Table 1. General Screening of Palladium Catalyst Systems.
entry | catalyst | base | time | solvent | additive | conversiona |
---|---|---|---|---|---|---|
1b | A | CsOH | 100 °C, 3 h | DMA | N/A | 75% |
2c | B | NaOH | 60 °C, 2 h | DMA | N/A | 30% |
3d | C | CsOH | 95 °C, 25 min | MIPO | N/A | 33% |
4e | C | CsOH | 95 °C, 25 min | MIPO | N/A | 0% |
5e | C | CsOH | 95 °C, 25 min | DMA | N/A | 6% |
6f | D | CsOH | 95 °C, 25 min | MIPO | N/A | 0% |
7f | D | CsOH | 95 °C,25 min | DMA | N/A | 14% |
8g | D | CsOH | 95 °C, 25 min | DMA | Na ascorbate | 57% |
9g | D | CsOH | 95 °C, 15 min | DMA | Na ascorbate | 63% |
The conversion was determined by LC-MS.
Condition reported by GSK46.
Condition reported by Eli Lilly48.
Condition reported by BCM26.
Reaction conditions: 1 (5 nmol), 250 equiv of aniline (400 mM), 2 equiv of catalyst (5 mM), 500 equiv of CsOH (1000 mM), H2O (2.5 μL), solvent (4.9 μL).
Reaction conditions: 1 (5 nmol), 250 equiv of aniline (400 mM), 2 equiv of catalyst (5 mM), 500 equiv of CsOH (1000 mM), H2O (2.5 μL), solvent (4.9 μL).
Reaction conditions: 1 (5 nmol), 250 equiv of aniline (400 mM), 2 equiv of catalyst (5 mM), 500 equiv of CsOH (1000 mM), 20 equiv of sodium ascorbate (40 mM), DMA (4.9 μL). DMA = dimethylacetamide. MIPO = 1-methoxy-2-isopropanol.