An asymmetric metal-templated route to amino acids with an isoquinolone core via a 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 skeleton was successfully elaborated via a straightforward Rh(III)-catalyzed C–H activation/annulation of various aryl hydroxamates with a series of robust chiral propargylglycine Ni(II) complexes derived from glycine (Gly), alanine (Ala) and phenylalanine (Phe) in a green solvent (methanol) under mild conditions (at room temperature under air). Notably, in the case of phenylalanine-derived complexes, the formation of unfavorable 4-substituted isoquinolone regioisomers was achieved by a catalyst control for the first time. The subsequent acidic decomposition of the obtained Ni(II) complexes provides the target unnatural α- and α,α-disubstituted AAs with an isoquinolone core in an enantiopure form.