Iron-catalyzed C2-C3 bond cleavage of phenylpyruvate with O-2: Insight into aliphatic C-C bond-cleaving dioxygenases

Iron(II)-phenylpyruvate complexes of tetradentate tris(6-methyl-2-pyridylmethyl)amine (6-Me-3-TPA) and tridentate benzyl bis(2-quinolinylmethyl)amine (Bn-BQA) were prepared to gain insight into C-C bond cleavage catalyzed by dioxygenase enzymes. The complexes we have prepared and characterized are [Fe(6-Me-3-tpa)(prv)][BPh4] (1), [Fe-2(6-Me-3- tpa)(2)(pp)][(BPh4)(2)] (2), and [Fe-2(6-Me-3-tpa)(2)(2'-NO2-pp)][(BPh4)(2)] (3), [Fe(6-Me-3-tpa)(pp-Me)][BPh4] (4), [Fe(6-Me-3-tpa)(CN-pp-Et)][BPh4] (5), and [Fe(Bn-bqa)(pp)] (8), in which PRV is pyruvate, PP is the enolate form of phenylpyruvate, 2'-NO2-PP is the enolate form of 2'-nitrophenylpyruvate, PP-Me is the enolate form of methyl phenylpyruvate, and CN-PP-Et is the enolate form of ethyl-3-cyanophenylpyruvate. The structures of mononuclear complexes 1 and 5 were determined by single-crystal X-ray diffraction. Both the PRV ligand in 1 and the CN-PP-Et ligand in 5 bind to the iron(II) center in a bidentate manner and form 5-membered chelate rings, but the alpha-keto moiety is in the enolate form in 5 with concomitant loss of a C-H-beta proton. The PP ligands of 2, 3, 4, and 8 react with dioxygen to form benzaldehyde and oxalate products, which indicates that the C2-C3 PP bond is cleaved, in contrast to cleavage of the C1-C2 bond previously observed for complexes that do not contain alpha-keto-carboxylate ligands in the enolate form. These reactions serve as models for metal-containing dioxygenase enzymes that catalyze the cleavage of aliphatic C-C bonds.