The oxidation of protected amino acids using an iron-based oxidant is described. Substrates of the general formula Ac-X-NHt Bu, where X = Gly (1), Ala (2), Val (3), Phe (4), Tyr (5), Trp (6), and Met (7) were constructed to model individual amino acid residues within a polypeptide chain. Oxidation of 1 by the iron catalyst [Fe-II(N4Py)(MeCN)1(ClO4)(2) (8) and KHSO5 leads to scission of the amino acid backbone and produces N -acetylformamide as the major product. Decomposition of the iron-based oxidant [Fe-IV(O) (N4Py)](2+), derived from 8, is slower in the presence of 2,2-d (2)-1(96% D) than with 1, giving a kinetic isotope effect of 4.8, which is consistent with [FeIv(O)(N4py)](2+) cleaving an alpha-CH bond of 1. Aliphatic amino acid substrates 2 and 3 do not react with [Fe-IV(O) (N4Py)](2+) under the same conditions used with 1. With substrates 4-7 oxidation of the amino acid side chain is observed. Decomposition of [FeIv(O)(N4Py)]2+ upon treatment with 10 equiv of I and 4-7 revealed that 5 is the most reactive toward the (FeO)-O-IV species. Pseudo-first-order rate constants of 17.0(5) x 10(-3), 3.15(8) x 10-3 and 5.8(2) x 10(-5) s(-1) were obtained for decomposition of [Fe-IV(O)(N4py)](2+) ([Fe] = 1 mM, 1:1 H2O/MeCN) by 6, 7, and 1, respectively.