Preparation of chiral derivatives of β-Ala containing the α-phenylethyl group: useful starting materials for the asymmetric synthesis of β-amino acids

被引：0
作者：
Ramón Guzmán-Mejía
Gloria Reyes-Rangel
Eusebio Juaristi
机构：
[1] Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional,Departamento de Química
来源：
Nature Protocols | 2007年 / 2卷
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摘要：
The use of microwave (MW) irradiation for the condensation reaction between acetophenone and α-phenylethylamine to prepare (R,R)-bis[α-phenylethyl]amine results in significantly reduced reaction times relative to the use of conventional heating. In this protocol, a secondary amine, (R,R)-bis(α-phenylethyl)amine is treated with acryloyl chloride to afford conjugated amide N,N-bis[(R)-α-phenylethyl]prop-2-enamide, (R,R)-3. 1,4-Addition of α-phenylethylamine to unsaturated (R,R)-3 affords propanamide N,N-Bis[(R)-α-phenylethyl]-3-N-[(S)-α-phenylethyl]amino-propanamide, (R,R,S)-4, which can be alkylated with high diastereoselectivity to give derivative N,N-Bis[(R)-α-phenylethyl]-3-N'-[(S)-α-phenylethyl]amino-propanamide, (R,R,S,S)-5. Hydrogenolysis of (R,R,S,S)-5 catalyzed by palladium hydroxide and final hydrolysis (4 N HCl) resulting in the formation of (S)-α-benzyl-β-alanine, (S)-7, is facilitated by MW irradiation. The use of MW irradiation in this step prevents racemization of the desired amino acid. The present protocol constitutes one of the simplest strategies for the asymmetric synthesis of biologically relevant α-substituted-β-amino acids since it takes advantage of inexpensive, commercially available β-Ala and either (R)- or (S)-α-phenylethylamine as chiral auxiliary. The required time for this protocol is ∼90 h, which can be carried out in 5 d.
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页码：2759 / 2766
页数：7
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