Studies On The Synthesis Of Polysubstituted Pyrroles And Optically Active Tetrahydropyrano[2,3-c]pyrazoles

The hetereocycle frameworks are important structural units that are frequently found in natural products, pharmaceuticals, and other synthetics. Therefore, the development of efficient and elegant synthetic strategies to access hetereocycles from readily available raw materials is particularly appealing and remains an important challenge in modern organic synthesis. In this thesis, we mainly focused on the developmnet of new methodologies for the synthesis heterocyclic compounds through organocatalyzed multicomponent reactions or cascade reactions.Part I: We have developed an organocatalyzed three-component reaction of 1,2-diones, aldehydes and arylamines, which provide an efficient approach to access polysubstituted pyrroles. Under the catalysis of 4-methylbenzenesulfonic acid monohydrate(20% mol), the reactions of a wide range of 1,2-diones, arylamines and aldehydes took place smoothly to generate the corresponding polysubstituted pyrroles in acceptable to good yields(up to 87%). This transformation features easy accessibility of starting materials, good functional group tolerance and transition metal free conditions. From a synthetic point of view, this protocol represents an extremely simple and efficient way to construct polysubstituted pyrroles in good yields.Part II: We have developed a bifunctional squaramide catalyzed enantioselective formal [3+3] annulation with pyrazolin-5-ones and Morita-Baylis-Hillman(MBH) acetates of nitroolefins, which provide an efficient approach to access enantiomerically enriched tetrahydropyrano[2,3-c]pyrazole derivatives. Under the catalysis of a(1R,2R)-1,2-diphenylethane-1,2-diamine derived bifunctional tertiary amine-squaramide catalyst(10 mol% loading), the reactions of a wide range of pyrazolin-5-ones and MBH acetates of nitroolefins ran smoothly to provide a series of densely functionalized tetrahydropyrano[2,3-c]pyrazoles in moderate to good yields(up to 82%) with high anti-selectivities(up to >20/1 dr) and excellent enantioselectivities(up to >99% ee). Moreover, representative transformation of the annulation product to a biologically mportant fused dihydroisoquinoline is achieved without any appreciable change in the diastereo- and enantioselectivity.