Multi-component Reactions And Multi-component Domino Reactions Based On Trapping Of Active Ylides With α, β-Unsaturated Carbonyl Compounds

Multi-component reactions (MCRs) and multi-component domino reactions represent the highly efficient synthetic strategies for rapid construction of diverse and complex molecules due to their high synthetic efficiency, atom economy, convergence, flexibility and simplicity. MCRs and multi-component domino reactions have attracted increasing attention in both academic and industrial community. Recently, we have discovered a novel multi-component reaction based on the trapping of ammonium or alcoholic oxonium ylides with imines and aldehydes. However, narrow substrate scope and catalyst limitation are obvious in these reactions. In this dissertation, we demonstrated the ammonium or alcoholic oxonium ylides could be efficiently trapped by Michael acceptor. Furthermore, we also demonstrated that much cheaper copper complexes were highly effective catalysts for these ylide trapping transformations.We have developed a novel one-pot three-component domino reaction ofα-aryl substituted diazoacetates, aryl amines andβ,γ-unsaturatedα-ketoesters. This is the first successful example of the ammonium ylide trapping process by a Michael acceptor. The present three-component domino reaction affords the efficient synthesis of poly substituted 2,3-dihydropyrrole derivatives in moderate to good yields (41-84%). Based on the results of control experiments, this reaction was proposed to proceed through sequential Michael addition, intramolecular cyclization and dehydration. Through a combination of X-ray structures and chemical structure correlation, the relative stereochemistry of all four diastereomers of pyrrolidine intermediates was rigorously determined.We then achieved a highly regioselective three-component reaction of alkyl substituted diazoacetates with aryl amines andβ,γ-unsaturated a-ketoesters. This reaction occurred smoothly via an 1,2-addition fashion to furnish densely functionalizedβ-hydroxyα-amino acid derivatives in high yields (71-94%) with good diastereoselectivity. We have also made a preliminary investigation on its asymmetric variant.Based on the aforementioned research results, we have presented the first example of highly regioselective three-component reaction via trapping of an ammonium ylide. When a-aryl substituted diazoacetates were used as the substrates, the three-component reaction proceeded in a tandem 1,4-addition/intramolecular cyclization manner, while a-hydrogen atom or alkyl substituted ones were used, the reaction occurred via an 1,2-addition pathway. The high regioselectivity observed can be rationalized by hard and soft acids and bases (HSAB) principle.Finally, we have developed a copper(II)-catalyzed highly diastereoselective Michael type three-component reaction of aryl diazoacetates, alcohols and chalcone. Copper complexes were found to be effective and efficient catalysts in this reaction. The three-component reaction performed well over a broad range of substrates to afford y-hydroxyl ketone derivatives in good to high yields (63-94%) with excellent diastereoselectivity (> 95:5 dr). This reaction can be scaled up to a ten-gram scale by using CUSO4 as the catalyst. The resulting three-component product can also be easily converted into polysubstituted furan, dihydrofuran and tetrahydrofuran derivatives.