The Construction Of All-carbon Quaternary Centers And Dihydrobenzofuran Skeletons Enabled By Radical Ractions

Radical reactions have attracted extensive attention in the construction of complex organic molecules and natural products due to their high efficiency,high regioselectivity,and excellent functional group tolerance.It is known that the addition of carbon-centered radicals to unsaturated bonds is an efficient strategy to construct CC bonds and cyclic framworks.This dissertation reports a sequential functionalization of activated trichloromethyl groups for the synthesis of diversely three alkyl chain substituted all-carbon quaternary centers.Moreover,the author also describes a onestep reaction for the construction C3-functionalized 2-aryl-2,3-dihydrobenzofuran derivatives based on radical annulation of phenols and electron-deficient alkenes.The chapter one summarized carbon-centered radical-involved reactions for the construction of all-carbon quaternary centers,including radical-invloved metal catalyzed cross coupling reactions and carbon-centered radical addition reactions toward carbon-carbon unsaturated bonds.In addition,the regioselectivity of radical addition to α,β-unsaturated compounds was discussed.In the second chapter,the author disclosed a boryl radical promoted three-step sequence to assemble all-carbon quaternary centers from activated trichloromethyl groups.The three C-Cl bonds were sequentially and selectively cleaved with the rational choice of a Lewis base-boryl radicals as the promoter in each step.The resulting carbon-centered radicals could be trapped by different alkenes,furnishing structurally diverse three alkyl chain substituted all-carbon quaternary centers.Moreover,Lewis base-BH3 complexes are meanwhile good hydrogen atom donors,so that the hydrodechlorination often takes place as the major side reaction pathway during the dechlorinative alkylation process.To address this issue,we introduced a cyano group onto the boron center to decrease the electron density,which could make the reduction polarity-mismatched,thus favoring the formation of coupling products.More importantly,the utility of this strategy was demonstrated by the synthesis of variants of two drug molecules,whose structures could be easily modulated by varying the alkene partner in each stepThe third chapter described an electrooxidative[3+2]annulation of phenols andα,β-unsaturated alkenes,synthesizing 2-aryl-2,3-dihydrobenzofuran skeletons.The ring construction started by a unique α-addition of carbon radicals derived from anodic oxidation of phenols to α,β-unsaturated alkenes.The subsequent anodic oxidation of the resulting alkyl radical intermediates followed by trapping with the phenolic hydroxy group assembles the 2,3-dihydrobenzofuran core.Such a tactic enabled the installation of various electrophilic functionalities at the C3 of the 2,3-dihydrobenzofuran framework,which was unattainable by other intermolecular reactions.The application of this method for a rapid synthesis of a bioactive natural product was demonstrated.