Multicomponent And Cross-coupling Reactions In Aqueous Medium

Exploration of nontoxic, safe "green" solvents as the organic reaction medium is one of the most significant areas in the Green Chemistry. The dissertation focuses on developing the use of cheap, eco-friendly water containing unique chemical and physical properties in place of organic solvents as the organic reaction medium to meet the requirements of Green Chemistry, and verifying that the organic reactions can be promoted using water as the medium. The research mainly concentrates on designing the multicomponent reactions and palladium-catalyzed cross couplings in aqueous medium.As a strating point, multicomponent reactions can be conducted in water catalyzed by acids or bases. The aqueous solution of Trition X100proves to be an efficient reaction medium for the Mannich reaction. The three-component one-pot reactions for the formation of polysubstituted4H-pyran derivatives can be performed in aqueous medium catalyzed by piperdine and SDS. The nonionic surfactant Triton X100that self-assembles in water to form micelles proves to diminish the hydrolysis of benzoyl chlorides, so the thioesterification can be realized via a one-pot three-component reaction in water. It can be concluded that water as the medium can enhance these reactions with high yields, avoiding the use of volatile and potential toxic organic solvents, and simpifing the pretreatment of starting materials (and solvents) and the seperation of products.Effects are also made to run the multicomponent reactions in polyethylene glycol/H2O. Spiro[dihydropyrdine-oxindole] derivatives are synthesized by the reaction of isatins,1,3-dicarbonyl compounds and2-naphthylamine in polyethylene glycol/H2O under catalyst-free conditions. The one-pot three-component processes of aldehydes,1,3-dicarbonyl compounds and6-aminouracils for the synthesis of polyfunctionalized pyrido[2,3-d] pyrimidines and uncyclized adducts, and the four-component one-pot domino reaction of aldehydes, malononitrile, amines and1,3-thiazolidinedione for the synthesis of dihydrothiophene ureidoformamides can also be performed under the identical conditions. The combination of polyethylene glycol and water avoids the use of any catalysts and toxic solvents in these multicomponent reactions. In addition, the protocol provides several merits, such as high yields, mild conditions, ease of the product isolation, and reaction medium can be reused by filtration, so it is more suitable for large-sacle operations.Palladium-catalyzed Heck, Stille couplings and the direct C-2arylation of indoles with aryl halides in aqueous medium are also investigated in the thesis. Based on the results, water as the medium can promote palladium-catalyzed cross-couplings. Meanwhile, Heck and Stille couplings can be promoted by adding appropriate sufartants in water to form micelles, and the direct C-2arylation of indoles with aryl halides can be accelerated by adding ethanol as the cosolvent. These cross-couplings in water have several advantages, such as mild conditions, high yields and selectivity, and free of toxic solvents during the reactions. Several important intermediates in total synthesis were also perapred by these protocols to further demonstrate their potential applications in organic synthesis. Furthermore, an extra study is made to verify that the stereochemical outcome of Stille and Suzuki-Miyaura couplings is dictated mainly by the ligands on palladium based on the investigations of the cross-couplings in water.