Study On Asymmetric Catalytic Reactions Based On 3-Vinylindoles

In the field of organocatalyst mediated asymmetric catalysis,chiral Br???nsted acids occupy a pivotal position.Among them,chiral phosphoric acids and chiral imidodiphosphoric acids are the main ones.After nearly two decades of exploration and development,asymmetric reactions catalyzed by chiral phosphoric acids are endless.As a powerful supplement,chiral imidodiphosphoric acids have also been applied to a variety of asymmetric reactions since its introduction in 2012,and all have shown superior enantioselectivity and broad substrate applicability.Based on the previous work experience,this thesis applies chiral imidodiphosphoric acids to various asymmetric reactions based on 3-vinylindoles.The details are described as below:First,we introduced the development of chiral imidodiphosphoric acid catalysts,and detailed described the catalytic systems formed in recent years.Secondly,we introduced research progress of a variety of asymmetric reactions involving3-vinylindoles,asymmetric Hetero-Diels-Alder reactions involving?,?-unsaturated?-ketoesters,and asymmetric synthesis of indole-substituted cyclopenta[b]indole structures.Then,we studied asymmetric Friedel-Crafts reaction of 3-vinylindole as an electrophile with pyrrole catalyzed by phosphoramidic acid.By changing the position of the benzene ring of 3-vinylindole,phenyl-3-vinylindole exhibits higher electrophilic activity.Under the optimal condition,A series of pyrrole-substituted1,1,1-triarylethane containing quaternary carbon centers were obtained with a maximum yield of 99%and ee value of 93%.The asymmetric Friedel-Crafts reaction of phenyl-3-vinylindole with indole catalyzed by phosphoramidic acid is also studied.Optically pure bisindole substituted 1,1,1-triarylethanes were obtained with a maximum yield of 99%and ee value of 98%and 27 reaction examples were expanded.Through the control experiments,we found that the formation of the double hydrogen bond between the imidodiphosphoric acid and the two substrates is very important for the feasibility of the reaction and the ability to control the enantioselectivities.Researched asymmetric Hetero-Diels-Alder reaction of 3-vinylindole and?,?-unsaturated?-ketoesters catalyzed by imidodiphosphoric acid.Through this reaction,we introduced the indole unit into the 3,4-dihydropyran structure for the first time,and successfully converted it to the tetrahydropyran structure by simple hydrogenation reduction.Through conditional screening,we determined that imidodiphosphoric acid bearing 3,5-?CF₃?₂ at 3,3'-position was the optimal catalyst.33 Reaction examples were extended with a maximum yield of 99%,ee value of 99%and a diastereoselectivity of>20:1,demonstrating the broad substrate applicability of imidodiphosphoric acid.The results of control experiments indicate that3-vinylindole reacts with?,?-unsaturated?-ketoesters through a synergistic process and the formation of a double hydrogen bond between the imidodiphosphoric acid and the two substrates is highly enantioselective vital.The absolute configuration of the product was 2S,3R,4R as determined by single crystal diffraction.Finally,we studied the asymmetric 1,6-addition/[3+2]cycloaddition reaction of p-quinone methylates and 3-vinylindole catalyzed by imidodiphosphoric acid.When1,6-addition occurred after p-quinone methylates participating in the reaction,the subsequent[3+2]cycloaddition reaction energy barrier is abnormally reduced,and the imidodiphosphoric acid can efficiently catalyze the reaction to give 3-indole substituted cyclopenta[b]indoles even at-40^oC.Under the optimal condition,we expanded 39 reaction examples with a maximum yield of 95%,an ee value of 99%,and>15:1dr.The p-quinone methylates containing a strong electron withdrawing group can also smoothly proceed.The results of control experiments indicate that unprotected N-H and naked indole 2-position are essential for the reaction to occur,and the formation of hydrogen bonds between the catalyst and the three molecular substrates is critical for obtaining excellent reaction results.The absolute configuration of the product was 9S,18S,25S,26S,33S as determined by single crystal diffraction.