Copper-Catalyzed Stereoselective [4+2] Cycloaddition Of β,γ-unsaturated A-Ketoesters And 2-Vinylpyrroles In Water

Water has unique physical and chemical properties and is the medium of all chemical reactions in organisms.Considering the environment,safety and cost,water is the most ideal solvent.However,for a long time,everyone has been taught to avoid the presence of water in the organic reaction as much as possible,and even to strictly remove water when using organic solvents.The potential of water as an organic reaction medium has been ignored until the 1980s,when Breslow’s research work overturned people’s understanding of water,they found that water can be used as a solvent for organic reactions,and can improve the reaction rate and stereoselectivity.With the in-depth study of aqueous organic reactions,people found that water as a solvent has many advantages,such as:(1)water-soluble compounds can be used directly without hydrophobic derivatization,eliminating the tedious protection-deprotection step in the synthetic route;(2)recovery and recycling of catalysts can be achieved by simple phase separation;(3)providing mild reaction conditions.Therefore,water as the medium of asymmetric catalytic reaction has great development space.A wide range of chiral metallic catalysts are used in the asymmetric synthesis.However,most of the Lewis acids are very sensitive to moisture and easy to decompose in water,limiting their application in the field of aqueous phase reactions.In addition,most organic compounds are largely water-insoluble,and solubility is believed to be a prerequisite for reactivity.Therefore,people often use strategies such as organic cosolvent,surfactant or introducing hydrophilic groups into non-polar compounds to increase the solubility of organic compounds.In this paper,we use compounds derived from natural amino acids as ligands.In the presence of water,the ligand and copper salt coordinate in sit to form a chiral metal catalyst,which can catalyze the stereoselective[4+2]cycloaddition reaction of β,γunsaturated α-ketone ester with 2-vinylpyrroles.The main content of this paper was divided into three parts:the first part summarized the development and application of metal catalysts and nonmetal catalysts in the field of aqueous phase asymmetric catalysis,and then we introduced the stereoselective[4+2]cycloaddition reaction of β,γ-unsaturated α-ketone ester;the the second part,we introduced the implementation process of asymmetric reactions catalyzed by chiral copper complex in pure water;the third part was the experiment part.In this paper,we have developed a copper-catalyzed asymmetric[4+2]cycloaddition of β,γ-unsaturated α-ketone ester with 2-vinylpyrroles,using pure water as the solvent,and the catalyst load was only 1 mol%.A series of chiral 3,4-dihydro-2H-pyran derivatives were obtained with high yields and excellent enantioselectivities.In addition,we investigated the coordination modes between substrates and catalysts by some control experiments,proposed the corresponding catalytic models and reaction mechanisms,and verified them in combination with DFT calculations.