Table 1.
Reaction discovery and Condition optimization.a
| ||||||
| Entry | Ligand | Reaction conditions (3h) | Conver-sion (%) | Yield(%)b 4a/4a’/4a’’/4a’’’ | ee (%)c (4a) | |
|---|---|---|---|---|---|---|
| 1 | L1 | NaBARF (10 mol %), DCE, 60°C | 95 | 49/8/8/15 | - | |
| 2 | JohnPhos | NaBARF (10 mol %), DCE, 60°C | 0 | 0 | - | |
| 3 | JohnPhos | NaBARF (10 mol %), DCE, 60°C, 10% Et3N | 0 | 0 | - | |
| 4 | (R)-L2 | NaBARF (10 mol %), DCE, RT | 70 | 55/−/−/− | −93 | |
| 5 | (S)-L3 | NaBARF (10 mol %), DCE, RT | 95 | 77/0/<3/<3 | 99 | |
| 6 | (S)-L3 | AgOTf (10 mol %), DCE, RT | <10 | 0 | - | |
| 7 | (S)-L3 | AgNTf2 (10 mol %), DCE, RT | <10 | 0 | - | |
| 8 | (S)-L3 | Ag(CH3CN)2BArF4 (10 mol %), DCE, RT | 60 | 40/−/−/− | 99 | |
| 9 | (S)-L3 | NaBARF (10 mol %), PhCF3, RT | 60 | 32/−/−/− | 99 | |
| 10 | (S)-L3 | NaBARF (10 mol %), THF, RT | 57 | 33/−/−/− | 99 | |
All reactions were run in sealed vials without replacing the atmosphere with Ar or N2. DCE = 1,2-dichloroethane. THF = tetrahydrofuran. NaBARF = sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate. Johnphos = (2-biphenyl)di-tert-butylph -osphine
Isolated yields.
Determined by HPLC using corresponding benzyl ester.