| Spiroheterocycles are a class of special spirocyclic compounds containing heteroatoms such as nitrogen,sulfur,and/or oxygen in the spiro ring systems.Due to their particular structure,they have been found to possess the advantageous features of good stereoselectivity and versatile biological properties,which enable them to find wide application in medicines,pesticides,dyes,materials and other fields.Although numerous spiroheterocyclic compounds have been documented so far,the majority of them possess N-atom and/or O-atom within the spiro-ring skeletons,while the S-containing spiroheterocycles are relatively less explored.However,this outcome does not devalue the importance of S-containing spiroheterocycles,as some of them have been found to display various biological activities.In order to construct this unique sulfur-containing spiro heterocyclic molecular structure,some effective synthetic methods have been developed.The literature investigations show that the existing methods mainly include intermolecular cycloaddition,acid-catalyzed condensation,and intramolecular cyclization reactions.Even though these methods have their own advantages for the synthesis of specific types of sulfur-containing spiro heterocyclic rings,the development of other methods for synthesizing this structure,especially non-metallic methods for synthesizing such heterocyclic compounds is still a research hotspot at this stage.In recent years,many chemists have introduced the hypervalent iodine reagents in all respects.Therefore the application of hypervalent iodine reagents underwent an unprecedented development.Due to many unique properties as nontoxic,environmentally-benign,and readily available,hypervalent iodine reagents have been referred to as "green" oxidants and have been vastly used in oxidative bond-forming reactions for the synthesis of a great diversity of heterocyclic compounds.Hypervalent iodine-mediated oxidations of a large number of aromatic rings and related compounds have been applied to the total syntheses of various biologically active natural products.Organic hypervalent iodine chemistry has experienced rapid development in the past few decades and has developed into an important research area of organic chemistry.The hypervalent iodine reagents are widely use in a variety of oxidation reactions as a class of low-toxic,easy to prepare,mild,high-selectivity,environmental friendly,oxidizing reagents that meets the requirement of green chemistry.Hypervalent iodine reagents,a class of non-metallic oxidant,have been successfully applied to the construction of the heterocyclic via oxidative C-C,C-hetero,hetero-hetero bond formation.In our previous work,there were reactions using hypervalent iodine(Ⅲ)-mediated synthesis of spirocyclic compounds through oxidative C-C,C-O,or C-N bond formation.These reactions always use phenyliodine-(Ⅲ)bis(trifluoroacetate)(PIFA),phenyliodine(Ⅲ)diacetate(PIDA),iodosylbenzene(PhIO)as oxidants.Based on our previous work and literature research,we started out our investigation by choosing(Z)-3-hydroxy-1-(2-hy droxyphenyl)-3-(2-iodophenyl)prop-2-en-1-ones 138a as model substrate and hypervalent iodine as oxidant to test the reactions conditions.Based on all the screening results,the optimal reaction conditions were concluded to be 1 mmol of substrate 138,3 equiv of PIDA,0.2 equiv of CuBr,0.2 equiv of 1,10-phen,2 equiv of KSC(S)OEt with DMSO as solvent at 80℃.So the construction of C-O and C-S bonds was carried out following the synthesis of the potential bioactive spirofurothiophene compounds via intramolecular oxidative tandem reaction.To study the adaptability of the new method to synthesize the target spirofurothiophene compounds,a series of substituted substrates were prepared to text the generality.Experimental results show that sixteen spirofurothiophene derivatives have been synthesized under optimal conditions.The structures of substrates and products have been well characterized by melting point,1H NMR,13C NMR and high resolution mass spectrometry.Through literature research,previous work,and experimental research results of this work,a reaction mechanism for the formation of spirofurothiophenes mediated by PIDA/CuBr-mediated oxidative coupling was proposed.In this work,we have presented a PIDA/CuBr-mediated spirocyclization reaction involving an intramolecular oxidative C-O bond formation step followed by C-S bond formation process,enabling a convenient synthesis of 3H,3’H-spiro[benzofuran-2,2’-benzo[b]thiophene]-3,3’-dione in satisfactory to good yield.This could represent an alternative strategy for the assemblage of S-containing spiroheterocycles,which features a cascade process introducing S-atom from the readily available potassium ethylxanthate at late stage,rather than utilizing the S-containing substrate.Further studies on the reaction mechanism are still in progress in our lab. |
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