Selective C-H Silylation Of Heteroarenes And Intramolecular C-H Amidation

As the most basic and common chemical bonds,C-H bond widely exist in various organic compounds.Thus,the activation of C-H bonds has always been a hot topic in organic synthesis.C-H bond activation is an efficient method to directly construct C-X bonds(X=C,N,O,S)from non-prefunctionalized reactants.Therefore,it can reduce reaction steps,improve atomic economy and synthetic efficiency,and provide an efficient synthetic way to construct complex target molecules from simple starting materials.Moreover,it is of great significance for the modification of natural products and drug molecules.In recent years,the activation of C-H bonds has made good progress and remarkable results have been achieved in the actual production process,providing impetus for the development of the fields of medicine,chemical industry,materials and agriculture.However,a variety of difficulties and challenges still remain.Efficient,economical,and convenient activation of C-H bonds is the goal that the field of green synthesis has been chasing.The research content of this paper includes selective C-H silylation of heteroarenes catalyzed by silver salts,selective C-H silylation of heteroarenes catalyzed by photocatalysis,and intramolecular C-H bond amidation under transition metal-free conditions.The details as follows:Part Ⅰ:The similar properties of silicon and carbon make organosilicon structure an ideal choice for replacing carbon structural units in drugs.Therefore,silanes play an important role in the field of medicine.Established Minisci-type decarboxylations have been limited to aliphatic carboxylic acids.As their analogues,silanecarboxylic acids have rarely been investigated.Silanecarboxylic acids are easy to synthesize,highly stable,easy to handle,and can undergo decarboxylation readily to generate silyl radicals under mild conditions.So far,decarboxylation of silanecarboxylic acids catalyzed by silver salts has not been reported.Herein,we developed a C-H bond silylation of N-heteroarenes with silanecarboxylic acids,in which AgNO3 as the catalyst,K2S2O8 as the oxidant,and MeCN as the solvent.This protocol provides a new method for the generation of silyl radical.Part Ⅱ:Modifying drug molecules by replacing carbon structural units with organosilicon structure can improve the biological activity and change the lipophilic and metabolic pathways of drug molecules.The traditional Minisci-type decarboxylationrelies on the combination of silver catalysts and peroxides to promote decarboxylation of alkyl carboxylic acids to generate radicals,which undergo an intermolecular addition with hetoroarenes to constuct C-C bonds.Although Minisci-type decarboxylation has been developed to a new stage enabled by photocatalysis,radical precursors are limited to aliphatic carboxylic acids and silanecarboxylic acids have been rarely studied.In this part of the work,we reported that C-H bond silylation of electron-poor heteroarenes was realized under blue light irradiation using silanecarboxylic acids as silyl radical precursors,4CzIPN as the photocatalyst,K2S2O8 as the oxidant and MeCN as the solvent.The protocol shows advantages such as mild and safe reaction conditions,without transition metal catalysts,moderate to excellent product yields,and high regioselectivity.Part Ⅲ:Amide structural units exist widely in natural products and drug molecules,and are important structural units in pharmaceutical applications.Therefore,the introduction of amide bonds has received extensive attention.Among them,intramolecular C-H amidation is an effective method,but such reactions always require the use of transition metal catalysts.Herein,we develop an efficient and facile method for intramolecular C-H bond amidation of N-phenoxy benzamide compounds in the combination of KOAc as the base and toluene as the solvent.