Palladium-Catalyzed Coupling Reactions Of Allyloxycarbonyl Oximes And Acetylenic Acids

Palladium-catalyzed decarboxylation coupling reaction being of several potential advantages such as mild reaction conditions, only stoichiometric byproduct CO2, high reactivity, high site-specification and regioselectivity, have proven to be a powerful shortcut for the assembly of carbon-carbon bond and carbon-heteroatom bond in organic synthesis. In the thesis, ten allyl oximes, six pyrazolo[1,5-a]pyridines and ten 2(5H)-furanones were synthesised from allyloxycarbonyl oximes or acetylenic acids in presence of palladium, depending on the optimization of reaction ligands, solvents, additives, reaction temperature and reaction time. The desired compounds were characterized by GC-MS,1H NMR and 13C NMR. Proposed reaction mechanism was further discussed according to previous reports and obtained data in the experiments. Three main points were included in this thesis as follows:(1) Palladium-catalyzed synthesis of allyl oxime from allyloxycarbonyl oxime. In the presence of Pd(PPh3)4 in dichloromethane (DCM), ten examples of allyl oximes were obtained at room temperature in only 8 minutes to give isolated yields from 74% to 90%. Among the selected substrates, ketoxime and aldehyde oxime were both found to be suitable for the reaction condition with good yields. It has little impact on the production rate when the benzene ring bearing substituent groups especially electron-withdrawing group on aldehyde oxime.(2) Palladium-catalyzed synthesis of 2-substituted pyrazolo[1,5-a]pyridines through decarboxylative coupling-cyclization reactions. Six examples of pyrazolo[1,5-a]pyridines were synthesized through decarboxylative coupling-cyclization reactions of N-iminopyridinium ylides and propiolic acids with isolated yields from 59% to 67% under the follow condition:catalytic system PdCl2/PPh3, base K2CO3, solvent DCM, temperature 25℃, time 24 hours. The desired compounds could be obtained with catalytic amount of PdCl2/PPh3 while propiolic acids were no necessary to be pre-function and N-iminopyridinium ylides to be benzoylation. Alkyl propiolic acid could be also decarboxylated to give moderate yield and it suffers lower yield with pyridine ring substituted in ortho-position comparing to para-position.(3) Palladium-catalyzed dehydrogenation coupling-cyclization reactions of acetylenic acids with iodonium ylides for the synthesis of 2(5H)-furanones. Under the optimal reaction condition:Pd(PPh3)4(3 mol%), K2CO3(2 equiv), DCM,25℃,6 h, ten examples of 2(5H)-furanones were obtained with isolated yield from 74% to 98%. Reaction yield was reduced if substrate was bonded with alkyl propiolic acid, but also up to 74%, compared with aryl propiolic acid. Malonic acid methyl iodine benzene and ethyl malonic acid iodine benzene were mostly suitable mostly for the reaction condition to give yield 98% and 93%.The thesis has provided a proposal to construct heterocyclic compounds which were widely applied in synthesis of natural products, drug intermediates and important materials. The group of heterocyclic compound was expanded by synthesis of 2-substituted pyrazolo[1,5-a]pyridines and 2(5H)-furanones through decarboxylative coupling-cyclization reactions. Moreover, further research on reaction mechanism would provide a theoretical and guiding significance for the application of palladium-catalyzed decarboxylative coupling reaction.