Organocatalytic Asymmetric Cascade Aerobic Oxidation And Semipinacol Rearrangement Reaction:A Visible Light-induced Approach To Access Chiral 2,2-disubstituted Indolin-3-ones

Along with the rapid growth of the highly sustainable photochemistry,cooperative photoredox and asymmetric catalysis has attracted increasing attention of chemists.Using photocatalytic methods for organic synthesis,compared with the traditional synthetic methods,photocatalytic reaction conditions are mild,friendly to the environment,by using sunlight as a safe,inexpensive,abundant and renewable source of chemical potential.Thus,the photocatalytic method for synthesis of chemical products is more and more popular,this paper mainly discusses the asymmetric synthesis a series of 2,2-disubstituted indolin-3-ones under visible light irradiation.2,2-disubstituted indolin-3-ones are privileged structural scaffolds widely existing in a number of pseudoindoxyl alkaloids,moreover,they are frequently harnessed as common synthetic intermediates for the total synthesis of many indole alkaloids and other molecules with important bioactivities.Synthetic chemists have developed many general and efficient methods to gain access to chiral 2,2-disubstituted indolin-3-ones.The methods have been reported,which usually requires a strong or not atom-economic oxidant.In the process of rearrangement,acidic,basic or heating conditions are generally required.The operation is difficult,including stepwise operation.In this paper,we use molecular oxygen as the green oxidant,with the screening of catalyst,solvent,temperature etc.,we have developed an enantioselective cascade aerobic oxidation and semipinacol rearrangement reaction of 2-aryl-3-alkyl substituted indoles via visible-light-driven synergetic photoredox and asymmetric organocatalysis.The current methodology presents an efficient and transition-metal free approach to access a range of pharmaceutically and biologically significant enantioenriched 2-aryl-2-alkyl-substituted indolin-3-ones in 64-90% yield with 58-94% ee.The mechanism study via control experiments demonstrates that the used chiral phosphoric acid catalyst presents stereocontrol for aerobic oxidation and the generated chiral 3-hydroxy intermediate plays a key role to affect the enantioselectivity of semipinacol rearrangement.