Transition Metal Catalyzed Cyclization Reactions And Application On Solid-supported Organocatalyst For The Asymmetric Reaction

Transition metal facilitated reactions have a long history in organometallic chemistry and new reactions continue to be discovered and developed.In recent years, the synthesis of organic heterocyclic and polycyclic molecules has especially benefited from novel Pd,Cu facilitated cyclization of heteroatoms to alkenes,alkynes and arenes.Transition-metal catalysis provides the opportunity to generate complex molecular frameworks from simple,readily available substrates in an efficient,easy and selective manner.It has been widely used in organic research area,eapecially for some biologic,pharmaceutical and materials interest heterocycles.The relatively low cost,low temperature and the realization of catalysis in many instances makes it an attractive reagent.Reasonablely,we can believe that transition metal will have a bright future.This thesis aims at the studies on the Pd,Cu-catalyzed multi-component cyclization reactions and solid-supported organocatalyst for the enantioselective Michael addition. It mainly consists of the following four parts:In chapter 1,a comprehensive overview in the field of Pd,Cu catalyzed cyclization is summarized.Copper and palladium salts can act as catalytic cross-coupling agents, Lewis acids and oxidizing agents and be used in oxidation reaction,C-C bond formation,the addition of nucleophiles to C-C multiple bonds to form some new organic heterocyclic and polycyclic molecules.In chapter 2,we introduced the concept of"click"chemistry and copper-(â… )-catalyzed 1,2,3-triazole multi-component reactions under green chemistry. Room temperature ionic liquids are environmentally benign solvents due to their unique chemical and physical properties,and have proved to be especially useful in the case of catalytic reactions,Herein,we have demonstrated that the ionic liquid/H₂O was a good reaction medium for the one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles using either halides at sp3-hybridized carbon atoms or halides at sp2-hybridized carbon atoms in good yields.Better performance was obtained than that of conventional reaction condition.This procedure permits extensive recycling of the solvent without substantial loss in activity within five times.On the basis of the current efforts,it seems to be likely that a number of metal catalyzed transformations could be performed equally well or even more effectively in this ionic liquid.In chapter 3,we extended the application of"click"chemistry to the field of solid-supported asymmetric Michael addition reaction.Recently,a significant amount of effort has been devoted towards the modification of the proline and it's derivatives, particularly chiral pyrrolidine-triazole,which are made through copper-mediated 1,3-dipolar cycloaddition between azides and alkynes(click chemistry),have been found to be very effective in asymmetric Michael addition reaction.These organocatalysts are generally considered environmentally benign because the use of metals is avoided,however,it would be even more desirable and economical to develop an immobilized,easily recoverable,and reusable catalyst to perform this reaction.We prepared a new silica-supported organocatalyst and successfully applied to the asymmetric Michael addition reaction of ketones to nitroalkenes.The reactions proceeded smoothly at room temperature to give high yields(up to 98%),excellent diastereoselectivities(syn/anti ratio up to 20:1),and excellent enantioselectivities(ee up to 93%).Furthermore,this procedure permits extensive recycling of the catalyst without substantial loss of activity.Therefore,Cu(â… )-catalyzed 1,3-dipolar"click"azide-alkyne cycloaddition provides the modular and tunable features for the solid-supported pyrrolidine-triazole catalysts. In addition,it is worthy of noting that the triazole moiety introduced cannot only act as a positive phase tag to complete the reaction in a broad range of solvents,but can also serve as an efficient chiral-induction group to ensure a high selectivity.On the basis of the current work,it seems likely that a number of asymmetric reactions could be performed equally well with this immobilized organocatalyst.In chapter 4,we summarized the Catellani reaction and a number of extention via this reaction,introduced palladium catalyzed addition to carbonyl groups and arylation.Finally,a powerful new methodology for the rapid synthesis of highly substituted poly-aromatic ketones,tertiary alcohols,and phenols has been developed. Of particular significance is that this methodology not only provide a new method for the synthesis of poly-aromatic products,but also is a good incorporation of domino reaction into typical Catellani reaction.Through a lot of work on the addition of ketones,aldehydes and enolates,possibly mechanism has been discussed,synthetic utility of palladium intermediates and their ability to show different reactivity patterns has been demonstrated.