Studies Of Multi-site Selective C-H Functionalization In Olefins

Due to the ubiquitous nature of C-H bonds in organic molecules,it is challenging to achieve selective functionalizations among different kinds of C-H bonds.Therefore,it is one of the focus of this field that to develop efficiently site-selective C-H functionalization.In this dissertation,several olefinic structural substrates were designed.Pd(II)-catalytic multisite-selective C-H functionalization in Cyclic Olefins was realized uising directing strategy and several valuable chemical structures was builded in the fields of biology and organic synthesis chemistry.The catalytic mechanism of related reactions was been studied.(1)Catalytic Multisite-Selective Acetoxylation Reactions at sp2 vs sp3 C-H Bonds in Cyclic OlefinsThe first Pd-catalyzed multisite-selective acetoxylation reactions were disclosed at an unactivated alkene sp2 C-H bond versus secondary allylic sp3 C-H bond in cyclic olefins via the modulation of directing groups.The different directing groups overcame the key challenge in differentiating C-H bonds and provide a new controlling approach for site-specific C-H activation.A wide variety of substrates were readily acetoxylated under operationally simple conditions.Mechanistic studies suggest that different Pd(IV)intermediates were involved in the multisite-selective acetoxylation reactions.a.The site-selectivity of the vinyl sp2 C-H bond could be achieved in cyclic olefins by using picolinamide(PA)as directing group.Kinetic isotope effect studies suggested that the sp2 C-H(D)bond breaking to form the cyclopalladium is rate limiting in the system.The H/D exchange also implied that the process occurred through the cyclopalladated intermediate.b.When Ts was employed as directing group,the 3-positon site-selectivity of the allylic sp3 C-H acetoxylation was obtained.Deuterated experiment’s result indicates that acetoxylation occurs through the postulated π-(1,2,3)-allylpalladium(IV)species.c.Furthermore,by introducing a methyl group on the NTs group,regioselective acetoxylation was also obtained between the two allylic sp3 C-H bonds(3-vs 6-position).It was suggested that acetoxylation occurs through the postulated π-(6,1,2)-allylpalladium species by deuterated experiment’s result and the synthesis of possible palladium(II)complex 7.(2)Synthesis of Spiro-dihydroquinoline and Octahydrophenanthrene Derivatives via Palladium-Catalyzed Intramolecular Oxidative ArylationA method for intramolecular sp2 C-H oxidative arylation of unactivated cyclic olefins had been developed to access spiro-dihydroquinoline and octahydrophenanthrene derivatives in a straightforward and efficient manner.Bearing picolinamide as the directing group,the alkenyl anilines cyclized to afford spiro-dihydroquinolines in moderate to excellent yields via direct oxidative arylation.Kinetic isotope effect studies suggested that the aryl sp2 C-H activation is rate limiting in the process.While the alkenyl benzylamines furnished the octahydrophenanthrene derivatives in moderate yields via sequential oxidative arylation and double acetoxylation.By deuterated labeling experiments and the synthesis Pd(II)complex 12,it is proved that this cascade reaction is initiated by the activation of olefins sp2 C-H and the catalytic cycling mechanism is different from that of oxidative arylation.(3)Palladium-catalyzed C-H Functionalization of Unactivated Olefins toward Synthesis of Indole DerivativesThe Heck type σ-alkyl Pd(II)intermediates were formed by the picolinamide(PA)protected substrate and using Pd(II)catalyst.The transient Pd intermediate was captured with a nucleophile(OAc),resulting in C-H cascade cyclization and acetoxylation.This protocol provided an easy,site-selective access to construct 3-monosubstituted indole compounds in a moderate yield.