Remote C-H Bond Functionalization Triggered By Fluoroalkyliation Of Thioacetylenes

The direct C-H bond functionalization is of significant importance in many areas,such as organic synthesis,medicinal chemistry and materials science.Directing group assisted metal-catalyzed C-H bond functionalization has made significant progresses over the past decades.However,additional steps are needed for the introduction and elimination of the directing groups,which limits the application of this strategy.As such,it is highly desirable to develop new strategy for the realization of direct functionalization of C-H bonds,especially unactivated C(sp~3)-H bonds.Recently,the radical translocation has become a highly efficient and site-selective strategy for the direct functionalization of alkyl C-H bonds.As compared to the versions triggered by radical initiation of alkenyl halides,the remote C-H bond functionalization triggered by radical addition to internal alkynes,remains largely unexplored.The decreased activity and unsatisfactory regioselectivity of alkyne radical addition may be responsible for the challenges.To address these challenges,this project focuses on the exploration of novel remote C-H bond halogenation reaction that is initiated by radical addition to thioacetylenes.The polarization of C-C triple bonds by sulfur substituents may account for the regioselective radical addition.By using fluoroalkyl bromides as the radical source,fac-Ir(ppy)3 as the photocatalyst,and EtBr as the solvent,(Z)-ε-bromo-β-fluoroalkylalkenyl alkenethioether are synthesized in moderate to good yields with excellent regio-,stereo-,and site-selectivity at room temperature.Various primary,secondary,and tertial C(sp~3)-H bonds are well tolerated under the conditions.Using DMSO as both the solvent and oxidant,a remote C(sp~3)-H oxygenation reaction has been developed.The created C-Br and C=O double bonds can be used for further functionalization,which may be attractive for synthetic applications.Of note,traditional reports on alkyne radical addition triggered remote C-H bond functionalization usually deliver the intramolecular functionalized products,while our work represents an unprecedented intermolecular remote C-H bond functionalization,thus constituting a new advance on the alkenyl radical-triggered remote C-H bond functionalization.