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Hindrance around a nitroxyl radical center was believed to be an essential requirement for a nitroxyl radical to be stable, because simple nitroxyl radicals with an α-hydrogen underwent rapid disproportionation to their corresponding nitrone and hydroxyl amine.
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Dupeyre and Rassat reported the synthesis of norpseudopelletierine N-oxyl {9-azabicyclo[3.3.1]nonane-3-one N-oxyl} as the first stable unhindered nitroxyl radical, in which any nitrone formation would be prohibited by Bredt's rule. Since then, a panel of bridged-bicyclic unhindered nitroxyl radicals have been synthesized
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Dupeyre and Rassat reported the synthesis of norpseudopelletierine N-oxyl {9-azabicyclo[3.3.1]nonane-3-one N-oxyl} as the first stable unhindered nitroxyl radical, in which any nitrone formation would be prohibited by Bredt's rule. Since then, a panel of bridged-bicyclic unhindered nitroxyl radicals have been synthesized. (a) Dupeyre, R. M.; Rassat, A. Tetrahedron Lett. 1975, 16, 1839-1840.
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Rychnovsky and Farmer et al. demonstrated for the first time that unhindered nitroxyl radicals indeed worked as catalysts in alcohol oxidations. However, since their research interest was focused on the development of enantioselective catalysts, the catalytic efficiency of the elaborated C2-symmetric derivative of ABNO was not further examined. Graetz, B.; Rychnovsky, S.; Leu, W.-H.; Farmer, P.; Lin, R. Tetrahedron: Asymmetry 2005, 16, 3584-3598.
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In 2008, Onomura et al. reported the synthesis of a panel of azabicyclo N-oxyls and preliminary results on the electrochemical oxidation of alcohols using them as mediators to confirm their potential for the electrochemical oxidation of hindered secondary alcohols. However, they offer few comments on the efficiency of azabicyclo nitroxyl radicals toward oxidation of various alcohols under chemical conditions. (a) Demizu, Y.; Shiigi, H.; Oda, T.; Matsumura, Y.; Onomura, O. Tetrahedron Lett. 2008, 49, 48-52.
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Ingold et al. reported that the decomposition rate of 9-azabiclo[3.3.1]nonane N-oxyl (ABNO) (3) was very slow, while 8-azabicylo[3.2.1]octane N-oxyl (4) dimerized irreversibly.11
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Rychnovsky et al. also reported that 2,5-dimethylbicyclo[2.2.1]heptane N-oxyl (5) was too unstable to isolate.
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We also synthesized 8-azabicyclo[3.2.1]octane and 7-azabicyclo[2.2.1] heptane and attemped their oxidation to the corresponding nitroxyl radicals. However, we failed to isolate these nitroxyl radicals; instead, the corresponding hydroxylamines were recovered.
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We speculate that the difference came from the stability of the oxoammonium ion generated in the catalytic cycle. For notes on the instability of 9-oxo-9-azabicyclo[3.3.1]nonane oxoammonium ion, see ref 20c.
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8a
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