Table 2. Optimization of the Reaction Conditions for the Transannular Amidobromination/Elimination Process Using 5a as the Model Compound.
| entry | catalyst | solvent | time (min) | yield (%)a |
|---|---|---|---|---|
| 1 | none | toluene | 60 | 78 |
| 2 | TFA | toluene | 30 | 67 |
| 3 | (PhO)2P(O)OH | toluene | 30 | 90 |
| 4 | (PhO)2P(O)NHTf | toluene | 15 | 66 |
| 5 | (±)-CSA | toluene | 20 | 67 |
| 6 | (PhO)2P(O)OH | THF | 30 | 36 |
| 7 | (PhO)2P(O)OH | MeCN | 30 | 85 |
| 8 | (PhO)2P(O)OH | CH2Cl2 | 30 | 96 |
| 9 | (PhO)2P(O)OH | CHCl3 | 30 | 83 |
| 10 | (PhO)2P(O)OH | DCE | 30 | 73 |
| 11b | (PhO)2P(O)OH | CH2Cl2 | 5 | 54 |
| 12c | (PhO)2P(O)OH | CH2Cl2 | 60 | 98 |
| 13d | (PhO)2P(O)OH | CH2Cl2 | 120 | 83 |
| 14 | none | CH2Cl2 | 300 | 39 |
a
Yield of pure product 6a after flash column chromatography purification.
b
Reaction carried out at 50 °C.
c
Reaction carried out using 2.5 mol % of the catalyst.
d
Reaction carried out using 1 mol % of the catalyst.