Kinetic and mechanistic studies detailing the oxidation of substrates derived from the 20 natural amino acids by the ferryl complex [Fe(IV)(O)(N4Py)](2+) are described. Substrates of the general formula Ac-AA-NHtBu were treated with the ferryl complex under identical conditions ([Ac-AA-NHtBu] = 10 mM, [Fe] = 1 mM, 1:1 H(2)O/CH(3)CN), and pseudo-first-order rate constants were obtained. Relative rate constants calculated from these data illustrated the five most reactive substrates; in order of decreasing reactivity were those derived from Cys, Tyr, Trp, Met, and Gly. Second-order rate constants were determined for these substrates by varying substrate concentration under pseudo-first-order conditions. Substrates derived from the other natural amino acids did not display significant reactivity, accelerating decomposition of the ferryl complex at a rate less than 10 times that of the control reaction with no substrate added. Ferryl decomposition rates changed in D(2)O/CD(3)CN for the Cys, Tyr, and Trp substrates, giving deuterium kinetic isotope effects of 4.3, 29, and 5.2, respectively, consistent with electron-transfer, proton-transfer (Cys and Trp), or hydrogen atom abstraction (Tyr) mechanisms. Decomposition rates for [Fe(IV)(O)(N4Py)](2+) in the presence of the Met and Gly substrates were identical in H(2)O/CH(3)CN versus D(2)O/CD(3)CN solvents. A deuterium kinetic isotope effect of 4.8 was observed with the labeled substrate 2,2-d(2)-Ac-Gly-NHtBu, consistent with [Fe(IV)(O)(N4Py)](2+) abstracting an alpha-hydrogen atom from Ac-Gly-NHtBu and generating a glycyl radical. Abstraction of alpha-hydrogen atoms from amino acid substrates other than Gly and oxidation of side chains contained in the amino acids other than Cys, Tyr, Trp, and Met were slow by comparison.

High-throughput screening and lab-scale optimization were combined to develop the catalytic system trans-RuCl((S,S)-skewphos)((R,R)-dpen), 2-PrONa, and 2-PrOH. This system hydrogenates functionalized α-phenoxy and related amides at room temperature under 4 atm H pressure to give chiral alcohols with up to 99% yield and in greater than 99% enantiomeric excess via dynamic kinetic resolution.

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N-Acetyl-AA(amino acid)-NHtBu derivatives of all 20 naturally occurring amino acids have been synthesized. Syntheses were performed via solution-phase methodology with yields that allow for access to gram quantities of substrates, in most cases. Syntheses include the coupling of a hindered amine, tert-butylamine, with each amino acid, either directly or in two steps using an activated ester isolated as an intermediate. The introduction of protecting groups was necessary in some cases. The development of synthetic sequences to access challenging substrates, such as the one derived from asparagine, are discussed.

A cross-linked catalyst organic framework was prepared by an alternating ring-opening olefin metathesis polymerization between dichloro{ N , N ′-bis({(2-diphenylphosphino)phenyl}methylidene)bicyclo[2.2.1]-hept-5-ene-2,3-diamine}ruthenium, 1,2- N -di( cis -5-norbornene-2,3- endo -dicarboximido)-ethane, and cis- cyclooctene catalyzed by RuCl 2 (=CHPh)(PCy 3 ) 2 in the presence of a BaSO 4 support. The heterogenized catalyst hydrogenated methyl benzoate at a similar rate to the homogeneous catalyst (0.0025 mol % catalyst, 10 mol % KO t Bu, 80 °C, 50 atm, tetrahydrofuran, 21 h, ∼15 000 turnovers during the first 1 h). The catalyst was used five times for a total of 121 680 turnovers. A study on the reusability of this catalyst showed that ester hydrogenations with bifunctional catalysts slow as the reaction proceeds. This inhibition is removed by isolating and reusing the catalyst, suggesting that future catalyst design should emphasize avoiding product inhibition.