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 <i>N</i>-acetyl amino acid methyl esters with H₂O₂ catalyzed by a very simple iminopyridine iron(ii) complex 1 easily obtainable <i>in situ</i> 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 (<i>N</i>-AcAlaOMe) or in competition with the side-chain functionalization (<i>N</i>-AcValOMe and <i>N</i>-AcLeuOMe). <i>N</i>-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 <i>N</i>-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.