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

Abstract

A general protocol for the asymmetric synthesis of artificial amino acids (AAs) comprising an isoquinolone skeletal was successfully elaborated via a straightforward Rh(III)-catalyzed C−H activation/annulation of various aryl hydroxamates with...

A synthetic route to artificial chiral α-amino acids featuring a 3,4-dihydroisoquinolone core through a Rh(iii)-catalyzed functionalization of allyl groups in chiral Ni(ii) complexes

“…9-12 Besides, in the case of a largescale synthesis, it is possible to isolate the Ni(II) salt as well, either by complexation with EDTA 15 or via ion-exchange chromatography. [9][10][11][12] The structure and absolute configuration of the minor diastereomer of AA (2S,4S)-5 was unambiguously established via single-crystal XRD analysis (Fig. 3).…”

“…Initially, we tested the coupling of readily available chiral Ni( ii ) complex ( S , S )- 1a based on ( S )-allylglycine (the complex was synthesized via diastereoselective alkylation, 11 a see the ESI‡ for synthetic details) with phenyl hydroxamate 2a under conditions similar to those described in our previous report for propargyl derivatives. 12 It was found that the reaction catalyzed by pentamethylcyclopentadienyl rhodium complex [Cp*RhCl 2 ] 2 (at 2.0 mol% loading) with addition of CsOAc (2 equiv.) in methanol smoothly proceeds at room temperature with excellent regioselectivity, giving only 3-substituted 3,4-dihydroisoquinolone derivatives as a mixture of diastereomers ( S , S , R )- 3aa and ( S , S , S )- 3aa in a ratio of 2.9 : 1 with 90% combined yield (Table 1, entry 1).…”

“…Finally, the transformation of Ni( ii ) complexes ( S , S , R )- 3ac and ( S , S , S )- 3ac into the target diastereomerically and enantiomerically pure AAs (2 S ,4 R )- 5 and (2 S ,4 S )- 5 was performed as shown in Scheme 3. The corresponding adducts 3ac were decomposed via a standard procedure 9–12 under acidic conditions in a mixture of 6 N HCl/MeOH at 60 °C and the AAs were isolated in 64% and 55% yields, respectively (Scheme 3). It is well-documented that the decomposition of the chiral Ni( ii ) complexes with HCl gives α-AAs without erosion of enantiopurity (see HPLC traces in the ESI, Fig.…”

“…9–12 Importantly, the chiral auxiliary was readily recovered from the resulting mixture in an enantiopure form as a hydrochloride salt (( S )- BPB ·HCl) in >90% yield via sequential filtration and extraction processes and it can be reused for the synthesis of the initial Ni( ii ) complexes 1 . 9–12 Besides, in the case of a large-scale synthesis, it is possible to isolate the Ni( ii ) salt as well, either by complexation with EDTA 15 or via ion-exchange chromatography. 9–12…”

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.…”