Table 1.
Optimization of global hydrogenation conditions
| s. no | GH substrate | Pd% (w/w) | solvent | time (h) | product ratioa (5a:6a:7) or (5b:6b) | yield % of 1a/1b (over 2 steps) |
|---|---|---|---|---|---|---|
| 1 | 4a | 40 | MeOH:EtOAc (1:1) | 20 | 61:0:39 | ndc |
| 2 | 4a | 40 | MeOH:EtOAc (1:1) | 4 | incomplete reaction | ndc |
| 3 | 4a | 40 | MeOH:H2O (1:1) | 4 | 50:0:50 | ndc |
| 4 | 4a | 40 | t-BuOH:H2O (1:1) | 4 | 67:0:33 | ndc |
| 5 | 4a | 30 | t-BuOH:H2O (1:1) | 1.5 | 56:44:0 | ndc |
| 6 | 4a | 30 | t-BuOH:H2O (1:1) | 3.0 | 90:10:0 | 60% |
| 7 | 4a | 30 | t-BuOH:H2O (1:1) | 3.5 | 83:0:17 | ndc |
| 8 | 4c | 100 | MeOH:EtOAc (1:1) | 72 | 68%b | ndc |
| 9 | 4c | 100 | tBuOH:H2O (1:1) | 16 | 17:83 | ndc |
| 10 | 4c | 100 | MeOH:H2O (5:1) | 24 | 95:5 | 61% |
| 11 | 4c | 50 | MeOH:H2O (5:1) | 72 | 90:10 | ndc |
a
based on 1H NMR analysis of crude reaction mixture filtered over celite;
b
isolated yield;
c
nd –not determined, the compound was not used to make 1a/1b.