Studies On Alkenylation Of C-H Bond In Chloroalkane With Cinnamic Acid/Alkyne And Application In Green Drug Synthesis

The chlorine-atom is widely found in nature.A wide range of molecules such as effective components in Traditional Chinese Herb,natural products and pharmaceuticals involve chlorines.Besides,various chlorinated compounds served as powerful and valuable building blocks in synthesis of drugs and materials.However,most traditional chlorinating processes usually result in serious pollutions.Hence,green and efficient chlorinating methods are highly desirable in modern pharmaceutical community.Herein,we demonstrated severous novel strategies for synthesis of chlorinated molecules.This thesis involves the following four chapters.The first part summarized the background of this research.A series of chlorine-involved natural products,drugs,bioactive molecules were depicted as representative examples at the beginning of this chapter.Then some traditional synthetic approaches to chlorinated compounds were described.Next the author reviewed the developments of novel accesses to these molecules by using simple alkyl chloride as the chlorine source via C(sp3)-H functionalization over the last decade.Finally the research proposal was demonstrated at the end of this part.The second chapter detailed the first new method for synthesis of chlorinated styrenes.After much efforts,we developed an efficient and environmentally-benign access to these compounds.We found that an array of chlorinated styrenes could be obtained in good yields by simply heating the mixture of cinnamic acids and/or β-nitrostyrenes with peroxide in 1,2-dichloroethane(DCE)for hours.The author shared the details of this discovery which includes optimization of the typical reaction conditions,the scope of substrate and the mechanistic studies.The third part depicted the secondary discovery of novel access to chlorinated olefins in details.After a series of modifications,an atom-transfer radical addition(ATRA)reaction of simple alkyl chloride with alkynes was achieved.Simply heating of alkynes with peroxides in alkyl chloride could afford a wide range of chlorinated olefins in good yields and chemo-selectivities.Also the details of this process could be found in this chapter.The final part summarized the whole essay.Also the author outlined the novelty and potential applications of these findings.Furthermore,the possible direction of this research field was suggested at the end of this thesis.