Study On The Pd-catalyzed Coupling Reaction Of N-tosylhydrazones Derived From Benzocyclic Ketones

Polyaryl olefins,a kind of important organic intermediates,are found in the molecular structure of all sorts of drugs,most of these drugs have showed good pharmacological effect.Therefore,the synthetic method of these types of compounds for the science researchers have became more and more active.Transition-metal-catalyzed coupling reaction has been widely applied to constructing C（sp²）-C（sp²）bonds due to its highly efficience,good selectivity and mild reaction conditions.Commonly organometallic reagents such as Grignard,organozinc,organotin,organosilicon,and organoboron reagents,are generally employed as the nucleophilic component for the cross-coupling reaction.In spite of the wide applicability of these reactions,the stoichiometric amount of the organometallic reagent was required.Moreover,these organometallic reagents had a certain limitations for the complex preparating and using process and harsh storge conditions.N-Tosylhydrazones,easily synthesized through the carbonyl compounds with N-tosylhydrazine,are common substrates in organic synthesis.Thus,the transition-metal-catalyzed cross-coupling reaction of N-tosylhydrazones not only expands the substrate scope of coupling partners but also furnishes novel and practical methodology for the carbonyl compounds.In consideration of the rapid development of N-tosylhydrazones in the area of organic synthesis in the past years,this paper provides a simple and effective method to constructing a series of polyaryl olefins via study on palladium-catalyzed coupling reaction of ketones,N-tosylhydrazine and aryl bromides/benzyl bromides.This paper mainly includes the following three parts:（1）Pd-catalyzed cross-coupling reactions of benzocyclic ketones,tosylhydrazide with aryl bromides.Palladium-carbene complex as an important intermediate undergoes migratory insertion of aryl andβ-hydride elimination to give benzocycloalkene derivatives,the yield is up to 96%.These compounds can be further asymmetric hydrogenation and therefore potential medical value of the resulting enantiopure alkanes.This method has advantages of convenient operation,available starting materials,broad substrate scopeis and gram scale synthesis.（2）Pd-Catalyzed cross-Coupling of benzocyclic ketones,tosylhydrazide with benzyl bromides.We chose coupling reagents contained two differentβ-H as the reaction substates,16 highly selective cyclic olefins was obtained in up to 93%yields and 10:1 selectivity via this method,including benzyl-substituted dihydronaphthalenes and 1H-indenes.DFT studies were performed to elucidate both the reaction mechanism and origin of such regioselectivity.The calculated results were consistent with the experimental resultscan,which favored the formation of cyclic olefins rather than exocyclic double bonds.This reaction The reaction can be realized through one-pot two-step process,high regioselectivity of products provided a novel and effective method for building intra-annular double bonds.（3）Pd-catalyzedcouplingreactionsofN-（cyclicyl（phenyl）methylene）-4-methylbenzenesulfonohydrazide with benzyl bromides.This reaction chose Pd（PPh₃）₂Cl₂ and PPh₃ as a efficient catalyst system,16 trisubstituted ethylene derivatives were obtained in 43-86%yields,which all derived from the benzylβ-H elimination under the presence of two differentβ-H.This method provided a powerful guarantee for highly selective synthesis of olefins utilizing hindered N-Tosylhydrazones.