Radicals, alkoxy cyclization

A possible mechanism for the formation of the furanones 6 and 7 is illustrated in Scheme 2. The initial alkoxy radical generated from the alcohol 5 and lead tetraacetate (LTA) undergoes /3-scission to produce the acyl radical intermediate 9. Subsequent cyclization to 10 proceeds through attack of the radical at the carbonyl oxygen. The resulting Pb(IV) intermediate 11 finally collapses via the reductive... 

Epoxides can also be reductively opened to form a radical. An example of an intramolecular cyclization of such a radical has recently been reported <06TL7755>. Treatment of 40 with Cp2TiCl generates an intermediate alkoxy radical, which then adds to the carbonyl of the formate ester. The product, 41, is formed as a 2 1 mixture of isomers at the anomeric carbon. This reaction is one of the first examples of a radical addition to an ester. The major byproduct of this reaction is the exo-methylene compound, 42, arising from a P-hydrogen elimination. 

Allenyl ethers are useful key building blocks for the synthesis of a-methylene-y-butyrolactones [129, 130], The synthesis of the antileukemic botryodiplodin was accomplished with the crucial steps briefly presented in Scheme 8.56. Bromoallenyl ethers 225 were easily prepared by base-induced isomerization from the corresponding /3-bromoalkyl alkynyl ether compounds and then subjected to electrophilic bro-mination with NBS. The resulting acetals 226 were converted into 2-alkoxy-3-methy-lenetetrahydrofurans 227 by dehydrohalogenation of the alkenyl bromide unit to an alkyne and subsequent radical cyclization employing tributyltin hydride [130],... 

The rate constants for reaction of Bu3SnH with the primary a-alkoxy radical 24 and the secondary ce-alkoxy radical 29 are in reasonably good agreement. However, one would not expect the primary radical to react less rapidly than the secondary radical. The kinetic ESR method used to calibrate 24 involved a competition method wherein the cyclization reactions competed with diffusion-controlled radical termination reactions, and diffusional rate constants were determined to obtain the absolute rate constants for the clock reactions.88 The LFP calibrations of radical clocks... 

Numerous different mechanistic approaches have been applied for this combination. First, cyclization of phenoxy-ethanols 203, in the presence of (diacetoxyiodo)benzene and iodine, gave a mixture of 1,4-benzodioxane 13 and 6-iodo-l,4-benzodioxane 204 via alkoxy radicals (Equation 36) <1997J(P 1)787, 1996TL2441>. 

The latter are known to cyclize rather readily to give epoxides and alkoxy radicals.258... 

Rearrangement is also observed in the irradiation of Formula 450 which gives the hydroxamic acid (Formula 451) (203). This interesting rearrangement probably involves ring opening in the alkoxy radical (Formula 452) followed by recombination with nitrous oxide and cyclization (203). Oxidative fission of alkoxy radicals produced in nitrite... 

The chirality of the sulfoxide led to only moderate control of stereoselectivity. a-Alkoxy radicals also undergo cyclization in a 5-exo and 6-exo mode, again with little control of stereoselectivity.41... 

Similar internal cyclizations occur when 2- (l-adamantyl)-ethanol is treated with lead tetraacetate to give the cyclic ether 83 217 >283 or with HOC1 to give 84 (Eq. (70)) 2831. These reactions apparently involve hydrogen abstractions by the initially formed alkoxy radical. 

Cyclization via epoxide fragmentation. Treatment of the epoxythionoimidaz-olide 1 with Bu3SnH and AIBN generates an alkoxy radical by fragmentation of the epoxy group with cyclization to a ds-fused bicyclic system (2). 

Other methods for the preparation of selenium-containing molecules for radical reactions have been used as well. In Scheme 8 the radical cyclization of compound 44 to the tetrahydrofuran derivative 45 is shown as a crucial step in natural product syntheses. Mixed acetal can also be used for the generation of radicals. 1-Alkoxy and 1-aminoalkyl radicals can be generated from 0,Se- and N,Se-acetals in a direct way. The corresponding 0,Hal- or N,Hal-mixed acetals are instable and this approach is rarely used. But the selenium-containing mixed acetals can be isolated and purified and are excellent radical precursors.241 For example, acetals such as 139 can be converted into the mixed 0,Se-aeetals by reaction with diisobutylaluminum phenyl selenide. The mixed acetal 140 is then used under radical reaction conditions for the efficient formation of new carbon-carbon bonds (Scheme 36).242... 

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