TEMPO as a radical trap

The anionic methylruthenium(II) species was autoxidized to a Ru(III) compound, RuMe(OEP). The methyl group of this compound was accidentally transformed into a coordinated carbon monoxide molecule by an excess of 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO) [158] on an attempt to use TEMPO as a radical trap for the measurement of the Ru-C bond energy in solution. This was the first transformation of a methyl group to carbon monoxide to be observed in the proximity of a metal. 

Cobalt-Carbon Bond Homolysis Studies with coenzyme Bi2 model compounds and TEMPO as a radical trap have allowed the determination of rate constants and activation parameters, which in turn led to estimates of the Co-C bond dissociation energies (BDEs). The key role of the homolytic Co-C cleaving step in these reactions was established by the following observations (Co11) is produced addition of external... 

While Yu et al. [15] reported the palladium-catalyzed ortho trifluoromethylation of arenes with an electrophilic trifluoromethylation reagent (Scheme 19.9), Liu and coworkers [69] developed a nondirected C-H trifluoromethylation method using the nucleophilic Ruppert-Prakash (TMSCFj) reagent (Scheme 19.43). Thus, indoles underwent trifluoromethylation in moderate yields at the C-2 position or, when the C-3 position was free, at the C-3 position in the presence of a Pd /bis-oxazoline catalyst, cesium fluoride, PhI(OAc)2 as the stoichiometric oxidant, and TEMPO as a radical trap. Similar to Yu s method, the mechanism was proposed to involve the formation of an Ar-Ph -CEj intermediate that reductively eliminates to form the Ar-CFj bond. 

TEMPO is widely used as a radical trap, as a structural probe for biological systems in conjunction with EPR spectroscopy, as a reagent in organic synthesis, and as a mediator in controlled free radical polymerisation. As well as alcohol oxidation, TEMPO also finds use in the oxidation of other functional groups, including amines, phosphines, phenols, anilines, sulfides and organometallic compounds [144]. 

This chapter will take a broad look at those reports where there is experimental evidence for reaction mechanisms and will deprioritize those papers where a mechanism is putative, suggested, or supported by one or two possibly ambiguous observations. In many studies, preliminary mechanisms are investigated through the addition of radical traps, yet such results need to be treated with caution, as described below. An example is the employment of TEMPO (2,2,6,6-tetramethylpiperidine-l-o grl) as a radical trap, awkward in this field because TEMPO is itself an oxidant or can be used as a co-oxidant. ... 

As a model study of methyl cobalamine (methyl transfer) in living bodies, a methyl radical, generated by the reduction of the /s(dimethylglyoximato)(pyridine)Co3+ complex to its Co1+ complex, reacts on the sulfur atom of thiolester via SH2 to generate an acyl radical and methyl sulfide. The formed methyl radical can be trapped by TEMPO or activated olefins [8-13]. As a radical character of real vitamin B12, the addition of zinc to a mixture of alkyl bromide (5) and dimethyl fumarate in the presence of real vitamin B12 at room temperature provides a C-C bonded product (6), through the initial reduction of Co3+ to Co1+ by zinc, reaction of Co1+ with alkyl bromide to form R-Co bond, its homolytic bond cleavage to form an alkyl radical, and finally the addition of the alkyl radical to diethyl fumarate, as shown in eq. 11.4 [14]. 

Copper Catalysts When N-hydroxyphthalimide is used as an oxygen source, a range of substrates can be selectively oxygenated using PhI(OAc)2 as an oxidant in the presence of CuCl catalyst (Equation 11.26) [62]. When a radical trap, TEMPO (2,2,6,6-tetramethyl-l-piperidinyloxy), is added to the reaction mixture, a TEMPO-trapped compound can be isolated (21%) along with 23% of the desired product. Therefore, a radical intermediate is most likely involved in this transformation [63]. 

