Radical mechanism, addition with alkyl halides

Recently, the iron-promoted Barbier-type addition of alkyl halides to aromatic aldehydes has been reported (Equation (26)).326 According to the proposed mechanism, the initial step is the formation of an alkyl radical, which can be reduced to the corresponding carbanion. This carbanion nucleophile can react, while coordinated to the iron pentacarbonyl complex, with the corresponding aldehyde. This stoichiometric method is limited with respect to substrate scope and yield. The same authors have also developed the Reformatsky-type addition of cr-halosub-stituted carbonitriles to aldehydes and ketones in the presence of iron pentacarbonyl.3... 

Oxidative Addition of Alkyl Halides to Palladium(0). The stereochemistry of the oxidative addition (31) of alkyl halides to the transition metals of group VIII can provide information as to which of the many possible mechanisms are operative. The addition of alkyl halides to d8-iridium complexes has been reported to proceed with retention (32), inversion (33), and racemization (34, 35) via a free radical mechanism at the asymmetric carbon center. The kinetics of this reaction are consistent with nucleophilic displacement by iridium on carbon (36). Oxi-... 

These reagents are useful in the 1,4-addition of alkyl groups to a,(l-unsaturated carbonyl systems and can also be reacted with alkyl halides to produce larger alkanes (Following fig.). The mechanism is considered to be radical based. 

The mechanisms of the usual organic reactions are now clearly established, and the reactions are classified as ionic, radical, and molecular. More detailed classifications have also been made. The mechanisms of many reactions involving non-transition metal compounds are clear enough for example, in the Grig-nard or Reformatsky reaction, the first step is the irreversible oxidative addition of alkyl halides to form Mg-carbon or Zn-carbon bonds, in which the carbon is considered to be a nucleophilic center or carbanion which reacts with various electrophiles. 

Oxidative-addition reactions of alkyl halides also occur with metal ions such as thallium(I). In this case, the HOMO is an s orbital on the metal of a symmetry. The concerted mechanism is now impossible and only a two-step reaction can occur. The same is true for reactions of metals in the free state, such as zinc or magnesium, with alkyl halides. Note that free radicals may be formed, instead of ions, in all cases discussed. Free radical reactions are usually allowed by symmetry. 

The oxidative addition of methyl iodide to Vaska s complex, shown in Equation 7.2, is a classic example of the oxidative addition of alkyl halides by an mechanism. Strong electrophiles that are sterically accessible, such as methyl iodide, benzyl bromide, allyl halides, and chloromethyl ethers, react with Lj(CO)IrX species by this pathway. A series of data supports addition of these electrophiles by an mechanism. For example, the trans stereochemistry of the kinetic product from addition of methyl iodide is inconsistent with a concerted three-centered mechanism radical traps do not affect the rate or products of the reaction the reaction rates are faster in more polar solvents - and the reactions are first order in both metal and electrophile. Higher aUcyl halides add by more complex mechanisms presented below. 

Oxidative addition of alkyl halides can also occur in certain cases by an outer-sphere electron transfer mechanism involving a coordinatively saturated metal center and an alkyl halide. This pathway is shown in Scheme 7.7. Oxidative addition by this initial outer-sphere electron transfer pathway tends to occur instead of an 5, 2 pathway when the electrophile is particularly susceptible to electron transfer, when the electrophile possesses some steric hindrance, when the electrophile possesses a weak C-X bond, and when the metal lacks an available coordination site. Because of the lack of a coordination site at the metal, the initial electron transfer occurs without prior coordination of the electrophile to the metal. This initial step parallels the electron transfer and subsequent radical chemistry that occurs when some carbanions are treated with alkyl halides. ... 

The usual sulfone synthesis by displacement of halide by sulfmate is assumed to have a nucleophilic 8 2 mechanism However, in special cases of alkyl halides with additional, electron-withdrawing substituents a radical substitution pathway has been observed (equation 32). Correspondingly, substitutions under formation of sulfones take... 

Radicals for addition reactions can be generated by halogen atom abstraction by stannyl radicals. The chain mechanism for alkylation of alkyl halides by reaction with a substituted alkene is outlined below. There are three reactions in the propagation cycle of this chain mechanism addition, hydrogen atom abstraction, and halogen atom transfer. 

Note This reaction involves a polar acidic mechanism, not a free-radical mechanism It is a Friedel-Crafts alkylation, with the slight variation that the requisite carbocation is made by protonation of an alkene instead of ionization of an alkyl halide. Protonation of C4 gives a C3 carbocation. Addition to Cl and fragmentation gives the product. 

The possibility that substitution results from halogen-atom transfer to the nucleophile, thus generating an alkyl radical that could then couple with its reduced or oxidized form, has been mentioned earlier in the reaction of iron(i) and iron(o) porphyrins with aliphatic halides. This mechanism has been extensively investigated in two cases, namely the oxidative addition of various aliphatic and benzylic halides to cobalt(n) and chromiumfn) complexes. 

Kinetic experiments have been performed on a copper-catalyzed substitution reaction of an alkyl halide, and the reaction rate was found to be first order in the copper salt, the halide, and the Grignard reagent [121]. This was not the case for a silver-catalyzed substitution reaction with a primary bromide, in which the reaction was found to be zero order in Grignard reagents [122]. A radical mechanism might be operative in the case of the silver-catalyzed reaction, whereas a nucleophilic substitution mechanism is suggested in the copper-catalyzed reaction [122]. The same behavior was also observed in the stoichiometric conjugate addition (Sect. 10.2.1) [30]. 

While a large number of studies have been reported for conjugate addition and Sn2 alkylation reactions, the mechanisms of many important organocopper-promoted reactions have not been discussed. These include substitution on sp carbons, acylation with acyl halides [168], additions to carbonyl compounds, oxidative couplings [169], nucleophilic opening of electrophilic cyclopropanes [170], and the Kocienski reaction [171]. The chemistry of organocopper(II) species has rarely been studied experimentally [172-174], nor theoretically, save for some trapping experiments on the reaction of alkyl radicals with Cu(I) species in aqueous solution [175]. 

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