Transition-metal-catalyzed Synthesis Of Heterocyclic Compounds And Mechanism Research

1.Oxadiazolone-enabled synthesis of primary azaaromatic aminesDespite their tremendous synthetic and pharmaceutical utility,primary azaaromatic amines remain elusive for access based on a generally applicable C-H functionalization strategy.An oxadiazolone-enabled approach is reported for convenient entry into N-unsubstituted 1-aminoisoquinolines through Co(III)-catalyzed redox-neutral,step-,atom-,and purification-economic C-H functionalization with alkynes.15N labeling experiment reveals the effectiveness of both oxadiazolone N-atoms as directing sites.The installed primary amine can be harnessed as a synthetically useful handle for attachment of divergent appendages.2.Associative covalent relay:an oxadiazolone strategy for Rh(III)-catalyzed synthesis of primary pyridinylaminesThe achievement of transition metal catalysis requires a tight control over electronic and steric environments at the catalytic center for each elementary catalytic step.A relay formalism is proposed herein for categorizing the way of interplay among reactants,target product,and catalytic center in the catalytic cycle,an important factor that can dictate overall catalysis viability and efficiency.In this formalism,transition metal catalysis can proceed via dissociative relay,associative covalent relay,and associative dative relay modes.An intriguing associative covalent relay process operates in Rh(III)-catalyzed oxadiazolone-directed alkenyl C-H coupling with alkynes and has allowed efficient access to a synthetically and pharmaceutically important class of compounds,primary pyridinylamines.Although the primary pyridinylamine synthesis mechanism is a posteriori rationalized,the relay formalism formulated herein can provide a priori an important mechanistic conceptual framework to base upon for future catalyst design and reaction development.3.Direct access to cobaltacycle via C-H activation:N-chloroamide-enabled room temperature synthesis of heterocycleCobaltacycle synthesis via C-H activation has been achieved for the first time,providing key mechanistic insight into cobalt catalytic chemistry.N-chloroamides are used as a directing synthon for cobalt-catalyzed room temperature C-H activation and construction of heterocycle.Alkynes as coupling partners allow convenient access to isoquinolones,a class of synthetically and pharmaceutically important compounds.The broad substrate scope enables a diverse range of substitution patterns to be incorporated into the heterocyclic scaffold.4.Co(III)-catalyzed N-chloroamide-Directed C-H activation for 3,4-dihydroisoquinolone synthesis3,4-Dihydroisoquinolone synthesis via Co(III)-catalyzed C-H activation has been achieved for the first time N-Chloroamides as a C-H activation directing synthon react effectively with alkenes at room temperature,enabling the incorporation of diverse reactive functionalities and substitution patterns into the target heterocycles.5.Synthesis of 2,5-disubstituted oxazoles via cobalt(III)-catalyzed cross-coupling of N-pivaloyloxyamides and alkynesA first time synthesis of 2,5-disubstituted oxazoles via Co(III)catalysis is described herein.The synthesis is achieved under mild condition through[3+2]cycloaddition of N-pivaloyloxylamides and alkynes.The reaction operates through an internal oxidation pathway and features a very broad substrate scope(applicable to aryl-and alkyl-substituted N-pivaloyloxyamides,aryl and alkyl alkynes).One-step synthesis of natural products texamine and balsoxin has been demonstrated via this protocol.