Stereoselectivity of cyclization of substituted 5-hexen-1-yllithiums: regiospecific and highly stereoselective insertion of an unactivated alkene into a carbon-lithium bond

Abstract

Substituted 5-hexen-1-yllithiums, which were prepared in solutions of n-C 5 H 12 -Et 2 O (3:2 by vol) by low-temperature lithium-iodine exchange between t-BuLi and the appropriate iodide, undergo clean, 5-exo-trig cyclization upon warming to give substituted (cyclopentyl)methyllithiums, in good yield and with a high degree of stereocontrol. In each case, the major product is the same isomer as that observed in studies of the isomerization of analogously substituted 5-hexen-1-yl radicals, but the organolithium cyclizations are invariably much more stereoselective than radical-mediated processes. Lewis base additives such as THF, TMEDA, and PMDTA serve to increase the rate of cyclization of the substituted 5-hexen-1-yllithiums, but such additives do not reduce the high stereoselectivity of the process. The observed regioselectivities and stereoselectivities of the intramolecular addition of a C-Li bond to an unactivated alkene suggest that the closure of the anion proceeds via a transition state that resembles a chair cyclohexane in which substituents preferentially occupy pseudoequatorial positions