Table 2. Optimization of Reaction Conditions for Reduction of Compound 4a.
| entry | reductant (g, equiv) | addictive (g, equiv) | solvent | temp. (°C) | yield (%)b | 5/Imp-6c |
|---|---|---|---|---|---|---|
| 1 | NaBH4 (0.1, 1.03) | / | THF/MeOH (1:1, v-v) | 25 | 89 | 79/21 |
| 2 | NaBH4 (0.1, 1.03) | AcOH (0.01, 0.06) | THF/MeOH (1:1, v-v) | 25 | 89 | 85/15 |
| 3 | NaBH4 (0.1, 1.03) | H2O (0.01, 0.22) | THF/MeOH (1:1, v-v) | 25 | 93 | 88/12 |
| 4 | NaBH4 (0.1, 1.03) | CaCl2·6H2O (0.1, 0.18) | THF/MeOH (9:1, v-v) | 25 | 92 | 91/9 |
| 5 | NaBH4 (0.1, 1.03) | MnCl2·H2O (0.1, 0.27) | THF/MeOH (9:1, v-v) | 25 | 89 | 92/8 |
| 6 | NaBH4 (0.1, 1.03) | MnCl2·H2O (0.1, 0.27) | THF/H2O (9:1, v-v) | 25 | 89 | 93/7 |
| 7 | NaBH4 (0.1, 1.03) | CeCl3·7H2O (0.1, 0.10) | THF/H2O (9:1, v-v) | 25 | 90 | 94/6 |
| 8 | KBH4 (0.15, 1.08) | CeCl3·7H2O (0.1, 0.10) | THF/H2O (9:1, v-v) | 25 | 93 | 94/6 |
| 9 | KBH4 (0.15, 1.08) | MnCl2·H2O (0.1, 0.27) | THF/H2O (9:1, v-v) | 10 | 95 | 96/4 |
| 10d | KBH4 (22.5, 2.16) | MnCl2·H2O (7.5, 0.27) | THF/H2O (9:1, v-v) | 10 | 96 | 97/3 |
a
Reaction conditions: compound 4 (1.0 g), catalyst, Lewis acid, solvent: 10 mL, 3 h.
b
The yield is crude (5 and Imp-6).
c
The ratio of the isomer was determined by HPLC equipped with an RI detector.
d
Compound 4 (75.0 g), solvent, 500 mL.