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.