Strategies From Enaminone To Heterocycles

Heterocycles widely exist in natural products,pharmaceuticals,and advanced materials.Consequently,a variety of strategies have focused on building heterocycles.Conventional method involves the condensation of carbonyl compounds with ammonia,alcohol or thiol,such as Paal-Knorr reaction,Hantzsch reaction.Howerver,there are still some respective limitations,such as harsh conditions,poor tolerance of functional groups.Recently,transition-metal-catalyzed cyclization reactions have been found to be efficient.But the requirment of metal may lead to potential contamination in products,which impedes their applications,especially in pharmaceutical industry.Therefore,effficient access to highly functionalized heterocycles under metal-free conditions is still highly desirable.Enaminone,endowed with nucleophilicity of enamine and electrophilicity of ketone,has been applied widely in the synthesis of heterocycles.The enaminone compounds may exist as three tautomers:iminoenol,iminoketone,and ketoenamine.The ketoenamine tautomer-based synthesis of the heterocycles has been extensively investigated.While the research of iminoenol and iminoketone remains rare.Recently,our group developed some simple and efficient methods to construct heterocycles based on the iminoenol tautomer in the presence of base.In our continuing efforts in enaminone chemistry,herein we present main results obtained in this thesis as follows:?1?An atom-efficient“one-pot”protocol has been developed to construct multisubstituted2-hydroxy-benzo[b][1,4]oxazinsstartingfrom N-?2-hydroxylaryl?enaminones.This procedure comprises a PIDA-mediated intramolecular iminoenol tautomer trapping reaction,followed by Et₃N-promoted aerobic oxidative ring-construction.In particularly,O₂molecule from air served as the oxygen source of the hydroxyl group in the titled products.This reaction proceeded smoothly at room temperature under air atmosphere and metal-free conditions.?2?An efficient hypervalent iodine?III?mediated approach to substituted quinoxalines from readily available N-?2-acetaminophenyl?enaminones has been developed.This reaction involves a PIDA-mediated intramolecular iminoenol tautomer trapping reaction,aerobic oxidative ring-construction and dehydration with wide range of functional groups in moderate to excellent yields under mild conditions.?3?A facile and direct access to 2,3,4-trisubstituted quinolines from N-unsubstituted enaminones and arynes has been developed.A direct C-arylation of enaminones and oxidative[4+2]cycloaddition reaction were involved in this procedure.?4?A novel protocol for the synthesis of 2,4,6-trisubstituted pyridines from N-unsubstituted enaminones and chalcones via base promoted tandem Michaelreaction/intramolecularnucleophilicaddition/elimination/aromatization sequence has been developed.This method provides an efficient,convenient route to 2,4,6-trisubstituted pyridines with good functional group tolerance under mild conditions in the absence of transition metal.