Table 1.
Optimization Studiesa
| entry | 3a (equiv) | 4a (equiv) | cat. 2 (mol%) | temp (°C) | time (h) | yieldb (%) | drc (anti:syn) | eed (%) (anti) |
|---|---|---|---|---|---|---|---|---|
| 1e | 1.4 | 1 | 2a (3.5) | 23 | 17 | 62 | 1:1 | ND |
| 2e | 1.4 | 1 | 2a (3.5) | -5 | 17 | 66 | 1:1 | (-)-67 |
| 3 | 1.4 | 1 | 2a (3.5) | -25 | 14 | 62 | 5:1 | (-)-96 |
| 4 | 2 | 1 | 2a (5.0) | -30 | 36 | 86 | 5:1 | (-)-94 |
| 5 | 2 | 1 | 2bf (5.0) | -30 | 36 | 80 | 6:1 | (+)-96 |
| 6 | 2 | 1 | 2c (5.0) | -30 | 36 | 75 | 4:1 | ND |
| 7 | 2 | 1 | 2a (3.5) | -30 | 24 | 86 | 5:1 | (-)-94 |
| 8 | 2 | 1 | 2a (2.5) | -30 | 36 | 90 | 5:1 | (-)-92 |
a
To mixture of catalyst 2, ketone 3a and 4Å MS in THF was added imine 4a in THF at the temperature shown in the Table.
b
Isolated yield.
c
Determined by the 1H NMR of the crude mixture.
d
Determined utilizing chiral HPLC.
e
To suspension of 3a, imine 4a, and 4Å MS in THF was added the catalyst 2 in THF.
f
(R,R)-catalyst 2b was used.
ND = not determined.