Oxoammonium‐ and Nitroxide‐Catalyzed Oxidations of Alcohols

Abstract

The discovery in 1959 of stable nitroxide‐based free radicals such as the prototypical 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) led to their use as electron spin resonance (ESR) spin labels in chemistry, biomedicine, and materials science. These nitroxides are prepared by the oxidation of secondary amines that contain no hydrogen atoms on the alpha‐carbons. The unique redox properties of nitroxides enable their use as oxidants in organic synthesis. The varied preparation and uses of oxoammonium salts as stoichiometric oxidants for alcohols are one subject of this review. Oxoammonium ions as oxidants for alcohols have a number of advantages, for example, the method is heavy‐metal free and some of the reactions can be performed in water or aqueous mixtures. A few side reactions are associated with these oxidations. The most serious is the fast reaction of the oxoammonium ion with free amines The several ways these oxidation reactions can be carried out are discussed in detail. They are: Oxidations using stoichimetric quantities of preformed oxoammonium salts carried out in either acidic, neutral, or basic conditions; reactions in which stoichiometric quantities of oxoammonium salts are generated in situ by disproportionation of a nitroxide in the presence of a strong acid; nitroxide‐catalyzed oxidations using a secondary oxidant; efficient nitroxide‐catalyzed oxidations of primary alcohols to carboxylic acids; and oxidations of primary alcohols or hemiacetals that can lead to lactones.

Design concept for α-hydrogen-substituted nitroxides

“…P ersistent nitroxides have intriguing structural and chemical properties [1][2][3] and possess a multitude of highly important applications, such as oxidation catalysts [4][5][6][7] , reagents in living polymerization reactions 8 , spin probes in biology 9 , radical traps in mechanistic investigations, spin trapping agents, medicinal agents 10,11 and in materials chemistry 12 . Designing and preparing stable nitroxides, as well as predicting their properties, remains an important challenge that must be met through a combination of computational methods and creativity 12 .…”

“…TEMPO (3) is a shelf-stable compound and is the catalyst of choice in industry 14 as well as in academia for the oxidation of primary alcohols to aldehydes [1][2][3][4][5][6][7] . It has many applications in evaluating radical formation in biological tissues 15,16 and is also the trapping agent of choice in mechanistic investigations of chemical processes when a radical intermediate is suspected 17,18 .…”

“…2) 19 . The magnitude of this challenge was succinctly described in a 2009 review: 'ynitroxides are prepared by the oxidation of secondary amines that contain no hydrogen atoms on the a-carbonsy If the amines carry a-hydrogens, the oxidation products are nitrones, not free-radical nitroxidesy' 1 .…”

“…It is not clear which of these mechanisms is operative, and the decomposition mechanism may depend on the structure of the nitroxide in question (see detailed discussion below). It should be noted that, while oxoammonium cations such as 11 are important species inferred in many catalytic oxidative processes, only a few oxoammonium salts, mainly of TEMPO derivatives, have been isolated as discrete stable materials [1][2][3] . For fully alkyl-substituted radicals such as 3, it has been shown that decomposition of the oxoammonium salt occurs predominantly via b-deprotonation by a base 1,32 .…”

“…It should be noted that, while oxoammonium cations such as 11 are important species inferred in many catalytic oxidative processes, only a few oxoammonium salts, mainly of TEMPO derivatives, have been isolated as discrete stable materials [1][2][3] . For fully alkyl-substituted radicals such as 3, it has been shown that decomposition of the oxoammonium salt occurs predominantly via b-deprotonation by a base 1,32 . For 3, the equilibrium between two nitroxides and the oxoammonium ion and hydroxylamine can also be catalysed by acid 1,32 .…”