Palladium-catalyzed Radical Cascade Cyclization Of 1,6-enynes With Ethyl Difluoroiodoacetate

Fluorine atoms can be found in a great number of organic compounds which possess some unique biological and pharmacological activities. The organic complexes can be significantly improved in physical and chemical properties by introducing fluorine atoms. A novel and efficient synthesis of fluorine-containing functional group has a very favorable prospect.1,6-enyne is a great radical acceptor which has the high chemical activity. The extensive research progress has been made in the synthesis of heteroatom-containing cyclic compounds, especially in the free radical cyclization reaction. Due to the good yield and chemical selectivity of this reaction, more and more attentions have been paid by organic chemists in recent years, and the developments of this reaction have also achieved rapidly. This thesis mainly concerns with the palladium-catalyzed free radical difluoromethyl reaction and this thesis chiefly involves the following two chapters: 1. The progress of radical and difluoromethyl reactionsIn chapter I, An overview of the history of radical chemistry and the characteristics of this type of reactions is summarized. The summary of the progress of the transition-metal catalyzed difluoromethyl reactions is also presented. According to the characteristics of the catalytic systems, we have elaborated on the characteristics of distinguishing catalytic systems and the application in the synthesis of organic compounds from the following four parts. 2. The progress of palladium-catalyzed radical cascade cyclization of 1,6-enynes with ethyl difluoroiodoacetateIn chapter II, A novel and convenient Pd-catalyzed radical cascade iododifluoromethylation cyclization of 1,6-enynes with ethyl difluoroiodoacetate is demonstrated. The proposed transformation presents high stereoselectivity under mild and facile reaction conditions, thereby allowing an efficient access to a variety of iodine-containing difluoromethylated pyrrolidines. A possible radical pathway for the transformation is proposed on the basis of the results of control experiments and relevant literature reviews. We believe that the reaction is initiated by difluoromethyl radical followed by the 5-exo-dig intramolecular cyclization process to achieve the reaction. The scope of the substrates was studied and a series of both fluorine/iodine-containing derivatives were obtained. The structures of the products were confirmed by 1H NMR, 13 C NMR and X-ray crystallographic analysis.