Palladium(Ⅱ)-catalyzed Aerobic Intramolecular Allylic C-H Activation For The Synthesis Of Indolines

Indolines,as important structural motifs,are embedded in many natural molecules,pharmaceuticals and synthetic intermediates.In recent decades,the preparation of indolines has attracted the attention of organic chemists,and many metal-free and metal-catalyzed protocols for the construction of indolines have been widely reported.Palladium,one of the most commonly used metals for catalytic reactions,has been applied to the construction of indolines.For example,palladium-catalyzed alkyl or aromatic C-H activation,Wacker oxidation,and allylic substitution are all efficient methods for the synthesis of indolines.The construction of indolines via allylic C-H activation could reduce the process of synthesis,and improve the atom economy of the reaction effectively.So far,the construction of indolines via palladium-catalyzed allylic C-H activation has not been reported.In this thesis,a novel method for the synthesis of indolines using a mild palladium（II）-catalyzed allylic C-H activation was developed.Firstly the palladium（II）-catalyzed allylic C-H activation reaction was optimized by screening solvents,palladium-catalysts,co-oxidants,additives,and temperature.It was found to be the optimized reaction conditions when using DMA as solvent,Pd（OAc）₂ as catalyst,oxygen as oxidant,catalytic amount of BQ as co-oxidant,40oC as temperature and 79%yield was obtained eventually.A wide range of substrates were surveyed to explore substrate scope.Substrates with electron-withdrawing or electron-donating groups are tolerable to the optimized reaction conditions,and the majority of 16examples gave moderate to good yields.Subsequently,the indoline products were successfully applied to synthesis of other valuable structures by a few simple steps,such as a dopamine D₂/D₄receptor antagonist and an intermediate used for the synthesis of an analogue of camptothecin T-2513.Finally,we discussed the reaction pathway with a proposed mechanism.