Reaction optimisation I: selectivity for formation of dihydropyranone 8.
| |||||||
|---|---|---|---|---|---|---|---|
| Entry | Solvent | Catalyst | Conversion (%) | Ratioa (8 : 9 : 10) | Yieldb (%) | dra | erc |
| 1 | MeCN | 11 | 100 | 20 : 15 : 65 | — | — | |
| 2 | DMF | 11 | 100 | 0 : 0 : 100 | 10: 97 | 80 : 20 | |
| 3 | CH2Cl2 | 11 | 100 | 20 : 50 : 30 | |||
| 4d | CH2Cl2 | 11 | 95 | 50 : 50 : 0 | 9: 40 | 95 : 5 | 96 : 4 |
| 5 | Et2O | 11 | 90 | 75 : 15 : 10 | |||
| 6 | MTBE | 11 | 63 | 65 : 30 : 5 | |||
| 7 | CPME | 11 | 97 | 85 : 15 : 0 | 8: 18 | 80 : 20 | 94 : 6 |
| 8 | CPME | 12 | 68 | 60 : 15 : 25 | |||
| 9 | CPME | 13 | 70 | 60 : 15 : 25 | |||
| 10 | EtOAc | 11 | 90 | 75 : 5 : 20 | |||
| 11 | i-PrOAc | 11 | 98 | 90 : 5 : 5 | 8: 20 | 80 : 20 | 95 : 5 |
a
Determined by 1H NMR spectroscopic analysis of the crude reaction product mixture, with values rounded to nearest 5.
b
Isolated yield of specified product.
c
Determined by chiral stationary phase HPLC analysis.
d
Reaction conducted at −60 °C, DMF = dimethylformamide, MTBE = methyl t-butyl ether, CPME = cyclopentyl methyl ether.