Radicals from halides

Intramolecular 5-exo radical additions to double bonds forming five-membered rings have been widely explored over the last few decades, and are probably the methods of choice to form such rings. The radicals can be produced in different ways. The classical tributyltin-mediated formation of radicals from halides, thionocarbonates, and so on, has been widely used. More recently, diiodosamarium-mediated radical formations have been explored. In these cases, aldehydes are reacted with Sml2 to generate ketyl radicals, which can be added to activated double bonds. 

The reactions of equations (7.92) and (7.93) are special cases of the Wurtz and Wurtz-Fittig reactions that were once prominent in elementary texts. Such reactions involve the formation of radicals from halides through reductive fission by electron transfer,... 

TABLE 4. Absolute kinetic data for halogen abstraction by some radicals from sulfonyl halides... 

The rapid desulfonylation of PhCHjSOj has been used successfully as a probe for laser flash photolytic investigations of various reactions generating sulfonyl radicals from sulfonyl halides . 

An alternate positive ion approach, similar to that in Eq. 5.4a is to obtain a carbon-halogen BDE, R X, from which it is possible to obtain the enthalpy of formation of the radical from which the hydrocarbon BDE can be derived. The advantage of this approach is that it is easier to measure the R appearance energy from RX than it is from RH because of the weaker RX bond. However, a limitation of the approach is that the enthalpies of formation of organic halides, required to determine the enthalpies of formation of the cations, are generally not known as accurately as those for hydrocarbons. 

Hydrogen halides will easily add to unsaturated compounds under radiolysis or photolysis. The free-radical chain reaction process is initiated by the dissociation of the halide or by the radiolytic production of radicals from the halide or the organic compound. Thus, for the radiolysis of a mixture of HBr and ethene the postulated initiation is... 

Chemically induced dynamic nuclear polarization (CIDNP) was first reported in 1967 in independent work from three different laboratories. The effects of free radicals on NMR spectra were revealed (Fig. 6) in studies of radicals from peroxides (equation 62) and azo compounds, as well as radicals generated from the reaction of alkyl halides and organolithium compounds. ... 

If the assumption of this reaction sequence is correct, the photolysis of tetraphenylphosphonium chloride must then only lead to biphenyl, diphenylphosphine, ethyl diphenyl-phosphinate and triphenylphosphine and its oxidation products. After 2 h of irradiation, biphenyl, diphenylphosphine and its oxidation products, triphenylphosphine and triphenylphosphine oxide, in a ratio of 3 1 5, along with raw material, are obtained. Ethyl diphenylphosphinate was detected in trace amounts7. These results support the postulate of the reversibility of phosphoranyl radical formation in such systems and indicate one-electron transfer processes15 in the formation and decomposition of the tetraarylphosphonium cation. This reaction is comparable to the observation of an electron transfer from halide ions to hydroxyl radicals or hydrogen atoms in aqueous solutions16,... 

Of all the radical reactions, the exo-l,5-cycIization of a hex-5-enyl radical to cyclopen-tylmethyl radical and its subsequent trapping by various reagents have attracted the most attention from synthetic chemists (Scheme 1) [4-7]. Starting materials that are most often used for the tin method (initiation of the chain by trialkyl tin radical) are halides, sulfides, selenides, or thionocarbonates. The generation and cyclization of the radical proceeds under exceptionally mild neutral conditions, and these conditions are compatible with a wide variety of common functional groups. A prototypical example of an application in carbohydrate chemistry is shown in Scheme 2 [8]. Readily available 2,3-di-O-isopropyl-ideneribonolactone 1 was converted into the bromoacrylate 2 in three steps. Radical... 

A radical eyclization was conducted with 2,2 -a/obisisobutyronitnle AIBN (37) as the radical initiator. Tributyltin hydride serves as the chain transfer reagent. Radical 38 arises from halide 15 through abstraction of an iodine atom, and this in turn cyclizes to radical 39. Compound 39 then abstracts a proton from tributyltin hydride. The resulting tributyltin hydnde radical reinitiates the radical mecha msm, in that it abstracts an iodine atom from another halide molecule 15 (see Chapter 14). 

If, oil the other hand, R- is unsaturated and can undergo cyclization rapidly, it will do so. This competition between reduction of the first formed radical R and its cyclization to a new cyclic radical R - is the same as discussed for the formation of free radicals from alkyl halides and tributyltin radicals. The only difference is in the way in which the carbon-centered radical is produced. 

The formation of the C-C bond occurs in a radical chain reaction (Scheme 1). Bromine abstraction from halide 1 by tin radicals 23 leads to carbon radicals 3 that react with alkenes 4 to give product radicals 5. Trapping of 5 by tributyltin hydride yields products 6 and the tin radical 2. 

RX - RCHO. Carbonylation of alkyl or aryl radicals generated with Bu3SnH/ AIBN from halides is usually not useful because reduction to the alkane is more facile. However, this radical conversion of RX to RCHO can be effected in yields of 40-70% if Bu3SnH is used in low concentrations (-0.05 M) and with 15-90 atm. of CO. 

Especially for alkyl halides 6 the transfer of a single electron from the metal center is facile and occurs at the halide via transition state 6C, which stabilizes either by direct abstraction of the halide to a carbon-metal complex radical pair 6D or via a distinct radical anion-metal complex pair 6E. This process was noted early but not exploited until recently (review [45]). Alkyl tosylates or triflates are not easily reduced by SET, and thus Sn2 and/or oxidative addition pathways are common. The generation of cr-radicals from aryl and vinyl halides has been observed, but is rarer due to the energy requirement for their generation. Normally, two-electron oxidative addition prevails. 

Following the prophetic speculations of Kharasch and Reinmuth [A] and the crucial CIDNP experiments of the Amsterdam group [22], the main features of the mechanism are now clear. Electron transfer from the magnesium surface to adsorbed organic halide gives rise to alkyl radicals and halide ions. Further recombination steps lead to the alkylmagnesium halide. Two matters especially remain controversial whether the electron transfer step involves a discrete radical anion intermediate, and to what extent radicals leave the metal surface to diffuse into the solution. Recent arguments have been summarized [23, 24], commented on [25], and pursued [26]. The implications for practical work may be summarized briefly as follows ... 

At first it was thought that the copper methyl might react with the silicon halide in the manner of a Grignard reagent, but copper ethyl and copper phenyl prepared in ether suspension did not react with silicon tetrachloride. Neither did free methyl radicals from lead tetramethyl react with elementary, silicon, but they did add on silicon that was being chlorinated. This suggests that the third step in the mechanism is the addition of methyl groups to the chlorinated silicon formed in the cuprous chloride reduction ... 

Our initial experiments to prepare the radical by the reaction of sodium atoms with phenyl iodide were inconclusive because the resolution was very poor when the parent halide was used as the matrix. Attempts to increase the resolution by using camphane or adamantane as a matrix were unsuccessful as immediately after formation the phenyl radical abstracted hydrogen from the matrix to form benzene and a radical from the matrix. Complete reaction also occurred with matrices of other saturated hydrocarbons which possessed only secondary hydrogens... 

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