Catalytic cycloisomerization of unsaturated organoiodides

Catalytic quantities of phenyllithium (PhLi) have been found to initiate novel 5-exo cycloisomerization of a variety of structurally diverse unsaturated organoiodides. The isomerization reaction appears to be a process of broad synthetic utility for the preparation of iodomethyl-substituted five-membered rings. Primary, secondary, tertiary, or aryl iodides tethered to a suitably positioned carbon-carbon pi-bond are converted cleanly to their cyclic isomers in good to excellent yield (i.e., 70-90%) by simply allowing a hydrocarbon-MTBE solution of the iodide to stand in the presence of a small quantity of PhLi at an appropriate temperature. The mechanism of the cycloisomerization was found to be substrate dependent: unsaturated aryl and primary alkyl iodides undergo isomerization via a three-step cascade (eqs 1-3) mediated by two reversible lithium-iodine exchange reactions bracketing an irreversible 5-exo cyclization of an unsaturated organolithium; unsaturated secondary and tertiary alkyl iodides apparently isomerize via a radical-mediated atom transfer process initiated by homolytic fragmentation of the ate-complex generated upon attack of PhLi on the iodine atom of the substrate.