Studies On The C(sp~3)-H Functionalization Of Alkyl Ketones,Alkyl Nitriles And Alkanes

Over the past few decades,research interest in the functionalization of free radical C(sp~3)-H has continuously grown.These reactions provide a very novel way to connect chemical structure fragments with complex molecules,which greatly shortens the reaction steps,has high atomic economy and is a breakthrough progress for the traditional synthesis methods that require prefunctionalization of organic reaction substrates.With the development of green chemistry,as well as the requirements for the atomic economy and the need of building new chemical structures in the modern chemical society,people are more committed to the new synthesis of C(sp~3)-H functionalization through the direct use of hydrocarbons method.However,because the C(sp~3)-H bond of some compounds is very inert,has large bond energy and weak acidity and basicity,the functionalization of C(sp~3)-H bond is still a very meaningful and challenging research field.In this paper,the research results on the functionalization of free radical C(sp~3)-H at home and abroad in recent years are summarized,the copper-catalyzed decarboxylation oxidation alkylation of alkynyl carboxylic acid and its application in organic synthesis are mainly introduced.This thesis is composed of two parts:1?In this paper,the characteristics of free radical and the advantages of free radical reactions are briefly described.Direct C(sp~3)-H functionalization is recognized as a reliable method for the construction of complex molecules due to its high atomic economy and easily available starting materials.The common functionalization of C(sp~3)-H bond is through the loss of one proton and one electron,forming a free radical at the same time,participating in the single electron transfer process.The research on the functionalization of C(sp~3)-H of alkylketones,alkylnitriles and alkanes in recent ten years and their application in synthesis are reviewed,and the mechanism of some chemical reactions is explained and summarized properly.2?The decarboxylation oxidation alkylation of alkynyl carboxylic acid with alkylketone and alkylnitrile catalyzed by copper was studied to construct new C-C bond and C-O double bond,thus providing a new method for the synthesis of?-diketone and?-ketonitrile and a new strategy for the synthesis of some drugs and natural compounds.This transformation is featured by wide functional group compatibility and easily obtained acetylenic acid as reaction raw material.The free radical trapping experiment shows that the reaction may be a free radical process,the isotope labeling experiment shows that the oxygen on the newly formed carbonyl group is derived from water,and the kinetic isotope effect experiment shows that the rate-determining step of the reaction may contain C(sp~3)-H bond breakage.