Predictable Selectivity in Remote C-H Oxidation of Steroids: Analysis of Substrate Binding Mode.

Predictability is a key requirement to encompass late-stage C-H functionalization in synthetic routes. However, prediction (and control) of reaction selectivity is usually challenging, especially for complex substrate structures and elusive transformations such as remote C(sp3 )-H oxidation, as it requires distinguishing a specific C-H bond from many others with similar reactivity. Developed here is a strategy for predictable, remote C-H oxidation that entails substrate binding to a supramolecular Mn or Fe catalyst followed by elucidation of the conformation of the host-guest adduct by NMR analysis. These analyses indicate which remote C-H bonds are suitably oriented for the oxidation before carrying out the reaction, enabling prediction of site selectivity. This strategy was applied to late-stage C(sp3 )-H oxidation of amino-steroids at C15 (or C16) positions, with a selectivity tunable by modification of catalyst chirality and metal.

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

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.

Hydrogen Atom Transfer (HAT) Processes Promoted by the Quinolinimide-N-oxyl Radical. A Kinetic and Theoretical Study.

A kinetic study of the hydrogen atom transfer (HAT) reactions from a series of organic compounds to the quinolinimide-N-oxyl radical (QINO) was performed in CH3CN. The HAT rate constants are significantly higher than those observed with the phthalimide-N-oxyl radical (PINO) as a result of enthalpic and polar effects due to the presence of the N-heteroaromatic ring in QINO. The relevance of polar effects is supported by theoretical calculations conducted for the reactions of the two N-oxyl radicals with toluene, which indicate that the HAT process is characterized by a significant degree of charge transfer permitted by the π-stacking that occurs between the toluene and the N-oxyl aromatic rings in the transition state structures. An increase in the HAT reactivity of QINO was observed in the presence of 0.15 M HClO4 and 0.15 M Mg(ClO4)2 due to the protonation or complexation with the Lewis acid of the pyridine nitrogen that leads to a further decrease in the electron density in the N-oxyl radical. These results fully support the use of N-hydroxyquinolinimide as a convenient substitute for N-hydroxyphthalimide in the catalytic aerobic oxidations of aliphatic hydrocarbons characterized by relatively high C-H bond dissociation energies.

Isotope effect profiles in the N-demethylation of N,N-dimethylanilines: a key to determine the pK(a) of nonheme Fe(III)-OH complexes.

N-demethylation of N,N-dimethylanilines promoted by [(N4Py)Fe(IV)=O](2+) occurs by an electron transfer-proton transfer (ET-PT) mechanism with a rate determining PT step. From the bell-shaped curve of the KDIE profile it has been estimated that the pK(a) of [(N4Py)Fe(III)-OH](2+) is 9.7.