Condition optimization for catalytic asymmetric hydrogenation of 1a.
| ||||
|---|---|---|---|---|
| Entry | Sub | Ligand | Conv.b (%) | eec (%) |
| 1d | 1a | (Rc,Sp)-DuanPhos | 89 | n.d. |
| 2e | 1b | (Rc,Sp)-DuanPhos | >99 | 98 |
| 3 | 1c | (Rc,Sp)-DuanPhos | n.r. | n.d. |
| 4 | 1b | (R,R)-QuinoxP* | >99 | 97 |
| 5 | 1b | (S)-SegPhos | >99 | 17 |
| 6 | 1b | (S)-BINAP | >99 | 10 |
| 7 | 1b | (R,R)-iPr-DuPhos | >99 | 3 |
| 8 | 1b | (R,S)-Cy-JosiPhos | >99 | 14 |
| 9 | 1b | (R)-BIPHEP | >99 | −30 |
| 10 | 1b | (R,R)-Ph-BPE | >99 | −86 |
| 11 | 1b | (S,S)-f-Binaphane | >99 | 61 |
| 12 | 1b | (2S,4S)-BDPP | >99 | 59 |
| 13e,f,g | 1b | (Rc,Sp)-DuanPhos | >99(99) | 99 |
| ||||
a
Unless otherwise mentioned, the reactions were performed with 1 (0.1 mmol), Rh(NBD)2BF4 (10 mol%), and a ligand (11 mol%) in 1.0 mL THF at 50 °C for 15 h.
b
Determined by crude 1H NMR.
c
Determined with chiral HPLC.
d
The reaction was performed in iPrOH.
e
Rh(NBD)2BF4 (1.0 mol%) and ligand (1.05 mol%) were used.
f
Isolated yield in parentheses.
g
1,2-DCE was used as the solvent. Pin = 2,3-dimethyl-2,3-butanediol; dan = 1,8-diaminonaphthalene.