Exploiting Coordination Effects for the Regioselective Zincation of Diazines Using TMPZnX⋅LiX (X=Cl, Br)

A new method for regioselective zincations of challenging N ‐heterocyclic substrates such as pyrimidines and pyridazine was reported using bimetallic bases TMPZnX⋅LiX (TMP=2,2,6,6‐tetramethylpiperidyl; X=Cl, Br). Reactions occurred under mild conditions (25–70 °C, using 1.75 equivalents of base without additives), furnishing 2‐zincated pyrimidines and 3‐zincated pyridazine, which were then trapped with a variety of electrophiles. Contrasting with other s‐block metalating systems, which lack selectivity in their reactions even when operating at low temperatures, these mixed Li/Zn bases enabled unprecedented regioselectivities that cannot be replicated by either LiTMP nor Zn(TMP) 2 on their own. Spectroscopic and structural interrogations of organometallic intermediates involved in these reactions have shed light on the complex constitution of reaction mixtures and the origins of their special reactivities.