Table 3. Selected Optimization for the Zinc-Mediated CAA Reaction.
| entrya | Zn (equiv) | solvent | additive | yield (%)a |
|---|---|---|---|---|
| 1 | 2.0 | EtOAc (0.4 M) | - | 9 |
| 2 | 2.0 | CH2Cl2 (0.4 M) | - | 53 |
| 3 | 2.0 | toluene (0.4 M) | - | 14 |
| 4 | 2.0 | EtOAc (0.4 M) | CuI (10 mol %) | 41 |
| 5 | 2.0 | CH2Cl2 (0.4 M) | CuI (10 mol %) | 59 |
| 6 | 3.0 | toluene (0.4 M) | CuI (10 mol %) | 51 |
| 7 | 3.0 | CH2Cl2 (0.8 M) | CuI (10 mol %) | 51 |
| 8 | 3.0 | toluene (1.6 M) | CuI (10 mol %) | 61 |
| 9 | 3.0 | toluene (1.6 M) | CuI (10 mol %), H2O (1.5 equiv) | 73 |
| 10 | 3.0 | CH2Cl2 (1.6 M) | CuI (10 mol %), H2O (1.5 equiv) | 72 |
| 11 | 3.0 | toluene (1.6 M) | CuI (10 mol %), H2O (1.5 equiv) | 93 |
| 12 | 3.0 | toluene (1.6 M) | CuI (10 mol %), H2O (1.5 equiv) | 100 |
a
Yields of 17a were determined by 1H NMR using 1,1,2,2 tetrachloroethane as an internal standard.