Table 3.
Synthesis of trans-Disubstituted and -Trisubstituted Pyrazolidinesa
| Entry | Substrate | RS | RL | R1 | Product | Yield(%)b | drc |
|---|---|---|---|---|---|---|---|
| 1 | 7 | H | C3H7 | p-ClPh | 35 | 70 | >20:1 (7:1) |
| 2d | 7 | H | C3H7 | β-styryl | 36 | 54 | 5:1 (5:1) |
| 3 | 30 | H | Ph | m-MePh | 37 | 66 | 13:1 (10:1) |
| 4 | 30 | H | Ph | p-tBuO2CPh | 38 | 55 | >20:1 (>20:1) |
| 5d | 30 | H | Ph | α-styryl | 39 | 63 | 11:1 (8:1) |
| 6d | 31 | Me | Me | p-tBuO2CPh | 40 | 80 | - |
| 7d | 32 | (CH2)5 | N-(Bn)-5-indolyl | 41 | 56 | - | |
| 8 | 33 | Me | Ph | p-PhPh | 42 | 83 | 6:1 (6:1) |
| 9 | 34 | Me | tBu | 6-MeO-2-naphthyl | 43 | 73 | >20:1 (12:1) |
Conditions: 1.0 equiv hydrazine, 1.2 equiv ArBr, 1.2 equiv NaOtBu, 2 mol % Pd(OAc)2, 2 mol % Dpe-phos, toluene (0.25 M), 70 °C, 4-12 h.
Isolated yield, average of two or more experiments.
Diastereomeric ratios are reported for the isolated products. Diastereomeric ratios in parentheses were observed in crude reaction mixtures.
The reaction was conducted using 1.2 equiv ArBr and 1.2 equiv of NaOtBu at 70 °C.