The Synthesis Of O-2-(2-Propylsulfinyl) Benzyl Glycosides By Green Oxidation Of Sulfides

Our glycochemistry group has recently developed a novel glycosylation method,inspired by interrupted Pummerer reaction,which involved O-2-（2-propylthiol）benzyl glycosides as latent donors and O-2-（2-propylsulfinyl）benzyl glycosides as active donors.This method utilized the latent-active strategy and remote activating manner,which proved to be powerful for complex oligosaccharide and glycoconjugate synthesis.Transformation of latent O-2-（2-propylthiol）benzyl glycosides to active O-2-（2-propylsulfinyl）benzyl glycosides only required simple oxidation of sulfides to sulfoxides by using bis（trifluoroacetoxy）iodobenzene（PIFA）,cyanuric chloride（CC）/urea-hydrogen peroxide（UHP）or m-CPBA as oxidants.Although application of these oxidation methods efficiently supplied various of O-2-（2-propylsulfinyl）benzyl glycosyl donors,the drawbacks including requirement of stoichiometric amount of oxidants,necessity to carefully controlling the reaction conditions to prevent over-oxidation and atomic diseconomy promoted us to search new oxidation methods.Through literature research,we found that the commonly used oxidants in preparation of sulfoxide are hydrogen peroxide,nitrogen oxides,halogen salts and so on.The target products can be effectively obtained by adjusting the reaction factors.But they have some disadvantages such as large amount of oxidants and peroxidation problems.We have successfully applied nitrogen oxide mediated sulfoxidation to transform latent O-2-（2-propylthiol）benzyl glycosides to active O-2-（2-propylsulfinyl）benzyl glycosides through literature research and experimental exploration.This method involved NOBF₄as catalyst,TBAB as additive and O₂ as terminal oxidant.In case of the acid sensitive substrates,catalytic amount of DTBMP was able to neutralize the acidity without affecting the oxidation efficiency.The method not only features the advantage of high efficiency,wide applicability and allowance for large scale synthesis,but also meets many aspects of green chemistry’s requirement,such as NOBF₄ and TBAB were catalytic quantities and environmentally friendly reagent O₂ used as terminal oxidant,high atom-economy,easy manipulation and purification processes.When we searched the NOBF₄ mediated oxidation reaction,we found that there was EDA complex formed.When nitrogen oxide and thioether were placed in a solvent,changes in the UV visible spectrum indicate that binary EDA complex were formed in the system.Interestingly,when TBAB was involved,a clear bathochromic displacement was observed,indicating the formation of a new EDA complex,possibly a ternary complex involved sulfide,NOBF₄ and TBAB,which might account for the high efficiency of the present oxidation reaction.