Fluorine-Containing Functionalization Reaction Of Enaminone

As the most electronegative element,fluorine possesses unique properties.The introduction of fluorine-containing functional groups into molecules is known to be capable of greatly improving their physical and chemical properties.Accordingly,the construction of fluorine-containing molecules is one of the hot issues of current research.Meanwhile,enaminones are a class of easily available,and broadly reactive molecules,they can be transformed into various organic compounds by different modes of reaction pathways.Therefore,investigating and establishing divergent fluoro-functionalization reactions of enaminones are of high significance for the synthesis of fluorinated organic molecules.The main body of this thesis target on the fluorine functionalization of enaminones,contain three different sections of research work.1)The[4+1]cycloaddition reactions of enaminones and Ethyl bromodifluoro-acetate have been achieved with the promotion of Na₂CO₃,leading to the synthesis of2,2-difluoro-2,3-dihydrofurans.The method employs no transition metal catalyst,enabling the construction of in cycle difluoro methylene compounds.In addition,in the presence of acid,the C-N bond cleavage of enaminones have been realized for the synthesis ofβ-keto enonic acids via one-pot,two-step operation.2)By employing organic base N,N-Diisopropylethylamine（DIPEA）to promote the formation of difluorocarbene from diethyl bromodifluoromethyl phosphonate,accessing successfully the cycloaddition reactions of difluorocarebene with NH-enaminones for the synthesis of gem-difluorinated dihydrofurans bearing NH-amino side chain.The work breaks the previous restriction that NH-enaminones do not tolerate such cycloaddition by means of modifying the difluorocarbene precursor.3)By using POCl₃ as reductant,the reductive C（sp²）-H trifluoromethylthiolation reactions between enaminones and sodium trifluoromethyl sulfonite have been accomplished for the synthesis ofα-trifluoromethylthioled enaminones.Under identical conditions,the enamino sulfones can also undergo analogous trifluoromethylthiolation reaction.In addition,by derivative transformation to the products,the trifluoromethylthio-functionalized pyrimidines,pyrazoles and isoxazoles.