Research On Palladium-Catalyzed Cascade Reactions Of Unsaturated Hydrocarbon

Transition metal-catalysis is an efficient method to construct C-C and C-X bonds.The booming of transition metal-catalysis promotes the rapid development of organic chemistry.Up to now,3 Nobel Prizes have been granted to this research field.In 2010,Heck,Negishi and Suzuki were awarded Nobel Prized for their original contribution on palladium-catalyzed cross-coupling reactions,which have been wildly applied in organic synthesis and pharmaceutical.With the demand for high synthetic efficience and the extensive attention on green chemistry,cascade reaction as a highly efficient synthetic strategy has attracted much research interest.These reactions avoided the isolation of intermidates,reducing the waste generation,thus are atom and step economical chemical processes.Besides,unsaturated hydrocarbon(including alkenes,alkynes and arenes)are important staple in oil and coal industry.From the aspect of science and human society,using unsaturated hydrocarbon as starting material,developing green and efficenet method to constrcut valuable chemical products is an important frontier and core of morden organic chemistry.In this context,we worked on the palladium-catalyzed cascade reaction of unsaturated hydrocarbon.Using simple alkenes and alkynes as starting material,novel and efficient palladium-catalyzed methods were designed to contruct valuable complex molecules.In the first part,we studied the palladium-catalyzed cascade reaction of alkenes.Based on Heck reaction,new Heck-type cascade reactions were designed for the synthesis of valuable benzohetercycle.In the sencod part,palladium-catalyzed cascade reactions of alkynes were studied.Using alkynols as simple starting materials,practical methods for the synthesis of trienes,cyclopentadienes(Cps)and N-heterocyclic have been developmented.Meanwhile,the hotspots such as C-H activation,oxygen oxidation are also involved in our research.The details are summarized as following:(1)Pd-catalyzed Heck-type cascade reaction.Similar to Heck reaction,intramolercular Heck reaction is an efficient way to construct benzoheterocycle.Besides,high regio-and stereoselectivity method to form C-C double bond is a center focus in organic synthesis.Recently,palladium catalyzed carbene migratory insertion reacyion has emerged as a powerful method for C-C double bonds formation.Therefore,we designed a palladium-catalyzed Heck-type cascade reaction with N-tosylhydrazones for the synthesis of functionalized olefins with high selectivity.(2)Pd-Catalyzed tandem oxidative arylation/olefination reaction.In the past decades,C-H activation has attracted extensive attention and received rapid development.The palladium-catalyzed coupling between arenes and olefins,commonly known as the Fujiwara–Moritani reaction,is an useful process for C(sp2)-C(sp2)bond formation.Similarly,the intramolecular Fujiwara–Moritani reaction is an efficient method for the benzohetercycle.Based on our previous Heck-type cascade reaction,we envisaged a tandem oxidative arylation/alkenylation of aromatic tethered C-C mutiple bond with two C-H bonds,a Fujiwara–Moritani-type difunctionalization reaction of C-C mutiple bond with aromatic C-H bond and vinylic C-H bond.Beside,O2 is used as terminal oxidant.(3)Pd-catalyzed C–H activation/oxidative cyclization of acetanilide with norbornene.Ligand directed C–H activation olefination reaction is an important C–C bond forming process,which has been extensively studied.However,the C–H activation/oxidative cyclization of alkenes have been rarely realized,since the facilate of ?-H elimination and the comparative oxidative Heck reaction is usually the dominant process.We anticipated that the strained alkenes,such as norbornenes,could offer a solution to control the corresponding ?-hydride elimination due to its strained structure and could undergo reductive elimination to afford the oxidative cyclization products.Thus,we designed an efficient Pd-catalyzed oxidative cyclization reaction for the synthesis of functionalized indolines by direct C–H activation of acetanilides.(4)Pd-catalyzed highly regio-and stereoselective assembly of C-C double bonds.1,3,5-Trienes and polyenes with conjugated double bonds are known to be valuable synthons that have widespread application in biological chemistry and material science.While the method for the stereoselective synthesis of conjugated polyenes are rare.In this work,we focused on the possibility of constructing multisubstituted polyenes using the readily available starting materials such as alkynol.Moreover,the halogenated products highlight the penitential application of this method.(5)Pd-catalyzed intermolecular [3 + 2] carbocyclization of alkynols and propiolates.Cyclopentadienes(Cps)are useful synthetic intermediates,such as valuable building blocks in organic synthesis and good reaction partners for the Diels–Alder reaction.Based on our previous work on alkynols,Pd-catalyzed intermolecular [3 + 2] carbocyclization of alkynols and electron-deficient alkynes for the synthesis of halocyclopentadienes(Cps)has been developed.This protocol employs simple propargyl alcohols as the C3 group to participate in the cyclization reaction,providing a highly convenient and atom-economical entry to the halo-cyclopentadiene framework.(6)Cu-catalyzed intermolecular oxidative cyclization of haloalkynes.Copper as a chip metal catalyst also attracted our attention which has been proved to be efficient in C-X bond formation.Besides,haloalkynes is a versatile feedstock.Therefore,we disclose an efficient protocol to construct 2-halo-substituted imidazo [1,2-a]pyridines via copper-catalyzed oxidative cyclization reaction of 2-aminopyridines and haloalkynes.The study shows that the reactive halide atom was retained and O2 was used as sole oxidant.