Simple Synthesis of 4‐Substituted 1(2H)‐Isoquinolinones via Electrophilic Trapping of Lithiated Mono‐ and Dianion Precursors

Abstract Synthetic routes have been developed to access 4‐substituted 1(2H)‐isoquinolinones from readily available precursors. This is achieved via electrophilic trapping of di‐ and monolithium anions derived from alkyllithium exchange of 4‐bromo‐1(2H)‐isoquinolinones and corresponding 4‐bromo‐1‐methoxyisoquinolines, respectively. Products derived from the latter are then hydrolyzed to the target 4‐substituted 1(2H)‐isoquinolinones. The methodology has potential application to access 4‐substituted 1(2H)‐isoquinolinones with additional substituents in either ring.