Heterolytic radicals addition reactions

The direct substitution steps are analogous to the Sw2 or S 2 displacements of heterolytic chemistry and are termed SH2 reactions radical substitutions that are most reasonably formulated as being initiated by addition of a radical to an unsaturated system (Equation 9.65) (analogous to addition-elimination sequences in heterolytic reactions) are considered in Section 9.4. 

The sensitivity of 46 to conjugate addition reaction conditions indicated to us the need for a mechanistically distinct approach to formation of the penultimate ring of strychnine. The fact that the weak carbon-iodide bond ( 57 kcal/mol) is readily cleaved heterolytically suggested the potential for a radical-mediated ring piperidine closure.52... 

In this chapter, we discuss reactions that either add adjacent (vicinal) groups to a carbon-carbon double bond (addition) or remove two adjacent groups to form a new double bond (elimination). The discussion focuses on addition reactions that proceed by electrophilic polar (heterolytic) mechanisms. In subsequent chapters we discuss addition reactions that proceed by radical (homolytic), nucleophilic, and concerted mechanisms. The electrophiles discussed include protic acids, halogens, sulfenyl and selenenyl reagents, epoxidation reagents, and mercuric and related metal cations, as well as diborane and alkylboranes. We emphasize the relationship between the regio-and stereoselectivity of addition reactions and the reaction mechanism. 

In heterolytic bond cleavage, a bond breaks such that both electrons in the bond stay with one of the atoms in homolytic bond cleavage, a bond breaks such that each of the atoms retains one of the bonding electrons. An alkyl peroxide is a radical initiator because it creates radicals. Radical addition reactions are chain reactions with initiation, propagation, and termination steps. Radicals are stabilized by electron-donating alkyl groups. Thus, a tertiary alkyl radical is more stable than a secondary alkyl radical, which is more stable than a primary alkyl radical. A peroxide reverses the order of addition of H and Br because it causes Br, instead of H, to be the electrophile. The peroxide effect is observed only for the addition of HBr. 

Addition mechanisms are broadly defined to be heterolytic, homolytic, or cyclic, which are processes that involve ionic or radical intermediates or are concerted, respectively. Concerted reactions will be discussed in Chapter 11. The emphasis here will be heterolytic (ionic) additions, although we will also consider some aspects of radical reactions. Addition reactions may be categorized further as being electrophilic or nucleophilic. In an electrophilic addition, a compoimd with a multiple bond reacts with an electrophilic reagent to produce an intermediate that subsequently reacts with a nucleophile. In nucleophilic addition, the unsaturated substrate reacts with a nucleophile to produce an intermediate that subsequently reacts with an electrophile to produce the final product. ... 

The excited-state molecules may return to the groimd state through radiationless decay, or imdergo homolytic dissociation reactions to form free radicals, which are believed to be the main protagonists in subsequent radiochemical reactions. Heterolytic bond cleavage may in addition result in the formation of charged species. 

Addition at the double C=C bond occurs via various mechanisms ionic, radical, or molecular. In this Section we consider briefly the mechanisms of heterolytic addition. Electrophilic addition reactions Adg are widely abundant. Halogens and hydrogen halides often add according to this mechanism. The addition of HX to the 7i-C=C bond in a polar medium where HX is ionized occurs in two steps... 

It has been suggested that the initial formation of iodine on addition of iodide to a diazonium salt solution is caused by oxidation of the iodide by excess nitrite from the preceding diazotization. Packer and Taylor (1985) demonstrated that, if urea was added as a nitrite scavenger (see Sec. 2.1) to a diazotization solution, that solution produced iodine much more rapidly than a portion of the same diazonium salt solution not containing urea, but eventually the latter reaction too appeared to follow the same course. This confirms the role of excess nitrite, and suggests that the iodo-de-diazoniation steps only occur in the presence of iodine or triiodide (I -). The same authors also found that iodo-de-diazoniation is much slower under nitrogen. All these observations are consistent with radical-chain processes, but not with a heterolytic iodo-de-diazoniation. 

Having a weak O—O bond, peroxides split easily into free radicals. In addition to homolytic reactions, peroxides can participate in heterolytic reactions also, for example, they can undergo hydrolysis under the catalytic action of acids. Both homolytic and heterolytic reactions can occur simultaneously. For example, perbenzoates decompose into free radicals and simultaneously isomerize to ester [11]. The para-substituent slightly influences the rate constants of homolytic splitting of perester. The rate constant of heterolytic isomerization, by contrast, strongly depends on the nature of the para-substituent. Polar solvent accelerates the heterolytic isomerization. Isomerization reaction was proposed to proceed through the cyclic transition state [11]. 

Without additives, radical formation is the main reaction in the manganese-catalyzed oxidation of alkenes and epoxide yields are poor. The heterolytic peroxide-bond-cleavage and therefore epoxide formation can be favored by using nitrogen heterocycles as cocatalysts (imidazoles, pyridines , tertiary amine Af-oxides ) acting as bases or as axial ligands on the metal catalyst. With the Mn-salen complex Mn-[AI,AI -ethylenebis(5,5 -dinitrosalicylideneaminato)], and in the presence of imidazole as cocatalyst and TBHP as oxidant, various alkenes could be epoxidized with yields between 6% and 90% (in some cases ionol was employed as additive), whereby the yields based on the amount of TBHP consumed were low (10-15%). Sterically hindered additives like 2,6-di-f-butylpyridine did not promote the epoxidation. 

These features all find counterparts in the heterolytic aromatic substitutions the rest of the reaction sequence in the radical additions becomes considerably more complex. The first point is that the removal of the hydrogen atom from the carbon that has been attacked in 40 is not spontaneous, but requires interaction with some other radical (Equation 9.100) or oxidizing agent (Equation 9.101). If the abstraction is by another radical (Equation 9.100), the... 

Results of recent study, however, have been interpreted in terms of a homo-lytic process. Schechter and Conrad [49] have observed that the production of methyl-3-nitroacrylate and methyl-2-hydroxy-3-nitropropionate in the reaction between N204 and methyl acrylate could not be explained on the basis of heterolytic addition, but was to be expected if a homolytic process were occurring. Brown [80] has shown that olefin nitration under circumstances in which the nitronium ion (N02+) is the reactant has characteristics entirely different from those of the N204-olefin reaction. Brand and I. D. R. Stevens [81] also believed the reaction of addition of nitrogen dioxide to olefins to involve radicals. According to these authors the following experimental facts provide evidence for this ... 

As we stated earlier, the majority of methods to form C-C bonds in a total synthesis are based on heterolytic processes involving the participation of carbanion- or carbocation-like species or imply the utilization of various cycloaddition reactions. The main reason radical reactions are generally less suited for this purpose can be easily understood if one takes into account the mechanisms involving homolytic scission/formation of covalent bonds. Typically these reactions proceed as a sequence of discrete steps initiation, chain propagation, and termination, as is shown for the radical addition at the double bond in Scheme 2.139. 

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