A general asymmetric synthesis of artificial aliphatic and perfluoroalkylated α-amino acids by Luche's cross-electrophile coupling reaction

Abstract

Aliphatic artificial α-amino acids (α-AAs) have attracted great interest in biochemistry and pharmacy. In this context, we developed a promising practical protocol for the asymmetric synthesis of these α-AAs through the selective and efficient intermolecular cross-electrophile coupling of Belokon's chiral dehydroalanine Ni(II) complex with different alkyl and perfluoroalkyl iodides mediated by a dual Zn/Cu system. The reaction afforded diastereomeric complexes with dr up to 21.3 : 1 in 24–95% yields (19 examples). Exemplarily, three enantiomerically pure aliphatic α-AAs were obtained through acidic decomposition of (S,S)-diastereomers of Ni(II) complexes. Importantly, the chiral auxiliary ligand (S)-BPB ((S)-2-(N-benzylprolyl)aminobenzophenone) was easily recycled by simple filtration after acidic complex decomposition and reused for the synthesis of the initial dehydroalanine Ni(II) complex.