Application Of Novel Redox-reagents In Trifluoromethylation And C-S Bond Construction

Fluorine-containing organic compounds,especially trifluoromethyl group,have a wide range of applications in the fields of agrochemicals,pharmaceuticals and materials science.Despite significant progress in trifluoromethylation over the past decade,the existing trifluoromethylation reagents require multistep synthesis,costly starting materials and limited large-scale applications.Trifluoroacetic anhydride and trifluoromethanesulfonic anhydride are two inexpensive and abundant chemicals,and thus represent attractive and practical trifluoromethylation reagents.However,the analogous transformations of trifluoromethyl radicals generating from trifluoroacetate or trifluoroacetic anhydride have confronted inevitable difficulties due to the high oxidation potential of the fluoroalkyl carboxylate anions(e.g.CF₃CO₂^-E^ox_1/2>+2.4 V vs SCE).The highly hydroscopic and corrosive trifluoromethanesulfonic anhydride?Tf₂O?as trifluoromethyl source is rarely explored.For its strong electrophilic nature,triflic anhydride is commonly used as alcohol and amine protecting agent.Therefore,it is of great significance and a certain challenge to realize the efficient use of trifluoroacetic anhydride and trifluoromethanesulfonic anhydride under mild reaction conditions.C-S bond construction is one of the hotspots in the field of modern organic synthesis.However,there are still some problems in the construction of C-S bonds:1)The strong coordination of thiolates to transition-metal catalysts often leads to catalyst deactivation,thus requiring a high catalyst loading and/or a high temperature to facilitate the desired reaction;2)limited substrates scope and poor functional group tolerance;3)most thiols are highly toxic compounds and the commercially available alkyl thiols or alkyl disulfides are few;4)specially designed ligands.We hope that the transition-metal catalyzed reductive coupling reaction can achieve the construction of C-S bonds with high selectivity under mild reaction conditions.The utilization of electrophilic sulfur???sources,in lieu of thiolates,may avoid the problem of catalyst deactivation and deliver a more efficient C-S cross-coupling reaction with broad functional group tolerance.Using inexpensive and abundant trifluoroacetic anhydride and trifluoromethanesulfonic anhydride,we have designed and synthesized two novel redox-active trifluoromethylating agents,namely N-hydroxybenzimidoyl chloride esters?NHBC esters?and Imidazolium sulfonate?IMDN-CF₃?with good stability,high reactivity and scalability.Using the redox active reagent strategy under mild reaction conditions,we have achieved the efficient activation of trifluoroacetic anhydride and trifluoromethanesulfonic anhydride,and applied them to a series of fluoroalkylation reactions.In addition,using the imidazolium sulfonateand triphenylphosphine in situ generated vulcanization reagent,we achieved the efficient construction of C-S bonds through a reductive cross-coupling reaction under mild reaction conditions.1.Redox-benzimidoyl chloride esters for photoinduced fluoroalkylationsWe have described an air-stable redox-active reagents N-hydroxybenzimidoyl chloride esters?CF₃-NHBC esters?with high reactivity and scalability,which prepared from inexpensive and abundant trifluoroacetic anhydride.The redox-active N-hydroxybenzimidoyl chloride esters?CF₃-NHBC esters?have been successfully employed in the photoinduced hydrotrifluoromethylation and heteroaryl migration of unactivated alkenes.The corresponding products can be obtained in good to excellent yields at room temperature,and this approach featured the practical conditions,broad substrate scope,and excellent functional group tolerance.A key design feature of N-hydroxybenzimidoyl chloride esters?CF₃-NHBC esters?is that by simply installing a chlorine to oxime,the stabilized electron-rich imine in harness,for surpassing the strong electron-withdrawing effect of CF₃ group in the redox-active ester,in favor of generating TFA radical and iminyl anion.Thus,the CF₃-bearing N-hydroxybenzimidoyl chloride?NHBC?ester could be activated by photocatalyst to selectively generate·CF₃ via N-O bond breaking followed by decarboxylative fragmentation.This strategy is called"leaving group assisted strategy".The redox-active N-hydroxybenzimidoyl chloride esters?R_F-NHBC esters?,including CF₂H-NHBC esters,C₂F₅-NHBC esters and C₃F₇-NHBC,have been also successfully employed in the photoinduced hydrofluorination and heteroaryl migration of unactivated alkenes.2.Redox-imidazolium sulfonamides for photoinduced fluorocarboborylation of alkenes and alkynesWe have described an air-stable redox-active imidazolium sulfonate reagentwith high reactivity and scalability,which prepared from inexpensive and abundant trifluoromethanesulfonic anhydride.The redox-active imidazolium sulfonate reagenthas been successfully employed in the photoinduced trifluoromethylation-borylation of alkynes and alkenes.The integrated reagent is applicable to regulate the reaction sequence of carbon and boron-centered radicals to access variousvinylboronates with high stereo-and regioselectivities.The1,2-trifluoromethylboronates can be obtained in good to excellent yields at room temperature with excellent functional group tolerance and broad substrate scope.A key design feature of redox-active imidazolium sulfonate reagent is that the cationic nature for surpassing the strong electron-withdrawing,favors the progressive formation of trifluoromethyl radicals by SET reduction under photocatalytic conditions.Meanwhile,this method can also be used to activate C₄F₉,C₆F₁₃,C₈F₁₇ and other fluorine-containing alkyl groups.The imidazolium sulfonate reagents(RF=C₄F₉,C₆F₁₃,C₈F₁₇ ect.)with high reactivity and scalability,which have been also successfully employed in the photoinduced fluorocarboborylation of alkenes and alkynes.The development and utilization of redox-active reagentprovided an effective method for the synthesis of various fluorine-bearing vinylboronates and alkylboronates.3.Reductive cross-coupling of redox-imidazolium sulfonamides with halides for constructing C-S bondWe have described an air-stable redox-active imidazolium sulfonate reagentwith high reactivity and scalability,which prepared from commercial and abundant arylsulfonyl chloride.The redox-active imidazolium sulfonate reagenthas been successfully employed in the Ni-catalyzed reductive cross-coupling with aryl halides,heteroaryl halides,alkenyl halides,alkyl bromide and alkynyl bromides for constructing C-S bond,including C?sp²?-S bond,C?sp³?-S bonds and C?sp?-S bond.The corresponding sulfides can be obtained in a yield of up to 94% under mild conditions with excellent functional group tolerance and broad substrate scope.A key design of this reaction is that the imidazolium sulfonate reagent could be reduced by triphenyl phosphorus to generate a electrophilic sulfur???in situ with high reactivity under mild reaction conditions.The utilization of electrophilic sulfur???sources,in lieu of thiolates,avoid the problem of catalyst deactivation and deliver a more efficient C-S cross-coupling reaction with broad functional group tolerance.