Amide Activation By Triflic Anhydride:An Emerging Way For Chemoselective Synthesis

This thesis mainly focuses on an emerging way for chemoselective synthesis known as amides activation by triflic anhydride?Tf₂O?and elaborates several new synthetic methods based on the Tf₂O-activated system to afford valuable heterocyclic compounds.The thesis includes five chapters as follows:Chapter OneIn this chapter,we demonstrated the brief introduction,several common synthetic routes and the versatile application of amides in organic transformations.As an ideal functional precursor of nitrogen containing compounds,amide plays vital role in synthetic field.The transformation of amides into new C-C bond formation is unfailing research pursuit.Chapter TwoNumerous applications of Tf₂O activated amides in organic synthesis have been displayed.Owing to the pronounced nucleophilicity of the amide carbonyl functionality,electrophilic amide activation and transition metal catalyzed amide C–N bond activation have received a great amount of attention in the last few decades,especially in the context of methodology development.Examples for the application of these reactions in total syntheses were provided for most of the classes of transformations.These new techniques could be alternative for the chemists whenever conventional transformations fail to provide satisfactory synthetic results.Very much an actively evolving subfield of organic synthesis,amide activation holds considerable potential for further elaboration and application in the synthesis of bioactive unnatural and natural products alike.Chapter ThreeA concise,novel and flexible metal-free single-step to synthesize functionalized quinolines is reported.Triflic anhydride-mediated?Tf₂O?activation of amides is discussed in the presence of pyridine to offer strong electrophiles,thereby showcasing excellent productivity,high regio-and chemoselectivity,and widely tolerable substrates.This approach provides a straightforward and efficient way to construct azaheterocycle structures.Chapter FourA metal-free brand-new one-pot multinitrogenation of amides for the chemo-and regioselective synthesis of 1,5-disubstituted tetrazoles has been developed.By means of electrophilic amide activation,and further C–C bond cleavage and rearrangement,a diverse set of functionalized 1,5-DST derivatives were selectively constructed under mild conditions.As showcased in the mechanisms,the chemoselectivity is easily switched by the selection of the starting materials in the reaction.Chapter FiveA selective Friedel-Crafts acylation of indoles via an uncommon cleavage of the amide C-N bond was achieved by the activation of triflic anhydride.This method offers a rapid and efficient access to high-bio value 3-acylindoles,performs a series of scrupulous mechanistic stuides and offers a strong courage that amides can be synthons in reactions to form new C-C bond under transition-metal-free conditions.