Synthesis of Functionalized Pyrazin-2(1H)‑ones via Tele-Nucleophilic Substitution of Hydrogen Involving Grignard Reactants and Electrophiles

The reaction of 6-chloro-1-methylpyrazin-2­(1H)-one with Grignard reactants followed by quenching with different electrophiles gave access to a variety of 3,6-difunctionalized 1-methylpyrazin-2­(1H)-ones. This regioselective three-component reaction represents the first example of a tele-nucleophilic substitution of hydrogen (SN H) in which the anionic σH adduct is quenched by electrophiles (other than a proton) before elimination takes place. Quenching the reaction with iodine (I2) or bromine (Br2) provides an alternative reaction pathway, yielding a 3-functionalized 6-chloro-1-methylpyrazin-2­(1H)-one or 5-bromo-6-chloro-1-methylpyrazin-2­(1H)-one, respectively. The halogens present offer opportunities for further selective transformations.