Synthesis of α-Amino Acids via Phosphine-Catalyzed Three-Component Coupling Reactions

膦催化三组分偶联反应合成α-氨基酸

• 批准号: 14550812
• 负责人: OHTA Tetsuo
• 金额: $ 1.98万
• 依托单位: Doshisha University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14550812/
• 关键词: γ-oxo-α-amino acid; phosphine; aldehyde; acetylenecarboxylate; phthalimide; α,β-diamino acid; アミノ酸

Protonation of the highly reactive zwitterionic intermediate produced in the reaction of triphenylphosphine with dimethyl acetylenedicarboxylate from the protic substrate having carbonyl moieties leads smoothly to vinylphosphonium salt, which underwent an intramolecular Wittig reaction to afford heterocyclic compound in one-pot. This reaction was successfully applied to the intermolecular three-component coupling reaction of acetylenecarboxylates, protic nucleophiles, and aldehydes catalyzed by phosphine. It was found that three-component coupling reaction of phthalimide, ethyl propiolate, and aldehydes in the presence of a catalytic amount of triphenylphosphine proceeded to afford the corresponding γ-oxo-α-amino acid derivatives in moderate to good yields. An efficient synthesis of α,β-diamino acid derivatives via vinylphosphonium salts generated from ethyl propiolate and triphenylphosphine was also developed. That is the reaction of ethyl propiolate with phthalimide in the presence of a catalytic amount of tirphenylphosphine gave ethyl 2,3-diphthalimidoylpropanoate in almost quantitative yield in polar solvent. Both amino acid derivatives could be obtained in optically active using chiral phosphine catalyst.

三苯基膦与乙炔二甲酸二甲酯反应生成的高活性两性离子中间体由含羰基的质子底物质子化，顺利地生成乙烯基鏻盐，后者经分子内Wittig反应一锅法得到杂环化合物。该反应成功地应用于膦催化的炔羧酸酯、质子亲核试剂和醛的分子间三组分偶联反应。结果表明，在催化量的三苯基膦存在下，邻苯二甲酰亚胺、丙炔酸乙酯和醛的三组分偶联反应可得到相应的γ-氧代-α-氨基酸衍生物，产率中等至较高。还发展了一种由丙炔酸乙酯和三苯基膦生成的乙烯基鏻盐合成α，β-二氨基酸衍生物的有效方法。即丙炔酸乙酯与邻苯二甲酰亚胺在催化量的三苯基膦存在下，在极性溶剂中反应，以几乎定量的产率得到2，3-二邻苯二甲酰亚胺基丙酸乙酯。这两种氨基酸衍生物都可以用手性膦催化剂得到。