Table 1 Optimization of the reaction conditionsa
From: Enantioselective [3+3] atroposelective annulation catalyzed by N-heterocyclic carbenes
| ||||||
|---|---|---|---|---|---|---|
Entry | Deviation from standard conditionsa | Yield 3 (%)b | er 3 (%)c | Yield 4 (%)b | Yield 5 (%)b | Yield 6 (%)b |
1 | None | 70d | 90:10 | <5 | <5 | <5 |
2 | No cat. A | 0 | − | 0 | 0 | 0 |
3 | B instead of A | <5 | − | <5 | <5 | <5 |
4 | C instead of A | <5 | − | <5 | <5 | 60 |
5 | D instead of A | 44 | −77:23 | <5 | 30 | 20 |
6 | No Mg(OTf)2 | 60 | 90:10 | <5 | <5 | 18 |
7 | LiCl instead of Mg(OTf)2 | 58 | 90:10 | <5 | <5 | <10 |
8 | In(OTf)3 instead of Mg(OTf)2 | 63 | 90:10 | <5 | <5 | <10 |
9 | Sc(OTf)3 instead of Mg(OTf)2 | 60 | 90:10 | <5 | <5 | <10 |
10 | Zn(OTf)2 instead of Mg(OTf)2 | 61 | 90:10 | <5 | <5 | <10 |
11 | CHCl3 as solvent | 40 | 80:20 | <5 | 15 | 23 |
12 | THF as solvent | 54 | 85:15 | <5 | <10 | 19 |
13 | Dioxane as solvent | 20 | − | <5 | <5 | 50 |
14 | No nBu4NOAc | 0 | − | 0 | 0 | 0 |
15 | DIPEA as base | 45 | 80:20 | <5 | 17 | 20 |
16 | Cs2CO3 as base | 40 | 75:25 | <5 | 20 | 22 |
17 | KOtBu as base | <10 | − | <5 | <5 | <5 |
18 | F instead of E | <5 | − | 76 | <5 | <5 |
19 | G instead of E | <5 | − | 70 | <5 | <5 |
20 | 10 mol% A | 69e | 91:9 | <5 | <5 | 13 |
21 | 2b instead of 2a | 60f | 75:25 | <5 | <5 | 18 |
22 | 2c instead of 2a | 60g | 71.5:28.5 | <5 | <5 | <5 |
- aStandard conditions: 1a (0.11 mmol), 2a (0.10 mmol, R = Me), nBu4NOAc (0.2 mmol), oxidant E (0.15 mmol), Mg(OTf)2 (20 mol%), cat. A (15 mol%), toluene (2.0 mL), room temperature, N2, 24 h
- bIsolated yield
- cDetermined by chiral HPLC
- d3aa as major product
- e48 h
- f3ab as major product
- g3ac as major product
