Phthalide Synthesis Through Dehydrogenated Lactonization Of The C（sp3）–H Bond By Photoredox Catalysis

Functionalization of inert C（sp~3）-H bonds has always been an important research topic in the field of organic synthesis,which has attracted extensive attentions of organic synthetic chemists.In this field,transition-metal-catalysis is one of the most investigated type of C（sp~3）-H bond functionalizations.However,in this type of reactions,in addition to the use of expensive transition-metal catalysts,excessive strong oxidants and high temperature are often also required to effectively promote the C（sp~3）-H bond activations.These harsh conditions,to some extent,greatly limit its scope of applications in organic synthesis.Due to the advantages of abundant,renewable and pollution-free of visible light,visible-light-promoted photocatalysis has been favored by chemists in the field of organic synthesis,and lots of remarkable achievements have been obtained.Therefore,it is of great significance to develop C（sp~3）-H bond activations with mild reaction conditions as well as high selectivity by means of visible-light-promoted photocatalysis.Phthalides are a kind of common organic compounds,which often have good biological activity.Phthalides represent some of the most frequently encountered structural units that are present in many interesting pharmaceutical,biological,and medicinal molecules,such as3-oxocitalopram,penicidone A and 5-hydroxytryptamine receptor antagonist.In addition,phthalide is often employed as a key precursor for the preparation of other heterocyclic compounds or complex natural products,thereby making it have critical applications in the fields of organic and pharmaceutical synthesis.In recent years,many different synthetic methods have been developed for the construction of these compounds.However,these established methods still have some disadvantages,such as the employments of transition metal-catalysts and harsh reaction conditions.Therefore,we attempt to prepare a series of functionalized phthalides by means of visible light-promoted photocatalytic C（sp~3）-H bond activation.After careful screening of reaction conditions,we developed a dehydrogenated lactonization of the C（sp~3）-Hs bond on benzyl site by visible-light-enabled photoredox catalysis.With the benzyl ethers as starting materials,organic dye-tpye Eosin Y as the photocatalyst,tetrabutyl ammonium bromide as hydrogen transfer agent and blue LED as the light source,this method expediently allowed the delivery of functionalized phthalides in Me CN using oxygen as the sole terminal oxidant under metal-free conditions at room temperature.Applying this method,diverse benzyl ethers could be smoothly transformed into the corresponding phthalides with good-to-excellent isolated yields.In addition,this method had also been successfully applied to the synthesis of 3-oxycitalopram analogues with crucial activity.Taken together,this reaction provides a green,simple,mild and effective synthesis method for the preparation of phthalides.