Study On The Atroposelective Construction Of Naphth-Quinolines By Povarov Reaction And Central-to-Axial Chirality Conversion

Enantioenriched axially chiral compounds are fascinating privileged scaffolds in drug discovery,catalyst design and material science.Many methodologies for the stereoselective preparation of atropisomeric compounds have been developed,such as atroposelective cross-couplings cycloadditions,central-to-axial(CTA)chirality conversion and kinetic resolutions.However,only a few examples have been reported by using CTA strategy.In this thesis,we have developed an efficient atroposelective construction of quinoline-naphthol skeletons by using chiral phosphoric acid catalyzed Povarov reaction followed by a CTA chirality conversionThis thesis consists of two chapters.The first chapter reviews the research progress of chiral conversion strategies.Mainly involves the chiral conversion of center-to-axial,axial-to-central,central-to-central,central-to-planar,central-to-helical,etc.In the second chapter,we successfully constructed the diaryl naphthol-quinoline backbones by using chiral phosphoric acid catalyzed Povarov Reaction and CTA chirality conversion strategy.The highly enantioselective Povarov reaction of 1-styrylnaphthols with anilines and aromatic aldehydes catalyzed by a chiral phosphoric acid in one pot was developed.After a systematicscreening of reaction conditions,including the adjustment of reaction temperature,time and concentration,the selection of substrate ratio,phosphoric acid catalysts of different structures and the change of different substituent of reaction substrates,the optimal reaction conditions were successfully obtained.Then we moved to evaluate the reaction scope of the Povarov reaction,a series of 2.,3,4-triaryl quinoline compounds with high yields(>80%),excellent stereoselectivity(>92%ee)were obatined,and the catalyst loading can be reduced to 1 mol%without affecting the enantioselectivity.Next,by exploring a series of oxidation conditions,including temperature,time,concentration,and the choice and ratio of oxidizing agents,we obtained the optimal reaction conditions and successfully achieved the diaryl axial chirality through the CTA chirality conversion strategy.