Phosphine-Catalyzed Cycloaddition Reactions Of Azomethine Imines

Dinitrogen-fused heterocycles are ubiquitous in pharmaceuticals and natural products with remarkable biological activities. Among various methodologies for the synthesis of dinitrogen-fused heterocycles, the1,3-dipolar cycloaddition has recently been established as one of the most powerful methods. The azomethine imine as a practical and efficient1,3-dipolar, has been extensively investigated for construction of dinitrogen-containing heterocycles.Our group has developed phosphine-catalyzed annulation reactions of cyclic azomethine imines with allenoates, affording biologically important dinitrogen-fused heterocycles. Inspired by this work, we conceived the possibility of introducing various dipolarophiles to react with azomethine imines to furnish cycloaddition reactions under phosphine catalysis conditions.Based on previous works, we develop an efficient phosphine-catalyzed [4+3] cycloaddition of aromatic azomethine imines with allenoates, providing dinitrogen-fused heterocyclic compounds in moderate to excellent yields. The reaction proceeds smoothly under mild conditions, providing an expedient access to highly valuable heterocyclic compounds with isoquinoline, quinoline and phenanthridine skeleton.In order to further expand1,3-dipolar cycloaddition, we try to seek and design new1,3-dipolar. An efficient method for the phosphine-catalyzed [3+2] cycloaddition reaction of azomethine imines with electron-deficient alkenes to give dinitrogen-fused bi-or tricyclic heterocyclic compounds in69%-94%yields would be described in this dissertation. Moreover, the groups installed on the heterocyclic products can be conveniently removed or transformed to other functional groups, making the reaction more useful. As a continuation of our research interest in developing1,3-dipolar cycloaddition reactions, we expect introduce ynones as dipolarophile to react with azomethine imines. The ynones was found to be a novel C3synthon when attacked by the nucleophilic phosphine catalyst in the intermolecular cyclization. Therefore, we present the phosphine-catalyzed [3+3] cyclization of azomethine imines with the ynones to deliver dinitrogen-fused heterocycles in67%-94%yield.During the research of phosphine catalyzed cycloadditions, we always observed and isolated thermal cycloaddition products when the reaction temperature is higher than the room temperature. This prompted us to further explore the reaction in detail. The thermal [3+2] cycloaddition reaction of N-acyliminophenanthridinium betaines with various allenoates has been investigated. The reaction was operationally simple and proceeded smoothly under mild reaction conditions, providing a variety of aromatic tetracyclic heterocycles in moderate to excellent yields.