Solid-Phase Radical Reactions

Solid-supported radical reactions started to be exploited in carbon-carbon bond formations due to the increased ability of the chemist to control radical processes. A deeper knowledge of the thermodynamic and kinetic aspects of the radical chains allows the minimization of unwanted side reactions. Radical reactions lead mainly to kinetically determined products. Favored reactions are those involving proximal functionalities, along with reactions leading to cyclized products. In these cases, a radical generated by a selective reaction is allowed to react with a non-radical, usually a double bond. The radical character in such a reaction is not destroyed during the process therefore, only catalytic amounts of radical initiator are required. The products generated in radical reactions are mostly not diffusion- 

When steric and electronic features of the radical intermediates do not allow the desired radical propagation steps to be sustained, the product yield may be low. In such cases, more favorable - but often undesirable - processes, such as H-abstrac-tion from the solvent, may become dominant [503]. Especially intriguing are scaffolds on which radical and ionic cyclizations lead to different products. Thus, Ber-teina et al. described the formation of l-alkylidene-5H-dihydrobenzofuran and l-alkyl-5-dihydrobenzofuran from o-iodobenzyl vinyl ethers. The former product was formed by an intramolecular Heck reaction, while the latter was formed in high yields in a radical cyclization [504], 

Sml2 [505] and AIBN [503, 504, 329] have been used as initiators for radical reactions. A means for obtaining a clean product has been described by Du and Armstrong [505], who selectively trapped the final radical product by reduction to an organosamarium species. The latter was then allowed to react with various polymer-bound electrophiles. Among the radical processes, the tandem ones are the most ambitious and fruitful, because more than one carbon-carbon bond at a time is formed, frequently with high stereochemical control. 

Solid-phase intermolecular radical reactions, as previously seen for supported cross-metathesis reactions, should offer the advantage of limiting side reactions, i.e. potential homo-coupling of the immobilized counterpart, due to the unfavorable distance between the reaction centers. 

Free-radical addition of haloalkanes to soHd-supported alkenes as the key step in 

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Routledge et al. [7] investigated the formation of dihydrobenzofuran 1 from an aryl halide precursor (Scheme 1). With polystyrene, more than 1 equivalent of AIBN was required, while the reaction was complete within 20 h using 6 mol% of AIBN on TentaGel resin (which has a polyethylene spacer between the polystyrene and the site of compound attachment). Addition of t-butanol helped prevent an alternative y -elimination pathway. An attempt to force the latter was made with thiyl linker 2, but only trace amounts of the )9-elimination product 3 were formed. Also investigated were the cyclizations of iodides 4, in which the cyclization of an alkyl radical to an acetylene is approximately 10 times slower than the aryl radical cyclization to a double bond. A direct comparison of the same reaction on solution phase was attempted, but yields could not be determined for the latter because of contamination by tin residues. This illustrates one advantage of solid-phase radical reactions mediated by tributyltin hydride, namely the ease of product purification. 

The results presented provide strong evidence that the method based on the application of hydrosilylation reactions for producing hydrolytically stable Si-C bonds is very promising. The broad experience has been acquired in the field of the introduction of sSiH groups and olefin radicals into a surface layer of silica by various procedures. A large body of basis for carrying out systematic researches into the formation Si-C bonds on silica surface by catalytic and thermal hydrosilylation reactions. The results obtained during the last decade of the studies on the solid-phase hydrosilylation reactions with the participation of modified silica surface are discussed in Refs. [119-137]. 

As is seen from Fig.17, the reactivity of 1-decene in the solid-phase hydrosilylation reaction is higher than that of 1-hexene. This can be accounted for by a higher electron density on a terminal carbon atom of a double bond of 1-decene since alkyl radicals are electron donors. For example, the positive induction effect of octyl groups is higher than that of butyl groups [144]. 

Bruk et al. [716] described the low-temperature radiation polymerization of crystalline TFE in detail. It has been established that three solid-phase postpolymerization reactions can take place when irradiated specimens are heated above the melting point low-temperature polymerization (in the interval 77 to IlOK), slow polymerization close to the melting point (in the interval 128 to 138 K), and rapid polymerization during melting of the crystal (142 K). Tabata et al. [717] have found that a significant post-polymerization takes place even in the liquid phase. Kinetic analysis has been made of the in-source and post-polymerizations [718,719]. Post-polymerization is explained by a long lifetime of polymer radicals in the hquid phase at —78 °C due to the slow combination rate of the polymer radicals caused by their rod-like shape. 

Lee MC, Choi W (2002) Solid phase photocatalytic reaction on the soot/Ti02 interface the role of migrating OH radicals. J Phys Chem B 106(45) 11818-11822... 

K2C03 3 H202 contains hydrogen peroxide of crystallization and the solid phase decomposition involves the production of the free radicals OH and HOi, detected by EPR measurements [661]. a—Time curves were sigmoid and E = 138 kJ mole-1 for reactions in the range 333—348 K. The reaction rate was more rapid in vacuum than in nitrogen, possibly through an effect on rate of escape of product water, and was also determined by particle size. From microscopic observations, it was concluded that centres of decomposition were related to the distribution of dislocations in the reactant particles. 

