Enantioselective Copper-Catalyzed Remote C(sp~3)-H Functionalizations Of N-fluorosulfonamides

As a highly regioselective method of C(sp3)-H functionalization,1,5-HAT has been well developed over the years.With the combination of this strategy and the transition-metal-catalyzed,chiral-ligand-controlled enantioselective transformation,we envision the remote functionalization of C(sp3)-H bond can be realized regio-and enantioselectively.This essay focuses on using N-fluorosulfonamide as substrate to achieve the remote enantioselective C(sp3)-H functionalization via a radical relay process.The key to these successes is the combination of transition-metal/chiral ligands-catalysis and the 1,5-HAT strategy.The method has demonstrated robust substrate tolerance,mild condition for the generation of N-centered radical and excellent regio-/enantioselective control.The first chapter focuses on the research background of remote C(sp3)-H functionalization with 1,n-HAT strategy.Three topics have been discussed based on the different initiating radicals including N-centered radical,O-centered radical and C-centered radical.The latest advances have been covered in this chapter.The second chapter introduced the reaction of copper-catalzyed remote enantioselective cyanation of C(sp3)-H bond via 1,5-HAT,which can be facilely used in the synthesis of chiral cyanated organic molecules.The reaction has demonstrated mild condition,great substrate scope,high yields,low catalyst loading and excellent enantioselectivity.Mechanistic studies indicate the involvement of a radical relay process initiated from the N-centered radical.The third chapter further disclosed the robustness of our previous established copper-catalzyed system and we successfully developed a copper-catalzyed remote enantioselective alkynylation of C(sp3)-H bond on linear primary sulfonamides.Likewise,the reaction shows high efficiency and the key to this success stems from the formation of enantioselective copper-ligand complex,which finally captured the in-situ generated carbon radical.Derivatization studies are also carried out well(deprotection,etc.)and these indicates promising synthetic uses in further application.The fourth chapter discusses an iron-catalzyed remote adidation of C(sp3)-H bond using N-fluorosulfonamides.Iron stands out as an inexpensive and non-toxic catalyst compared with its counterparts and it helps to form the iron-azide complex to realize the facile azido-ligand transfer onto the remote carbon radical.The reaction indicates general functional group tolerance,great transformation efficiency and broad derivative ability of azide group such as Click chemistry,etc.Further studies on remote enantioselective azidation is underway.