Nickel-catalyzed Aryl CO Bond Coupling Reaction

Transition-metal-catalyzed cross-coupling of aryl halides with alcohols is an effective strategy to construct C-O bonds to synthesize alkyl aryl ethers that are prevalent in many pharmaceuticals and natural products.Although Pd,Cu-catalyzed C-O bond crosscoupling reactions has been successfully developed,the use of earth abundant Ni catalysts is attractive but less studied,possiblely due to the difficult reductive elimination step for Ni catalysis.This thesis aims to develop new strategies to tackle the reductive elimination problem for Ni-catalyzed C-O coupling reactions.There are five chapters in this article,namely:The first chapter summarizes the research progress of transition-metal-catalyzed C-O bond coupling reactions and organophotoredox/nickel dual catalytic C-O bond coupling reactions.It is proposed to use cheap nickel as a catalyst,organic amine as a base,and develop a new type of catalytic system to realize the aryl C-O bond coupling reaction by adjusting the valence of nickel.The second chapter introduces a highly effective hydroxylation reaction of aryl halides with water under synergistic organophotoredox and nickel catalysis.The catalytic system uses water as a hydroxyl source;BODIPY as photocatalyst,and DIPEA as the base.This method solves the problem of substrate functional group compatibility caused by using palladium and copper as catalysts and using strong bases as or generating hydroxyl groups.Significantly,aryl bromides,less reactive aryl chlorides as well as complex drug molecules served as effective substrates to afford phenols with a wide range of functional groups.The practical usefulness of the method is demonstrated by gram scale reactions.Mechanism studies have shown that light and photocatalysts are indispensable and play a vital role in the nickel catalytic cycle.The Ni(?)species in the reaction system are obtained by photocatalytic oxidation of Ni(?).The third chapter introduces the study of light-promoted nickel-catalyzed etherification of aryl electrophiles with alcohols.Air-stable Ni(?)-aryl complexes were developed as nickel catalysts,and organic amines were used as bases without any additional photosensitizer.This method has excellent functional group tolerance and wide substrate applicability.A variety of(hetero)aryl electrophiles,including aryl bromides,chlorides and aryl sulfonates,can be coupled with aliphatic primary and secondary alcohols.Intramolecular C-O coupling can also be realized,allowing for the synthesis of oxygen heterocycles.Mechanism studies indicate that light promote the transformation of Ni(?)aryl complexes into active Ni(?)intermediates followed by a Ni(?)/Ni(III)catalytic cycle.The fourth chapter introduces the research of organic reducing agent promoted nickel catalyzed hydroxylation reaction of aryl halide with water.Similarly,green and economic water is used as hydroxyl source and organic amine as base.This method solves the challenging substrates,including aryl halides containing substituents at the ortho position and complex multifunctional structures.In addition,the synthesis of dihydroxy and trihydroxy compounds can also be achieved.Mechanism studies show that nickel can be converted from divalent to monovalent in the presence of organic reducing agent phenylsilane,allowing for a Ni(?)/Ni(III)catalytic cycle.The innovation of this research is the activation of catalyst with a mild organic reducing agent instead of photocatalyst and light.