Table 1.
Evaluation of reaction conditions for reductive hydroalkylation.
 | |||
|---|---|---|---|
| Entry | Deviation from standard conditions | Yield (%) | 9a:10aa |
| 1 | None | 90(88)(81b) | >95:5 |
| 2 | NiCl2, NiCl2·DME, NiCl2(Py)4, NiI2 or Ni(COD)2 instead of NiCl2(PPh3)2 | 50–74 | 92:8–>95:5 |
| 3 | DMF, DMA, DMPU or MeCN instead of NMP | 70–92 | 92:8–94:6 |
| 4 | DMSO, THF or toluene instead of NMP | Trace–10 | ND |
| 5 | No Mn | Trace | ND |
| 6 | Mn (1 equiv.) instead of Mn (1.5 equiv.) | 70 | >95:5 |
| 7 | Mn (2 equiv.) instead of Mn (1.5 equiv.) | 90 | >95:5 |
| 8 | Zn instead of Mn | 44 | 80:20 |
| 9 | 8 (1.5 equiv.) instead of 8 (2 equiv.) | 70 | >95:5 |
| 10 | 8 (2.5 equiv.) instead of 8 (2 equiv.) | 91 | >95:5 |
| 11 | 40 °C instead of RT | 90 | >95:5 |
| 12 | 10 mol % NiCl2(PPh3)2 instead of 15 mol % | 92 | 92:8 |
Reactions were carried out on 0.1 mmol scale.
DMA N,N-dimethylacetamide, DMF N,N-dimethylformamide, NMP N-methyl-2-pyrrolidone, DMPU N,N′-dimethylpropyleneurea, DMSO dimethyl sulfoxide, THF tetrahydrofuran, DME 1,2-dimethoxyethane, Py pyridine, COD 1,5-cyclooctadiene, RT room temperature, ND not determined.
aYields and regioisomeric ratios were determined by GC analysis with n-tridecane as internal standard. Values in parentheses denote yields for isolated and purified products.
bThe reaction was conducted on 2 mmol scale.