Optimization of reaction conditions in bulk.
| Entry | Bulk reactionsa | |||||
|---|---|---|---|---|---|---|
| Solvent | T (°C) | Conc.b | Catalyst | Time | er (+)/(−)c | |
| 1 | THF | r.t. | 10−2 M | S,S-3 | 5 h | 20/80d |
| 2 | THF | r.t. | 10−4 M | S,S-3 | 5 h | 24/76d |
| 3 | ACN | r.t. | 10−2 M | S,S-3 | 5 h | 15/85e |
| 4 | ACN | r.t. | 10−4 M | S,S-3 | 5 h | 18/82d |
| 5 | ACN | 60 | 10−2 M | S,S-3 | 5 h | 20/80d |
| 6 | ACN | 82 | 10−2 M | S,S-3 | 5 h | 33/67e |
| 7 | ACN | r.t. | 10−2 M | R,R-4 | 5 h | 80/20e |
| 8 | ACN | 82 | 10−2 M | R,R-4 | 5 h | 64/36e |
a
All the reactions were performed in a round bottom flask under magnetic stirring.
b
Concentration 10−2 M: 0.12 mmol of 1, 0.15 mmol of 2 and 10% (0.01 mmol) of catalyst (3 or 4) in 10 mL of solvent. Concentration 10−4 M: 0.1 mL of mixture 10−2 M are diluted with 9.9 mL of solvent.
c
The er was calculated by enantioselective HPLC analysis (see ESI for more details).
d
The er was determined on reaction crude.
e
The er was determined on the isolated product (see ESI for more details): entry 3: yield 46%; entry 6: 63%; entry 7: yield 49%; entry 8: 68%.