Lithium Zincate-Enabled Divergent Synthesis: Regioselective One-Pot Formation of Heteroaryl Compounds

We present a lithium zincate-enabled, divergent one-pot synthesis for regioselective C–C bond formation in heteroaryl compounds. By modifying the zinc coordination environment, a single set of reagents (ZnCl₂, organolithium R1Li, and diethyl (5-halo)thenylphosphate) was found to generate two distinct products through either a consecutive reaction sequence or two-independent intermolecular steps. This approach extends the versatility of lithium organozincates to regioselective CAr(sp2)-Cthienyl(sp2) and Cthenyl(sp3)-CAr(sp2) couplings without requiring transition metals and/or arenes pre-activated with a boronic acid moeity. With a broad substrate scope and reliance on zinc and lithium—abundant, non-toxic metals—this approach offers a sustainable route to complex molecules with relevance for pharmaceuticals and materials science.