Preparation And Reactivity Of Diacyl Sulfur Ylide

Sulfur ylides are a class of zwitterionic compounds.Their carbanion has strong nucleophilicity and often serves as a one carbon building block in organic synthesis to construct three-membered compounds through reactions with unsaturated double bonds.Due to the stabilizing effect of acyl groups on carbanions,monoacyl sulfur ylides exhibit excellent stability and diverse reactivities.They can be used as the precursors of carbenes,and their carbanions and acyl oxygen atom can serve as nucleophilic sites in organic reactions.Typically,the sulfide/sulfoxide fragment of sulfur ylides overflows the reaction system as byproducts and cannot be fully utilized.Due to the stabilizing effect of the two acyl groups on the carbanion,the activity of diacyl sulfur ylides is relatively low.Therefore,studies on their reactivity are limited.This dissertation focuses on the preparation of diacyl sulfur ylides,the nucleophilic properties of their acyl oxygen and carbanion,and the reutilization of their dialkylsulfonium and dialkyloxosulfonium fragments.(1)Based on the electrophilicity of electron-deficient alkynes,two kinds of bifunctionalization reactions of acetylenic sulfones and dimethyl sulfoxide have been developed.Under heating conditions in an oil bath,a series of diacyl sulfur ylides was rapidly and efficiently synthesized from dimethyl sulfoxide and acetylenic sulfones through a combination of the Michael addition and 4e-electron ring-opening process with complete atomic utilization.Under microwave heating conditions,the free methyl radical generated from the decomposition of dimethyl sulfoxide facilitated the further elimination of the S-methyl group in diacyl sulfur ylides,yielding a range ofα-methylthio-β-carbonyl sulfones.This reaction ingeniously utilizes dimethyl sulfoxide as both an economical solvent and reagent,and by precisely controlling the heating methods and temperature,selectively produces diacyl sulfur ylides and α-methylthio-β-carbonyl sulfones.(2)A deoxygenative cyclization reaction involving the participation of the acyl oxygen atom in diacyl sulfur ylides has been developed.Triflic anhydride and 2-chloropyridine were used as activating agents to tandemly activate the acyl oxygen atom in diacyl sulfur ylides,leading to the synthesis of a series of 2-alkyl/arylthiol benzo[b]thiophene 1,1-dioxides.Our synthetic method is a novel strategy,avoiding the cyclization strategies with internal alkynes as starting materials.In this process,triflic anhydride first activates the acyl oxygen atom to yield vinyl trifluoromethanesulfonates as intermediates,while 2-chloropyridine subsequently activates to generate pyridinium intermediates via an addition-elimination process.The pyridinium intermediates undergo an tandem selective ipso-aromatic electrophilic addition,1,2-sulfonyl migration,and aromatization process to afford the final products.The deactivated sulfonyl group determines the site-selectivity of the electrophilic addition via the ipso-attack,while the following sulfonylmigration controls the regioselectivity.Additionally,gram-scale experiments and product transformations demonstrated potential applications of our reaction.Some 2-methylthio and methanesulfonylbenzo[b]thiophene 1,1-dioxides show fluorescence properties in the solid state and in their solutions.(3)A nucleophilic pyridination reaction involving the acyl oxygen atom in diacyl sulfur ylides has been developed.The Mukaiyama reagent(2-chloro-1-methylpyridinium iodide)was utilized as a novel pyridine source for the first time,leading to the synthesis of a series of pyridoxy and methylthio derived vinyl sulfones.Additionally,bromine and iodine atoms can also serve as leaving groups and nucleophilic reagents to promote the reaction.Experimental results indicated that the active order is as following: 1-methyl-2-chloropyridinium iodide > 1-methyl-2-bromopyridinium iodide > 1-methyl-2-iodopyridinium iodide.The electron-withdrawing pyridinium and halogen atoms effectively increase nucleophilicity of the acyl oxygen atom,while the electron-withdrawing effect of the oxygen atom significantly reduces the nucleophilicity of the nitrogen atom in pyridine,facilitating the displacement of the N-methyl group with the halide anion.The reaction is metal catalystfree,and it can be successfully scaled up and used to modify camphor sulfonic acid.Furthermore,this reaction is successfully extend to α-acyl-α-cyano diacyl sulfur ylides and α,α-cyclic diacyl sulfur ylides.(4)Two types of demethylated halogenation reactions involving diacyl sulfur ylides carbanions have been developed.Sulfuryl chloride and selectfluor were used as halogen sources to directly construct halogencontaining quaternary carbon centers,resulting in the formation of two classes of α-halogenated α-methylthio-β-carbonyl sulfones in high yields.Electrophilic chlorination is a reagent-controlled reaction,in which sulfuryl chloride acts as the source of chlorine.The reaction selectively produces products with a chlorine-containing quaternary carbon center through a simple ionic mechanism,effectively avoiding the generation of chlorinated olefin byproducts.On the other hand,the fluorination reaction is solvent-controlled,using selectfluor as a radical initiator,single-electron oxidant,and fluorine radical source to establish an stable fluorine-containing quaternary carbon center in products in 1,2-dichloroethane.The two types of demethyl halogenation reactions offer several advantages,including mild conditions,wide substrate applicability,and without metal catalysts.Moreover,chlorinated products can act as the acyl reagents under neutral conditions,selectively acylating less steric alkylamines.(5)Based on the oxidation properties of dimethyl sulfoxide,a reaction was developed under Kornblum-like conditions to directly prepare benzyl methyl sulfoxide from benzyl halide,benzyl trimethylammonium tribromide,and dimethyl sulfoxide.In this process,benzyl halides react with the in-situ generated dimethyl sulfide to obtain benzyl methyl sulfide.Phenyltrimethylammonium tribromide is used as the oxidant,and dimethyl sulfoxide provides an oxygen source to jointly oxidize sulfides to sulfoxides.This reaction has a wide range of substrates and provides a direct and simple method to synthesize benzyl methyl sulfoxides,without generation of the over-oxidized product sulfones,which are formed with conventional oxidizing agents.The role of DMSO in the Kornblum oxidation reaction is changed from an oxygen source to an S(O)Me source.The experimental results indicate that,contrary to the substrate activity in the Kornblum oxidation reaction,the reaction activity is benzyl chloride>benzyl bromide>benzyl p-toluenesulfonate in the current reaction.