Access To β-carbonyl Disulfides From Cyclic Alcohols Through Radical Ring-opening Strategy

Unsymmetric disulfides are widely present in natural products and biologically active molecules.They not only play an irreplaceable role in the field of life science s,but also promote the development of chemical pharmacy,material chemistry and food chemistry.Therefore,it is of great significance to develop general and efficient methods for the synthesis of unsymmetric disulfides.Traditional methods for the synthesis of unsymmetric disulfides involved the construction of S-S bonds,such as oxidative cross coupling of two different mercaptans,the nucleophilic substitution of electrophilic monosulfide reagents(RS-LG,LG = leaving group)with mercaptans.However,these methods are far from perfect and the limitations still exist: the use of malodorous mercaptans,the generation of unavoidable homo-coupling byproducts,and poor functional group compatibility.In order to solve the above shortcomings,recently,the exploration of disulfide reagents to synthesize unsymmetric disulfides through C-SSR bonds formation has become a research hotspot.This strategy is mainly based on the cross-coupling and nucleophilic substitution process,whereas the strategy through free radical has less been addressed.Along these lines,the author merged sulfides synthesis with free radicals process,selected cyclopropanol derivatives as free radical precursors,benzenesulfonate dithioester as sulfur source,used visible light-induced strategies,and developed a green,economical and efficient method to synthesize unsymmetric disulfides.The author obtained the optimal reaction conditions by screening the combination of photocatalyst,addtive,solvent,cyclopropanol,disulfuration reagent.With the optimal conditions in hand,the anticipated product was obtained in 73%yield.Dithiosulfonates with structural diversity have been developed to explore the reactivities in this transformation.Besides,a broad range of functional groups were tolerated,delivering various β-carbonyl disulfides.The ring-expansion product seven-member ring cyclic ketone was obtained via a smooth conversion of bicyclopropanol.A set of mechanism experiments proved that the reaction proceeded through radical ring-opening/radical substitution sequence: initially,in the presence of base,deprotonation of cyclopropanol followed by SET oxidation by the excited state of photocatalyst provided alkoxy radicals,which subsequently underwentβ-scission to form the β-conbonyl alkyl radical.Next,the nucleophilic alkyl radical reacted with the disulfuration reagent to afford the desired unsymmetric disulfide products.The resulting p-toluenesulfonyl radical was reduced by reductive state of photocatalyst to give the corresponding sulfinic anion,regenerating the photocatalyst to complete the catalytic cycle.