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

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14550812
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 有機工業化学
• Research Institution: Doshisha University
• Principal Investigator: OHTA Tetsuo Doshisha University, Faculty of Engineering, Professor, 工学部, 教授 (50213731)
• Project Period (FY): 2002 – 2003
• Keywords: γ-oxo-α-amino acid / phosphine / aldehyde / acetylenecarboxylate / phthalimide / α,β-diamino acid

Research Abstract

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.