Studies Of Palladium-Catalyzed C-H Bond Activation

Transition-metal-catalyzed C-H functionalization reactions have emerged as one of the most efficient and straightforward methods for the construction of C-C bonds in organic synthesis, which have received considerable attention and intensive study in recent years. In particular, chelation-assisted C-H activation has been a hotspot in this field because of its excellent regioselectivity and reactivity. In this thesis, we investigated the palladium-catalyzed regioselective C-H bond functionalizations of arenes using free-amine as the directing group. Besides, we developed the direct C-H bond functionalization of indoles by palladium catalysis. The discussions and results are listed as following:1. Palladium-Catalyzed Free-Amine Directed C-H Bond Alkenylation and CycloaminationA novel protocol for palladium-catalyzed free-amine directed alkenylation of C(sp2)-H and cycloamination is described. Substituted biaryl-2-amines react with various alkenes, including electron-deficient alkenes, aryl alkenes and alkyl alkenes, to give the corresponding phenanthridines with exclusive regioselectivity. The use of a-branched styrenes leads to the formation of tricyclic compounds with seven-membered amine ring. Besides, the alkenylated products are obtained by employing of tert-butyl ethylene. The study of the key palladacycle intermediate and intermolecular kinetic isotope experiments imply that the palladium-mediated C-H cleavage might be involved in the catalytic alkenylation. Control experiments demonstrate that the method operates via a free-amine directed alkenylation, followed by a subsequent hydroamination cyclization reaction.2. Palladium-Catalyzed Free-Amine Directed C-H Bond Arylation(1) A palladium(II)-catalyzed arylation of biaryl-2-amines with arylboronic acids using free-amine as directing group in aqueous media has been developed. By employing soluble silver salt, the poisoning effect of free-amine to Pd(II) is reversed, which allows the significant improvement of regioselectivity and reactivity to give the C(sp2)-H arylation products in high yields. In addition to acting as oxidants, mechanistic investigation demonstrates that silver ion plays key role as a promoter in the reaction, which is favorable to the formation of the cyclopalladation intermediate. The addition of water is crucial to improve the arylation yields and DMSO/H2O(2:1) can give the best results.(2) A palladium (Ⅱ)-catalyzed free-amine directed arylation of biaryl-2-amines with aryl iodides in acid media has been developed. The load of catalyst is low,2.5mol%Pd(OAc)2can deliver the arylated products in high yields. The free-amine groups are unmodified in the presence of TFA. When the substituent was at the2’-or3’-position of biaryl-2-amine. mono-arylated product was obtained as the only prouduct; diarylated products were completely formed by the use of biaryl-2-amine with C4’-substituents or without substituents.3. Palladium-Catalyzed Free-Amine Directed C-H Bond CarbonylationA novel method for the synthesis of phenanthridinones has been developed:treatment of biphenyl-2-amine with carbon monoxide in the presence of3mol%Pd(OAc)2and1.5equiv Cu(OTFA)2in trifluoroethanol at70℃. The scope of the carbonylation reaction is broad and tolerates a variety of useful functional groups. Biologically and pharmaceutically significant phenanthridinones can be obtained in high yields at the ambient pressure of CO. By employing this methodology, the known bioactive molecules Phenaglydon and PJ34were synthesized efficiently. A plausible reaction mechanism has been proposed based on the experiment results of palladacycle intermediate.4. Palladium-Catalyzed Cross-Coupling Reaction of Indoles with ArylsiloxanesA Pd(OAc)2-catalyzed cross-coupling between indoles and arylsiloxanes in acidic medium has been developed. High reactivity and regioselectivity for the formation of C2-arylated indoles under mild condtions were achieved in the presence of TBAF and Ag2O at room temperature. Slow addition of trimethoxyarylsilane can improve the yields of cross-coupling products. This arylation reaction demonstrates a remarkable tolerance toward functional groups at the indoles and arylsiloxanes. Notably, electron-deficient arylsiloxanes present high efficiency in this system to give the arylated indoles in excellent yields.5. Palladium-Catalyzed Regioselective Oxidative Home-Coupling of Indoles and One-Pot Synthesis of Acetoxylated BiindolylsMild conditions have been developed to achieve Pd-catalyzed homocoupling of indoles with excellent regioselectivity in the presence of Cu(OAc)2·H2O in DMSO at room temperature in high efficiency. This method provides a simple route to2,3’-biindolyls from the electron-rich to moderately electron-poor indoles. The reaction tolerates the bromide substituent on indoles. In addition, a one-pot approach to C3-position acetoxylated biindolyls is realized via the palladium-catalysis by the use of AgOAc as oxidants under O2atmosphere. The possible pathway for the formation of biindolyls and acetoxylated biindolyls are discussed.