Organolithium-mediated cyclizations of unsaturated compounds: Applications to organic synthesis

Date of Completion

January 1998

Keywords

Chemistry, Organic

Degree

Ph.D.

Abstract

Catalytic quantities of phenyllithium (PhLi) or one molar equivalent of methyllithium (MeLi) have been found to initiate novel cycloisomerization of a variety of structurally diverse unsaturated organoiodides. The isomerization reaction appears to be a process of broad synthetic utility. Primary, secondary, tertiary, or aryl iodides tethered to a suitably positioned carbon-carbon $\pi$-bond are converted cleanly into their cyclic isomers in good to excellent yield (i.e., 70-90%) by simply allowing a hydrocarbon-ether solution of the iodide to stand in the presence of a catalytic quantity of PhLi or a stoichiometric amount of MeLi at an appropriate temperature. The mechanism of the cycloisomerization was found to be substrate dependent: unsaturated aryl iodides undergo isomerization via a three-step cascade 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 or MeLi on the iodine atom of the substrate. The cycloisomerization of unsaturated primary alkyl iodides appear to be mediated by either radical or anionic processes depending on the solvent and reaction temperature.^ Regioselective ortho-lithiation of either N,N-diallyl-2-fluoro or N,N-diallyl-3-fluoroaniline initiates an anionic cascade leading to a 3,4-disubstituted indoline. The transformation involves loss of LiF from the ortho-lithiated species, regioselective intermolecular addition of an organolithium to the benzyne intermediate, and cyclization of the resulting (6-substituted 2-(N,N-diallylamino)phenyl) lithium. ^

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