STEREOSELECTIVITY OF CYCLIZATION OF SUBSTITUTED 5-HEXEN-1-YLLITHIUMS - REGIOSPECIFIC AND HIGHLY STEREOSELECTIVE INSERTION OF AN UNACTIVATED ALKENE INTO A C-LI BOND

Substituted 5-hexen-l-yllithiums, 6-10, which were prepared in solutions Of n-C5Hl2-Et2O (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, 11-14, 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. Ab initio molecular orbital calculations at the 3-21G level, which support this transition-state structure (chair-like geometry with a C(1)-C(5) distance of 2.18 angstrom), suggest that the ground-state structure of 5-hexen-l-yllithium is essentially that of a cyclohexane chair [C(1)-C(5) distance of 3.35 angstrom] in which the lithium atom is coordinated with the C(5)-C(6) pi-bond (Li-C(5) distance of 2.41 angstrom and Li-C(6) distance of 2.38 angstrom). The stabilizing interaction of the lithium atom with the pi-system of the remote alkene moiety appears to be an important component of the cyclization since it serves to establish a chair-like geometry prior to the activation step leading to (cyclopentylmethyl)lithium. Calculation of the difference in energy between an axially substituted transition state and one bearing an equatorial substituent gave product ratios that were in very good agreement with experimental observations. The activated complex was also modeled via molecular mechanics calculations with modified MM2 parameters, and the results of these analyses were found to be in good accord with both the ab initio results and the experimentally observed selectivities. The preference of a substituent for the pseudoequatorial position in the chair-like transition state is, to a reasonable approximation, given by the conformational energy of the substituent in the cyclohexane system, and the stereoselectivity of cyclizations of substituted 5-hexen-1-yllithiums may be anticipated by recourse to such values.