Cleavage radical-mediated

Kim and coworkers introduced silyl radical mediated addition of alkyl radical to silyloxy enamine 76. The silyloxy enamine moiety is readily accessible from a variety of functionalities. The mechanistic concept is illustrated in the Scheme 12 and involves the addition of R radical to 76 to give the radical adduct 77 and the subsequent homolytic cleavage of N-O bond to yield the desired product 78 and a silyloxy radical 79. The latter undergoes 1,2-phenyl migration to give the silyl radical 80 that abstracts halogen from the alkyl halide to regenerate the R radical. 

This approach was the first application of non-enediyne carbon centered radical mediated DNA cleavage agents that were not only capable of binding to DNA but could also be sequence specific. Further work is still needed to elucidate and confirm the sites of cleavage, nature of binding of these molecules and the mechanism of hydrogen abstraction from the nucleic acid backbone. 

S. Hanessian and R. Ldger, Expedient assembly of carbocyclic, heterocyclic, and polycyclic compounds by Me3Sn radical mediated carbocyclizations of dienes and trienes A novel oxidative cleavage of the C-Sn bond, J. Am. Chem. Soc. 7)4 3115 (1992). 

Selenides are more readily cleaved by tin radicals than are thioethers. Two examples of the tin radical mediated cleavage of selenides are listed in Table 3.48 (Entries 8 and 9) more examples have been reported [768,773,821-823], The carbon-centered radicals initially formed by homolytic C-Se bond cleavage can either be directly reduced to the alkane by treatment with a tin hydride, or may add to multiple bonds before reduction. Entry 10 in Table 3.48 is an example of the formation of a polycyclic indoline through radical cyclization. Radical-mediated cleavage proceeds under mild,... 

Examples of radical-mediated C-alkylations are listed in Table 5.4. In these examples, radicals are formed by halogen abstraction with tin radicals (Entries 1 and 2), by photolysis of Barton esters (Entry 3), and by the reduction of organomercury compounds (Entry 4). Carbohydrate-derived, polystyrene-bound a-haloesters undergo radical allylation with allyltributyltin with high diastereoselectivity (97% de [41]). Cleavage from supports by homolytic bond fission with simultaneous formation of C-H or C-C bonds is considered in Section 3.16. 

Radical-mediated cleavage proceeds under mild, essentially neutral reaction conditions and is well suited for the release of sensitive organic compounds from insoluble supports. Because non-volatile, tin-derived byproducts are formed during these cleavage reactions, purification of the resulting products will, however, generally be required. 

Two plausible mechanistic pathways have been proposed for the thermal decomposition of alkylsilver compounds either a radically-mediated cleavage of the carbon-silver bond or a process by which the breaking of the silver-carbon bond and formation of the carbon-carbon bond are concerted. Mechanistic studies by Whitesides and coworkers in which the product ratios obtained for the thermal process... 

In QSAR 1.113, 62% of the variance is accounted for by and 28% is explained by log P. It appears that free-radical-mediated toxicity is responsible for the growth-inhibitory effects of the phenols. Homolytic bond dissociation energies related to the homolytic cleavage of the OH bond in the following reac-tion (X—C6H4OH + CeHsO. X—CgH O. + CeHgOH) have been used in lieu of values. The net result is similar, as seen in QSAR 1.114(242). 

Sterically hindered ketones were more difficult to reduce with tin hydrides but reduction at high pressure (1 GPa) without radical or Lewis acid catalyst in methanol at 55 °C was effective.Reduction of the very hindered ketone (92) did not occur at atmospheric pressure but proceeded usefully at high pressure (equation 25). The absence of radical intermediates allowed even a,P-epoxy and cyclopropyl ketones such as (93) to be reduced in high yield, largely without cleavage of the strained ring (equation 26). Under conventional AIBN-initiated conditions radical-mediated processes predominated. 

More recently, a radical-mediated variation of this addition-fragmentation has been explored. The reaction, summarized in Scheme 77 for a one-carbon expansion, involves the generation of a radical at the terminus of a chain by homolytic cleavage of a carbon-heteroatom bond. Addition of the radical to the carbonyl produces a bicyclic intermediate, which on cleavage of the alternate bond regenerates the ketone carbonyl group with formation of a new radical. The sequence is terminated by the reduction of the radical with the tributyltin hydride reagent. The near neutral conditions of the reaction avoid the reclo-... 

Wnuk, S.F., and Robins, M.J., Stannyl radical-mediated cleavage of Jt-deficient heterocyclic sulfones. Synthesis of a-fluoro esters and first homonucleoside a-fluoromethylene phosphonate, J. Am. Chem. Soc., 118, 2519, 1996. 

Acylaminoradicals (102), which can be generated by butyltin radical-mediated cleavage of a C—S bond, cyclize with good regio- and stereoselectivity to afford pyrrolizidinones (103) <84JA8209>. 

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