Synthesis Of Chromones And Isocoumarins Via Metalcatalyzed Annulation Reactions Of Ynamides

Ynamides are alkynes that are connected with and activated by a nitrogen atom due to its conjugation with the C-C triple bond. And also for the nitrogen atom,ynamides show very good regioselectivity. Recently, with the development of this area, ynamides have been employed for the synthesis of various heterocyclic compounds like furans, pyroles, indoles, etc and demonstrated excellent reactivity and potential for further utilizations in organic synthesis. In this dissertation, we introduce our research in metal-catalyzed annulation reactions for the elaboration of chromones and isocoumarins.Chromones and isocoumarins are benzoxa-six-membered cyclic compounds,which differ with each other for the position of oxygen. Both of the two compounds have proved to exhibit significant bioactivities and potential value in medical science,such as anticancer, antibacterial activities and working as enzyme inhibitors. As important members of these two categories, 2-aminochromones and3-aminoisocoumarins also have many different biologic activities but the investigations are limited for few efficient synthetic strategies. Therefore, exploring more robust synthetic methods is crucial for expanding the diversity of these two categories and testing their utilization potential in biology and medical science.In this dissertation, two parts of work are introduced. In Chapter 2, we introduce a novel and efficient annulation reaction between ynamides and2-methoxyaroyl chlorides promoted by Lewis acid. This method has many advantages over other alternatives, such as simple operations, mild reaction condition, wide substrate scope and high yields, which make it very promising for use. More importantly, this is the first example of acylium ion-induced annulation reaction of ynamides by a tandem Friedel-Crafts acylation/oxo-Micheal addition/elimination strategy, which also contributes to the theory of acylation reactions of C-C triple bond and its further application in synthesis.In Chapter 3, a Pd-catalyzed annulation reaction is described for the synthesisof 3-aminoisocoumarins. Compared with other protocols like C-H activation, this method avoids adding excessive amount of oxidants and the substrates need no pre-functionalization. It is a very straightforward, efficient and simple route for the preparation of 3-aminochromones. And the merits also include high reaction yields,good substrates tolerance and excellent regioselectivity.