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

Straightforward calculations such as determinations of p K a 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- a ]pyrazine. Thus, regioselective metalations of 6-chloroimidazo[1,2- a ]pyrazine using TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl) such as TMPMgCl·LiCl and TMP 2 Zn·2MgCl 2 ·2LiCl provided Zn- and Mg-intermediates, that after quenching with various electrophiles gave access to polyfunctionalized imidazopyrazine heterocycles. Additionally, the use of TMP 2 Zn·2MgCl 2 ·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.