| As a major branch of heteroatomic alkynes,ynamides are an important class of intermediates for organic synthesis.They have become a hot research topic in recent years because of their high reactivity and unique regioselectivity compared with ordinary alkynes and their ability to construct many useful heterocyclic skeletons through tandem cyclization reactions.While the chemistry of noble metal-catalyzed ynamides has been well developed in the past studies,there is still broad space for the development of non-noble metal catalysis and metal-free catalysis,which are more in line with today’s green chemistry concepts,to be further explored.On the other hand,chiral Br(?)nsted acids,as an important part of the emerging field of organocatalyst in recent decades,have attracted the attention of chemists for their excellent catalytic properties and have been successfully used in asymmetric catalytic reactions of various functional groups,including ynamides.Based on this,we have carried out a series of non-noble metal-and metal-free catalyzed cyclization reactions to synthesize a variety of valuable heterocyclic compounds with ynamides as the core and carried out related asymmetric studies.This thesis is divided into four main parts as follows:In the first part,the basic structural properties and preparation of ynamides are introduced,and a series of developed noble metal-catalyzed reactions of ynamides are highlighted,and the importance of developing new non-noble metal and metal-free catalytic methodologies is presented,along with examples of the application of ynamides in the synthesis of heterocyclic compounds.Subsequently,the basic structure and catalytic principles of chiral Br(?)nsted acids are then described,their development in the field of asymmetric catalysis is summarized,and the special applications shown in the field of asymmetric catalysis of ynamides are emphasized.Finally,we conclude the above background and look for the remaining deficiencies and challenges,and then propose the research topic and its significance.In the second part,the tandem oxidative cyclization reaction of indoly-ynamides catalyzed by zinc catalyst was investigated,and the efficient synthesis of a series of challenging indole-fused seven-and eight-membered lactams and other similar medium-sized lactams was successfully achieved,and such products have potential biological and pharmaceutical applications.The asymmetric mode of this oxidation reaction was also subsequently achieved by employing the chiral substrate.In the third part,the model of catalytic ynamides was further extended to the metalfree field.A Br(?)nsted acid-catalyzed intramolecular dearomatic cyclization reactions of naphthol-ynamides was realized,and two novel classes of azaspirocyclic compounds were synthesized in a diverse manner.Subsequently,the catalytic asymmetric dearomatization reactions of the same substrates were achieved in combination with chiral Br(?)nsted acids,and chiral azaspiroenone products were successfully prepared with generally good enantioselectivity.Finally,the reaction mechanism has also been explored to some extent.In the fourth part,the previous reaction of chiral Br(?)nsted acid-catalyzed ynamides was extended from intramolecular to more challenging intermolecular reaction.An intermolecular asymmetric[4+2]cycloaddition reaction of para-quinone methides(pQMs)with ynamides catalyzed by chiral Br(?)nsted acid was realized to synthesize 4aryl-chromen compounds with high enantioselectivity.This reaction is the first asymmetric reaction on p-QMs with alkynes and also the first intermolecular asymmetric reaction initiated by chiral Br(?)nsted acid activation of alkynes.Subsequently,two important compounds,chiral 4-aryl-dihydrocoumarins and 4-arylcoumarins,were further realized by simple product derivatization,respectively.More in-depth mechanistic investigation of the reaction process as well as theoretical calculations are in progress. |
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