Asymmetric Organocatalytic Domino Reactions For The Synthesis Of Tetrahydropyridines And Chroman Derivatives

This thesis is composed of three parts:1. The review of asymmetric organocatalytic domino reactionsAsymmetric organocatalytic domino reaction has grown rapidly to become one of the most exciting and current fields in organic chemistry during the past few years. Organocatalytic domino reactions have emerged as powerful tools to give a rapid increase in molecular complexity from simple and readily available starting materials with a minimum of manual operations, thereby saving time, effort, and production cost. Additionally, these processes generally show very high stereoselectivities. Therefore, organocatalytic domino reactions have played an important role in the synthesis of key skeletons of complex compounds and natural products. This chapter illustrates the development of asymmetric organocatalytic domino reactions from its very beginning up to the present.2. Enantioselective construction of tetrahydropyridine derivatives with a quaternary stereocenter via organocatalytic multicomponent cascade reactionThe functionalized tetrahydropyridine and piperidine ring systems are not only important starting materials for numerous biologically active compounds, but are also important structural building blocks of many natural products and drug molecules. We have developed an efficient method for the synthesis of substituted tetrahydropyridine through a proline-mediated multicomponent cascade Knoevenagel/Michael/Mannich/Intramolecular cyclization reaction, which employed commercially available aromatic amines, formaldehyde and P-ketone esters directly. The merit of this cascade process is highlighted by its high efficiency of producing three new C-C bonds, two C-N bonds and an all-carbon quaternary stereocenter in one operation, which otherwise is a big challenge to access by traditional strategies.3. Enantioselective synthesis of functionalized chroman derivatives via an organocatalytic one-pot reaction An efficient, asymmetric, one-pot synthesis of a novel tetracyclic ring system incorporating both chroman and bicycle-[2.2.2]-octane structural units was accomplished through sequential Michael/Michael/Michael/Aldol reaction of nitroolefin enoates andα,β-unsaturated ketones. Six stereogenic centers including two quaternary stereocenters, and thereby single stereoisomer were obtained with excellent diastereo- and enantioselectivity in moderate yields.