Nitrogen Radical Initiated Cascade Reaction Of Terminal Alkynes: Synthesis Of α-amino-α-aryl Ketones

-Amino--aryl ketone is a key motif in various biologically active natural products andpharmaceuticals, such as N-methylwelwitindolinone C isothiocyanate, anesthetic ketamineand new thiamethoxam class of drug prasugrel. Also,-Amino--aryl ketones serve asvaluable precursors for the synthesis of various heterocycles and important syntheticintermediates, such as1,2-amino alcohols. However, there are few reports for the synthesis of-amino--aryl ketones. For the existing synthetic methods of-amino--aryl ketones,prefunctionalizaiton of substrates and harsh conditions are always needed. So far, there is nomethod for the synthesis of-amino--aryl ketone.via multifunctionalization of simplemolecule. Therefore, the development of straightforward strategy for the synthesis of this keymotif from commercial available chemicals under the mild conditions is still a greatchallenge.Herein, this thesis studies that Cu(OTf)2–catalyzed cascade reaction of terminal alkynesfor the synthesis of α-amino-α-aryl ketones, with N-Fluorobenzenesulfonimide (NFSI) asnitrogen source and aryl source, alcohol compounds as oxygen source. Recently, Matsunagaet. al reported that Cu-catalyzed intermolecular carboamination of alkenes, with NFSI asnitrogen source and carbon source. Murakami et. al developed Cu-and Rh-catalyzedaminative multifunctionalization of terminal alkynes for the synthesis of-amino--allylketones. In this report,-imino metal carbene intermediate and Claisen-[3,3]-sigmanrearrangement were involved in this transformation. In2013, our group disclosedCu-catalyzed intermolecular aminocyanation and diamination of alkenes with NFSI. Inspiredby above works, here in, we construct the C–N, C–C（aryl）and C=O bonds to terminal alkynesfor the synthesis of-amino--aryl ketones in one step, with NFSI as radical nitrogen sourceand aryl source, menthol as oxygen source. Furthermore, the proposed mechanism isdiscussed in this thesis. The reaction might be proceeded via cascade nitrogen-centred radicaladdition/aryl migration/desulfonylation/oxygenation/semi-pinacol rearrangement process.This approach achieved under mild conditions and don’t need pretreatment. This approachmight be a new avenue to develop aminative multifunctionalizaiton of alkynes throughnitrogen-centred radicals as initiators.