Sequential Heck Cross-Coupling and Hydrothiolation Reactions Taking Place in the Ligand Sphere of a Chiral Dehydroalanine Ni(II) Complex: Asymmetric Route to β-Aryl Substituted Cysteines

Abstract

A practically useful protocol for the asymmetric synthesis of artificial β-aryl-substituted cysteine derivatives was developed through sequential Pd(II)-catalyzed Heck cross-coupling with aryl iodides and hydrothiolation reaction with various alkyl thiols in the presence of triethylamine taking place in the ligand sphere of a robust and bench-stable chiral dehydroalanine Ni(II) complex. The subsequent acidic decomposition of the single diastereomeric Ni(II) complexes led to the target enantiopure cysteine derivatives.

An asymmetric metal-templated route to amino acids with an isoquinolone coreviaa Rh(iii)-catalyzed coupling of aryl hydroxamates with chiral propargylglycine Ni(ii) complexes

“…11–13 Importantly, the chiral auxiliary was readily isolated from the resulting mixture in an enantiopure form as a hydrochloride salt (( S )- BPB ·HCl) in >90% yield by sequential filtration and extraction processes and it can be reused for the synthesis of starting Ni( ii ) complexes 1 . 11–13 On the other hand, in the case of a large-scale synthesis, it is possible to recover the Ni( ii ) ions either by complexation with EDTA 21 or by ion-exchange chromatography. 11–13…”

“…11–13 On the other hand, in the case of a large-scale synthesis, it is possible to recover the Ni( ii ) ions either by complexation with EDTA 21 or by ion-exchange chromatography. 11–13…”

“…It is worth noting that functionalization and modification of the ligand sphere of robust and bench-stable chiral Ni( ii ) complexes allowed us to obtain a broad library of challenging enantiomerically pure AAs. 13…”

Pd(II) Complexes of Chiral Proline-Derived Ligands: Application for Dynamic Thermodynamic Resolution of α-Amino Acids and Their Antibacterial Activities

“…Previously, Belokon’s group made early pioneering contributions to the asymmetric metal-templated synthesis of amino acids. − The groups of Saghyan, Larionov, and Magdesieva also fruitfully work in this field. − In recent years, our group has made considerable efforts and reported several efficient protocols to obtain N , C -unprotected α- and β-amino acids in an enantiopure form using metal complexes, including Ni­(II) complexes and Cu­(II) complexes. − However, the methods for Ni­(II) complexes required relatively high reaction temperatures or prolonged reaction time at room temperature, which led to low reaction efficiency . As for the resolution method via Cu­(II) complexes, the limitation is the inability to achieve configurational interconversion of α-amino acids and dynamic resolution of the racemic α-amino acids.…”