Alkoxyl Radical-Mediated C-C/C-H Bond Functionalization

The C-C bond and the C-H bond are widely found in nature and constitute the basic structure of organic molecules.Therefore,modification of the C-C/C-H bond is of great significance in drug synthesis.However,since the bond dissociation energy of the C-C/C-H bond is relatively high,and controlling the regioselectivity of the corresponding reactions still remains challenging,it is still difficult to efficiently and selectively activate the C-C/C-H bond in the organic molecules.The utilization of alkoxy radical-mediatedβ-carbon elimination reactions and hydrogen atom transfer processes can provide an efficient strategy for regioselective functionalization of C-C/C-H bonds.The main research contents in this thesis are:1)alkoxy radical-mediated ring-opening functionalization reactions and 2)alkyloxy radical-mediated intramolecular sequential hydrogen atom transfer and heteroaryl migration to realize tertiary-alcohol-directed heteroarylation of remote C(sp3)-H bond.This thesis mainly includes the following four parts:The first part reviews the generation of alkoxy radicals,especially mediated by visible light,and related investigations on the cleavage and functionalization of C-C/C-H bonds promoted by these radicals.In addition,the basis and significance of my project are introduced in this part.In the second part,a rapid and efficient ring-opening selenation of cyclobutanols to afford y-selenylated alkyl ketones has been described.A series of selenium ethers were synthesized under mild conditions using cheap manganese acetate as oxidant and diselenide as free radical scavenger.The protocol is highly efficient and practical,and features good compatibility of functional groups and wide range of substrates.The third part introduces tertiary-alcohol-directed remote C(sp3)-H bond heteroarylation.The alkoxy radical generated from free tertiary alcohol under visible light promotes continuously remote HAT and heteroaryl migration to synthesize y-heteroaryl ketones.The reaction condition is mild and the transformation has well functionality tolerance.This protocol provides an efficient srategy for the late-stage modification of alkyl ketones.In the fourth part,a series of 3-coumaranones and indanones were prepared via selectively C-C bond cleavage promoted by the alkoxyl radical generated from the addition of aryl radicals to cyclic ketones.DFT studies and isotope labeling experiments demonstrated that capturing hydrogen atom is the decisive step for the selectivity of the reaction.