Table 1.
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entry | catalyst system | catalyst loading | solvent | molarity | base | reaction time | isolated yield | ratio 5a:6aa |
1 | PdCl2(dppf)·CH2Cl2 | 2 mol % | THF/H2O (9:1) | 0.1 | Cs2CO3 | 22 h | 63 | 100:0 |
2 | PdCl2(dppf)·CH2Cl2 | 2 mol % | i-PrOH/H2O (9:1) | 0.1 | NEt3 | 22 h | 23 | 100:0 |
3 | PdCl2(dppf)·CH2Cl2 | 2 mol % | Toluene/H2O (9:1) | 0.1 | Cs2CO3 | 22 h | -- | 20:80 |
4 | PdCl2(dppf)·CH2Cl2 | 5 mol % | THF/H2O (9:1) | 0.1 | Cs2CO3 | 18 h | 30 | 100:0 |
5 | Pd(PPh3)4 | 2 mol % | THF/H2O (9:1) | 0.1 | Cs2CO3 | 40 h | 62 | 100:0 |
6 | Pd(OAc)2 + 2 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.1 | Cs2CO3 | 45 h | 78 | 92:8 |
7 | Pd(OAc)2 + 3 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.1 | Cs2CO3 | 45 h | 72 | 97:3 |
8 | PdCl2(CN)2 + 2 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.1 | Cs2CO3 | 45 h | 69 | 95:5 |
9 | PdCl2(CN)2 + 3 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.1 | Cs2CO3 | 45 h | 70 | 96:4 |
10 | PdCl2 + 2 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.1 | Cs2CO3 | 45 h | 72 | 95:5 |
11 | PdCl2 + 3 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.5 | Cs2CO3 | 22 h | 72 | 100:0 |
12 | PdCl2 + 2 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.5 | Cs2CO3 | 22 h | 68 | 100:0 |
13 | PdCl2 + 3 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.5 | K3PO4 | 22 h | 67 | 92:8 |
14 | PdCl2 + 3 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.5 | KHCO3 | 22 h | 62 | 82:18 |
15 | PdCl2 + 3 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.5 | K2CO3 | 22 h | 67 | 97:3 |
16 | PdCl2 + 3 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.5 | pyridine | 22 h | -- | 20:80 |
17 | PdCl2 + 3 equiv PPh3 | 2 mol % | THF/H2O (9:1) | 0.5 | NEt3 | 22 h | -- | 55:45 |
Ratio of 5a:6a in isolated material by GC assay.