Oxidative functionalization of aliphatic and aromatic amino acid derivatives with H2O2 catalyzed by a nonheme imine based iron complex

Abstract

The oxidation of a series of N-acetyl amino acid methyl esters with H₂O₂ catalyzed by a very simple iminopyridine iron(II) complex 1 easily obtainable in situ by self-assembly of 2-picolylaldehyde, 2-picolylamine, and Fe(OTf)₂ was investigated. Oxidation of protected aliphatic amino acids occurs at the α-C–H bond exclusively (N-AcAlaOMe) or in competition with the side-chain functionalization (N-AcValOMe and N-AcLeuOMe). N-AcProOMe is smoothly and cleanly oxidized with high regioselectivity affording exclusively C-5 oxidation products. Remarkably, complex 1 is also able to catalyze the oxidation of the aromatic N-AcPheOMe. A marked preference for the aromatic ring hydroxylation over Cα–H and benzylic C–H oxidation was observed, leading to the clean formation of tyrosine and its phenolic isomers.