Iron-Catalyzed Defluorination Borylation Of Unactivated Aliphatic Gem-Difluoroalkenes

Objective:We will explore an efficient and environmentally friendly catalytic system with green and low-toxic iron salts as catalysts for the synthesis of organoboron compounds using gem-difluoroalkenes as substrates.The substrate range and functional group tolerance in the iron-catalyzed system will be examined as well.The substrate range and functional group tolerance of this method were investigated in the iron-catalyzed system.Moreover,the synthetic transformation of boron-containing products and their applications in natural products will be evaluated.Finally,the mechanism of its reaction was further explored and explained.Methods:1.Using iron salt as catalyst,unactivated aliphatic gem-difluoroalkenes were reacted with bis(pinacolato)diboron(B2pin2)under the effects of bases,ligands and solvents.2.After extraction,drying and concentration,the crude mixture can be purified by silica gel flash chromatography to afford the product.And the product was identified by 1H NMR,13C NMR and high resolution mass spectrometer.3.The conditions of combination of temperature,solvents and catalysts was screened to find the best reaction conditions;the substrate range of the reaction was studied in the optimized condition and the transformation of boron-containing product was explored.4.The mechanism of iron-catalyzed reaction was explored by radical inhibition experiments,deuterium-labeling experiments,and suspected intermediate exploration experiments.Results:1.In this iron-catalyzed reaction system,it was found that unactivated aliphatic gem-difluoroalkenes could undergo defluoroborylation to synthesize 1,2-bis(boryl)alkane compounds.2.Under the optimized reaction conditions with Fe(OAc)2 as catalyst,t-BuONa as base,2-(di-tert-butylphosphine)biphenyl as ligand and t-BuOH as additive,the product can be obtained with more than 80%yield determined by 1H NMR.3.The substrates containing aromatic rings,aromatic heterocycles,rich-and electron-deficient groups and related natural product derivatives can be converted to the desired products under the standard conditions.4.The boron-containing products can undergo the downstream transformations.Conclusion:1.The defluoroborylation of unactivated aliphatic gem-difluoroalkenes under a green and efficient iron-catalyzed system was discovered.The reaction has good efficiency,a wide substrate range and good functional group tolerance.Preliminary mechanistic studies indicate that double β-F elimination is involved in the catalytic cycle.The related natural product derivatives and boron-containing products can also be further transformed and application.