Studies On Transition Metal-Catalyzed Fluoroalkylation Of Unsaturated Bonds

This thesis mainly aims at the studies on the transition metal-catalyzed fluoromethylation of unsaturated bonds, which chiefly involve the following eight chapters. Chapter I:In chapter I, We discussed the transition metal-catalyzed trifluoromethylation of unsaturated bonds, which divided two parts:(1) Transition metal-catalyzed trifluoromethylation of alkenes, including trifluoromethylation couple with intramolecular cyclization or migration, and intramolecular trifluoromethylation to construct C-C bond and C-X bond based on the difunctionalization strategy;(2) Transition metal-catalyzed trifluoromethylation of alkynes, including intramolecular trifluoromethylation and intermolecular trifluoromethylation to construct C-CF3 bond based on the difunctionalization strategy. Chapter II:In chapter II, we discussed an efficient copper-catalyzed trifluoromethylation reaction of oximes. As we know, oximes are fascinating synthetic reagents since they have both nitrogen and oxygen atoms. This reaction provides a convenient method to construct C-CF3 bond and C-O bond. A variety of useful trifluoromethyl-substituted 4,5-dihydroisoxazolines are thus synthesized. Chapter III:In chapter III, we developed a copper-catalyzed intermolecular cyanotrifluoromethylation of alkenes. Nitriles, holding the post of versatile building blocks in organic transformations, are widely known in pharmaceuticals, agricultural chemicals, and optoelectronic materials. This methodology allows a wide range of substrate scope, including styrene derivatives and aliphatic olefins, which demonstrate the wide compatibility of this new methodology in organic synthesis. Chapter IV:In chapter IV,we summarized rencent researches on the cyclization of 1,6-enynes. Strategies for 1,6-enynes cyclization can be classified into two types, that is, transition-metal-catalyzed cyclization and radical cyclization. Herein, we report a novel three-component reaction of 1,6-enynes、Togni’s reagent with TMSCN or TMSN3 by copper catalyst,respectively. This methodology allows a wide range of substrate scope to access cycloaddition products, which show great potential of subsequent transformation in organic chemistry. Chapter V:In chapter V, the developments for trifluoromethylation of alkynes were summed up. The rarely reported on this aspect is in part because of the highly reactive of the vinyl radical intermediates, which are less stable than their saturated analogs. Another reason is the low activity of trifluoromethyl radical for the fact that the sp-hybridized carbons exert a strong attraction for these π-electrons. Herein, we reported two methods to synthesize trifluoromethyl-substituted 2H-azirines and β-trifluoromethylated acrylonitriles. The potential of 2H-azirines has been demonstrated for practical synthesis. Various CF3-containing pyridines are synthesized. Chapter VI:In chapter VI,we summarized the important role of 2H-azirines and the related synthetic methods. Inadition, we discussed an unprecedented route to introduce CF3 group along with the synthesis of spiro-2H-azirines. The significance of this method is threefold:(1) The produced 2H-azirines represent not only a valuable class of compounds found in natural products, but also an important synthetic motif in organic synthesis;(2) The trifluoromethyl group of the product is importance for the modification of this novel fragments;(3) We have developed a novel pyrrolidine derivatives bearing a spirocyclic skeleton motif via cascade cyclization. Chapter VII:In chapter VII, the very recent progress in transition-metal catalyzed difluoroalkylation of unsaturated bonds is summarized in detail, which divided two parts:(1) Transition metal-catalyzed difluoroalkylation of alkenes, including difluoroalkylation of alkenes via direct C-H functionalization and the difunctionalization strategy;(2) Transition metal-catalyzed difluoroalkylation of alkynes. Chapter VIII:In chapter VIII,we have reviewd the studies on transition metal-catalyzed difluoroalkylation reaction and the related alkynes difluoroalkylation in recent years. Subsequently, we developed a palladium-catalyzed aryldifluoroalkylation of alkynes with arylboronic acids and ethyl difluoroiodoacetate in one pot. A variety of aryl boronic acids and alkynes can be applied in this reaction, which makes it a general method to synthesize fluoro-containing products. Preliminary mechanistic studies indicated that a possible radical pathway was involved in this transformation.