Studies Of Annulation Reactions Of Di/Trifluorodiazoethane With 2H-azirines Or 1,1-dicyanoalkenes

Fluoroalkyl group-functionalized N-heterocycles,amides and cyanocyclopropanes are three interesting classes of compounds possessing wide applications in organic synthesis,biochemistry,pharmaceutical,and agrochemicals.In recent years,significant achievements have been made in the construction of fluorine-containing Nheterocycles by the cycloaddition reactions of fluorine-containing diazo compounds.However,the preparation of pyrazolines that are substituted by both trifluoromethyl and trifluoromethyl-imine groups from trifluorodiazoethane is still challenging.Secondly,diazo-amides are mainly obtained via the nucleophilic addition reaction of diazo compounds with α-carbonyl imines,while the use of trifluorodiazoethane for the synthesis of the corresponding diazo-amides in a straightforward reaction manner is still not reported.Although the cyclopropanation reaction of fluorinated diazo compounds with olefins has been reported to construct fluorine-containing cyclopropanes,the synthesis of fluoroalkyl and cyano groups dual-functionalized cyclopropanes are very limited.Only four reports documented the introduction of fluoroalkyl and cyano groups into cyclopropanes with the narrow substrate scope and/or tedious reaction operations.Therefore,in this thesis,the applications of difluoro-and trifluorodiazoethane in cyclization reactions and radical reactions are developed for the efficient synthesis of trifluoromethylated N-heterocycles,diazo-amides and difluoro/trifluoromethyl-cyanocyclopropanes.The details are as follows:In the first part,a diethylzinc-promoted unconventional annulation of 2,2,2-trifluorodiazoethane with 2H-azirines has been achieved,and a series of 3-trifluoromethyl pyrazolines are synthesized in good yields with excellent diastereoselectivities(98% yield,dr > 20:1).Functionalized 3-trifluoromethylpyrazole and 3,5-ditrifluoromethyl pyridazines can be obtained by the elimination or ring expansion reaction of the obtained cyclization products.The mechanism study shows that α,β-unsaturated trifluoromethylamine is likely the key intermediate of the reaction,and the transformation involves two [3 + 2] cycloaddition steps in association with one dinitrogen extrusion process in one pot.In the second part,a series of diazo-substituted amides has been synthesized by diethylzinc-promoted tandem radical addition/Mannich reaction of 2H-azirines with2,2,2-trifluorodiazoethane or ethyl diazoacetate in up to 89% yield.Functionalized trifluoromethyl amide,hydrazone and oxazoline compounds can be obtained by the hydrogen reduction and oxidation reaction of the obtained diazo-substituted amides.The control experiments show that the oxygen atom in the product amide is derived from oxygen,and the reaction mechanism could involve free radical addition,ternary ring opening and Mannich addition steps.In the third part,annulation reactions of 1,1-dicyanoalkenes with difluoromethyl or trifluoromethyl diazo reagents are reported,and a series of trans difluoro-and trifluoromethyl-substituted cyclopropane-1,1-dicarbonitriles are produced in good to excellent isolated yields with excellent diastereoselectivities without any catalyst or additive.Under basic conditions,highly functionalized methyl ester or amides containing fluoro-cyanocyclopropane can be obtained by alcoholysis or hydrolysis of the cyclization products.