[Synthesis]
The methylation reaction was carried out by General Method 2 using 2-ethylpyridine and trimethylcyclotriboroxane as raw materials. Upon completion of the reaction, the products were purified by column chromatography to give two products: 21 (2-propylpyridine) as a colorless oil (19.1 mg, 79% yield) and 13a (2-isobutylpyridine) as a colorless oil (3.0 mg, 11% yield).
The NMR data for 21 (2-propylpyridine) are as follows:
1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 4.8 Hz, 1H), 7.58 (td, J = 7.6, 1.6 Hz, 1H), 7.14 (d, J = 8.0 Hz, 1H), 7.11-7.08 (m, 1H), 2.77 (t, J = 7.6 Hz, 2H), 1.81-1.71 (m, 2H), 0.97 (t, J = 7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ 162.35, 149.26, 136.25, 122.83, 120.94, 40.49, 23.19, 13.94;
HRMS (EI): calculated value C8H11N (M+) 121.0891, measured value 121.0893.
The NMR data of 13a (2-isobutylpyridine) are as follows:
1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 4.4 Hz, 1H), 7.58 (td, J = 7.6, 1.6 Hz, 1H), 7.12-7.08 (m, 2H), 2.65 (d, J = 7.6 Hz, 2H), 2.15-2.05 (m, 1H), 0.93 (d, J = 6.8 Hz, 6H); 13C NMR (100 MHz).
13C NMR (100 MHz, CDCl3) δ 161.89, 149.50, 136.34, 123.81, 121.19, 47.93, 29.57, 22.74;
HRMS (EI): calculated value C9H13N (M+) 135.1048, measured value 135.1046.
Reaction conditions: in a 40 mL reaction tube, the substrate (0.2 mmol, 1 eq.), Pd(OAc)2 (4.5 mg, 0.02 mmol, 10 mol%), methyl cycloboroxane (55.7 μL, 0.4 mmol, 2 eq.), Cu(OAc)2 (72.8 mg, 0.4 mmol, 2 eq.) and benzoquinone (43.2 mg, 0.4 mmol, 2 eq.) were mixed together. 0.4 mmol, 2 eq.) were dissolved in 1 mL of acetic acid and reacted under oxygen atmosphere. The reaction tube was sealed with a PTFE-lined cap and the reaction mixture was stirred at 100 °C for 24 hours. After completion of the reaction, it was neutralized to pH=8-9 with 4N NaOH aqueous solution and then treated with 10 mL of saturated Na2S aqueous solution. The mixture was filtered through a diatomaceous earth pad and the diatomaceous earth was washed with 20 mL of dichloromethane. The filtrate was washed twice with saturated brine and the organic layer was dried with Na2SO4 and concentrated in vacuum. The residue was purified by silica gel column chromatography (eluent: hexane:ether=10:1) to give the methylated product. |