Regioselective Functionalization Of Arenes Via Thianthrenium Salts

Simple arenes are important industrial raw materials in the fields of chemical medicine and functional materials.The development of general and efficient approaches for the regioselective C（sp²）-H functionalization of arenes has been a hotspot in synthetic chemistry,and plays a significance role in drug development and functional material modification.However,the current methods normally require the pre-installation of aryl halides and metal reagents,or the use of large excess of simple arenes for improving the reaction activity,which results in low atom-and step economy.Therefore,developing a general approach for direct regioselective C（sp²）-H functionalization of arenes is very much in demand.This thesis aims at the development of a“transient mediator”approach for the regioselective C（sp²）-H functionlization of simple arenes.By using thianthrene S-oxide（TTSO）as the transient mediator,the regioselective arylation,alkenylation,borylation,thiocyanation and selenocyanation have been developed via the Pd catalysis or photocatalysis.1)Two methods for preparation of arylthianthrenium salts from simple arenes have been developed in a regioselective manner.The electrophilic thianthrenation of simple arenes have been realized by treating thianthrene S-oxide（TTSO）with Tf₂O.Mechanistic studies unveiled that this reaciton was proceeded via a thianthrenium dication intermediate.The formal thianthrenation of simple arenes via a sequence of Ir-catalyzed regioselective C（sp²）-H boronation and Cu-mediated thianthrenation of arylborons.2)The para-selective arylation and alkenylation of mono-substituted arenes have been realized via electrophilic thianthrenation/Pd-catalyzed thio-Suzuki-Miyaura coupling sequence.This method features broad substrate scope and remarkable heterocycle compatibility,which can be used for the late-stage functionalization of complex bioactive scaffolds and the efficient synthesis of some pharmaceuticals,including Tetriprofen,Ibuprofen,Bifonazole,LJ570.3)The site-selective borylation of simple arenes has been realized via a sequence of electrophilic thianthrenation/Pd-catalyzed borylation.This protocol features mild conditions,broad functional group tolerance,and could be employed for the installation of Bpin group in natural products or drug molecules regioselectively.4)The photoinduced thiocyanation/selenocyanation of aryl thianthrenium salts have been realized by using aryl thianthrenium salts as a bifunctional reagent,which undergo the homolytic cleavage of the C（sp²）-S bond to generate aryl radical and thianthrene radical cation under the irradiation.Subsequently,the thianthrene radical cation(TT^+·)can serve as a transient SET mediator to oxidize S（Se）CN^-to S（Se）CN^·,followed by the formation of final products via the radical-radical cross-coupling with aryl radical.This protocol does not require the addition of photosensitizers and oxidants,features good functional group and heterocycle tolerance.