Palladium-catalyzed Dearomative Arylation And Tandem Reaction Of Indoles

Indoline skeleton is widely present in pharmaceutical intermediates and natural products.In particular,polycyclic indolines possess potential activities in the pharmaceutical industry.The synthesis of indoline compounds by conventional chemical methods have many steps and less efficiency,but the indoline compounds can be efficiently synthesized by dearomatization reaction in one step.Therefore,dearomatization of indoles has become an efficient and straightforward method to access indoline derivatives.This paper concentrated on the investigation of palladium-catalyzed dearomative arylation reaction of indoles and the dearomative arylation/anionic capture sequence.And N-tosylhydrazones,which led to a series of polycyclic indolines bearing carbon-based stereocenters.The paper was divided into two parts.Part 1.By using palladium/^tBu-XPhos as a catalyst system,an efficient intramolecular dearomative arylation of C3-acetoxy indoles was achieved,delivering indolin-3-ones bearing C2-quaternary stereocenters in good yields?17 examples,50-92%?Through systematically screening the solvents,bases,ligands and additives,the optimal reaction conditions were defined as:5 mol%Pd?OAc?₂ as catalyst,10 mol%^tBu-XPhos as ligand,N,N-dimethylformamide as solvent,sodium carbonate as base,at 100 ^oC.Furthermore,the enantioselective variant of the reaction was achieved by employing chiral phosphoramidite ligand.Part 2.By using palladium/dppf as a catalyst system,a domino reaction involving intramolecular arylative dearomatization followed by intermolecular coupling between alkyl-pd and N-tosylhydrazones was achieved,delivering tetracyclic indolines bearing contains quaternary and tertary stereocenters in moderate yields?25 example,43-67%?,By systematically screening the conditions involving solvents,bases and ligands,the optimal reaction conditions were defined as:10 mol%Pd?OAc?₂ as catalyst,12 mol%dppf as ligand,and 1,4-dioxane as solvent,potassium phosphate as base,at 100 ^oC.The enantioselective variant of the arylvinylation reaction was achieved under the condition of:10 mol%Pd?OAc?₂ as catalyst,20 mol%chiral phosphoramidite as ligand,1,4-dioxane as solvent,potassium phosphate as base,at 80 ^oC.The reaction synthesized several optically active arylvinylation compounds in moderate yields?6 examples,50-68%?and moderate enantioselectivites?75-79%ee?.