Study On PhICl₂-Mediated Novel Synthesis Of S（Se）CN-containing Heterocycles

Thiocyanates and selenocyanates have been recognized as ubiquitous scaffolds widely found in many natural products and pharmaceutical targets.In the meanwhile,they also severed as versatile building blocks for the synthesis of various sulfur-and selenium-containing compounds.Therefore,chemists have devoted a great deal of efforts to developing efficient and novel methods for the synthesis of organic thio/selenocyanates in recent decades.This thesis mainly focused on the in situ generation of a series of electrophilic thio/selenocyanate reagents including thio/selenocyanogen and thio/selenocyanogen chloride from the reaction of PhICl₂ with inorganic thio/selenocyanate salts.Those reactive reagents would react with various substrates to afford the sulfur-and selenium-containing heterocycles.The full text was divided into five parts:In Chapter 1,we briefly introduced the biological activities and synthetic applications of organic thio/selenocyanates and systematically summarized recent methodologies for the preparation of thio/selenocyanates.We then demonstrated the research background and significance of our project.In Chapter 2,the novel synthetic method for the synthesis of thiocyanated 2-pyridones was investigated.The thiocyano group could be directly inserted into the position opposite to the carbonyl group in the 2-pyridones with electrophilic thiocyanogen chloride in situ generated from the reaction of PhICl₂ with NH₄SCN.We also realized the derivatization of naturally occurring ricinine by the newly developed method.This method features high-yielding,excellent regioselectivity and great functional group tolerance.In Chapter 3,we introduced a novel method for the synthesis of thio/selenocyanated isocoumarins.o-（1-Alkynyl）benzoates were used as the substrates which could undergo the electrophilic addition and intramolecular cyclization with thio/selenocyanogen chloride to afford the C4 thio/selenocyanated isocoumarins.Control experiments ruled out the formation of hypervalent iodine intermediate PhI（SCN）₂.The mechanism for the in situ generation of thiocyanogen chloride has been revised.Those results provided new ideas for thio/selenocyanation reaction.In Chapter 4,we realized the synthesis of thio/selenocyanated isobenzofuranones with o-alkenyl benzoic acids as substrates.This transformation proceeded via electrophilic addition of thio/selenocyanogen chloride to alkene moiety followed by the nucleophilic attack to construct C–O bond,thus afforded a series of desired products.Surprisingly,when the internal o-alkenyl benzoic acids were subjected to the reaction,the thio/selenocyanated 3,4-dihydroisocoumarins were obtained as sole type of products.Control experiments and mechanism investigation revealed that different types of products formed in this transformation could be ascribed to the electronic effect of substituents on the alkene moiety.In Chapter 5,we developed a novel method for the synthesis of selenazole skeleton with selenocyanogen as the terminal selenocyanate reagent and K₂CO₃ as promotor,which was different from the commonly encountered Hantzsch-based methods.Electrophilic addition of selenocyanogen to enaminone,followed by intramolecular cyclization led to the formation of 2-amino-1,3-selenazoles.Gram-scale synthesis of the target product revealed the potential synthetic application of this novel method.Moreover,this transformation used the commercially available KSe CN as the selenium source,thus avoided the participation of expensive and inconvenient selenourea.This method also features mild reaction conditions and broad substrate scope.In conclusion,we investigated the synthetic applications of in situ generated thio/selenocyanogen and thio/selenocyanogen chloride as electrophilic thio/selenocyanate reagent.The successful synthesis of thio/selenocyano-containing 2-pyridones,isocoumarins,isobenzofuranones and 1,3-selenazoles revealed the promising synthetic applications of our strategies with broad substrate scope and excellent regioselectivity.Results of our study provided new ideas for the synthesis of sulfur-or selenium-containing heterocycles.