Breaking the tert -Butyllithium Contact Ion Pair: A Gateway to Alternate Selectivity in Lithiation Reactions.

The effects of Lewis basic phosphoramides on the aggregate structure of t- BuLi have been investigated in detail by NMR and DFT methods. It was determined that hexamethylphosphoramide (HMPA) can shift the equilibrium of t- BuLi to include the triple ion pair ( t -Bu-Li- t -Bu) - /HMPA 4 Li + which serves as a reservoir for the highly reactive separated ion pair t -Bu - /HMPA 4 Li + . 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 sp 3 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.