Rhodium-Catalyzed C-H Bond Functionalization Of 2,4-Diarylquinazolines

Quinazoline skeleton compounds are widely found in natural products and drug molecules,and have many biological activities,such as anti-inflammatory and anti-fungal.The development of new strategies for the synthesis of quinazoline derivatives has become a research hotspot in the field of organic synthesis.Transition metal-catalyzed direct functionalization of C-H bond is one of the emerging strategies for constructing C-C bond and C-X?O,S,N etc.?.Among them,rhodium catalyzed transformation has the advantages of high reaction activity and regioselectivity and wide functional group compatibility.It is expected that a series of novel quinazoline derivatives can be obtained via introducing various functional groups into quinazoline skeleton compounds by C-H activation reactions.In addition,quinazolines are pyrimidine-containing nitrogen frameworks,which could be used as the intrinsic directing group in C-H activation reaction.In this thesis,with quinazoline skeleton as the intrinsic directing group,trifluoromethyl thio,cyano,alkyl,allyl and amino groups were introduced into the ortho-position of 2-aryl quinazoline via Rh-catalyzed C-H bond activation reactions.A series of quinazoline derivatives were synthesized.The thesis involves the following five parts.In part one,AgSCF₃ as the nucleophilic trifluoromethylation reagent,quinazoline as the intrinsic directing group,we developed an efficient route to the4-aryl-2-[2-?trifluoromethylthio?aryl]quinazoline derivatives through a directed Rh-catalyzed C-H iodination and trifluoromethylthiolation tandem reaction.The reaction proceeded under mild reaction conditions,exhibited good functional group tolerance with a broad scope of substrate and excellent regioselectivity in good to excellent yields.Nitrile group is a key structural unit in a variety of drug molecule.In Part two,based on the fact that the C-CN bond of acetonitrile can be cleaved under mild conditions,we developed Rh-Cu/TMSCF₃ catalyzed C-H iodization/cyanidation tandem reaction for the synthesis of 4-aryl-2-[2-Cyanoaryl]quinazolinederivatives.The reaction exhibited good functional group tolerance with a broad scope of substrate,and the yield was greatly affected by the substituents of the substrate.The alkyl group plays a vital role in a myriad of biological processes.The introduction of a methyl to a quinazoline skeleton compound may alter it's biological and physical properties.In part three,alkyl trifluoroborates were used as the methylation reagent for Rh?III?-catalyzed ortho-alkylation of 2,4-disubstituted quinazoline via C-H bond activation.The reaction proceeded well with a broad substrate scope,providing a direct way to access high functional quinazoline core structure derivatives in high yields.Allyl-containing nitrogen heterocyclic compounds are the key structural units of many natural products and bioactive compounds.The construction of the allyl-containing heterocyclic structural unit has attracted the attention of chemists.In part four,rhodium-catalyzed high regioselectivity reaction of 2,4-diarylquinazolines with allylic acetate was described,leading to allylated quinazoline derivatives with high efficiency and good tolerance of functional groups.In part five,we developed a method of highly regioselective Rh?III?-catalyzed aminations of 2,4-diarylquinazolines with N-Fluorobenzenesulfonimide.A simple classical[RhCp*Cl₂]₂/AgSbF₆ catalytic system was required without adding base.