Nickel-Catalyzed Intramolecular Alkene Difunctionalization by Ball-Milling

Abstract

A mechanochemical nickel-catalyzed intramolecular difunctionalization reaction of alkene tethered aryl halides with alkyl halides is herein described. This method allows for synthesis of 3,3-disubstituted heterocycles, namely oxindoles, with shorter reaction times than solution-phase counterparts. Additionally, this process is solvent minimized, with DMA used in liquid-assisted grinding (LAG) quantities and circumvents the need for chemical activation of the terminal reductant (manganese) through mechanical grinding. The process can be scaled up to yield over a gram of product and modest enantioinduction is possible by utilizing a chiral PyrOx ligand. (Figure presented.).