A Study Of Mn（OAc）₃-promoted Sulfonation Reaction Via The SO₃^– Radical

Sulfonic acid compounds（R-SO₃H）are widely used in various fields such as organic synthesis,materials science,fine chemicals,natural products,and medicinal chemistry.The introduction of sulfonic acid groups into molecules can significantly alters their physicochemical properties,including water solubility and surface activity,making them useful in modifying drug molecules and improving polymer materials.As a result,sulfonic acid compounds can be employed to synthesize functional molecules such as surfactants,dyes,drugs,fluorescent probes,catalysts,and material molecules.The traditional electrophilic sulfonation reaction is the main method for incorporating sulfonic acid group structures into molecules.However,this approach suffers from harsh reaction conditions,poor positional selectivity,and low functional group tolerance,which limit its green preparation and application.To overcome these limitations,a new mild and efficient sulfonation reaction strategy based on a radical sulfonation mechanism is proposed.This thesis investigates the construction of aromatic sulfonic acid compounds and heterocyclic sulfonic acid compounds using manganese（III）acetate(Mn³⁺)/hexafluoroisopropanol（HFIP）oxidation system with inorganic sulfur salts.The study is divided into three main parts:The first part explores the direct sulfonation of aromatic substrates such as unbiased aromatics,substituted naphthylamines/naphthols,and electron-rich five-membered heterocycles using green and inexpensive potassium metabisulfite（K₂S₂O₅）as the sulfonation reagent.The Mn³⁺/HFIP oxidation system enables the synthesis of the target sulfonic acids or sulfonates under mild conditions with a yield of 29-99%.This method has significant advantages over the conventional electrophilic sulfonation method,including mild reaction conditions,good functional group tolerance,good selectivity,and no waste acid generation.Mechanistic studies confirm that the reaction proceeds via a SO₃^-radical-involved homolytic aromatic substitution（HAS）type reaction.The second part of the thesis focuses on the use of Mn³⁺in the construction of heterocyclic sulfonate compounds.The study demonstrates a SO₃^-radical-based sulfonation-cyclization cascade reaction,which is further optimized to make the use of oxidant and solvent greener and more efficient.The sulfonation-cyclization tandem synthesis strategy is then employed to introduce sulfonic acid groups into the heterocyclic skeletal structures of oxindole,quinolinone,isoquinoline-1,3-dione,benzoxazine and azaspiro[4,5]-trienone.The study demonstrated the synthesis of over 70 heterocyclic sulfonates with 49-99%overall yields,highlighting the synthetic potential of SO₃^-radicals as a synthetic synthon for building heterocyclic skeletons and introducing sulfonyl groups into the molecules.Additionally,the study transforms the obtained heterocyclic sulfonic acids into sulfonyl chlorides,sulfonyl fluorides,sulfonamides,sulfonate esters,sulfonyl azides,and other sulfonyl-containing compounds,demonstrating the application of sulfonates as core intermediates in modular derivative synthesis.The study also demonstrates the coupling of sulfonates with functional molecules such as amino acids and mecarbinates,illustrating the application of this method in the field of post-functionalization modification.