Asymmetric Synthesis of Perfluoroalkylated α‐Amino Acids through Generated Radicals Using a Chiral Ni(II) Complex

Abstract

AbstractPerfluoroalkylated α‐amino acids (PFAAs) are a unique class of compounds for biochemistry and pharmaceutical science. In this context, we report the successful intermolecular coupling of the Belokon’s chiral dehydroalanine Ni(II) complex with a variety of perfluoroalkyl iodides. A 4‐cyanopyridine/B2Pin2 catalytic system generates perfluoroalkyl radicals, which after trapping by the ligand sphere of a chiral Ni(II) complex provide the diastereomeric complexes with up to >20 : 1 dr (seven examples). The obtained major (S,S)‐diastereomers were easily isolated by simple silica column chromatography in 33–54 % yields. The perfluoroalkylated α‐AA was subsequently released from the obtained Ni(II) complex through aqueous HCl treatment. The chiral auxiliary ligand ((S)‐BPB=(S)‐2‐(N‐benzylprolyl)aminobenzophenone) can be easily recycled after the acidic complex decomposition and reused for the synthesis of the starting dehydroalanine Ni(II) complex.