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

三苯基膦与含有羰基基团的二甲基乙炔二羧酸酯反应生成的高活性两性离子中间体，通过分子内Wittig反应在一锅中生成杂环化合物，从而顺利地生成乙烯基膦盐。该反应成功地应用于膦催化的乙炔羧酸酯、亲核试剂和醛的分子间三组分偶联反应。研究发现，在一定催化量的三苯基膦存在下，邻苯亚胺、丙酸乙酯和醛的三组分偶联反应可得到相应的γ-氧-α-氨基酸衍生物，产率中等至较高。以丙酸乙酯和三苯基膦为原料制备乙烯基磷酸盐，高效合成α，β-二氨基酸衍生物。即丙酸乙酯与邻苯二甲酰亚胺在一定催化量的苯基膦存在下，在极性溶剂中以几乎定量收率得到2,3-二苯二甲酰丙酸乙酯。采用手性膦催化剂，两种氨基酸衍生物均具有旋光性。

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.