Table 1. Evaluations of Catalysts 1 in the Mannich Reaction of 7a with 8a To Afford 9aa.
| entry | catalyst system (equiv) | time (h) | yield (%)b | erc |
|---|---|---|---|---|
| 1 | 1a (0.3) | 96 | <5 | 82:18 |
| 2 | 1a·CF3COOH (0.3) | 72 | 99 | 87:13 |
| 3 | 1a·CF3COOH (0.3), CF3COOH (0.3) | 48 | 85 | 94:6 |
| 4 | 1a·CF3COOH (0.3), (PhCH2O)2POOH (0.3) | 48 | 99 | 96:4 |
| 5 | 1a (0.3), (PhCH2O)2POOH (0.3) | 72 | 99 | 92:8 |
| 6 | 1a (0.3), CF3COOH (0.3), (PhCH2O)2POOH (0.3) | 48 | 99 | 96:4 |
| 7 | 1b·CF3COOH (0.3), (PhCH2O)2POOH (0.3) | 72 | 77 | 87:13 |
| 8 | 1c·CF3COOH (0.3), (PhCH2O)2POOH (0.3) | 48 | >99 | 63:37 |
| 9 | 1d·CF3COOH (0.3), (PhCH2O)2POOH (0.3) | 120 | 48 | 93:7 |
| 10 | 1e·CF3COOH (0.3), (PhCH2O)2POOH (0.3) | 48 | 89 | 94:6 |
| 11 | 1f (0.3) | 168 | 11 | – |
| 12 | 1f (0.3), (PhCH2O)2POOH (0.3) | 120 | 0 | – |
| 13 | 1g/CF3COOH (1:0.8) (0.3), (PhCH2O)2POOH (0.3) | 96 | 80 | 16:84 |
a
Conditions: 7a (0.75 mmol, 3.0 equiv), 8a (0.25 mmol, 1.0 equiv), and catalyst system (as indicated, equiv relative to 8a) in toluene (1.65 mL) at rt (25 °C).
b
Determined by 1H NMR analysis before purification.
c
Determined by HPLC analysis after purification.