Selective C-H Amination And Arylation Reaction

Regioselectivity and stereoselectivity have always been the topics of organic chemistry.The pursuit of higher regioselectivity and stereoselectivity drives the development of organic chemistry.Carbon-hydrogen(C-H)bond is the most basic chemical bond of organic compounds,which makes the selective C-H activation occupy an important part of synthetic chemistry.The direct functionalization of C-H bond represents an attractive strategy for the rapid and efficient construction of carbon-carbon and carbon-hetero bonds.Our group has been working on the development of C-H bond cleavage and functionalization.This thesis focuses on the selective C-H amination and arylation,including iodoarene-catalyzed stereospecific intramolecular sp3 C-H amination,enantioselective palladium-catalyzed intramolecular a-arylative desymmetrization,and alternative synthesis of skeletons of tetraphenylenes and 1-phenyltriphenylene from o-iodobiaryls.Part 1:Saturated nitrogen heterocycles are ubiquitous structural motifs in bioactive molecules,including alkaloid natural products and pharmaceuticals.The most efficient way to form many saturated N-heterocycles would be to construct a C-N bond by substituting an H atom on a C(sp3)-H group with N atom.We have developed a new synthesis of ?-lactams via an iodoarene-catalyzed intramolecular tertiary C-H amination.The products form efficiently using a simple organocatalyst and m-CPBA as oxidant under mild conditions in short times.DFT calculations show that the preferred pathway for this reaction involves an iodonium cation intermediate and proceeds via a concerted C-H activation/C-N bonding transition state,allowing the stereospecific construction of chiral quaternary centers in a 'memory-of-chirality'transformation.Part 2:Highly oxygenated and densely substituted bicyclo[m.n.1]frame-work is highly important building blocks in basic structural motifs of many natural products and bioactive compounds.1 Most of these compounds contain quaternary carbon centers adjacent to a bridged ketone.Pd-catalyzed intramolecular ?-arylation of carbonyl compounds represents an attractive strategy.We have described a highly enantioselective Pd-catalyzed intramolecular a-arylative desymmetrization of 1,3-diketones providing various functionalized bicyclo[m.n.1]architectures with several stereocenters.The generated tertiary center in our method can be prevented to be racemized by this rigid structural property under basic conditions.It has been found that planar chirality and central chirality have a significant impact on the stereochemical outcome,but they have different effects in this a-arylative desymmetrization.The utility of this protocol has been highlighted via enantioselective total synthesis of(-)-parvifoline using this a-arylative desymmetrization as the key step.We expect broad utility of this simple protocol for the synthesis of many other natural products.Part 3:Aryl-aryl bond formation constitutes one of the most important subjects in organic synthesis.The recent developments in direct arylation reactions forming aryl-aryl bond have emerged as very attractive alternatives to traditional cross-coupling reactions.We have reported an efficient method to build two aryl-aryl bonds simultaneously via direct C-H arylations.This reaction sequence involves rupture of two C-H bonds and two C-I bonds,as well as the formation of an eight-membered ring.This palladium-catalyzedreaction represents as one of the few efficient methods for the formation of flexible ?-expanded cyclooctatetraenes.We used this method to rapidly build a library of ?-conjugated tetraphenylenes.The initial mechanism experiments indicated the transformation may a Pd(IV)spiropalladacycle intermediate.This development will help both synthetic and material chemists making this direct arylation a valuable tool for easy synthesis of various tetraphenylenes.Part 4:Fused polycyclic aromatic hydrocarbons(PAHs),as atomically precise graphene segments,have attracted tremendous attention because of their high electron density,narrow HOMO-LUMO gaps,low redox potentials,strong ?-? stacking abilities,aromaticity,and excellent chemical stability.Recently,C-H activation technology has received significant attention as a reliable strategy to provide a more efficient and rapid access to PAHs from small arenes.We have reported an efficient method to build triphenylene-cored aromatics via Pd-catalyzed annulative dimerization of o-iodobiaryls.This reaction sequence involves rupture of two C-H bonds and two C-I bonds,as well as the formation of a benzene ring.Using 1,6,11-trichloro-4-(4-chlorophenyl)triphenylene(TCCT)as a building block,the synthetic route to the fully fused,small graphene nanoribbons follows two-step protocol involving the late-stage arylation and subsequent cyclodehydrogenation.The possibility of a Pd(IV)spiropalladacycle intermediate was ruled out in the catalytic cycle on the result of our initial mechanism experiments.Given the functional ?-systems of interest in chemistry and material,we anticipate that our strategy will simplify the synthesis and structural elaboration of graphene nanoribbons.