Copper Catalyzed Alkene Intramoleculer Oxythiocyanation For The Synthesis Of Isoxazolines And Parazoles

Organic thiocyanates are important synthetic intermediates for the construction of various valuable sulfur-containing compounds.They belong to the chemical class of organic chalcogen-cyanates(R–S–C?N),in which the heteroatom S is attached by a single bond to the organic substituent(alkyl,aryl,and so on)and by another one to the CN group.Organic thiocyanates have been widely applied in pharmaceuticals,pesticides,organic dyes,and et.al.They are utilized in the preparation of various types of sulfur compounds and heterocyclic compounds,and also used to determine the amino acid sequence in peptide and protein as well as fluorescent markers.Isoxazolines and pyrazoles are important heterocyclic compounds,which exhibit various pharmaceutical and biological activities.In recent years,these types of N-heterocyclic compounds receive more and more attentions due to their biochemical and physiological activities,such as antibacterial,anti-inflammatory,anti-tumor,and so on.So far,the chemists have successfully synthesized isoxazolines compounds containing alkyl,azide,halogens,trifluoromethyl,and cyano groups.As part of our research interests on copper-catalyzed synthesis of heterocycles,we disclose here a novel Cu(II)-catalyzed intromolecular oxythiocyanation of unactivated alkenes for the synthesis of SCN-substituted isoxazolines under mild conditions.As an important synthetic intermediate,SCN-substituted isoxazolines was treated with sodium azide in the presence of Zn Br₂to give the corresponding tetrazole,which realized the double superposition of bioactive functional groups.