Optimisation of reaction conditionsa.
| ||||||
|---|---|---|---|---|---|---|
| Entry | Cat. | Solvent | Yieldb (%) | drc | er | er |
| anti-14d | syn-15d | |||||
| 1 | 3 | CH2Cl2 | 72 | 72 : 28 | 87 : 13 | 94 : 6 |
| 2e | 3 | CH2Cl2 | 76 | 85 : 15 | 85 : 15 | 83 : 17 |
| 3f | 3 | CH2Cl2 | 64 | 83 : 17 | 82 : 18 | 82 : 18 |
| 4g | 3 | EtOAc | 78 | 68 : 32 | 82 : 18 | 90 : 10 |
| 5g | 3 | DMC | 76 | 66 : 34 | 85 : 15 | 94 : 6 |
| 6g | 3 | Et2O | 80 | 75 : 25 | 89 : 11 | 92 : 8 |
| 7g,h | 3 | Et2O | Quant. | >95 : 5 | 88 : 12 | — |
| 8g,i | 16 | Et2O | 45 | 74 : 26 | 87 : 13 | >99 : 1 |
| 9g | 17 | Et2O | 99 | >95 : 5 | 79 : 21 | — |
| 10g,j | 18 | Et2O | 99 | >95 : 5 | 98 : 2 | — |
| 11g | 19 | Et2O | 91 | 95 : 5 | 99 : 1 | — |
| 12g | 19 | CPME | 65 | >95 : 5 | 99 : 1 | — |
| 13g | 19 | CPME | 92 | 95 : 5 | 99 : 1 | — |
a
Reactions performed on 0.5 mmol scale with 1.0 equiv. of 2 and 1.5 equiv. of 9.
b
Combined yield of diastereoisomers determined by 1H NMR analysis of the crude reaction mixture using 1,3,5-trimethoxybenzene internal standard.
c
Determined by 1H NMR analysis of the crude reaction mixture.
d
Determined by HPLC analysis on a chiral stationary phase.
e
10 mol% (R)-BTM used.
f
Reaction temperature was 40 °C.
g
Precipitation of product from reaction mixture.
h
48 h reaction time.
i
168 h reaction time.
j
96 h reaction time.