Investigation On Palladium-catalyzed Oxidative Cyclizations Of Alkenes And Alkynes

In the past decades, as versatile building blocks in raw materials and intermediates, alkenes and alkynes have been widely used in organic synthetic chemistry, material science, pharmaceutical chemistry, etc. The transition- metal-catalyzed effective transformation of alkenes and alkynes through effective activation of carbon-carbon unsaturated bond has been rapidly developed to an important field of organometallic chemistry. And the palladium catalyzed reactions became a powerful tool for the construction of carbon-carbon and carbon-heteroatom bonds. For the traditional Pd0-catalyzed functionalizations of alkenes and alkynes, raw materials always required to be pre-prepared. Generally, the reactions undergo oxidative addition, migration insertion and β-H elimination, which produce at least one kind of harmful by-product. In comparison, PdII-catalyzed transformation of alkenes and alkynes can be initiated not only by transmetallation or C-H activation(instead of oxidative addition), but also by nucleopalladation, which is simple, efficient and green. In addition, among the PdII initiated reactions, quenching ways were also more diversified. Besides the pathway of PdII/Pd0, high- valent Pd can be obtained by using strong oxidants, which offers some bonds construction that is hard to be achieved with reductive elimination of PdII. Moreover, PdII is inert to air and moisture, which is easy handling. Due to the diversified initiating and quenching ways, palladium catalyzed oxidative transformations of multiple bonds usually have diversity, which can be used to build complex functionalized molecules. Therefore, how to achieve the chemical- and regio-selective cyclizations via selective cleavage and formation of bonds has the vital significance in the development of functional molecules.In this context, with alkenes and alkynes as subtrates, we achieve selective cleavage of carbon-carbon, carbon-palladium bonds and the formation of carbon-carbon, carbon-heteroatom bonds. And we developed a series of simple, efficient and environmental friendly Pd-catalyzed oxidative cyclizations, which used to construct nitrogen-containing functionalized molecules including oxazole, pyrrole and quinoline. See the following for details:(1) Construction of oxazole derivatives through the Pd-catalyzed/Cu- mediated cascade oxidative cyclization. With propargyl esters and benzyl amine as subatrates, a series of tri-substituted oxazoles were obtained via cascade formation of C-N and C-O bonds. This protocol has good functional group tolerance and high regioselectivity. In addition, this transformation removed four hydrogen atoms and obtained the oxygen atom from water, which shows atom economy.(2) The synthesis of pyrroles through the arylation/Wacker cyclization cascade reaction of unactive olefins. Compared with active olefins, there are less reports about oxidative Heck reactions of unactive olefins. We developed a palladium catalyzed cascade arylation/amination of alkenyl C-H bond. With available high allyl amines and aryl boric acid as starting materials, polysubstituted pyrrole compounds were obtained by one-step. The transformation sequentially undergoes the oxidative Heck reaction of unactive olefins and intramolecular aza-wacker cyclization.(3) Synthesis of 3-bromo-pyrroles by intermolecular oxidative cyclization of bromoalkynes and N-allylamines. Based on our continuous research of bromoalkynes, we reported a novel palladium catalyzed oxidative cyclization reaction, which efficiently affords 3-bromo-pyrroles by one step with high selectivity. Among palladium catalyzed reaction with bromoalkynes, bromine atom is usually difficult to be retained. Our protocol only removed two hydrogen atoms and retained the bromine atom, which show atom economy and could be used for further functionalizations. Besides, compared with C-2 position of pyrrole, C-3 position is harder to be functionalized. This approach offers a convenient route to 3-substituted-pyrroles.(4) Synthesis of quinolines via palladium catalyzed intermolecular aerobic a nnulation of alkenes and alkynes. We prepared a series of 2,3-bisubstituted quinolines via Pd/Cu co-catalyzed system with molecular oxygen. This reaction underwent the intermolecular amination of alkyne, intramolecular insertion of olefin and the oxidative cleavage of C-C bond. It’s worth noting that not only being a green oxidant, oxygen is also the key feature of cleavage of C-C bond. This method has advantages like easy-operation, good functional group tolerance, broad substrate scope and high regioselectivity.(5) Controllable oxidative cyclization of enyne. Based on the strategy of transient-ligand assisted selective oxypalladation, we developed a Pd-catalyzed an oxidant- induced selective cyclization of enynes, which provides rapid assembly of various highly functionalized cyclene and bicyclic-cyclopropane skeletons. O2 atmosphere resulted in the unexpected 6-endo-Heck cyclization and alkenyl migration to afford cycloolefins. In contrast, copper(II) halides led to a 5-exo-trig cyclization and synergetic cleavage of C–Pd bond to get cyclopropanes. This shows high regio-selectivity, mild conditions and excellent functional group compatibility. Amide group activated the alkynes, transferred the oxygen atom and regenerated by obtained oxygen atom from water. In addition amides achieved further modifications. Moreover, the regenerated amides could be used for the further modifications, which work as a multi-functional group in our strategy.