Study On The Iron-catalyzed Reductive Denitrification Cross-coupling Reaction Of Nitroolefins And Cyclobutanone Oxime Ester

Transition metal-catalyzed reductive cross-coupling reaction is an efficient method to construct a variety of organic molecules through two electrophilic reagents.As a class of versatile organic synthesis intermediates,nitro-containing compounds have been widely used in various fields and have received extensive attention.Traditional cross-coupling reactions mostly use halogenated alkanes as substrates.Compared with halogenated alkanes,the preparation process of nitro-containing compounds has the advantage of fewer by-products.It is of great significance to develop cross-coupling reactions with nitro group as a leaving group.However,nitro-containing compounds are easy to produce side reactions under reductive conditions,such as reduction to amines,imines,hydroxylamines,oximes.Therefore,it is challenging to construct C-C bonds by denitrational reductive cross-coupling reactions.In this thesis,an iron-catalyzed reductive denitro cross-coupling reaction of nitroalkenes with cyclobutanone oxime esters to construct Csp²-Csp³ bonds has been developed.The research contents are as follows:（1）The synthesis steps of nitroalkenes and cyclobutanone oxime esters,as well as the related experimental operations on the reductive denitro cross-coupling reaction have been introduced in this thesis.（2）The optimal reaction conditions were determined as follows:nitroalkenes（0.3mmol）and cyclobutanone oxime esters（0.45 mmol）,Fe（OAc）₂（10 mol%）,Zn（1.0equiv.）,2,2’-biquinoline（10.1 mol%）,isoquinoline（2.0 equiv.）,DMA/Ph Me（solvent1.0 m L,0.8 m L DMA and 0.2 m L Ph Me）.The reaction was performed at 60 ^oC for 24h under argon atmosphere.（3）Investigation of substrate scope showed that this reaction had good functional group tolerance.Both electron-rich and electron-poor nitroalkenes or cyclobutanone oxime esters were proved to be compatible with the reaction system and gave good yields.Radical trapping experiments indicated that the reaction was proceeded by a free radical mechanism.Gram-scale experiment proved the synthetic utility of this reductive denitro cross-coupling reaction.Based on the preliminary mechanism studies,a possible reaction mechanism has been proposed.