Table 1.
Optimization of the reaction conditions.a
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| Entry | Solvent | Cat. (5 mol %) | T (°C) | t (h) | Yield 3aa (%)b | drc |
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| 1 | CH2Cl2 | – | rt | 96 | 52 | 5:1 |
| 2 | toluene | – | rt | 120 | 48 | 6:1 |
| 3 | ClCH2CH2Cl | – | rt | 96 | 51 | 6:1 |
| 4 | toluene | – | 50 | 72 | 50 | 5:1 |
| 5 | ClCH2CH2Cl | – | 50 | 48 | 55 | 5:1 |
| 6 | toluene | – | 70 | 24 | 66 | 7:1 |
| 7 | ClCH2CH2Cl | – | 70 | 24 | 59 | 7:1 |
| 8 | CHCl3 | – | 70 | 24 | 46 | 6:1 |
| 9 | EtOAc | – | 70 | 24 | 26 | 6:1 |
| 10 | THF | – | 70 | 24 | 65 | 3.5:1 |
| 11 | acetone | – | 70 | 24 | n. d. | – |
| 12 | CH3CN | – | 70 | 24 | 58 | 3:1 |
| 13d | toluene | – | 70 | 24 | 64 | 7:1 |
| 14d | toluene | SQ-1 | 70 | 24 | 61 | 7:1 |
| 15d | toluene | SQ-1 | 50 | 24 | 73 | 7:1 |
| 16d | toluene | THIO-1 | 50 | 24 | 55 | 4:1 |
| 17d,e | toluene | – | 70 | 24 | 44 | 7:1 |
| 18d,e | toluene | SQ-1 | 50 | 24 | 61 | 7:1 |
aReaction conditions: 3aa (0.1 mmol) and 4a (0.3 mmol) in 1 mL of solvent at T (°C); bisolated yield after column chromatography; cdetermined by 1H NMR of the crude reaction mixture; dreaction conditions: 3aa (0.2 mmol) and 4a (0.6 mmol) in 1 mL of solvent at T (°C); e50 mg of molecular sieves 4 Å were used.