Table 2. Optimization of Reaction Conditions for the Intramolecular Cyclizationa.
| entry | X | base | yield (%)b | ee of 3 (%)c | ee of 4a (%)c |
|---|---|---|---|---|---|
| 1 | Cl | K3PO4 | 10 | 95 | ND |
| 2 | Cl | DBU | 0 | 95 | ND |
| 3 | Cl | Cs2CO3 | 0 | 95 | ND |
| 4 | Br | DMAP | 0 | 65 | ND |
| 5 | Br | DBU | 82 | 65 | 22 |
| 6 | Br | KOtBu | 86 | 65 | 57 |
| 7 | Br | Cs2CO3 | 90 | 65 | 65 |
| 8d | Cl | KOtBu | 71 | 95 | 84 |
| 9e,f | Cl | Cs2CO3 | 97 | 93 | 93 |
a
Reaction Conditions: 3 (1.0 equiv), base (4.0 equiv), ethyl acetate.
b
Isolated yield.
c
Determined by chiral HPLC analysis.
d
THF used as solvent.
e
DMF used as solvent.
f
Base added at 0 °C.