Chromium-Catalyzed Defluorinative Reductive Coupling Of Aldehydes With Gem-Difluoroalkenes

Fluorine chemistry has always been a hot research field in the development history of organic synthetic chemistry,because introducing fluorine-containing groups into drug molecules will change their original biological and chemical characteristics,which are reflected in the biological active molecules: it has stronger lipophilicity,metabolic stability and membrane permeability,which can further enhance the activity of drug molecules.In the past few decades,many fluorine-containing organic compounds have been developed in the fields of medicine,pesticide and chemical industry.One of the special structural units,monofluoroalkene,has attracted great attention of scientists.Because the amide bond is an important functional group of many biological and drug molecules,and the stereological and electronic configuration of monofluoroalkenes is very similar to that of amide,corresponding monofluoroalkenes can be used to replace amide molecules.In addition,monofluoroalkenes have stable conformation,resistance to hydrolase and stronger solubility.Therefore,the introduction of monofluoroolefins into the field of pharmaceutical chemistry has attracted extensive attention of organic synthetic chemists.At present,an efficient and convenient way to synthesize monofluoroalkenes is to carry out defluorinative reductive coupling reaction through Gem-difluoroalkene.It has been reported that transition metals such as Cobalt,Rhodium,Ruthenium,Nickel,Palladium,Copper,Iron,Manganese,Zinc and other transition metals participate in the cross coupling of Gem-difluoroalkenes with aryl boric acids,alkyl halides,carboxylic acids,and amino derivatives,effectively expanding the scope of synthesis and application of monofluoroalkenes.However,up to now,no case has been reported about the synthesis of monofluoroalkenes by transition metal Chromium catalysis.This paper introduces the successful realization of the Chromium-catalyzed defluorinative reductive coupling of aldehydes with Gem-difluoroalkenes by our research group.The catalytic system is characterized by using chromium as a catalyst,manganese as a reducing agent,and trimethylchlorosilane as a promoter.Under this condition,a variety of monofluoroalkenes can be obtained.After simple desiliconization protection of β-fluorinated allylic alcohol structural unit.The reaction conditions are mild,the operation is simple,and the substrate range and functional group tolerance are good in the process of substrate universality inspection.The yield of the obtained product is moderate to excellent and maintains high stereochemical selectivity.Moreover,we have successfully realized the product scale enlargement and drug molecular transformation through our method,which proves the practicability of this method and shows its potential application value in the field of medicine and biochemistry.