Dearomatization Of Indole Via A Heck/Suzuki Cascade Reaction

Heck cascade reactions have become hotspots in organic synthesis research due to its convenient and efficient feature in series reactions.Traditional Heck cascade reactions are most focused on olefins and alkynes,while this reaction based on the indole 2,3 position is not much.Dearomatization of indole provide an efficient and rapid method to synthsis of C2-C3bisfunctionalized indulines,which is widely existed in natural products as well as pharmaceutically active molecules.In this dissertation,based on the Heck/Suzuki cascade reaction,bisarylation of indole and asymmetric dearomatization of indole have been developed respectively.First,the palladium/cyclohexylphosphine ligand was used as the catalyst system and the aryl boronic acid was used as the arylating agent to achieve the deavailability of the indole.The optimum reaction conditions were as follows:5 mol%Pd?OAc?₂ as catalyst,10 mol%PCy₃.HBF₄ as ligand,acetonitrile as solvent,potassium carbonate as base,reaction temperature is 100?.A series of 2,3-disubstituted indoline compounds containing continuous quaternary carbon and tertiary carbon centers were synthesized in moderate to good yields.The asymmetric dearomatization of indole was studied by using palladium/chiral phosphonamide ligand as the catalyst system and tetraphenylborate as the coupling reagent to realize the asymmetric Heck/Suzuki cascade dearomatization reaction.The optimum reaction conditions were as follows:5 mol%Pd?OAc?₂ as catalyst,10 mol%chiral spirocycloferamide as ligand,toluene as solvent,potassium carbonate as base,reaction temperature of 80?.A series of chiral indoline compounds were synthesized by moderate to good yields and enantioselectivity.