Table 1 Optimization of resolution of phosphindole oxide 1aa
| ||||||||
|---|---|---|---|---|---|---|---|---|
entry | ligand | 3aa:3aaʹb | 3aa | 1a | C (%)e | sf | ||
yield (%)c | ee (%)d | yield (%)c | ee (%)d | |||||
1 g | (R)-binap | 2.5:1 | 71 | 38 | <5 | — | — | — |
2 g | (R)-segphos | 1.1:1 | 46 | 74 | <5 | — | — | — |
3 h | (R)-segphos | 1.8:1 | 42 | 71 | <5 | — | — | — |
4 | (R,R)-Ph-bod | >20:1 | 22 | 73 | 39 | 98 | 57 | 30 |
5 | L1 | >20:1 | 31 | 89 | 66 | 45 | 34 | 23 |
6 | L2 | >20:1 | 46 | 90 | 48 | 92 | 51 | 53 |
7 | L3 | >20:1 | 41 | 94 | 50 | 88 | 48 | 122 |
8 | L4 | >20:1 | 49 | 97 | 47 | >99 | 51 | >211 |
9 | L5 | >20:1 | 40 | 90 | 44 | >99 | 53 | >80 |
10 | L6 | >20:1 | 30 | 81 | 31 | >99 | 55 | >50 |
11i | L4 | >20:1 | 48 | 94 | 47 | >99 | 52 | >116 |
12j | L4 | >20:1 | 29 | 76 | 31 | >99 | 57 | >35 |
13k | L4 | >20:1 | 49 | 97 | 47 | >99 | 51 | >211 |
- aUnless noted otherwise, the reactions were performed with 1a (0.20 mmol, 1.0 equiv.), 2a (1.5 equiv.), catalyst (2 mol%), and KOH (5 mol%) in THF/H2O (1.0/0.1 mL) at 70 °C for 20 h under N2. bDetermined by 1H NMR. cIsolated yield. dDetermined by chiral HPLC. eCalculated conversion, C = ee1a/(ee1a + ee3aa). fSelectivity factor (s)=ln[(1-C) (1-ee1a)]/ln[(1-C) (1 + ee1a). gThe catalyst was generated in situ from [RhCl(coe)2]2 (2 mol%) and the bisphosphine ligand (5 mol%). h1,4-Dioxane instead of THF, [RhCl(coe)2]2 (5 mol % of Rh) and (R)-segphos (10 mol %) was used as the catalyst, and KOH (2.0 mmol) was used. i1,4-Dioxane instead of THF. jToluene instead of THF. kConducted at 60 °C. Unless specified otherwise, the dr value of 3aa was >20:1.
