Table 2. Optimization of Reaction Conditiona.
| entry | base | concn (M) | solvent (PhCH3:H2O) | temp. (°C) | time (h) | yield (%)b | ee (%)c |
|---|---|---|---|---|---|---|---|
| 1 | KOH | 0.15 | 8:1 | 25 | 1 | 50 | 83 |
| 2 | KOH | 0.15 | 8:1 | 0 | 1 | 71 | 85 |
| 3 | KOH | 0.15 | 8:1 | –20 | 1 | 84 | 87 |
| 4 | KOH | 0.10 | 8:1 | –20 | 2 | 96 | 92 |
| 5 | KOH | 0.05 | 8:1 | –20 | 2 | 92 | 93 |
| 6 | KOH | 0.025 | 8:1 | –20 | 5 | 85 | 92 |
| 7 | KOH | 0.05 | 8:1 | –40 | 4 | 92 | 93 |
| 8 | KOH | 0.05 | 16:1 | –40 | 4 | 92 | 93 |
| 9 | KOH | 0.05 | 32:1 | –40 | 4 | 92 | 93 |
| 10 | K2CO3 | 0.05 | 8:1 | –20 | 48 | 75 | 92 |
| 11 | Cs2CO3 | 0.05 | 8:1 | –20 | 24 | 70 | 92 |
| 12 | K3PO4 | 0.05 | 8:1 | –20 | 4 | 81 | 92 |
| 13d | KOH | 0.05 | 8:1 | –20 | 24 | 85 | –81 |
a
Reactions were performed with 2.0 equiv of tert-butyl carbamate 8 and 1.2 equiv of base under the given conditions.
b
Isolated yields.
c
Enantiopurity was determined by high-performance liquid chromatography (HPLC) analysis using a chiral column (DAICEL Chiralpak AD-H).
d
Reactions were performed with catalyst 10, and the enantiomer of 11a was obtained.