Origin of Long-Range Hyperfine Couplings in the EPR Spectra of 2,2,5,5-Tetraethylpyrrolidine-1-oxyls.

Cyclic nitroxides with several bulky alkyl substituents adjacent to the nitroxide group are known to demonstrate a much higher stability to bioreduction than their tetramethyl analogues. Among these so-called "sterically shielded" nitroxides, the pyrrolidine derivatives are the most stable. The EPR spectra of some sterically shielded pyrrolidine-1-oxyls were reported to show one or two large additional doublet splittings with a hyperfine coupling (hfc) constant (ca. 0.2-0.4 mT). To determine the origin of these hfc, a series of 2-R-2,5,5-triethyl-3,4-bis(hydroxymethyl)-pyrrolidine-1-oxyls with methylene groups stereospecifically enriched with deuterium were prepared, and their CW EPR spectra were studied. In addition, these nitroxides were investigated using quantum chemical calculations on the UB3LYP/def2-TZVP level and NBO analysis. The apparent constants were assigned to hfc with γ-hydrogen in the side chain, with the contribution of the NBO orbital ßπ*(N-O) to the natural localized molecular orbital ßσ(C-H) playing the major role. This interaction is efficient if the ethyl substituent is in the pseudoaxial position of the ring and the CH2-CH3 bond is codirected with (parallel to) N-O. The apparent constant aH increases with the Boltzmann population of this conformation.

Stable Bicyclic Functionalized Nitroxides: The Synthesis of Derivatives of Aza-nortropinone-5-Methyl-3-oxo-6,8-diazabicyclo[3.2.1]-6-octene 8-oxyls.

In recent decades, bicyclic nitroxyl radicals have caught chemists' attention as selective catalysts for the oxidation of alcohols and amines and as additives and mediators in directed C-H oxidative transformations. In this regard, the design and development of synthetic approaches to new functional bicyclic nitroxides is a relevant and important issue. It has been reported that imidazo[1,2-b]isoxazoles formed during the condensation of acetylacetone with 2-hydroxyaminooximes having a secondary hydroxyamino group are recyclized under mild basic catalyzed conditions to 8-hydroxy-5-methyl-3-oxo-6,8-diazabicyclo[3.2.1]-6-octenes. The latter, containing a sterically hindered cyclic N-hydroxy group, upon oxidation with lead dioxide in acetone, virtually quantitatively form stable nitroxyl bicyclic radicals of a new class, which are derivatives of both 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TEMPON) and 3-imidazolines.