Study On The Reaction Of Constructing N-fluoroalkylated Heterocyclic Compounds Based On Trifluoromethyl Olefin Building Block

Nitrogen heterocycles are widely found in natural products,and pharmaceutical and pesticide molecules.Incorporation of trifluoromethyl group（CF₃）into nitrogen heterocycles containing drug molecules can significantly improve their lipophilicity,metabolic stability,and bioavailability.Therefore,the development of efficient,and mild methodologies for the synthesis of CF₃-containing nitrogen heterocycles are of great significance.Trifluoromethyl olefins are becoming the popular building blocks in the synthesis of trifluoromethylated compounds for their structural diversity and high reactivity.In this thesis,we are committed to synthesizing new trifluoromethyl olefins,investigating their reactivities,and providing convenient methods for the construction of CF₃-containing nitrogen heterocycles.The details are as followings:Firstly,the regioselective N-vinylation of nitrogen heterocycles was achieved at room temperature using（β-trifluoromethyl）vinyl sulfonium salt as the vinylating reagent,triethylamine as the base,and acetonitrile as the solvent.A series of nitrogen heterocycles containing trifluoromethyl olefins were obtained in moderate to good yields.This method is operationally simple under mild conditions,easy to scale up,and tolerates a wide range of nitrogen heterocycles,e.g.NH-containing azoles,and indoles.Secondly,the hydrogenation of these nitrogen heterocycles containing trifluoromethyl olefins was investigated using catalytic Pd/C under atmospheric pressure H₂.A series of N-trifluoroisopropyl azoles and indole were obtained in good yields.Finally,we have demonstrated a facile method for the preparation ofα-trifluoromethyl diamines through aza-Michael addition of the tetrazolyl（trifluoromethyl）alkenes.When aliphatic primary or secondary amines are used as Michael donors,the Michael adducts could be obtained in excellent yields without additives.In the case of azole substrates,triethylamine or DBU was added as a base to facilitate the reaction.