3.3. Procedure
2-3-[(Ethylsulfanyl)methyl]phenylpyridine, 6b. Under an argon atmosphere, ethanethiol (2.42 mmol, 0.179 mL) and sodium hydride (2.41 mmol, 58 mg) were dissolved in dry DMF (dimethylformamide, 3 mL) and stirred at room temperature in a sealed microwave vial for 15 min. 2-[3-(Bromomethyl)phenyl]pyridine, 5 (1.61 mmol, 400 mg) in dry DMF (3 mL) was then added, and stirred under microwave irradiation (maximum power 300 W, dynamic heating) at 150 °C for 15 min. After cooling, the solvent was removed in vacuo and the crude mixture was diluted in H2O (25 mL) and DCM (25 mL). The product was extracted with DCM (2 × 25 mL), washed with H2O (5 × 25 mL) and brine (25 mL). The organic layers were dried over anhydrous MgSO4, filtered, and concentration in vacuo. The crude product was purified using flash column chromatography (7:3 DCM:EtOAc) yielding 263 mg of the expected product, 6c, as a yellow oil in 71% yield. 1H NMR (500 MHz), Chloroform-d δ (ppm): 8.70 (d, J = 4.8 Hz, 1H), 7.96 (s, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.77–7.73 (m, 2H), 7.43 (dd, J = 7.5, 7.5 Hz, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.24 (ddd, 6.3, 4.8, 2.3 Hz, 1H), 3.81 (s, 2H), 2.48 (q, J = 7.5 Hz, 2H), 1.25 (t, J = 7.5 Hz, 3H). 13C NMR (126 MHz), Chloroform-d δ (ppm): 157.3, 149.7, 139.6, 139.2, 136.7, 129.4, 128.9, 127.4, 125.5, 122.1, 120.6, 36.0, 25.4, 14.4. HRMS (m/z). Calc. for [C14H15NS + H]+ 230.0998. Found 230.0998.
2-3-[(Propylsulfanyl)methyl]phenylpyridine, 6c. Same methodology as 6b, using propane-1-thiol (1.97 mmol, 0.178 mL), and reacting for 20 min in the microwave. After workup, 300 mg of the expected product, 6c was found, without purification in >99% yield as a yellow oil. 1H NMR (500 MHz), Chloroform-d δ (ppm): 8.70 (d, J = 4.8 Hz, 1H), 7.96 (s, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.78–7.73 (m, 2H), 7.43 (dd, J = 7.5, 7.5 Hz, 1H), 7.39 (d, J = 7.5 Hz, 1H), 7.24 (ddd, J = 6.5, 4.8, 2.1 Hz, 1H), 3.79 (s, 2H), 2.44 (t, J = 7.2 Hz, 2H), 1.64–1.57 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H). ). 13C NMR (126 MHz), Chloroform-d δ (ppm): 157.2, 149.6, 139.6, 139.3, 136.7, 129.4, 128.8, 127.4, 125.5, 122.1, 120.6, 36.3, 33.6, 22.6, 13.5. HRMS (m/z). Calc. for [C15H17NS + H]+ 244.1154. Found 244.1155.
2-3-[(Phenylsulfanyl)methyl]phenylpyridine, 6d. Same methodology as 6b, using benzenethiol (1.86 mmol, 0.190 mL). After workup, 418 mg of the expected product, 6d as a yellow oil in 99% yield. 1H NMR (500 MHz), Chloroform-d δ (ppm): 8.70 (d, J = 4.8 Hz, 1H), 7.93 (s, 1H), 7.87 (d, J = 7.6 Hz, 1H), 7.76–7.72 (m, 2H), 7.67 (d, J = 8.0 Hz, 1H), 7.39 (dd, J = 7.6, 7.6 Hz, 1H), 7.36–7.33 (m, 2H), 7.27–7.21 (m, 3H), 7.20–7.16 (m, 1H), 4.20 (s, 2H). 13C NMR (126 MHz), Chloroform-d δ (ppm): 157.2, 149.6, 139.6, 138.0, 136.7, 130.0 (2C), 129.3 (2C), 128.9, 128.8 (2C), 127.4, 126.4, 125.8, 122.1, 39.2.
