Palladium-Catalyzed Cyclization Reaction of o-Haloanilines, CO₂ and Isocyanides: Access to Quinazoline-2,4(1H,3H)-diones

Quinazoline-2,4(1H,3H)-diones are core structural subunits frequently found in many biologically important compounds. The reaction of 2-​aminobenzonitrile and CO₂, which was frequently studied, only provided N3-unsubstituted quinazoline-2,4(1H,3H)-dione compounds. Herein we report palladium-catalyzed cyclization reactions of o-haloanilines, CO₂ and isocyanides to prepare N3-substituted quinazoline-2,4(1H,3H)-diones. Electron-rich o-bromoanilines participated in the cyclization reaction using Cs₂CO₃ at high temperature, and electron-deficient o-bromoaniline or o-iodoaniline substrates conducted the reaction using CsF as base to deliver corresponding quinazoline-2,4(1H,3H)-dione products in good yields.