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4 and the volatiles were removed under reduced pressure. The residue was purified by flash chromatography.
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4 and the volatiles were removed under reduced pressure. The residue was purified by flash chromatography.
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Determination of the Kinetic Isotope Effects According to the general experimental procedure with 2-(2-deuterophenyl)pyridine (D-1, 39 mg, 0.25 mmol) and phenylboronic acid (122 mg, 1.00 mmol) for 72 h. Flash chromatography (pentane-EtOAc, 20:1 → 10:1) gave a mixture of 2a and D-2a as a yellow oil (17 mg, 65, The isotope effect was determined by integration of the ESI-HRMS data in consideration of the isotope pattern of 2a. The deuterated species D-2a and compound 2a were obtained in a ratio of 4.5:1. According to GP 1 with 2-ethoxy-2-phenylpyridine (6, 10 mg, 50 μmol, 2-(2-ethoxy-6-deuterophenyl)pyridine (D-6, 10 mg, 50 μmol) and phenylboronic acid (24 mg, 0.2 mmol) for 4 h. The ratios of D-6 to 6 (0.87:1) were determined before the reaction (0 h) and after a reaction time of 4 h (1.05:1) by integration of the corresponding ESI-HRMS data in consideration of the isotope pattern of 6. The k
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Determination of the Kinetic Isotope Effects According to the general experimental procedure with 2-(2-deuterophenyl)pyridine (D-1, 39 mg, 0.25 mmol) and phenylboronic acid (122 mg, 1.00 mmol) for 72 h. Flash chromatography (pentane-EtOAc, 20:1 → 10:1) gave a mixture of 2a and D-2a as a yellow oil (17 mg, 65%). The isotope effect was determined by integration of the ESI-HRMS data in consideration of the isotope pattern of 2a. The deuterated species D-2a and compound 2a were obtained in a ratio of 4.5:1. According to GP 1 with 2-ethoxy-2-phenylpyridine (6, 10 mg, 50 μmol), 2-(2-ethoxy-6-deuterophenyl)pyridine (D-6, 10 mg, 50 μmol) and phenylboronic acid (24 mg, 0.2 mmol) for 4 h. The ratios of D-6 to 6 (0.87:1) were determined before the reaction (0 h) and after a reaction time of 4 h (1.05:1) by integration of the corresponding ESI-HRMS data in consideration of the isotope pattern of 6. The kinetic isotope effect was calculated to be 1.21.
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As a side product the doubly arylated product is always formed <15% with respect to the monoarylated compound, We assume that the primary kinetic isotope effect for the second arylation and the first arylation should be similar. Therefore, the measured value of 4.5 is slightly too high since 2a is consumed faster than D-2a. However, the error should be smaller than 12, Hence the primary kinetic isotope effect for the first arylation is about 4.0-4.5 to 1
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As a side product the doubly arylated product is always formed (<15% with respect to the monoarylated compound). We assume that the primary kinetic isotope effect for the second arylation and the first arylation should be similar. Therefore, the measured value of 4.5 is slightly too high since 2a is consumed faster than D-2a. However, the error should be smaller than 12%. Hence the primary kinetic isotope effect for the first arylation is about 4.0-4.5 to 1.
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2-(2,6-Dideuterophenyl)pyridine (D2-1) and 2-(2,6-Dibromophenyl)pyridine 2-(2-Bromophenyl)pyridine22 (466 mg, 2.0 mmol, Cu(OAc)2 (363 mg, 2.0 mmol, and 1,1,2,2-tetra- bromoethane were heated in a sealed reaction tube at 130°C for 24 h. 23 Dichloromethane (10 mL) and Na2S (aq sat, 10 mL) were added. The mixture was filtered over Celite and the filtrate was washed with brine (2 x 10 mL, The combined organic layers were dried over MgSO4 and the volatiles were removed under reduced pressure. The residue was purified by flash chromatography (pentane-MTBE, 20:1, 2-(2-Bromo-6-deuterophenyl) pyridine To a solution of 2-(2,6-dibromophenyl)pyridine (313 mg, 1.0 mmol) in THF (20 mL) at -78°C was added dropwise n-BuLi (1.68 M solution in hexanes, 0.60 mL, 1.00 mmol).23 The mixture was stirred for 30 min. Then, D2O (2.0 mL) was added and stirring was continued for additional 30
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Kalyani, D.1
Dick, A.R.2
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Sanford, M.S.4
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Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128, 6790.
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Yu, J.-Q.4
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