Copper-catalyzed Defluorination And Intramolecular Asymmetric Oxygen Heterocyclic Synthesis

As a cheap metal that exists in large quantities on the earth,copper has a variety of valence states and convenient storage,and has always been a hot object in the field of transition metal catalysis.Natural products and drug molecules containing fluorine and oxygen heterocyclic fragments in their structures are widely found in nature,and the construction of these two types of compounds has always been a common concern and enthusiastic field of synthetic chemists at home and abroad.By drawing on the previous experience of our research group in copper catalysis,this paper realizes the construction of difluoromethyl compounds and intramolecular asymmetric synthesis of oxygen heterocyclic compounds by coppercatalyzed in-situ defluorination,and discusses the mechanism of the latter.This paper is mainly divided into four chapters,the first chapter is a literature review,summarizing the research progress of copper-catalyzed reactions,and introducing the synthesis of difluoromethyl and the synthesis of asymmetric oxygen heterocyclic compounds.Chapter 2 mainly introduces the work of cuprous chloride catalyzed the defluorination of trifluoromethyl to difluoromethyl.Chapter 3 mainly introduces the work of intramolecular synthesis of benzodihydrofuran compounds catalyzed by cuprous iodide.Chapter 4 mainly introduces the work of copper nanomaterials to catalyze the asymmetric synthesis of cyclic ether compounds within the molecule of diketones.The main research findings are summarized below:1:Using an inexpensive monovalent copper salt as a metal catalyst,adding carbene ligand and tert-butanoate sodium as a base,at equivalent B2pin2,β-F elimination occurs,directly constructing difluoromethyl compounds from trifluoromethyl compounds.Most difluoromethyl reagents are toxic and not easy to preserve,our method does not require the addition of additional difluoromethyl reagents,directly in situ construction of difluoromethyl in situ,and the method can be further applied to difluoromethyl compounds to construct monofluorocompounds.2:Using cuprous iodide as a metal catalyst,a diamine ligand was added,and cesium carbonate was used as a base to construct phenylpropyldihydrofuran epoxy compounds in the molecule.Benzodihydrofuran has always been an important structure in drugs,and the substrate can be further transformed to construct a variety of drug structures.3:Using copper nanomaterials as metal catalysts,chiral dinitrogen ligands were added,and cesium pivarate was used as bases,and asymmetric epoxy compounds were constructed intramolecularly.The synthesis of chiral compounds using copper nano elements is rare,and the reaction mechanism needs to be further explored and verified with theoretical calculations.