Synthesis Of 2-Pyrones Via Palladium-Catalyzed Selective Cross-Coupling Reactions And Study On Copper-Catalyzed Chan-Lam Cross-Coupling Reactions

Transition metal-catalyzed cross-coupling reaction is one of the most powerful and efficient methods for the construction of C-C or C-heteroatom bonds. It plays an important role in organic chemistry and has been widely used for the synthesis of natural products, pharmaceuticals and advanced materials. Furthermore, most of researches were focused on palladium and copper in all of the transition metals. This paper concentrated upon the reactions catalyzed by palladium or copper and their applications in the cross coupling reactions to be studied in detail from three parts.Recently, the palladium-catalyzed cross-coupling reactions of multifunctional substrates which proceed stepwise and display regioselectivity are more attractive for organic chemists. Diversified structures, often containing bioactive scaffolds, could be generated via different transformations to introduce various substituents successively in specific positions of the molecular skeleton. This strategy opens the door for numerous synthetic applications to diversified structures. Among others, the site-selectivity Suzuki cross-coupling reaction is a particularly popular method in organic synthesis all along.As a privileged fragment, the 2-pyrone scaffold is found in many natural products and pharmaceuticals that exhibit remarkable biological activities (such as antimicrobial and anticancer, herbicide and HIV-protease inhibitor). With the goal of a diversified library of 2-pyrones, in part one, the palladium-catalyzed site-selectivity Suzuki cross-coupling reactions of 3-bromo-6-methyl-4-tosyloxy-2-pyrone with arylboronic acids via diversity-oriented synthesis provided a general, efficient and practical synthesis of 3,4-disubstituted 2-pyrones. The results indicated that arylboronic acids with electron-donating or -withdrawing groups could be successfully employed in the reaction to give the corresponding 2-pyrone derivatives in good to excellent yields. Meanwhile, it was found that water was crucial to the reaction with promoting the C-3 selectivity of substrate.In part two, an efficient and facile route has been developed for the generation of 3-alkoxyl-6-methyl-4-sulfanyl-2-pyrones via palladium catalyzed cross-coupling reactions of C-O bond formation. The combination of Pd(OAc)2 and PCy3 showed good efficiency in the oxyalkylation reactions of 3-bromo-6-methyl-4-sulfanyl-2-pyrones, which afforded the desired 3-alkoxyl-6-methyl-4-sulfanyl-2-pyrones in fair yields.Copper-catalyzed C-X (N, O, S) cross-coupling reactions, as a simple, convenient, efficient and readily available method, have became a principle approach for organic synthesis. On the other hand, NaBPh4 is a stable, non-toxic and commercially available phenylating agent, and has been applied in various metal-catalyzed reactions. In part three, copper catalyzed C-N bond formation via NaBPh4 was studied in detail. The results demonstrated that catalytic Cu(OAc)2·H2O displayed high efficiency in the Chan-Lam cross-coupling reactions of NaBPh4 and N-H containing compounds. Furthermore, the reactions proceeded smoothly with various amines to generate the corresponding products in moderate to excellent yields.