DDQ-catalyzed Oxidative C(sp~3)-H Bond Functionalization

It can be said that oxidation is the foundation of many biological and chemical processes.The C?sp³?-H bond oxidative functionalization is an important oxidative transformation,and simple raw materials can be directly converted into more valuable molecular through this transformation.So far,most of researches on C?sp³?-H functionalization are based on transition metal catalysis?Pd,Cu,Ru,Rh,etc.?,still limited researches of organocatalysis are available in the territory.2,3-Dichloro-5,6-dicyano-1,4-benzoquinone?DDQ?is known for facilitating many C-H bond transformations,relying on its one-electron reduction potential and hydrogen abstraction capacity.Consequently,it is of great significance to develop a metal free reaction system in which DDQ-catalyzed oxidative C?sp³?-H bond functionalization.According to the literatures and our previous researches,a metal-free catalyzed aerobic oxidation system was developed and applied it in benzylic C?sp³?-H bond oxidation and oxidative cross coupling reaction.A visible-light-induced aerobic oxidation of benzylic C?sp³?-H bond of alkylarenes promoted by DDQ/TBN/AcOH was developed.Visible-light-excited DDQ spontaneously relaxes to the longlived n-?*triplet excited state by intersystem crossing.The triplet-excited DDQ?³DDQ*?has very strong oxidizing ability and can oxidize alkylarenes to carbonyl compounds smoothly.Using oxanthene as a model substrate,the effects of solvents,temperature,amount of catalyst,amount of AcOH and presence or absence of visible light on the reaction were investigated.Under the optimal conditions?1 mol%DDQ,5 mol%TBN,20 mol%AcOH,O₂,blue LED light?,a range of alkylarenes including xanthenes,thioxanthenes and9,10-dihydroacridines could be oxidized into corresponding ketones in excellent yields?91%-99%?.Besides,based on the determination of the intermediate?9H-xanthen-9-ol?,we proposed a plausible reaction mechanism.Compared with the traditional thermal reaction,this photocatalytic protocol showed higher efficiency.The DDQ/TBN/O₂ catalytic system was successfully applied in oxidative C-O coupling between benzylic C?sp³?-H bond and O-H bond?carboxylic acids?.The strategy realized C-O bond formation by direct C-H bond functionalization in a simple and efficient catalytic system.It could successfully diminish the usage of transition-metal catalysts and stoichiometric amount of terminal oxidants.Using diphenylmethane as the model substrate,the effects of solvents,temperature and catalyst dosage on the reaction were investigated.Under the optimal conditions?20 mol%DDQ,20 mol%TBN,O₂,100 ^oC?,a range of diarylmethanes could successfully couple with various carboxylic acids in excellent yields?61%-95%?.Besides,phthalides could also be synthesized smoothly via intramolecular oxidative cyclization,catalyzed by DDQ.Phthalides are a class of active compounds that have great potential in pharmaceutical and biological applications,and have been used from academia to industry.In conclusion,we have reported DDQ-catalyzed oxidative C?sp³?-H bond oxidation and oxidative cross coupling reaction.The merits of mild reaction conditions,good functional group compatibility,metal-free conditions and atom economy are fully exhibited in this research.