Asymmetric Corss-Couplings Via The Merger Of Photoredox And Cobalt Catalysis

Transition metal-catalyzed asymmetric coupling reaction is an important and efficient strategy for the precise construction of carbon-carbon bonds.The development of catalytic asymmetric coupling reactions using cheap,readily available,environmentally friendly transition metals is an important research frontier in this field.As an earth-abundant transition metal,cobalt is considered to be an ideal metal catalyst because of its low price and low toxicity.However,the development of cobalt-catalyzed asymmetric coupling reaction lags behind,and organometallic reagents are generally required as nucleophilic reagents,resulting in harsh reaction conditions and poor functional group compatibility.In recent years,visible light catalysis has been proven the capacity of generating highly active open-shell intermediates under mild conditions,which brings new opportunities for green synthetic chemistry.This thesis discribed a new asymmetric strategy through the combination of photocatalysis and cobalt catalysis,which successfully avided the use of organometallic reagents or metal reducing agents in cobalt-catalyzed coupling reactions.Moreover,new asymmetric photochemical transformations were developed through exploiting the unique properties of organic cobalt intermediates.The research in this thesis includes:First,we developed an asymmetric reductive Grignard-type addition reaction of aryl iodides with aldehydes based on the nucleophilicity of aryl cobalt intermediates.Chiral benzyl alcohol products can be obtained by the cooperative visible-light photocatalysis and cobalt catalysis strategy(52-99% yields,87-99% ee).In addition,this method can be successfully applied to the stereo-divergent synthesis of chiral amino alcohols and the catalytic asymmetric synthesis of chiral drug chlorpentine.The mechanism study with the isotope effect shows that the stereoselective migration insertion process of aromatic cobalt species to aldehyde is the rate determining step in this reaction.Subsequently,considering the multi-coordinating nature of cobalt,we developed a cobalt/photoredox catalyzed dynamic kinetic asymmetric radical coupling reaction using alkyl Hantzsch esters and heteroaryl trifluorsulfonate as starting materials,providing a series of heteroaryl axial chiral compounds(53-99% yields,80-97% ee).According to the results of fluorescence quenching,cyclic voltammetry and other mechanism experiments,we proposed the possible mechanism of the reaction.Furthermore,a class of axially chiral heteroaryl products were found to show good circularly polarized luminescence properties.Finally,based on the previously developed cobalt/photoredox catalytic dynamic kinetic conversion process,an asymmetric reductive coupling reaction of heteroaryl trifluorsulfonate with commercially available alkyl halides and organic reducing agents was developed to provide convenient access heteroaryl axial chiral compounds with 45-83% yields and 79-95% ee.Compared with the previous work,this trasnsformation employs commercial available radical precursors instead of alkyl Hantzsch esters,which avoids the preparation of radical precursors and has confirmed to be step economy.In addition,this protocol shows good functional group tolerance,broad substrate scope,and primary alkyl radicals can also work well in this transformation.