Research On The Influence Of Fluorine Effects For The Synthesis And Character Of Nitrogen Heterocycles

Due to its unique properties,fluorine has broad applications in drug modification and organic synthesis.In this dissertation,the basic properties of fluorine,that is,strong electron-withdrawing property and conformational effect are studied in the bridged amide and pyrroline ring systems.The main research content is divided into the following two parts:Part ?: We developed a strategy for the synthesis optically active(1R,4R,5S)-5-fluoroquinuclidin-2-one from 2-cyclopenten-1-one,using asymmetric 1,4-addition,?-fluorination of aldehyde,and Schmit-Aübé reaction as key steps.To further investigate the effect of different amounts of fluorine atoms on the amide's pKa,we used a similar strategy to synthesize(1R,4R)-5,5-difluoroquinuclidin-2-one.Part ?: We have developed a general method for the synthesis of optically active 2-aryl 4-fluoropyrrolidines from 4-fluoroproline,in which photomediated decarboxylation was used to generate free radicals and the fluorine gauche effect to control the conformation of free radical intermediates.The method has the following characteristics: 1)mild conditions and excellent yields;2)good substrate generaliity and functional group compatibility.Finally,we provided plausible explanation of the energy difference of proline intermediates and the stereoselectivity through DFT calculation.The work carried out in this paper will provide valuable information for further understanding of the basic properties of fluorine.