Title

Preparation of carbocycles via cycloisomerization of unsaturated organolithiums: Part A. Benzyne-tethered alkyllithiums. Part B. 6-heptenyllithiums

Date of Completion

January 2002

Keywords

Chemistry, Organic

Degree

Ph.D.

Abstract

The intramolecular addition of an organolithium to a tethered benzyne intermediate has been developed as a simple route to functionalized benzo-fused carbocycles. Starting with an appropriate ω-(2-fluorophenyl)alkyliodide, this novel, five-step, one-pot synthetic sequence involves lithium-iodine exchange, ortho-lithiation, loss of LiF to form an aryne intermediate, cyclization, and electrophilic trapping of the resulting aryllithium. Each step is highly dependent on the reaction conditions. Investigations into the scope of this method show that 4-substituted indans, 3-substituted benzocyclobutenes, and 5-substituted tetralins may be constructed with complete regioselectivity. ^ The cyclization of 6-heptenyllithium has been investigated for the formation of six-membered rings. While not as facile as the cyclization of the analogous 5-hexenyllithium, the 6-exo cyclization has been shown to proceed with complete regioselectivity to generate methylcyclohexane in good yield. Cyclization of methyl-substituted 6-heptenyllithiums proceeds with modest stereoselectivity. The cyclizations of methyl-substituted 6-heptenyl radicals were explored for comparison to the anionic cyclizations. ^