Table 4.
Screening of Demethylation Conditions of Rubellin Precursor 110
| ||||||
|---|---|---|---|---|---|---|
| entry | solvent | reagent (equiv) | additive (equiv) | temp (°C) | time (h) | products observed |
| 1 | CH2Cl2 | BBr3 (10) | −78 | 1 h | C23 O-demethylation | |
| 2 | CH2Cl2 | BBr3 (10) | −78–0 | 2 h | decomposition | |
| 3 | CH2Cl2 | BBr3 (10) | −78 | 4 h | C23 O-demethylation; decomposition | |
| 4 | CH2Cl2 | BBr3 (3) | −78 | 15 | C23 O-demethylation | |
| 5 | CH2Cl2 | BBr3 (10) | −40 | 1 | C23 O-demethylation; decomposition | |
| 6 | CH2Cl2 | BBr3 (10) | amylene (11) | −40 | 1 | C23 O-demethylation; decomposition |
| 7 | None | Pyr-HCl (200) | 200 | 1 | decomposition | |
| 8 | CH2Cl2 | BCl3 (10) | 0 | 24 | C23 O-demethylation; decomposition | |
| 9 | CHCl3 | TMSl (4) | 0 | 0.5 | C1/8 O-demethylation; decomposition | |
| 10 | CH2Cl2 | AlCl3 (10) | 23 | 5 | mixture of demethylated epimers | |
| 11 | CH2Cl2 | AlCl3 (10) | EtSH (10) | 0 | 0.25 | C1/8 O-demethylation; decomposition |
| 12a | THF | MgI2·OEt2 (10) | 50 | 3 | C1/8 O-demethylation; epimerization | |
| 13 | PhMe | MgI2·OEt2 (12) | 100 | 2 | 112 major; not full conversion | |
| 14 | PhMe | MgI2·OEt2 (14) | 100 | 3 | 112 | |
a
Initial experiments with MgI2·OEt2 were allowed to cool for 30 min to 1 h before quenching. This gave epimerization of the C18 center as well as iodinated byproducts. Entries 13 and 14 were quenched within 10–15 min of removal from the heating oil bath.