TEMPO has also been utilized as a functionalizable trap in radical cyclization reactions. Bergman demonstrated the use of alkenyl iodides with tributyltin hydride and TEMPO to produce cyclized 7V-alkoxyamine products [18a], This methodology has been used as a key step in the synthesis of several novel analogs of the CC-1065 and duocarmycin antitumor antibiotics [19, 21]. In an example from Roger s laboratory, aryl iodide 15 was cyclized and trapped with TEMPO to give A -alkoxyamine product 16 (Scheme 6). This was further elaborated to A -BOC-/so-CBI (17), an analog of the DNA alkylation promoting subunit found in CC-1065 and duocarmycin. 

An investigation of why hydroxide makes the Tollens silver mirror test for aldehydes more sensitive has focused on thermodynamic versus kinetic factors. Electrochemistry tends to rule out the former the electromotive force (emf) of an appropriate cell changes little with pH. Exploring the kinetics, single electron transfer processes were confirmed by addition of a radical trap (TEMPO), which slowed the reaction. Rate measurements point to the rate of the formation of the anion of the gm-diol (i.e. the hydrate anion) as the key parameter affected by added hydroxide, a factor that also explains how the rapidity of the test varies with the structure of the aldehyde. 

A reagent such as TEMPO that specifically reacts with radicals is called a radical trap such compounds are clearly very useful as mechanistic probes. 

Activation rate constants (fean) for a specific ATRP reaction are typically determined from model studies in which the transition metal complex is reacted with a model alkyl halide in the presence of a radical trapping agent, such as 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO) or SGI. This works for every catalyst complex, even less active complexes based on... 

Organosiliconboranes having bulky substituents on the boron, e.g. R3SiB[N(CHMe)2]2, exhibit UV absorption at wavelengths longer than 300 nm. Photolysis of this band afforded a pair of silyl and boryl radicals that can be trapped quantitatively by nitroxide (TEMPO) as shown in Reaction (1.4) [10]. 

The formed acyl radicals are reactive towards efficient radical trapping reagents such as 2,2,6,6-tetramethylpiperidine-l-oxyl radical (TEMPO), diphenyl diselenide and diphenyl disulphide, and A-f-butyl-a-phenylnitrone giving the respective adducts. ... 

Meunier and coworkers investigated the degradation of arteflene using manganese(II) TPP as a heme model. They were able to spin-trap the secondary C-centred radical with the piperidyl radical (TEMPO) and the adduct 64c was fully characterized following acetylation of the crude reaction mixture (Scheme 20). An arteflene-heme adduct was not observed and the authors suggest that this is attributable to steric hindrance factors. However, this could be further evidence that endoperoxide antimalarials do not target heme. 

Photo-stimulated reactions of neopentyl iodide with several carbanionic nucleophiles have been studied in which inhibition experiments with the TEMPO radical trap suggest the reaction occurs via an SrnI mechanism.76 Comparison of 22 nucleophiles in then. Srn 1 reactions with iodobenzene by Fe(II)- and photo-induction has revealed that both are enhanced by high electron-donation ability of the nucleophile. The radical anion Phl is a key intermediate.77 The SET reactions of perfluoroalkyl iodides have been reviewed.78 Flash photolysis of H2O2 was used to generate HO and 0 radicals which were reacted with a, a. z-trifluorotolucnc (TFT) and 4-fluorotoluene (4FT) and the rate constants calculated.79 The diminished reactivity of TFT towards HO or O with respect to toluene or benzene was consistent with radical addition to the aromatic ring, whilst the reactivity of 4FT was of the same order as electron-deficient toluenes, which favour H abstraction from the aliphatic side-chain. 

Scheme 10.11 shows a PRE-mediated 5-exo-trig radical cyclisation in which the controlled thermal formation of active radicals from the dormant alkoxyamine 2 is facilitated by steric compression of the alkoxyamine C—O bond by the bulky N-alkyl and O-alkyl groups [8]. Intramolecular H-bonding between a —CH2—OH and the nitroxyl oxygen of the incipient nitroxide in a six-membered cyclic transition structure further facilitated the dissociation of 2. After cyclisation, the resultant primary cyclopentylmethyl radical was trapped by the free nitroxide to form the new dormant isomerised alkoxyamine 3, which is more stable than 2 since the O-alkyl is now primary. The same reaction using TEMPO as the nitroxide component did not work presumably because the C—O bond in the alkoxyamine precursor is much stronger. 

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