Search

Herein is reported the first preparation of stable α-deuterium nitroxides of the IAPNO family. The confirmation and characteristics of the α-deuterium nitroxides and their α-hydrogen analogues are compared and analyzed. Such α-deuterium nitroxides may find use in biology, medicine and physical chemistry.

Conditions for the oxidation of primary aliphatic, benzylic, allylic, and propargylic alcohols and secondary benzylic alcohols including benzoin in the presence of newly developed stable α-hydrogen nitroxyl radicals as the catalyst are elaborated.

2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) catalyzes the direct oxidation of primary alkyl alcohols to symmetric ­esters at 1–2 mol% loadings. These rapid reactions take place at room temperature to afford the products in yields of 55–99%.

Nitroxides (nitroxyl radicals) hold a unique place in science due to their stable radical nature. We have recently reported the first design concept providing a general solution to the problem of designing and preparing monocyclic α-hydrogen nitroxides. The initial studies were limited to aryl derivatives. We now report a wider study showing that alkyl substituents may be employed as well. In addition, we report several additional examples of aryl substituents and reveal some of the structural limitations with regard to nitroxide stability as a function of the α-carbon substituent.

Conditions for the oxidation of primary aliphatic, benzylic, allylic, and propargylic alcohols and secondary benzylic alcohols including benzoin in the presence of newly developed stable α-hydrogen nitroxyl radicals as the catalyst are elaborated.

Stable nitroxides (nitroxyl radicals) have many essential and unique applications in chemistry, biology and medicine. However, the factors influencing their stability are still under investigation, and this hinders the design and development of new nitroxides. Nitroxides with tertiary alkyl groups are generally stable but obviously highly encumbered. In contrast, α-hydrogen-substituted nitroxides are generally inherently unstable and rapidly decompose. Herein, a novel, concept for the design of stable cyclic α-hydrogen nitroxides is described, and a proof-of-concept in the form of the facile synthesis and characterization of two diverse series of stable α-hydrogen nitroxides is presented. The stability of these unique α-hydrogen nitroxides is attributed to a combination of steric and stereoelectronic effects by which disproportionation is kinetically precluded. These stabilizing effects are achieved by the use of a nitroxide co-planar substituent in the γ-position of the backbone of the nitroxide. This premise is supported by a computational study, which provides insight into the disproportionation pathways of α-hydrogen nitroxides.

TEMPO catalyzes the direct oxidation of aldehydes (I) to mixed anhydrides in the presence of pivalic acid.

The process is generally efficient under conditions A), where for the diols (V) formation of lactones is observed.