Breaking the <i>tert</i> -Butyllithium Contact Ion Pair: A Gateway to Alternate Selectivity in Lithiation Reactions

Abstract

The effects of Lewis basic phosphoramides on the aggregate structure of <i>t-</i>BuLi have been investigated in detail by NMR and DFT methods. It was determined that hexamethylphosphoramide (HMPA) can shift the equilibrium of <i>t-</i>BuLi to include the triple ion pair (<i>t</i>-Bu-Li-<i>t</i>-Bu)^-/HMPA₄Li⁺ which serves as a reservoir for the highly reactive separated ion pair <i>t</i>-Bu^-/HMPA₄Li⁺. Because the Li-atom's valences are saturated in this ion pair, the Lewis acidity is significantly decreased; in turn, the basicity is maximized which allowed for the typical directing effects within oxygen heterocycles to be overridden and for remote sp³ C-H bonds to be deprotonated. Furthermore, these newly accessed lithium aggregation states were leveraged to develop a simple γ-lithiation and capture protocol of chromane heterocycles with a variety of alkyl halide electrophiles in good yields.