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

Abstract

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 (S N H ) in which the anionic σ H adduct is quenched by electrophiles (other than a proton) before elimination takes place. Quenching the reaction with iodine (I 2 ) or bromine (Br 2 ) 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. Copyright © 2019 American Chemical Society.