Modular Synthesis Of Quinazolinone-fused Phenanthridinones By Palladium Catalyzed Cascade C-H/N-H Arylation Reaction

Quinazolinones are an important class of heterocyclic scaffolds, frequently found in naturally occurring alkaloids,biologically and therapeutically active compounds such as anticancer, antibacterial, anticonvulsant, sedative, antidiabetic, analgesic and several others.Molecules containing this motif have received considerable attention in organic and medicinal chemistry, and much effort has been focused on the synthetic methods of quinazolinone derivatives.In particular, the synthetic strategies of ring-fused quinazolinones, as the core structural skeletons in a variety of natural products and pharmaceutical molecules, have been intensely explored in recent years.Starting from 2-phenylquinazolinone and 1,2-dibromobenzene were selected as the coupling partners to investigate the feasibility of a palladium-catalyzed twofold arylation sequence process.In general, for the selected model reaction of 2-phenylquinazolinone and 1,2-dibromobenzene, Xphos (20 mol%) for Pd(OAc)2 (10 mol%)was found to be the best catalyst system with K2CO3 as the base in DMF at 160℃ for 72 h to produce the corresponding target in 85% yield.In summary, we have developed a general and highly regioselective method for the modular synthesis of ring-fused quinazolinones through palladium-catalyzed tandem C-H/N-H 2-fold arylation sequence. Various structurally diverse phenanthridinone-fused quinazolinones can be obtained in moderate to good yields starting from 2-aryl quinazolinones and 1,2-dihaloarenes. This Pd-catalyzed tandem double arylation will provide a useful tool for the discovery of drugs and organic materials.