Study On C?H Trifluoromethylation And Carbon Oxygen Bond Formation Reaction Of Heteroaromatic Compounds

The first nickel-catalyzed C-H trifluoromethylation of pyridine N-oxides and free anilines with Togni's reagent as trifluoromethyl source has been achieved,respectively.A variety of 2-CF₃ pyridine derivatives and trifluoromethylated anilines were synthesized.Under the action of sodium hydroxide,a series of N-methoxyquinolin-2?1H?-ones were synthesized using a stable and easily available N-methoxyquinoline-1-ium tetrafluoroborate as starting material.Using alkyl substituted N-methoxyquinoline?pyridine?tetrafluoroborate as raw material,diverse N-heteroaromatic aldehydes and ketones were synthesized by the oxidation of six-membered N-heteroaromatic compounds without using transition metals.1.Nickel-catalyzed C-H trifluoromethylation of pyridine N-oxides with Togni's reagentScheme 1 Nickel-catalyzed C-H trifluoromethylation of pyridine N-oxidesThe first nickel-catalyzed C-H trifluoromethylation of pyridine N-oxides with Togni's reagent has been achieved.The optimal reaction conditions were obtained as the combination of pyridine nitrogen oxide as substrate,Togni's reagent as trifluoromethyl source,10 mol%NiCl₂·6 H₂O,KOAc?3.0 equiv?in DMF under argon atmosphere at 50 ^oC for 24 hours?Scheme 1?.Trifluoromethylation proceeds smoothly under mild conditions with moderate functional group compatibility.Notable advantages of this method include the use of low cost nickel catalyst,and its simple convenient operation.The reaction can also be scaled up to gram scale and can be applied to synthsize trifluoromethylated biologically active molecules.Owing to the facile strategy,this method is a better alternative for the synthesis of 2-CF₃pyridine derivatives.2.Nickel-catalyzed direct C-H trifluoromethylation of free anilines with Togni's reagentScheme 2 Nickel-catalyzed direct C-H trifluoromethylation of free anilinesAn efficient nickel-catalyzed C-H trifluoromethylation for the synthesis of trifluoromethylated free anilines has been developed for the first time.The C-H trifluoromethylation can be carried out under the conditions with the readily available aromatic free amines as starting materials,Togni's reagent as trifluoromethyl source,10 mol%Ni?OH?₂ as catalyst,K₂CO₃?3.0 equiv?as base and DMSO as solvent under argon atmosphere at 35 ^oC for 2 hours to obtain the desired products in good to excellent yields?Scheme 2?.This protocol exhibits a broad functional group tolerance,good regio-and chemoselectivity under mild conditions.The newly developed economical one-step method affords a convenient way to synthesize trifluoromethylated free anilines.3.A facile and environmental friendly strategy for the synthesis of N-methoxyquinolin-2?1H?-onesScheme 3 A one step method for the synthesis of N-methoxyquinolin-2?1H?-onesA facile and environmental friendly one-step protocol for the construction of N-methoxyquinolin-2?1H?-ones has been explored,using a stable and easily available N-methoxyquinoline-1-ium tetrafluoroborate as starting material,1.5 equiv.of sodium hydroxide as base and dioxane/H₂O?1:1?as solvent at room temperature underairatmospherefor48h?Scheme3?.Aseriesof N-methoxyquinolin-2?1H?-ones were synthesized by carbon oxygen bond construction reaction.The method features simple operation,mild and environmentally friendly reaction conditions,and good functional group tolerance.4.Transition-metal-free oxidation of benzylic C-H bonds of six-membered N-heteroaromatic compoundsScheme 4 Transition-metal-free oxidation of heterobenzylic C-H bondsA one-step oxidation of heterobenzylic C-H bonds was discovered and developed under the conditions of N-methoxyquinoline?pyridine?-1-ium tetrafluoroborate as substrate,3.0 equiv cesium fluoride as base and ethyl acetate as solvent?Scheme 4?.Diverse six-membered N-heteroaromatic aldehydes and ketones were obtained in moderate to excellent yields at room temperature under air atmosphere for 15 h.This method exhibits a good functional group tolerance,mild reaction conditions,and without using toxic reagents and transition metals.