TABLE 1.
Effect of Reaction Conditions on Condensation Reactions of 3 with 2-Naphthaldehyde
 | |||||||
|---|---|---|---|---|---|---|---|
| entry | base | solvent | aldehyde:sulfone: base (molar equiv) | additive (molar equiv) | T, rxn time (h) | (%) E/Z ratio;a yieldb | |
| 1 | DBU | CH2Cl2 | 1.0:1.2:4.0 | -- | rt, 2 | 33/67; 90% | |
| 2 | DBU | CH2Cl2 | 1.0:1.2:4.0 | -- | −78 °C, 3.5 | 50/50; 96% | |
| 3 | DBU | THF | 1.0:1.2:4.0 | -- | rt, 2 | 19/81; 84% | |
| 4 | DBU | THF | 1.0:1.2:4.0 | -- | −78 °C, 4 | 4/96; 84% | |
| 5 | DBU | PhMe | 1.0:1.2:4.0 | -- | rt, 48 | 16/84; NAc | |
| 6 | DBU | DMF | 1.0:1.3:2.6 | -- | rt, 20 | 74/26; NAc | |
| 7 | DBU | DMF | 1.3:1.0:2.0 | -- | rt, 15 | 74/26; NAc | |
| 8 | DBU | DMPU | 1.3:1.0:2.0 | -- | rt, 17 | 78/22; 93% | |
| 9 | DBU | DMF-DMPUd | 1.3:1.0:2.0 | -- | −78 °C, 3.5 | 25/75; NAc | |
| 10 | DBU | DMPU | 1.3:1.0:2.0 | -- | 75 °C, 2.5 | 78/22; NAc | |
| 11 | DBU | THF | 1.0:1.3:3.9 | MgBr2 (1.8) | rt, 48 | 10/90; 78% | |
| 12 | DBU | THF | 1.2:1.0:3.0 | MgBr2 (1.4) | rt, 48 | 7/93; 78% | |
| 13 | DBU | THF | 1.2:1.0:3.0 | ZnBr2 (1.4) | rt, 48 | 15/85; 74% | |
| 14 | NaH | THF | 1.0:1.3:2.6 | -- | rt, 20; 70 °C, 2 | Only Z, 84% | |
| 15 | NaH | THF | 1.0:2.0:4.0 | -- | rt, 1 | Only Z, 90% | |
| 16 | NaH | THF | 1.0:2.0:4.0 | 18-Crown-6 (6.0) | rt, 1.5 | 40/60, NAc | |
| 17 | NaH | THF | 1.0:2.0:4.0 | 15-Crown-5 (6.0) | rt, 1.5 | 12/88, NAc | |
| 18e | K2CO3 | DMF | 1.0: 2.0:18.0 | TBAB (0.2) | rt, 18 | 55/45, NAc | |
a
Relative ratio of diastereomers in the crude reaction mixture determined by 19F NMR prior to isolation. No change in ratio was observed after purification.
b
Yields of isolated, purified products.
c
Product not isolated from reaction mixture.
d
A 1:1 mixture of DMF and DMPU was used to prevent freezing at −78 °C.
e
Reaction conditions were identical to those described in ref. 11.