Calculation-assisted regioselective functionalization of the imidazo[1,2-]pyrazine scaffold zinc and magnesium organometallic intermediates.

Straightforward calculations such as determinations of p values and N-basicities have allowed the development of a set of organometallic reactions for the regioselective functionalization of the underexplored fused N-heterocycle imidazo[1,2-]pyrazine. Thus, regioselective metalations of 6-chloroimidazo[1,2-]pyrazine using TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl) such as TMPMgCl·LiCl and TMPZn·2MgCl·2LiCl provided Zn- and Mg-intermediates, that after quenching with various electrophiles gave access to polyfunctionalized imidazopyrazine heterocycles. Additionally, the use of TMPZn·2MgCl·2LiCl as base for the first metalation allowed an alternative regioselective metalation. Nucleophilic additions at position 8 as well as selective Negishi cross-couplings complete the set of methods for selectively decorating this heterocycle of the future.