Organic radical chemistry scheme

Fig. 5.9 Scheme of organic radical chemistry and fate of characteristic organic groups. RH hydrocarbon, R organic radical, RO2 organic peroxo radical, ROOH organic peroxide, RO organic 0x0 radical, RCHO aldehyde, RCOOH carbonic add, RC(OC)R keton, R=R olefin. Reaction between RO or RO2 and NO or NO2 are not included in this scheme. 

In more recent studies, the Barton group has shown that 0-acyl thiohydroxamates (thiohydroxamate esters) are convenient sources of alkyl radicals.490,51,52 Barton s thiohydroxamate ester chemistry is mild and easily executed, and the intermediate organic radicals are amenable to a wide variety of useful transformations. A thiohydroxamate ester of the type 125 (see Scheme 23) can be formed... 

This chapter contains a survey of free-radical-mediated multicomponent reactions (MCRs), which permit the coupling of three or more components. Even though they are not technically classified as MCRs, remarkable intramolecular radical cascade processes have been developed. Some examples, such as those shown in Scheme 6.3, use an isonitrile or acrylonitrile as the intermolecular component for each reaction [6]. These examples demonstrate the tremendous power of the combination of inter- and intramolecular radical cascade processes in organic synthesis. Readers are advised to be aware of remarkable intramolecular aspects of modem radical chemistry through excellent review articles published elsewhere [1, 7]. It should also be noted that there has also been remarkable progress in the area of living radical polymerizations, but this will not be covered here. 

Tris(thioalkyl)silanes may be prepared by reaction between ClsSiH and thiols in a manner similar to the preparation of alkoxysilanes and are useful reagents for radical reductions of alkyl halides or alkenes in organic chemistry (Scheme... 

Metal-catalyzed living radical polymerization can be traced back to metal-catalyzed radical addition reactions to alkenes, sometimes collectively called Kharasch or atom-transfer radical addition (ATRA) reactions in organic chemistry (Scheme 2).33 Thus, a... 

In essentially all the reactions discussed so far, the radicals were generated by thermal or photochemical homolysis. There is another way to produce radicals and this is represented in Scheme 8.1. It consists in removing an electron from an electron-rich species represented by an anion or by adding one electron to an electron-deficient entity, now represented by a cation. It is possible, of course, to oxidise a radical to a cation or reduce it to an anion. This constitutes an alternative way of destroying radical character, in addition to recombination and disproportionation. Such transformations are referred to as redox processes they are exceedingly important in radical chemistry and their impact on organic synthesis can hardly be overstated. 

It is well known from chemical history that the discoveries of the first stable organic radicals, such as triphenylmethyl, diphenyl-picrylhydrazyl, tri-tert-butylphenoxyl, and nitroxides are very significant contributions to theoretical chemistry. The relative stabilities of these radicals were attributed by chemists to the participation of an unpaired electron in conjugated ir-electron systems. Classical stable radicals can thus be thought of as a superposition of many resonance structures with different localizations of an unpaired electron. The first stable radical obtained by Pilotti and Schwerin in 1901 in the pure state can be described by a variety of tautomeric and resonance structures as shown in Scheme 1. 

DNA synthesis depends on a balanced supply of the four deoxyribonucleotides [1]. In all living organisms, with no exception so far, this is achieved by reduction of the corresponding ribonucleotides (substrates can be either ribonucleoside diphosphates NDP or ribonucleoside triphosphates NTP) by NADPH (Scheme 10-1), through a complex free radical chemistry. The substrate specificity is modulated by a sophisticated allosteric mechanism which makes it possible for a single protein to regulate the reduction of all four conunon ribonucleotides. This aspect will not be discussed here. Three well-characterized classes of ribonucleotide reductases (RNRs) have been described so far, which all are radical metalloenzymes [2-5]. 

The tertiary amine motifs are widely found in natural products and bioactive compounds. In principle, double electron oxidation of tertiary amines can produce iminium intermediate, which is able to be trapped by a diverse range of nucleophiles (Scheme 3.2a). Alternatively, single-electron oxidation of tertiary amines would form a-aminoalkyl radical (Scheme 3.2b). The further organic transformations of a-aminoalkyl radical have become one new trend for modification of tertiary amines. The exploitation of a-aminoalkyl radical chemistry constitutes an important complement to the well-studied oxidative iminium ion chemistry. 

The addition of halocarbons (RX) across alkene double bonds in a radical chain process, the Kharasch reaction (Scheme 9.29),261 has been known to organic chemistry since 1932. The overall process can be catalyzed by transition metal complexes (Mt"-X) it is then called Atom Transfer Radical Addition (ATRA) (Scheme 9.30).262... 

If an electron is transferred from a reducing agent to an arenediazonium ion, an aryldiazenyl radical (8.47) is formed. As discussed in this section, the latter dissociates rapidly into an aryl radical and N2 (Scheme 8-28). This type of dediazoniation was observed by Griess (1864 c), albeit not in our present formulation. He found that arenediazonium ions formed iodoarenes and N2 in the presence of iodide ions. More important for synthetic organic chemistry were some dediazonia-tions discovered in the late 19th and early 20th centuries, which are catalyzed by metals and metal ions, namely the Sandmeyer, Pschorr, Meerwein, and related syntheses (see Ch. 10). 

The one-electron oxidation of enol silyl ether donor (as described above) generates a paramagnetic cation radical of greatly enhanced homolytic and electrophilic reactivity. It is the unique dual reactivity of enol silyl ether cation radicals that provides the rich chemistry exploitable for organic synthesis. For example, Snider and coworkers42 showed the facile homolytic capture of the cation radical moiety by a tethered olefinic group in a citronellal derivative to a novel multicyclic derivative from an acyclic precursor (Scheme 8). 

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