Tempo-mediated

The identification of both phenylethyl and 1-phenyl-1,2,3,4-lelrahydronaphthalenyl end groups in polymerizations of styrene retarded by FeCl3/DMP provides the most compelling evidence for the Mayo mechanism.316 The 1-phenyl-1.2,3,4-tetrahydronaphthalenvl end group is also seen amongst other products in the TEMPO mediated polymerization of styrene,317318 However, the mechanism of formation of radicals 96 in this case involves reaction of the nitroxide with the Diels-AIder dimer (Scheme 3.63). The mechanism of nitroxide mediated polymerization is discussed further in Section 9.3.6. 

Catala and coworkers167JuiS made the discovery that the rate of TEMPO-mediated polymerization of S is independent of the concentration of the alkoxyamine. This initially surprising result was soon confirmed by others.23 69 Gretza and Matyjaszewski169 showed that the rate of NMP is controlled by the rate of thermal initiation. With faster decomposing alkoxyamines (those based on the open-chain nitroxides) at lower polymerization temperatures, the rate of thermal initiation is lower such that the rate of polymerization becomes dependent on the alkoxyamine concentration, Irrespective of whether the alkoxyamine initiator is preformed or formed in situ, low dispersities require that the alkoxyamine initiator should have a short lifetime. The rate of initiation should be as fast as or faster than propagation under the polymerization conditions and lifetimes of the alkoxyamine initiators should be as short as or shorter than individual polymeric alkoxyamines. 

The thermal decomposition of the phenylelhyl alkoxyamine with TEMPO and the fraction of living ends in TEMPO-mediated S polymerization has been studied by Priddy and coworkers.143 179 They concluded that to achieve >90% living ends conversions and/or nitroxide concentrations should be chosen to give V/ less than 10000.143 However, disproportionation or elimination is most important during polymerizations of methacrylates and accounts for NMP being less successful with... 

Scheme 11.12 TEMPO mediated oxidation of primary alcohols. (After [95]).

In presence of 3 equivalents of oxidant, TEMPO mediates then the rapid conversion into ketomalonic acid. The pH of the reaction medium is critical at pH 7 no reaction occurs, while at high alkalinity TEMPO+ undergoes basic dismuta-tion. At pH 10, even the immobilized catalyst is stable and can be used during several subsequent reactions [95]. 

Lemoine, S. Thomazeau, C. Joannard, D. et al. Sucrose tricarboxylate by sonocata-lyzed TEMPO-mediated oxidation, Carbohydr. Res., 2000, 326, 176-184. 

In this review, synthesis of block copolymer brushes will be Hmited to the grafting-from method. Hussemann and coworkers [35] were one of the first groups to report copolymer brushes. They prepared the brushes on siUcate substrates using surface-initiated TEMPO-mediated radical polymerization. However, the copolymer brushes were not diblock copolymer brushes in a strict definition. The first block was PS, while the second block was a 1 1 random copolymer of styrene/MMA. Another early report was that of Maty-jaszewski and coworkers [36] who reported the synthesis of poly(styrene-h-ferf-butyl acrylate) brushes by atom transfer radical polymerization (ATRP). 

Furthermore, electrochemical oxidation with TEMPO mediated aromatization of 6-membered cyclic dienes" and transformation of alkenes to alkenones also took place" . 

Recently, two groups reported controlled radical polymerizations starting from maltooligosaccharides (ATRP [182] and TEMPO-mediated radical polymerization [183]), which will certainly lead to new synthetic routes towards amylose-containing block copolymers. 

Oxidation of Cu with O2 is markedly slower than the analogous oxidation by TEMPO. The existence of a copper-centered dehydrogenation step was supported by investigating kinetic isotope effects and Hammett correlation studies using different substituted benzyhc alcohols. The /1-hydrogen abstraction was postulated to occur in a concerted mechanism with an -coordinated TEMPO radical bgand (Scheme 4). As such, this TEMPO-mediated copper-catalyzed oxidation of alcohols bears resemblance... 

Ru/SILIA CAT TEMPO-MEDIATED OXIDATION OF ALKENES TO a-HYDROXYACIDS... 

Table 6.3 Silia Cat TEMPO-mediated oxidation of vie diols to a-hydroxy acids.

Nevertheless, Celia et al. have proved that employing MCPBA as secondary oxidant in TEMPO-mediated oxidations may have a number of advantages when a one-pot oxidation of an alcohol with a concurrent alkene epoxidation or a Baeyer-Villiger oxidation is desired.6 The use of MCPBA as a secondary oxidant in TEMPO-mediated alcohol oxidations was recently reviewed.7... 

Anelli s protocol for the TEMPO-mediated oxidation of alcohols... 

Anelli s TEMPO-mediated oxidation can be accelerated by the addition of a quaternary ammonium salt, like Aliquat 336, acting as a phase transfer catalyst. This can be advisable in the oxidation of hindered secondary alcohols but can encourage the over-oxidation of primary alcohols to carboxylic acids.16... 

