An enantioselective six-step synthesis of (1S,2R)-ephenamine starting from readily available chiral amino acid is disclosed presenting 26% overall yield and high optical purity. The use of chiral phenylglycine as starting material was also studied and did not present satisfactory results due to a very sensitive a-carbonyl/benzylic stereogenic center that, in our hands, led to racemization.
Keywords:
chiral auxiliary; chiral amino alcohols; (1S,2R)-ephenamine
| entry | Reagent (equiv.) | Solvent | Temperature / °C | time / h | Yield / % | anti/syna a The ratio was determined by 1H NMR spectra from 1,2-amino alcohol obtained through Boc deprotection of 11. THF: tetrahydrofuran; DIBAL-H: diisobutylaluminium hydride; rt: room temperature. |
|---|---|---|---|---|---|---|
| 1 | NaBH4 (3.0) | MeOH | -40 | 6 | 86 | 3.0/1 |
| 2 | NaBH4 (3.0) | EtOH | -78 | 4 | 95 | 1.1/1 |
| 3 | NaBH4 (3.0) | MeOH | rt | 16 | 90 | 1/1 |
| 4 | Zn(BH4)2 (2.0) | THF | -78 | 6 | 88 | 1.2/1 |
| 5 | L-selectride (2.0) | THF | -78 | 6 | 90 | 1/1.6 |
| 6 | LiAlH(OtBu)3 (2.0) | THF | -78 | 4 | 90 | 1.1/1 |
| 7 | DIBAL-H (2.0) | THF | -78 | 4 | 92 | 1/1 |
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