Table 1. Initial Exploration of the Regioselective Deprotonation/Oxidation of Amorphadiene.
| entrya | R-Li (equiv) | additive (equiv) | KOtBu (equiv) | solvent | temp (°C) | time (h) | conversion of AD (%)b | yield (%)c | 3:6d |
|---|---|---|---|---|---|---|---|---|---|
| 1 | n-BuLi (0.67) | TMEDA (0.67) | none | hexanes | 0 | 16 | 35 | ND | 3:1 |
| 2 | s-BuLi (0.67) | TMEDA (0.67) | none | cyclohexane | 0 | 16 | 6 | ND | 5:1 |
| 3 | n-BuLi (1.0) | none | 1.0 | hexanes | 0 | 24 | 25 | ND | 2:1 |
| 4 | n-BuLi (1.0) | none | none | THF | –78 | 1 | <5 | ND | ND |
| 5 | n-BuLi (1.2) | none | 1.2 | THF | –78 | 1 | <5 | ND | ND |
| 6 | n-BuLi (1.2) | TMP (1.2) | none | THF | –78 | 1 | <5 | ND | ND |
| 7 | n-BuLi (1.2) | TMP (1.2) | 1.2 | THF | –78 | 1 | 72 | 60 | >20:1 |
| 8 | n-BuLi (1.5) | TMP (1.5) | 1.5 | THF | –78 | 1 | 78 | 72 | >20:1 |
| 9 | n-BuLi (2.0) | TMP (2.0) | 2.0 | THF | –78 | 1 | 89 | 81 | >20:1 |
| 10 | n-BuLi (2.0) | TMP (2.0) | 2.0 | THF | –40 | 1 | <5 | ND | ND |
| 11 | n-BuLi (2.0) | TMP (2.0) | 2.0 | THF | –25 | 1 | <5 | ND | ND |
| 12 | n-BuLi (3.0) | TMP (3.0) | 3.0 | heptane | 23 | 24 | 68 | 39 | 3:1 |
a
All reactions performed on a 0.5 mmol scale of AD at 0.1 M concentration with 1 equiv of B(OiPr)3 and 2 equiv of H2O2 relative to n-BuLi.
b
Determined via 1H NMR analysis of crude reaction mixtures by comparing the relative amounts of AD to 3 and 6 combined.
c
Isolated yields.
d
Ratios determined on crude reaction mixtures by 1H NMR.