Research On Asymmetric Catalytic Reaction Based On Continuous Flow Technology

Continuous flow technology has the advantages of process safety,precise control of reaction conditions,and easy realization of automatic control,hence,its application in organic synthesis is becoming more and more extensive.In this paper,the asymmetric catalytic fluorination of?-keto esters and chlorination of pyrazolone compounds using bis?oxazoline?metal complexes as catalysts in a continuous flow system were studied,providing an efficient continuous flow synthetic method for a series of chiral?-keto ester fluoride and pyrazolone chloride.Firstly,a highly enantioselective homogeneous fluorination of cyclic?-keto esters catalyzed by diphenylamine linked bis?oxazoline?-Cu?OTf?₂ complexes has been established in a continuous flow microreactor.The microreactor allowed an efficient transformation with reaction times ranging from 0.5 to 20 min,and the desired products were afforded in high yields?up to 99%?with excellent enantioselectivities?up to 99%ee?at a low catalyst loading of 1 mol%.Secondly,the asymmetric chlorination reaction of pyrazolone compounds catalyzed by chiral bis?oxazoline?-metal complexes was further developed under continuous flow technology.With a chiral diphenylamine bis?oxazoline?-Cu?acac?₂complex catalyst,the corresponding chlorinated products were obtained with higher yields and good enantioselectivities in a continuous flow system.In this paper,the combination of continuous flow technology and asymmetric catalytic reaction provides a novel synthetic process for the two kinds of asymmetric catalytic halogenation,and provides a certain reference for the application of continuous flow technology in the field of asymmetric catalysis.