Atom Transfer Cyclization Reactions of α-Iodo Esters, Ketones, and Malonates: Examples of Selective 5-Exo, 6-Endo, 6-Exo, and 7-Endo Ring Closures

Article abstract of DOI:10.1021/jo00274a034

The preparation and free-radical cyclization reactions of unsaturated α-iodo esters, ketones, and malonates have been investigated.For example, sunlamp irradiation of methyl 2-iodo-6-heptenoate in benzene in the presence of 10 mol percent hexabutylditin produces methyl 2-(iodomethyl)cyclopentanecarboxylate (cis and trans) and methyl 3-iodocyclohexanecarboxylate in a ratio of 93/7 in a combined yield of 86percent.The γ-iodo carbonyl products can either be isolated (in most cases) or converted in situ to deiodinated products (with Bu3SnH) or lactones (by heating).Five-, six-, or seven-membered rings selectively form, depending on chain length and alkene substitution.Terminal alkene substituents favor exo cyclization while internal alkene substituents promote endo cyclization.A preference for endo closure is also observed when there is a carbonyl group "inside" the forming ring.A detailed analysis of reaction rates indicates that these isomerizations proceed by an iodine atom transfer chain mechanism, and thus the observed selectivities are due to the kinetic substituent effects.The results contrast the thermodynamically controlled hydrogen atom transfer cyclizations of Julia.A new procedure for the removal of tin byproducts is described.