N,O-bidentate Directing Group Assisted C-C And C-N Bonds Formation Via Palladium Catalyst

Transition-metal-catalyzed carbon-carbon and carbon-nitrogen bonds formation have always been a research hotspot in the field of organic chemistry. It is the most direct, economical and efficient way to achieve these transformations started from simple and basic C–H bonds. Particularly, N-heterocycles, such as β-lactam, pyrrolidone, pyrrolidine and their benzo- structures quinolinone, tetrahydroisoquinoline, indoline, are important “privileged scaffolds” among natural alkaloids, biologically active compounds, and commercial drugs, which are of pivotal importance to research. In this thesis, we mainly studies the Pd(OAc)2 as the catalysis to achieve C-C, C-N bonds assisted by N,O-bidentate directing group.First, we developed an inexpensive and readily available N,O-bidentate directing group, glycine dimethylamine, which started from the simplest amino acid. The directing group was first applied to the palladium-catalyzed β-C(sp3)–H arylation. To note, because of its own particularity, ortho-substituted aryl iodide has seldom been used in C-H activation. However, ortho-substituted aryl iodides are the main substrates for the synthesis of important drugs such as carteolol and procaterol. Gratifyingly, a broad range of ortho-substituted aryl iodides could be employed in our developed β-C(sp3)-H arylation reacton.Second, the novel N,O-bidentate directing group was further and applied to the palladium-catalyzed intramolecular amination. The strategy could be used to activated δ-C(sp2)–H bonds effectively, at the same time, a series of quinolinone derivatives could be synthesized in good yield under mild reaction condition. More importantly, with the previous study in hand, quinolinones could be synthesized efficiently by using the two-step one–pot method.Finally, we also developed a oxalyl amide directed ortho-alkynylation of β-arylethamine and γ-arylpropamine derivatives via palladium catalyst. Importantly, the alkynylated β-arylethamine oxalyl amide could be easily converted to the valuable synthon, dihydroisoquinoline derivative, in good yield.