Condition optimizationa.
| ||||||
|---|---|---|---|---|---|---|
| Entry | Solvent | Base/L | [Pd] | Yieldb (%) | drb | eec (%) |
| Major/minor | ||||||
| 1 | THF | DBU/L1 | Pd(dba)2 | 94 | 14.7 : 1 | 98/31 |
| 2d | THF | DBU/L1 | Pd(dba)2 | >95 | 12.7 : 1 | 97/59 |
| 3e | THF | DBU/L1 | Pd(dba)2 | >95 | 12.7 : 1 | 97/30 |
| 4 | MeCN | DBU/L1 | Pd(dba)2 | 91 | 14.2 : 1 | 98/42 |
| 5 | DMF | DBU/L1 | Pd(dba)2 | 90 | 14.0 : 1 | 97/11 |
| 6 | Toluene | DBU/L1 | Pd(dba)2 | >95 | 11.4 : 1 | 96/69 |
| 7 | THF | Et3N/L1 | Pd(dba)2 | 92 | 5.1 : 1 | 90/83 |
| 8 | THF | TMG/L1 | Pd(dba)2 | >95 | 8.7 : 1 | 95/84 |
| 9 | THF | KOtBu/L1 | Pd(dba)2 | >95 | 11.0 : 1 | 97/55 |
| 10 | THF | DBU/L2 | Pd(dba)2 | >95 | 4.0 : 1 | 79/31 |
| 11 | THF | DBU/L3 | Pd(dba)2 | >95 | 9.8 : 1 | 98/77 |
| 12 | THF | DBU/L4 | Pd(dba)2 | >95 | 18.6 : 1 | 95/30 |
| 13 | THF | DBU/L5 | Pd(dba)2 | >95 | 15.0 : 1 | 98/65 |
| 14 | THF | DBU/L4 | Pd2(dba)3 | >95 | 15.3 : 1 | 98/54 |
| 15 | THF | DBU/L4 | [Pd(C3H5)Cl]2 | 86 | 13.3 : 1 | 98/16 |
| 16 | THF | DBU/L4 | Pd(OAc)2 | >95 | 15.0 : 1 | 98/9 |
| 17f | THF | DBU/L4 | Pd(dba)2 | >95 | 31.0 : 1 | 98/11 |
| 18g | THF | DBU/L4 | Pd(dba)2 | 92h | 32.3 : 1 | 99/52 |
Reaction conditions: 1c (0.1 mmol), 2a (1.5 equiv.), [Pd] (10 mol%), L (11 mol%), base (1.2 equiv.), solvent (1.0 mL), 5 Å MS (50 mg), 30 °C, 10–72 h.
Yield and diastereomeric ratio were measured by analysis of 1H NMR spectra using 1,3,5-trimethoxybenzene as the internal standard.
Determined by chiral HPLC.
2a′ instead of 2a.
2a′′ instead of 2a.
0 °C instead of 30 °C.
−20 °C instead of 30 °C.
Isolated yield for the reaction at the 0.2 mmol scale, 72 h.