2-(3-[(4-Methylphenyl)sulfanyl]methylphenyl)pyridine, 6e. Under an argon atmosphere, 4-methylbenzenethiol (0.70 mmol, 87 mg) and trimethylamine (0.70 mmol, 0.099 mL) were dissolved in dry EtOH (2 mL) and stirred at room temperature in a sealed microwave vial for 15 min. 2-[3-(Bromomethyl)phenyl]pyridine, 5 (0.44 mmol, 110 mg) in dry EtOH (2 mL) was then added and the mixture was stirred under microwave irradiation (maximum power, 300 W, dynamic heating) at 150 °C for 20 min. After cooling, the solvent was removed in vacuo and the crude mixture diluted with H2O (25 mL) and EtOAc (25 mL). The product was extracted with EtOAc (2 × 25 mL), washed with H2O (2 × 25 mL) and brine (25 mL). The organic layers were dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (8:2 hexane:Et2O) yielding 65 mg of the expected product, 6e as a yellow oil in 51% yield. 1H NMR (500 MHz), Chloroform-d δ (ppm): 8.70 (d, J = 4.8 Hz, 1H), 7.90 (s, 1H), 7.87 (d, J = 7.6 Hz, 1H), 7.72 (m, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.39 (dd, J = 7.6, 7.6 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H), 7.25 (d, J = 8.1 Hz, 2H), 7.21 (ddd, J = 7.4, 4.8, 1.2 Hz), 7.06 (d, J = 8.1 Hz, 2H), 4.15 (s, 2H), 2.30 (s, 3H). 13C NMR (126 MHz), Chloroform-d δ (ppm): 157.2, 149.6, 139.6, 138.3, 136.6, 132.4, 131.5, 130.9 (2C), 129.6 (2C), 129.3, 128.8, 127.4, 125.7, 122.1, 120.5, 39.9, 21.0. HRMS (m/z). Calc. for [C19H17NS + H]+ 292.1154. Found 292.1151.
2-(3-[(4-Methoxyphenyl)sulfanyl]methylphenyl)pyridine, 6f. Same method as 6b, using 4-methoxybenzenethiol (1.10 mmol, 0.136 mL). The crude product was purified using flash column chromatography (9:1 DCM:hexane) yielding 203 mg of the expected product, 6f as a yellow oil in 60% yield. 1H NMR (500 MHz), Chloroform-d δ (ppm): 8.69 (ddd, J = 4.8, 1.8, 0.9 Hz, 1H), 7.86 (d, J = 7.7 Hz, 1H), 7.81 (s, 1H), 7.73 (ddd, J = 9.7, 7.9, 1.8 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1H), 7.37 (dd, J = 7.7, 7.7 Hz, 1H), 7.28 (d, J = 8.8 Hz, 2H), 7.25–7.21 (m, 2H), 6.79 (d, J = 8.8 Hz, 2H), 4.07 (s, 2H), 3.76 (s, 3H). 13C NMR (126 MHz), Chloroform-d δ (ppm): 159.3, 157.2, 149.6, 139.5, 138.6, 136.6, 134.2 (2C), 129.4, 128.8, 127.5, 126.0 (2C), 125.6, 122.1, 120.6, 114.5, 55.3, 41.3. HRMS (m/z). Calc. for [C19H17NOS + H]+ 308.1104. Found 308.1109.
2-3-[(Ethylsulfanyl)methyl]phenylpyridine chloro-palladacycle, 1b. Under an argon atmosphere, PdCl2 (1.17 mmol, 208 mg) was dissolved in dry MeCN (10 mL) and heated under reflux until a red solution had formed. AgBF4 (2.36 mmol, 460 mg) in dry MeCN (5 mL) was added to the PdCl2 solution and heated under reflux for 2 h, forming a white precipitate. The precipitate was filtered off, and 6b (1.13 mmol, 260 mg) dissolved in dry MeCN (10 mL), was added to the filtrate and heated under reflux for 4 h. The solution was cooled to room temperature, filtered over celite, and the solvent removed in vacuo. The crude solid was dissolved in MeCN (5 mL), and NaCl (26.0 mmol, 1.52 g) dissolved in H2O (5 mL) was added, and stirred at room temperature for 3 h. The solvent was removed in vacuo, and the crude mixture dissolved in DCM (25 mL) and H2O (25 mL). The crude product was extracted with DCM (2 × 25 mL), washed with H2O (2 × 25 mL) and brine (25 mL), and dried over anhydrous Na2SO4. The mixture was filtered over celite, and the solvent removed in vacuo, yielding 347 mg of the expected product, 1b as a yellow solid in 83% yield. 1H NMR (500 MHz), Chloroform-d δ (ppm): 9.15 (d, J = 5.5 Hz, 1H), 7.84 (ddd, J = 7.8, 7.8 Hz, 1H), 7.64 (d, J = 7.8 Hz, 1H), 7.33 (d, J = 7.7 Hz, 1H), 7.26–7.23 (m, 1H), 7.08 (dd, J = 7.7, 7.7 Hz, 1H), 7.03 (d, J = 7.7 Hz, 1H), 4.25 (bs, 2H), 3.20 (q, J = 7.4 Hz, 2H), 1.57 (t, J = 7.4 Hz, 3H). 13C NMR (126 MHz), Chloroform-d δ (ppm): 165.5, 165.3, 150.5, 148.1, 144.4, 139.0, 125.0, 124.7, 122.9, 122.2, 118.7, 45.8, 33.8, 14.8. HRMS (m/z). Calc. for [C14H14NPdS]+ 333.9876. Found 333.9878. Elemental Analysis. Calc. (%) for C14H14NPdSCl: C 45.42, H 3.81, N 3.78; found C 45.50, H 3.75, N 3.83.