Apart from sodium hypochlorite, a number of alternative secondary oxidants for TEMPO-mediated alcohol oxidations can be employed. These include cerium (IV) ammonium nitrate (CAN),24 trichloroisocyanuric acid (TCCA),25 oxone ,26 MCPBA,2,3,7 PhI(OAc)2,27 W-chlorosuccinimide,28 sodium bromite,29 electrooxidation,8,21 H5IO626 and a polymer-attached diacetoxybromide (I) complex.30... 

One important limitation of TEMPO-mediated oxidations, under Anelli s conditions, originates from competing reactions produced by HOC1, generated in situ from NaOCl. This problem can be solved by the use of [bis(acetoxy)iodo]benzene (BAIB) as a secondary oxidant following the protocol of Piancatelli and Margarita27 which has proved to be particularly efficient in difficult substrates,34 and it is a highly recommended alternative to Anelli s procedure when oxidations with oxoammonium salts are desired. 

The use of [bis(acetoxy)iodo]benzene as secondary oxidant in TEMPO-mediated oxidations was first reported in 1997 by Piancatelli, Margarita el al.21 In the foundational paper, it was stated that the reaction ... can be performed in an open flask without any particular precautions, e.g. inert atmosphere or dry solvents. .. . In fact, not following these particular precautions could be mandatory, as Mickel et al.35 found that, in the oxidation of a difficult substrate on a big scale, results were not reproducible unless 0.1 equivalents of water are added to the reaction mixture. One advantage of the employment of [bis(acetoxy)iodo]benzene is that, iodobenzene, a rather inert side compound, is generated, which needs not be removed before performing many subsequent reactions. 

TEMPO-mediated oxidations can be performed under almost neutral conditions. Therefore, acid- and base-sensitive functionalities and protecting groups can remain unchanged during TEMPO-mediated oxidations. 

Although TEMPO-mediated oxidations under Anelli s protocol are routinely performed at a slightly basic pH of 8.6 9.8,10 obtained by buffering the bleach solution with NaHCX>3, sometimes, in order to avoid base-induced side reactions, it is advisable to adjust the pH at 6.5-7.5 by adding an acid.13 A proper adjustment of the pH for example allows to obtain carbonyl compounds without a-epimerization in difficult substrates in which other common oxidants fail.42... 

The most serious limitation of TEMPO-mediated oxidations under Anelli s conditions is posed by the presence of HOC1—generated in situ— as a secondary oxidant, a quite reactive chemical that adds to olefins and produces electrophilic chlorination in many electron-rich substrates. 

In variance with Anelli s conditions, TEMPO-mediated-oxidations—under the protocol of ... 

Sulfides are transformed very easily into sulfoxides during TEMPO-mediated oxidations. It is even possible to oxidize sulfides without affecting alcohols in the same molecule.48... 

Lactols are easily transformed into lactones in TEMPO-mediated oxidations.49 When the oxidation of a diol leads to a hydroxyaldehyde that is able to equilibrate with a hemiacetal, the latter is further oxidized to a lactone.50 Interestingly, as TEMPO-mediated oxidations can be very selective in favouring oxidations of less hindered alcohols, lactone formation from diols can be very regioselective.500... 

For a detailed account of TEMPO-mediated oxidations see chapter 5. 

Among common alcohol oxidants, TEMPO-mediated oxidations have been the subject of a close scrutiny, aimed at finding optimum conditions for the selective oxidation of primary alcohols. In fact, TEMPO-mediated oxidations, that is oxidations in which an oxoammonium salt acts as a primary oxidant, have a great tendency to operate quicker with primary alcohols, regardless of the secondary oxidant employed and the exact experimental conditions. 

When a TEMPO-mediated oxidation of an 1,4- or 1,5-diol leads to an hydroxyaldehyde able to equilibrate with a lactol, the lactol is normally further oxidized to a lactone.7... 

A scant look at the facts might suggest that the selective oxidation of primary alcohols in TEMPO-mediated oxidations can be explained solely on steric grounds. Things are not so simple, as it was found8 that the primary oxidants, that is oxoammonium salts, when used stoichiometrically, react quicker with primary alcohols when present as oxoammonium chlorides, while the reverse selectivity, that is selective oxidation of secondary alcohols, is observed when oxoammonium bromides are employed. 

The very common TEMPO-mediated Anelli s protocol for the oxidation of alcohols, involving a biphasic CH2Cl2-water mixture containing catalytic TEMPO, or an analogue thereof, and sodium hypochlorite as a secondary oxidant, shows a great selectivity for the oxidation of primary alcohols in the presence of secondary ones9 and has found some use in Synthetic Organic Chemistry.10... 

Other TEMPO-mediated oxidations reported to possess selectivity for the oxidation of primary alcohols versus secondary ones, include oxidations involving Q1CI2/O2,15 NaBr02,16 NCS17 and trichloroisocyanuric acid18 as secondary oxidants. 

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