| dc.description.abstracteng | Metal-catalyzed C─H and C─C functionalizations have become an increasingly viable approach, which allows the direct formation of C─C and C─heteroatom bonds in an atom- and step-economical manner. However, the significant accomplishments in this field have heavily relied on the use of precious transition metals, such as rhodium, palladium, ruthenium, and iridium, over the last few decades. The high cost and potential toxicity of these metals limit the applications in pharmaceutical and fine chemical industries. Therefore, developing efficient and economic C─H and C─C functionalization by inexpensive and Earth-abundant metals is highly desirable. In this thesis, we summarize our recent achievements in direct C─H and C─C bond transformations by cobalt(III)- and manganese(I)-catalysis.
In the first project, a cobalt(III)-catalyzed C─H/N─O functionalization was achieved for the synthesis of substituted isoquinolines derivatives. Notable features of this developed annulation reaction were a wide substrate scope applicable and tolerance of various functional groups, affording the isoquinolines in good yields with high regio-selectivities. The mechanistic findings, including H/D exchange, competition experiments and KIE studies, revealed a reversible and facile BIES-type C─H metalation pathway was involved.
In the second project, a good site- and regio-selective cobalt(III)-catalyzed C─H annulation of various nitrones approached the novel and useful indole synthesis. The versatile cobalt(III) catalyst proved to be particularly effective for challenging unsymmetrically substituted alkynes, when employing a catalytic amounts of Piv-Leu-OH as ligand, delivering unprotected indoles in good yields with excellent levels of regioselectivity.
In the third project, we developed the first cobalt(III)-catalyzed position-selective C─H functionalization, which fully tolerated strongly coordinating heterocycles, such as pyridines, pyrimidines, and pyrazoles. The preliminary mechanistic studies, especially the H/D exchange experiments, indicated that the positional selectivity of the reaction is determined in the C─N bond forming step.
In the fourth project, a cobalt(III)-catalyzed domino C─H/N─H allylation reaction of aryl imidates with dioxolanones was accomplished. The reaction was performed under mild reaction conditions with water and generated CO2 as the only byproducts. Aryl-substituted imidates bearing various electron-donating and electron-withdrawing groups are compatible with the reaction conditions, delivering the cyclization products in good yields with high levels of regio-selectivity.
In the fifth project, a manganese(I)-catalyzed decarboxylative C─H/N─O allylation in water was developed. When indole substrates were employed, the reaction features a broad substrate scope and good functional group tolerance. This organometallic C─H activation was also tolerant to air and water. Moreover, this versatile C─H allylation was also successfully applied to the amino acids and aryl ketimines, delivering the allylation products in good yields with high levels of chemo- and regio-selectivities.
In the sixth project, a synergistic Brønsted acid/manganese(I)-catalyzed C─H hydroarylation with high chemo- and regio-selectivities in continuous flow was accomplished. With the assistance of carboxylic acid, the undesired β-O elimination could be avoided and provided a robust access to allylic carbonates in high yields with excellent chemo- and regio-selectivities. Mechanistic findings indicated that a fast organometallic C─H metalation step, as well as an intramolecular proton transfer was involved.
In the last project, we have developed versatile C─C activations in water by inexpensive and Earth-abundant manganese catalysis. The organometallic C─C functionalizations, including C─C allylations, C─C alkenylations, and C─C alkylations, occurred efficiently in environmentally-benign solvent with excellent levels of chemo-, regio-, and position-selectivities. This result was showcased by the synthesis of 1,2,3-tri-substituted arenes, which could not be achieved by C─H activation. | de |