Unusual C-6 lithiation of 2-chloropyridine-mediated by BuLi-Me2N(CH2)2OLi.: New access to 6-functional-2-chloropyridines and chloro-bis-heterocycles

The reaction of 5-chloropyridine with alkylithium generally results in nucleophilic addition leading to the loss of chlorine atom while exclusive directed ortho metalation is obtained using LDA. Herein it is shown that the BuLi-Me2N(CH2)(2)OLi (BuLi-LiDMAE) superbase promotes an unprecedented regioselective C-6 lithiation. The method was successfully applied to the preparation of potentially useful chlorinated pyridinic and bis-heterocyclic synthons.