Cyclization of Aryllithiums Tethered to Methylenecycloalkanes:  Stereoselective Synthesis of 4<i>a</i>-Substituted <i>cis</i>-Hexahydrofluorenes

Abstract

The cyclization of an aryllithium tethered to a methylenecycloalkane, generated from 2-(o-bromobenzyl)-1-methylenecycloalkanes 1, 2, and 3 by low-temperature lithium-bromine exchange, has been found to be a kinetically slow but thermodynamically favorable process that proceeds at a convenient rate in an exclusively 5-exo fashion when solutions of the aryllithium in n-heptane-di-n-butyl ether (9:1 v/v) are warmed to 45 degrees C. The cyclization affords stereoisomerically pure cis-fused products (7 and 8) when the methylenecycloalkane is five- or six-membered but it is less stereoselective when the methylenecycloalkane is seven-membered. The ring-closure of the aryllithium derived from 2-(o-bromobenzyl)-1-methylenecyclohexane (2) provides an experimentally convenient route to stereoisomerically pure 4a-substituted cis-hexahydrofluorenes in 60-90% isolated yield.