Gold(?)-Catalyzed Enantioselective Cyclopropanation Of ?-Aryl Diazoacetates With Enamides And Synthesis Of Novel Chiral Phosphine Ligands

As an important organic framework,cyclopropylamines are commonly found in biologically active molecules and complex pharmaceutical drugs.The conventional method for preparing a cyclopropylamine compound is realized by a transition metal catalyzed coupling reaction of a boronic acid ester with an amine compound,or a cyclopropanation reaction in which a transition metal participates under the control of a ligand,and problems of these reactions exist.It is a lengthy reaction step or asymmetric synthesis is not implemented.In order to solve these problems,we envisage how to directly prepare cyclopropylamine compounds by one-step method,and improve the reaction efficiency.Moreover,we have added chiral ligands to the reaction and can also obtain high enantioselectivity product.At present,there are not many reports on the synthesis methods of cyclopropylamines.Therefore,the progress of efficient chiral cyclopropylamine synthesis is still a research hotspot of current organic chemists.Based on the traditional synthesis of cyclopropylamines,starting from the unique structure of enylamine molecules,high enantioselectivity synthesis of cyclopropylamine is carried out by screening the diazo esters with different substituents at the ?-position,screening of catalysts and reaction conditions.Part ?: Gold(?)-Catalyzed Enantioselective Cyclopropanation of a-Aryl Diazoacetates with EnamidesA gold catalyzed enantioselective cyclopropanation of enamides with ?-diazoarylacetate compounds,providing access to synthetically useful building blocks,are reported.Through the screening of a series of conditions,the problem that the diazo ester participates in the reaction is too fast to control the enantioselectivity of the reaction is successfully overcome.With a chiral binol-derived phosphoramidite-gold(?)complex,the reaction performed well over internal or teminal enamides to give the desired products in excellent yields and enantioselectivities.The realization of the reaction enriches the method for constructing a cyclopropylamine compound under the transition metal catalysis.Starting from a simple substrate,a target having excellent enantioselectivity can be obtained in one step.Part ?: Synthesis and Application of Novel Chiral Phosphine LigandsExploring novel chiral ligands has always been the focus of asymmetric synthesis research,and it is also inseparable from chiral ligands to do asymmetric reactions.Starting from a series of iodine compounds with unique skeletons,it is only necessary to add cheap cuprous iodide and cesium carbonate to the reaction system to prepare novel triphenylphosphine chiral ligands simply and efficiently.After obtaining a new chiral phosphine ligand,we also tried a series of reactions.