Evidence indicates [28,29] that in most cases, for organic materials, the predominant intermediate in radiation chemistry is the free radical. It is only the highly localized concentrations of radicals formed by radiation, compared to those formed by other means, that can make recombination more favored compared with other possible radical reactions involving other species present in the polymer [30]. Also, the mobility of the radicals in solid polymers is much less than that of radicals in the liquid or gas phase with the result that the radical lifetimes in polymers can be very long (i.e., minutes, days, weeks, or longer at room temperature). The fate of long-lived radicals in irradiated polymers has been extensively studied by electron-spin resonance and UV spectroscopy, especially in the case of allyl or polyene radicals [30-32]. 

At present, the chemisty of selenophenes and tellurophenes is a relatively scantily studied area. Nevertheless, a number of new valuable contributions dealing with their chemistry have emerged. Electrophilic cyclization of l-(l-alkynyl)-2-(methylseleno)arenes provides a route to a variety of 2,3-disubstituted benzo[fe]selenophenes, as illustrated by the preparation of the system 88. Other useful electrophiles for similar reactions are E or NBS <06JOC2307>. Similar chemistry has also been employed in preparation of 2,3-disubstituted benzo[f>]selenophenes on solid phase <06JCC163>. In addition, syntheses of 2,3-dihydroselenolo[2,3- >]pyridines have been achieved using radical chemistry <06OBC466>. 

Polymer oxidation is similar to oxidation of low-molecular-weight analogs in the liquid phase and has several peculiarities caused by the specificity of solid-phase free radical reactions of macromolecules. Several monographs are devoted to this field of chemistry [11,12,33-41],... 

Diffusion of particles in the polymer matrix occurs much more slowly than in liquids. Since the rate constant of a diffusionally controlled bimolecular reaction depends on the viscosity, the rate constants of such reactions depend on the molecular mobility of a polymer matrix (see monographs [1-4]). These rapid reactions occur in the polymer matrix much more slowly than in the liquid. For example, recombination and disproportionation reactions of free radicals occur rapidly, and their rate is limited by the rate of the reactant encounter. The reaction with sufficient activation energy is not limited by diffusion. Hence, one can expect that the rate constant of such a reaction will be the same in the liquid and solid polymer matrix. Indeed, the process of a bimolecular reaction in the liquid or solid phase occurs in accordance with the following general scheme [4,5] ... 

Rapid bimolecular reactions are limited by diffusion of reactants in the liquid and solid phases. Diffusion occurs in polymers much more slowly than in liquids. Hence, such rapid reactions as recombination of free radicals occurs in polymers with rate constants of a few order of magnitude more slowly than in solution. For example, the reaction of sterically hindered phenoxyl with the peroxyl radical... 

Unfortunately, the appeal of solid phase extractions on small scale fades as the scale increases due to the cost and inconvenience of using large amounts of fluorous silica gel. Here, modified techniques to reduce the tedium of repeated extractions are attractive. For example, Crich has recently introduced the minimally fluorous selenide C6Fi3CH2CH2C6H4SeH[171. This selenol is added in catalytic quantities to tin hydride reductions of reactive aryl and vinyl radicals. The high reducing capacity of the aryl selenide suppresses undesired reactions of product radicals without suppressing the reactions of the aryl and vinyl radicals themselves. After the reaction is complete, the selenol can be recovered by a modified continuous extraction procedure. 

Two mechanisms of mechanochemical reactions are most likely. First, under the action of mechanical stress, intermixing occurs at the molecular level. Second, the product forms on the surface of macroscopic reacting species. Formed in the solid phase, the radicals generated recombine so that mechanolysis proceeds as a reversible reaction. However, the term reversibility should be applied only to the bond formation between radicals. For example, the structure of recombined product can be and is different from that of the starting material. It is the main feature that disturbs conventional reversibility of the radical recombination during mechanolysis. 

The photoinduced reaction of chloranil with various 1,1-diarylethenes is another example of an intramoleclar [2 -I- 2] cycloaddition as reported by Xu and co-workers [86]. Although not interesting from the preparative point of view, the diverse reaction outcomes caused by parallel reaction pathways with and without single-electron transfer and various secondary reactions of the primary products show that the photochemistry involving haloquinones is far from being explored. Another interesting example in this context is the reaction of dichlorobenzoqui-none with various diarylacetylenes in the solid phase via photoinduced electron transfer as reported by Kochi and co-workers [87]. Here, time-resolved spectroscopy revealed the radical ion pair of the two reactants to be the first reactive intermediate that then underwent coupling. 

Free radicals generated by zinc and alkyl iodides easily add to oxime ethers (e.g. 106, equation 75), providing good yield of corresponding hydroxylamines 107. This reaction has also been performed in solid-phase bound oxime ethers. ... 

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