2-3-[(Propylsulfanyl)methyl]phenylpyridine chloro-palladacycle, 1c. Same method as 1b using 6c (0.55 mmol, 113 mg), yielding 179 mg of the expected product, 1c as a yellow solid in 85% yield. 1H NMR (500 MHz), Chloroform-d δ (ppm): 9.11 (d, J = 5.5 Hz, 1H), 7.82 (ddd, J = 7.8, 7.8, 1.7 Hz, 1H), 7.62 (d, J = 7.7 Hz, 1H), 7.30 (d, J = 7.8 Hz, 1H), 7.22 (ddd, J = 7.5, 5.5, 1.3 Hz, 1H), 7.05 (dd, 7.7, 7.7 Hz, 1H), 7.00 (d, J = 7.7 Hz, 1H), 4.27 (bs, 2H), 3.15 (t, J = 7.8 Hz, 2H), 1.96 (m, 2H), 1.07 (t, J = 7.4 Hz, 3H). 13C NMR (126 MHz), Chloroform-d δ (ppm): 165.5, 165.3, 150.5, 148.1, 144.4, 139.0, 125.0, 124.6, 122.9, 122.1, 118.7, 46.6, 41.4, 23.3, 13.3. HRMS (m/z). Calc. for [C15H16NPdS]+ 348.0033. Found 348.0032. Elemental Analysis. Calc. (%) for C15H16NPdSCl: C 46.89, H 4.20, N 3.65; found: C 47.02, H 4.08, N 3.56.
2-3-[(Phenylsulfanyl)methyl]phenylpyridine chloro-palladacycle, 1d. Same method as 1b using 6d (1.51 mmol, 418 mg). The crude product was purified using flash column chromatography (100% consisting of 98:2 DCM:MeOH) yielding 446 mg of the expected product 1d as a yellow solid in 71% yield. 1H NMR (500 MHz), Chloroform-d δ (ppm): 9.14 (d, J = 5.5 Hz, 1H), 7.91–7.89 (m, 2H), 7.83 (ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.62 (d, J = 7.7 Hz, 1H), 7.36–7.33 (m, 3H), 7.29 (d, J = 7.7 Hz, 1H), 7.20 (ddd, J = 7.7, 5.5, 1.2 Hz, 1H), 7.06 (dd, J = 7.7, 7.7 Hz, 1H), 7.00 (d, J = 7.7 Hz, 1H), 4.63 (s, 2H). 13C NMR (126 MHz), Chloroform-d δ (ppm): 166.0, 165.5, 150.8, 147.8, 144.6, 139.1, 132.8, 131.9 (2C), 129.9, 129.6 (2C), 124.9, 124.8, 122.9, 122.3, 118.8, 53.1. HRMS (m/z). Calc. for [C18H14NPdS]+ 381.9876. Found 381.9876. Elemental Analysis. Calc. (%) for C18H14NPdSCl: C 51.69, H 3.37, N 3.35; found C 51.50, H 3.28, N 3.41.
2-(3-[(4-Methylphenyl)sulfanyl]methylphenyl)pyridine, 1e. Same method as 1b, using 6e (0.54 mmol, 158 mg). 1H NMR (500 MHz), Chloroform-d δ (ppm): 9.19 (d, J = 5.5 Hz, 1H), 7.84 (dd, J = 7.6, 7.6 Hz, 1H), 7.79 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 7.6 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.23–7.21 (m, 1H), 7.16 (d, J = 8.1 Hz, 2H), 7.08 (dd, J = 7.6, 7.6 Hz, 1H), 7.00 (d, J = 7.6 z, 1H), 4.60 (bs, 2H), 2.32 (s, 3H). 13C NMR (126 MHz), Chloroform-d δ (ppm): 166.0, 165.5, 150.7, 147.9, 144.5, 140.4, 139.1, 132.0 (2C), 130.3 (2C), 129.4, 124.8, 122.9, 122.2, 118.8, 53.5, 21.2. HRMS (m/z). Calc. for [C19H16NPdS]+ 396.0033. Found 396.0050. Elemental Analysis. Calc. (%) for C19H16NPdSCl: C 52.63, H 3.84, N 3.29; found C 52.79, H 3.73, N 3.24.
2-(3-[(4-Methoxyphenyl)sulfanyl]methylphenyl)pyridine, 1f. Same method as 1b, using 1e (0.62 mmol, 190 mg). 1H NMR (500 MHz), Chloroform-d δ (ppm): 9.18 (d, J = 5.5 Hz, 1H), 7.86–7.83 (m, 3H), 7.65 (d, J = 7.9 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.23 (ddd, J = 7.6, 5.5, 1.4 Hz, 1H), 7.08 (dd, J = 7.6, 7.6 Hz, 1H), 6.99 (d, J = 7.6 Hz, 1H), 6.87 (d, J = 8.9 Hz, 1H), 4.58 (s, 2H), 3.77 (s, 3H). 13C NMR (126 MHz), Chloroform-d δ (ppm): 165.9, 165.5, 161.2, 150.8, 147.8, 144.5, 139.1, 134.0 (2C), 124.8, 123.5, 122.9, 122.2, 118.8, 115.1 (2C), 55.5, 54.4. HRMS (m/z). Calc. for [C19H16NOPdS]+ 411.9982. Found 411.9991. Elemental Analysis. Calc. (%) for C19H16NOPdSCl: C 50.91, H 3.60, N 3.12; found C 50.80, H 3.47, N 3.19.