Light-promoted Nickel-catalyzed CO Coupling Reaction Of Halogenated Aromatic Hydrocarbons With Chiral Alcohols

Alkyl aryl ethers are versatile structural components and are widely found in natural products,agrochemicals,and pharmaceuticals.Nucleophilic aromatic substitution,the Mitsunobu reaction,and transition-metal-catalyzed cross-coupling of aryl halides with chiral alcohols are an effective strategy to synthesize chiral alkyl aryl ethers.Due to the use of earth abundant an cheap Ni catalysts is attractive.This thesis aims to develop new strategies to tackle Synthesis of chiral aryl ethers with preserving configuration for lightpromoted nickel-catalyzed.The first part of this thesis introduces chiral ethers that are prevalent in many pharmaceuticals and natural products.And introduces the existing methods for synthesizing chiral alkyl aryl ethers.Based on studying these research,proposes some problems in synthetic methods:?-H elimination of aromatic by-products and high reaction temperature.These problems will reduce the chirality value of the product when synthesizing alkyl aryl chiral ethers.Based on these problems,In the second part,we put forward the solution and finally put forward the design of configuration preserving for the synthesis of alkyl aryl chiral ether.light-promoted nickel-catalyzed C-O bonds cross-coupling of aryl halides with chiral alcohols.The method has the following advantages:(1)Light promotes Ni(?)/Ni(?)catalytic cycle,effectively avoids the aromatic byproducts eliminated by ?-H,and efficiently realizes the chiral C-O bond coupling reaction.(2)Organic amines were used as bases,avoid solubility and post-processing problems.(3)Mild reaction conditions,avoid the decrease of ee value in the product caused by high temperature.(4)Intermediates of drug molecules can be prepared on a gram scale.