One-Pot Synthesis of α-Halo β-Amino Acid Derivatives via the Difunctional Coupling of Ethyl α-Diazoacetate with Silyl Halides and N,O-Acetals or Aromatic Tertiary Amines

Abstract

The difunctionalization of ethyl α-diazoacetate (EDA) using silyl halides as a nucleophile and N,O-acetals as an electrophile under metal-free conditions is described. This process undergoes a novel three-component coupling (3-CC) reaction using EDA, which leads to a one-pot preparation of α-halo β-amino acid esters. Also, this protocol could be adapted to accept an electrophile composed of aromatic tertiary amines. In both 3-CC reactions, the key reaction intermediate is an iminium intermediate that can be easily and effectively generated either from N,O-acetals or from aromatic tertiary amines.