Studies On The C-H Functionalization Of Acrylamide Derivatives

As one of the important means of contemporary organic synthesis,the C-H functionalization doesn't require pre-functionalization of the substrate,reduces the emission of waste such as halide and inorganic salt,simplifies the reaction step and has high atomic economy.Therefore,for the sustainable development of green chemistry,the development of C-H functionalization has a very important significance.Nitrogenous heterocyclic compounds containing oxindole or isoquinolinone skeleton are widely present in natural products,alkaloids and drug activity molecules,but there are still many problems in the synthetic methods of nitrogenous heterocyclic compounds,such as harsh reaction conditions,the use of expensive or more toxic reagents,the narrow range of substrates,the complex operation and so on.Therefore,it is of great value to study the synthetic methods of the nitrogen-containing heterocyclic compounds by C-H functionalization.In this paper,we mainly research the construction of nitrogen-containing heterocyclic compounds by C-H functionalization,using acrylamide derivatives to construct the oxindole and isoquinolinone derivatives.The main contents are as follows:1.Cascade radical addition/cyclization of N-arylacrylamides with ketones catalyzed by a Br?nsted acid was used to synthesize oxindole derivatives.In addition,?-Peroxyketones were also prepared using N-arylsulfonyl-acrylamides as substrates under acid-catalyzed conditions.2.In the presence of methanesulfonic acid as catalyst and TBHP as oxidant,a radical addition/cyclization of acrylamide derivatives with ketones or alcohols was described,providing an efficient path to synthesize 4-substituted isoquinoline-1,3-dione derivatives.In addition,the products can be transformed into tetrahydrofuro isoquinolinone derivatives.3.In the presence of Cu?OAc?₂ as catalyst and 1,10-phen as ligand,a radical addition/cyclization of acrylamide derivatives with NFSI was described,giving a new method for the synthesis of sulfonamide-containing isoquinoline-1,3-dione derivatives.4.In the presence of Pd?OAc?₂ as catalyst and DPE-phos as ligand,an efficient radical cascade difluoroalkylation/cyclization of acrylamide with ethyl difluorobromoacetate was described,developing a new synthetic method of isoquinoline-1,3-dione derivatives containing an ester group.In addition,the product of the reaction can be reduced by NaBH₄ to give an isoquinoline-1,3-dione derivative containing a hydroxyl group.The fluoro reagent can be extended to perfluoroalkyl iodide and bromodifluoromethylphosphonate.5.In the presence of AgNO₃ or Ru?bpy?₃Cl₂·6H₂O as catalyst,an efficient method for the synthesis of sulfone-containing isoquinolinonediones has been achieved via radical cascade addition/cyclization of acrylamide with sulfide or sulfonyl chloride.The above research contents mainly use the following research methods:1.The influencing factors of the reaction were screened by the starting substrates in every part,and the optimum reaction conditions were obtained.The applicability of the reaction substrate was also explored.The screening factors of the reaction include the type and amount of catalysts and additives,reaction temperature and time,the molar ratio of raw materials,atmosphere,solvents and so on.2.The structure of the target products was characterized by NMR,MS,IR and melting point instrument,and the structure of the target product was confirmed.3.Through the design of control experiments,free radical capture experiments and dynamic experiments,the reaction mechanism was proposed.