Study On Tf₂O Promoted Conversion Of Amide And Trifluoromethylation Of Benzylic Position In Aza-Aromatics

This thesis mainly focuses on the triflic anhydride（Tf₂O）promoted electrophilic activation of amide,nitro-containing arenes,ketone,sulfoxide,nitriles and other compounds.Based on this strategy,several synthetic processes have been illustrated such as:the synthesis of 2-alkyl/aryl benzoxazole;formation ofα-allyl/allenyl modified amides via intermolecular claisen rearrangement;controllable direct functionalization of N-containing arenes benzylic C（sp3）-H bond via Tf₂O promoted eletronphilic activation.This paper includs the following four chapters:Chapter IThis chapter is a brief introduction and divide into two sections to declare the development of triflic anhydride application in organic synthesis.The relevant contents are demonstrated as followsSection One As one of the most important building blocks in organic chemistry,the chemistry of amide has always been valued by organic chemists.In past decades,researchers employed triflic anhydride as the emergent reagent to realize the electrophilic-activation of amide.Numerous works based on this Tf₂O promoted amide acvtivation have been reported,such as the modification of amide and the reduction of amide.In this section,the recent progress of Tf₂O promoted electronphilic activation of amide and other compounds will be summarized.Section Two Due to the unique fluorine effect of fluorine atom,the cooperation of fluoroalkyl groups into pharmaceutical compounds could dramatically affect the physical properties of drugs.Based on this,the trifluoromethyl group as one of the most important fluoroalkyl groups received extensive attention from medicinal chemists.Owing to its inherent trifluoromethyl group,the Tf₂O have been used as trifluoromethyl reagent to realize corresponding transformation.In this section,we mainly focus on the development of trifluoromethylation process which employed the Tf₂O as the direct trifluoromethyl reagent.ChapterⅡIn this chapter,we reported a transition-metal-free approach to realize the formation of 2-alkyl/aryl benzoxazoles.Amides were employed as the alkyl/aryl sources and interacted with benzoxazoles,another coupling partner,after activated by Tf₂O.The mild reaction conditions,and particularly insensitivity to air and water,further enhance the synthetic potential of this strategy in pharmaceutical synthesis.ChapterⅢHerein,we demonstrated a new transition-metal-free strategy that combine allyl and allenyl groups into theαposition of tertiary amides via an intermolecular claisen rearrangement.In this progress,amides were activated by triflic anhydride to generate the pivatol keteniminium ion intermediates,which exhibit strong electrophilic activity.It is worthy noting that is the indispensability of inorganic base caesium carbonate in this transformation.This atom-economical process deliversαposition-modified amides under mild conditions in moderate to good yields and showcases a broad substrate compatibility.ChapterⅣControllable realizing the direct functionalization of nitro-containing arenes benzylic C-H bonds have been completed here.Tf₂O was employed in this reaction to realize the electronphilic-activation of 2-methylqunolines and generate the N-trifluoromethylsulfonyl quinolinium salt intermediate.The trifluoromethyl radicals could be produced via homolysis of this salt and triggered the subsquenced radical chain reaction pathway.While increasing the reaction temperature,the trifluorosulfinyl could be smoothly installed into the benzylic position of nitro-containing arenes via intramolecular 2,3-rearrangement.Control experiments supported this proposed reaction pathway.