Visible-light-mediated Asymmetric Carbene Transfer Reactions By Chiral Phosphoric Acids Catalysis

Carbenes are significant synthetic intermediates in organic synthesis.Transition metal-catalyzed carbene transfer reactions have been remarkable development.The development of catalytic photochemical conversion in metal-free is still in its infancy.With the development of the photochemical carbene transfer reaction,free carbene species can be effectively obtained from a method without metal catalysis,and the cycloaddition reaction,the rearrangement reaction,X–H insertion reaction and coupling reaction can occur.Recently,although some progress has been made in this field,the challenges and shortcomings still exist.Currently,the available approaches are mainly limited to the application of aryl diazoacetates.There are few reports on the application of fluorinated diazoalkanes,pyridotriazoles,diaryl diazo and indole diazo in visible light-mediated carbene transfer reactions.Therefore,developing other types of diazo compounds efficiently and further enriching the types of reaction substrates are directions that needs to be worked out in this field in the future.Secondly,due to the high reactivity of carbene,how to realizing the asymmetric carbene transfer mediated by visible light is another problem that chemists need to be considered and resolved.Based on this,the visible-light-mediated asymmetric carbene transfer reaction was studied in this paper.The main research contents include the following parts:Part 1.The first visible-light-mediated formal carbene transfer reaction of aryl diazoesters with 1,3-diketones has been developed.In a photochemical carbene transfer reaction with visible light and Brnsted acid catalyst,chiral 1,4-dicarbonyl compounds were obtained with high yield and enantioselectivity.The mechanism studies showed that the reaction occurs through singlet-free carbene,and the DFT calculations illustrated the enantioselective control of the stereo center.This is the first case of an asymmetric photochemical carbene transfer reaction catalyzed by organocatalyst.This method is practical,robust,and cost-effective.Part 2.The visible light-mediated carbene transfer reaction of pyrazolone diazo compounds with pyrazolones was developed.A series of spiropyrazolone derivatives containing azaketal structures was achieved with high yield and excellent enantioselectivity catalyzed by phosphoric acid catalyst.The control experiments and mechanism studies showed that the carbene participating in the reaction is a triplet structure,and the first asymmetric carbene transfer reaction-involving triplet carbene was established.The results expanded the carbene precursor of the light carbene transfer reaction,and the catalytic asymmetric N–N bond insertion reaction of pyrazolone diazo compounds and pyrazolones was realized.This method has the advantages of mild reaction conditions,transition metal-free,good functional group compatibility.The reaction can be amplified and grams of synthesis,and the product can be easily chemically converted.Part 3.We developed visible light-mediated three-component carbene transfer reactions of aryl diazoacetate,1,3-diketones and N-dimethylformamide.A series ofα,α,α-trisubstituted esters were obtained in moderate yields from the direct insertion of functional groups into C–C single bonds without transition metal catalysis.The visible light-mediated asymmetric three-component reaction of organic catalysis was explored.α,α,α-Trisubstituted ester was afforded in 44% yield and 30% ee using a chiral bifunctional catalyst.Further studies of the catalytic asymmetric reaction are ongoing.