Visible-Light Photoredox-Catalyzed Remote C(Sp~3)–H Bond Functionalization

Solar energy,as the most ideal energy source on the earth,is an abundant and renewable green energy.In nature,the photosynthesis process by which green plants use solar energy to assimilate carbon dioxide and water to produce organic matter and release oxygen is of great significance for achieving energy conversion and maintaining the development of all life on Earth.Organic photochemical synthesis by mimicking the photosynthesis of plants in nature has always been the dream of organic chemists.Such a chemistry ideally should directly convert solar energy into chemical energy under mild conditions.Visible-light photoredox catalysis utilizes the optical properties of photocatalysts to promote redox processes in organic photochemical reactions.This process produces active intermediates such as radicals and radical ions under mild conditions,and has been widely used in organic synthesis in recent decades.The intramolecular hydrogen atom transfer(HAT)process of the radical intermediates produced by visible-light photoredox catalysis has achieved the regioselective remote C(sp~3)–H bond functionalization under mild conditions,and opens a new way for remote C(sp~3)–H bond functionalization.Recently,the visible-light photoredox catalysis combined with HAT provides an effective synthetic tool for remote C(sp~3)–H functionalization,and some excellent results have been achieved.The aim of this thesis is to develop novel visible-light photoredox-catalyzed remote C(sp~3)–H bond functionalization.And using these methods,the remote C–C bond can be constructed,and the challenging problems in this field can be solved.This thesis can be divided into three major parts:The first part:An efficient and unified strategy for primary,secondary and tertiary aliphatic?-C(sp~3)–H vinylation of amides with alkenyl boronic acids is reported.These reactions are catalyzed by visible light organic photoredox agents.Regioselective?-C(sp~3)–H vinylation of amides is controlled by 1,5-hydrogen atom transfer(1,5-HAT)of an amidyl radical generated in situ.The salient features of this transformation include absence of transition-metals,redox neutrality,mild reaction conditions and broad substrate scope,which makes the method highly attractive.The second part:We have developed an amidyl radical-triggered Minisci-type reaction that allows site-selective C(sp~3)–H/C(sp~2)–H coupling under photoredox conditions.This approach provides a mild and highly regioselective reaction affording remote C(sp~3)–H heteroarylated amides at room temperature under transition-metal free,weakly basic,and redox-neutral conditions.Non-prefunctionalized heteroarenes,such as purines,thiazolopyridines,benzoxazole,benzothiazoles,benzothiophene,benzofuran,thiazoles and quinoxalines,can be alkylated directly.The reaction features good functional group tolerance and broad substrate scope,and provides a unique strategy for the late-stage functionalization of complex bioactive molecules.Sequential and orthogonal C–H functionalization of different heteroarenes by taking advantage p H value or polarity of radicals has also been achieved.DFT calculations explain and can predict the site-selectivity and reactivity of this reaction.This strategy expands the scope of the Minisci reaction and serves as its alternative and potential complement.The third part:The enantioselective remote C(sp~3)–H cyanation of carboxamides has been realized enabled by mergering photoredox catalysis and copper catalysis.The protocol was the integration of photoinduced amidyl radical mediated intramolecular1,5-HAT with the chiral copper complex-catalyzed radical cyanation in a site selectivity and enantiocontrolled way.This strategy gives cyanated amides in high yields and high enantioselectivities with good functional group tolerance and broad substrate scope,and represents an efficient method for enantioselective radical cyanation of remote C(sp~3)–H bonds.