °C (dec).

1H NMR (CDCl3, 500 MHz): δ = 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).

13C NMR (CDCl3, 125 MHz): δ = 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).


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Methyl (E)-3-(2-(Pyridin-2-ylsulfonyl)phenyl)acrylate (9)

White solid; yield: 70 mg (92%); mp 141–142 °C.

1H NMR (CDCl3, 500 MHz): δ = 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): δ = 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.

HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H14NO4S+: 304.0638; found: 304.0630.


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No conflict of interest has been declared by the author(s).

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-1385-6119.
  • Supporting Information

Corresponding Author

M. Bhanuchandra
Department of Chemistry, School of Chemical Sciences and Pharmacy, Central University of Rajasthan
Bandarsindri, Rajasthan-305817
India   

Publication History

Received: 28 January 2021

Accepted after revision: 08 February 2021

Accepted Manuscript online:
08 February 2021

Article published online:
23 February 2021

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Zoom Image
Scheme 1 Palladium-catalyzed o-C–H olefination of 2-pyridyl sulfoxides
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Figure 1 Directing groups that fail to provide o-C–H olefination product
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Scheme 2 Substrate scope of unactivated alkenes. Reagents and conditions: 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.
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Scheme 3 Substrate scope of activated alkenes. Reagents and conditions: 1a (0.25 mmol), 4 (0.5 mmol), DMF (2.5 mL), 13 h, O2 atmosphere; isolated yields.
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Scheme 4 Substrate scope of 2-pyridyl sulfoxides. Reagents and conditions: 1 (0.25 mmol), 4 (0.5 mmol), DMF (2.5 mL), 13 h, O2 atmosphere; isolated yields. a Calculated by 1H NMR.
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Scheme 5 Synthesis of palladacycle 6 and o-olefinated sulfoxide
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Scheme 6 Kinetic isotopic effect
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Scheme 7 Plausible catalytic cycle of the o-C–H olefination
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Scheme 8 Transformation of the directing group