KO^<i>t</i>Bu-Mediated Synthesis of Dimethylisoindolin-1-ones and Dimethyl-5-phenylisoindolin-1-ones: Selective C–C Coupling of an Unreactive Tertiary sp³ C–H Bond

A new reaction for the synthesis of dimethylisoindolinones has been presented from 2-halo-N-isopropyl-N-alkylbenzamide substrates and KOtBu by the selective C–C coupling of an unreactive tertiary sp3 C–H bond. The reaction manifested an excellent selectivity toward a tertiary sp3 C–H bond over primary or sec C–H bond. Moreover, biaryl C–C coupling along with alkyl–aryl C–C coupling can be achieved in one pot using dihalobenzamides for the synthesis of biaryl 5-phenylisoindolin-1-ones. It seems that the reaction proceeds via a radical pathway in which the aryl radical translocates via 1,5-hydrogen atom transfer (HAT), forming a tertiary alkyl carbon-centered radical. The generated tertiary alkyl radical could attack the benzamide ring in a 5-exo/endo-trig manner followed by the release of an electron and a proton, leading to a five-membered isoindolinone ring. HAT seems to be responsible for the selective functionalization of the tertiary alkyl group over primary and secondary C–H bonds.