Studies On The Synthesis Of Carbonyl Compounds By Transition Metal Catalyzed Oxidative Reaction

In recent years,oxidation coupling reaction has been rapid developed and been one of the hotspots in organic chemistry.Moreover,it is a commonplace that oxidation coupling reaction has been applied to chemical and pharmaceutical production.In organic synthesis chemistry,oxidation coupling reaction has been an important method to construct C-C or C-X bonds.Compared to conventional coupling reaction,the oxidation coupling reaction not only reduces the complicated pre-functionalization of the substrates,shortens the reaction route,and improves the reaction efficiency,but also the source of raw materials is more extensive.In one word,the oxidative coupling reaction greatly improves the practicality of the reaction and reduces the production cost.Transition metal catalyzed oxidative coupling reaction has been a hotspot for its efficient reactivity and the reusability of catalyst,however,exploring the reaction with the advantages of mild conditions,high efficiency,environmentally friendly,and high atomic and cost economy has been the relentless pursuit of scientific research workers.For the above reasons,this thesis is concerned with studies on the synthesis of carbonyl compounds by transition metals(such as Cu,Ag and Fe)catalyzed oxidative reaction,and the contents of this thesis are as following:(1)A method to the synthesis of β-ketophosphonates from alkynes is presented.The terminal alkynes are converted into alkynylphosphonates under the conditions of CuI,O2 and base.Then,β-ketophosphonates are prepared via Ag-catalyzed hydration of alkynylphosphonates.β-ketophosphonates are important intermediates in organic pharmaceutical synthesis.(2)A general solution for the synthesis of various β-ketophosphonates through copper/iron-catalyzed oxyphosphorylation of alkynes with H-phosphonates is developed.This reaction uses readily available terminal alkynes and H-phosphonates as the starting materials and O2 as the oxidant,obtaining the desired product under the role of Cu/Fe catalysts,with the advantages of mild conditons,high functional group tolerance and operation simplicity.The control experiments showed that the reaction proceeded through a radical process,and TEMPO-trapped compound was observed when TEMPO was added to the reaction.(3)A new strategy for the synthesis of β-CF3/CHF2 ketones through copper catalyzed oxidative coupling of vinylarenes with ICH2CF3/ICH2CHF2 is presented in the paper.Fluorine-containing molecules are widely used in drags and materials based on the unique and useful chemical properties.The method uses readily available vinylarenes and ICH2CF3 as the starting materials and TBHP as the oxidant,obtaining the desired product β-CF3 ketones under the role of Cu/Ag catalysts.More importantly,the reaction is also applicable to the synthesis of β-CHF2 ketones when the vinylarenes and ICH2CHF2 are used as the starting materials.The control experiments showed that the reaction proceeded through a radical process,and TEMPO-trapped compound(TEMPO-CH2CF3)was observed when TEMPO was added to the reaction.(4)A novel iron-catalyzed oxidative coupling of indoles with a-amino carbonyl compounds to synthesize 3-acylated indoles is developed.Indoles are ubiquitous in natural products,bioactive molecules,and are used as valuable starting materials in organic synthesis.The method uses indoles and a-amino carbonyl compounds as the starting materials and TBHP as the oxidant,obtaining the desired product 3-acylated indoles under the role of Fe catalyst,with the advantages of mild conditons,high functional group tolerance and operation simplicity.Moreover,the control experiments showed that the reaction proceeded through a radical process.