Reaction optimisation for the catalytic, enantioselective cycloaddition/rearrangement cascade of 1-naphthaldehyde 7a to benzoisochromene 8a.
| ||||
|---|---|---|---|---|
| Entrya | Lewis acid 12b | t [h] at 0 °C | Yield 8a + 9a [%] (ratio)c | ee8a, (9a) [%]d |
| 1 | 12a | —e | <10% | n.d. |
| 2 | 12b | —e | <10% | n.d. |
| 3 | 12c | —e | <10% | n.d. |
| 4 | 12d | —e | 88 (77 : 23) | 89 (90) |
| 5 | 12e | —e | 90 (76 : 24) | 37 (39) |
| 6 | 12f | —e | 87 (100 : 0) | 54 |
| 7 | 12g | —e | 86 (76 : 24) | 65 (67) |
| 8 | 12d | 0.5 | 88 (100 : 0) | 89 |
a
The reactions were performed in CH2Cl2 as the solvent with a substrate concentration of c = 20 mM.
b
12a–12d: Ar′ = 3,5-dimethylphenyl; 12a: Ar = 2,4,6-trifluorophenyl; 12b: Ar = 2-(trifluoromethyl)phenyl; 12c: Ar = 3-biphenyl; 12d: Ar = 2,6-dimethylphenyl. 12e–12g: Ar = 2,6-dimethylphenyl; 12e: Ar′ = 3′,5′-dimethyl-2-biphenyl; 12f: Ar′ = 3,5-difluorophenyl; 12g: Ar = 2,3-dimethylphenyl.
c
Yield of isolated mixture 8a and 9a; the ratio was determined by 1H NMR analysis of crude product.
d
The enantiomeric excess (ee) of 8a and 9a was determined by chiral-phase HPLC analysis. n.d. = not determined.
e
The reaction was quenched at −78 °C.