Radical Initiators in Organic Synthesis

Scheme 1). Therefore azo compounds have been widely used as radical initiators in organic synthesis [2],... 

Azo compounds are widely used as radical initiators in organic synthesis [1], AIBN (2,2 -azobisisobutyronitrile) is the most commonly used initiator because of its high decomposition ability and stability. Azo compounds are decomposed by heat to the corresponding alkyl radicals and nitrogen [1]. As previously described, it is known that they undergo decomposition via the cis form by absorbing light [3]. 

AIBN is one of the most widely used radical initiators in organic synthesis. It is commercially available as white crystals, whose melting point is 65 °C with a half-life of 10 h in toluene at 65 °C. It is often used with trialkyltin hydrides in synthetic reactions (Scheme 6) [9]. 

Benzoyl peroxide is one of the most widely used peroxide radical initiators in organic synthesis (Scheme 11) [1], It appears as white crystals with melting point 105-106 °C. This compound is decomposed by heat to form phenyl radical and carbon dioxide via benzoyloxy radical (Scheme 12). 

As described above, there are many kinds of radical initiators in organic synthesis. Each initiator has its individual advantages and disadvantages, and we should therefore choose the most suitable initiator according to the reaction conditions. 

The use of free-radical reactions in organic synthesis started with the reduction of functional groups. The purpose of this chapter is to give an overview of the relevance of silanes as efficient and effective sources for facile hydrogen atom transfer by radical chain processes. A number of reviews [1-7] have described some specific areas in detail. Reaction (4.1) represents the reduction of a functional group by silicon hydride which, in order to be a radical chain process, has to be associated with initiation, propagation and termination steps of the radical species. Scheme 4.1 illustrates the insertion of Reaction (4.1) in a radical chain process. 

Addition of phosphonyl radicals onto alkenes or alkynes has been known since the sixties [14]. Nevertheless, because of the interest in organic synthesis and in the initiation of free radical polymerizations [15], the modes of generation of phosphonyl radicals [16] and their addition rate constants onto alkenes [9,12,17] has continued to be intensively studied over the last decade. Narasaka et al. [18] and Romakhin et al. [19] showed that phosphonyl radicals, generated either in the presence of manganese salts or anodically, add to alkenes with good yields. 

Carbon-carbon bond formation is a fundamental reaction in organic synthesis [1, 2,3,4], One way to form such a bond and, thus, extend a carbon chain is by the addition of a polyhalogenated alkane to an alkene to form a 1 1 adduct, as shown in Scheme 1. This reaction was first reported in the 1940s and today is known as the Kharasch addition or atom transfer radical addition (ATRA) [5,6], Historically, Kharasch addition reactions were conducted in the presence of radical initiators or... 

Curran2 has reviewed recent applications of the tin hydride method for initiation of radical chain reactions in organic synthesis (191 references). The review covers intermolecular additions of radicals to alkenes (Giese reaction) as well as intramolecular radical cyclizations, including use of vinyl radical cyclization. 

This class of ion-radicals is characterized by the localization of an unpaired electron at the atom bearing a free (valence) electron pair. Although their applicability in organic synthesis remains an open question, the preparative methods and electron structure of carbene ion-radicals attract some attention of the researchers. Probably, it is an initial step to a new chapter in organic ion-radical chemistry. 

The voltammetric response of curcumin and carthamin must, in principle, be dominated by the oxidation of the phenol and/or methoxyphenol groups (see Scheme 2.2). The electrochemistry of methoxyphenols has claimed considerable attention because of their applications in organic synthesis [159-163]. As studied by Quideau et al., in aprotic media, 2-methoxyphenols are oxidized in two successive steps into cyclohexadienone derivatives [163], whereas a-(2)- and a-(4-methoxyphenoxy) alkanoic acids undergo electrochemically induced spirolac-tonization to develop synthetically useful orthoquinone bis- and monoketals. In the presence of methanol, the electrochemical pathway involves an initial one-electron loss, followed by proton loss, to form a monoketal radical. This undergoes a subsequent electron and proton loss coupled with the addition of alcohol to form an orthoquinone monoketal. The formal electrode potential for the second electron transfer... 

Stereochemistry in radical reactions for organic synthesis has not been studied very extensively, because mild or low temperature-promoted radical reaction methods are extremely limited and the stereoselectivity in radical reactions is generally rather poor. Recently, however, stereoselective organic synthesis with radical reactions has become popular, since mild radical reaction methods such as the Barton decarboxylation, Et3B-initiated Bu3SnH reaction, etc. have been developed. Normally, low temperature-initiated radical reactions induce high stereoselectivity. 

For reviews, see Giese, B. Radicals in Organic Synthesis Formation of Carbon-Carbon Bonds, Pergamon, Elmsford, NY, 1986, pp. 69-77 Vogel, H. Synthesis 1970, 99 Huyser, E.S. Free-Radical Chain Reactions, Wiley, NY, 1970, pp. 152-159 Elad, D. Fortschr. Chem. Forsch. 1967, 7, 528. Hyponitrites have been used to initiate this reaction see Dang, H.-S. Roberts, B.P. Chem. Commun. 1996, 2201. 

Hexaorganodistannanes are used in organic synthesis for bringing about free radical reactions where termination by hydrogen transfer from a trialkyltin hydride must be avoided. Typically, 5-10 mole% of the distannane is used, and the reactions are initiated by irradiation with a sun lamp. Examples are given in equations 18-45 and 18-46.58-59... 

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