Study On Iron-Catalyzed Construction Of C-C And C-B Bonds Through Activation Of Inert C-O Bonds

The application of iron-catalysis in the activation of inert bonds has less been disclosed compared with other metal catalysts such as palladium and nickel.In order to make full use of the value of iron-catalysis and have a deep understanding of the properties of iron,this work employs iron as catalyst and boron as reducing agent to achieve the cross-electrophilic coupling reaction of phenol substrates with alkyl bromides and decarbonylative borylation of carboxylic acids via activation of inert carbon-oxygen bonds.In addition,the applications and mechanisms of the related reactions have been studied,which improved the understanding of iron-catalysis,providing a good platform for the application of iron-catalysis in synthetic chemistry.PartⅠ:Iron-catalyzed cross electrophilic coupling reaction via activation of inert C-O bondsThis article used aryl carbamates as raw materials to realize the iron-catalyzed,boron-promoted cross electrophilic coupling reaction between the phenol substrate and the alkyl bromides through activation of the phenolic C-O bond.The reaction was well compatible with various sensitive functional groups,some heterocycles such as pyridine and quinoline could also deliver the desired products with good efficiency.Late-stage functionalization of some natural products and drug molecules afforded the target products with moderate to excellent yields.The gram-scale reaction was also performed with good efficiency.The utilization of the directing effect of carbamate group,sequential reaction of C-H activation/electrophilic cross-coupling performed with accepted yields.One-pot synthesis was carried out through naphthol as raw material and provided the desired product with a synthetically useful yield.In-depth exploration and DFT calculations of the mechanism proved that iron can be reduced to Fe~Ⅰunder the system of alkali and boron.Therefore,it is speculated that the reaction has involved the catalytic cycle of Fe~Ⅰ/Fe~Ⅲ.The iron reacted with alkyl bromides firstly,and then processed oxidation addition and reduction elimination continuously to obtain the target product.PartⅡ:Iron-catalyzed activation of inert ester groups to construct carbon-boron bonds through cleavage C-O bondsIn this work,iron-catalyzed decarbonylative borylation was developed with the ester having a directing effect as starting material.This reaction has very good functional group compatibility,such as halogen,silicon group,ester group,etc.Aromatic and heteroaromatic substrates could undergo this transformation smoothly,providing the corresponding products in moderate to excellent yields.Moreover,this reaction realized the activation of inert alkyl carboxylate to decarbonylative borylation with moderate to excellent yields for the first time.Late-stage functionalization of some natural products and drug molecules afforded the corresponding products with moderate to excellent yields.The gram-scale syntheses could perform smoothly.Furthermore,in-depth exploration of the mechanism proved that iron was reduced to Fe~Ⅰby borane reagents,and then underwent oxidative addition of the C-O bond with the help of the directing group,followed by decarbonylation and reductive elimination to deliver the desired product...