Hypervalent Iodine(?)-Promoted Intramolecular Dehydrogenative Coupling Reaction Of Thioamides

Benzothiazine derivatives are important S,N-containing heterocyclic compounds.Benzothiazine scaffold as a privileged structure in pharmaceuticals exhibits versatile activities,such as anti-HIV,antimycobacterial,anti-inflammatory,and antitumor activities.Therefore,the synthesis of benzothiazines has been an ongoing attractive research field.Despite the advanced progress in the area,most of the reported approaches rely on either intramolecular SNAr processes or metal-catalyzed C-S bond coupling reactions,both using substituted haloarenes as the reactants and accompanying by harsh reaction conditions,low functional group tolerance,and by-products generation such as amides.Thus,developing an efficient and mild approach for the synthesis of 1,3-benzothiazines is highly desired.Thioamides,as versatile synthons in organic synthesis,are extensively applied in the synthesis of natural products and pharmaceuticals.Meanwhile,thioamides have multiple reaction centers and could react with various electrophilic or nucleophilic reagents,which are widely used in the construction of heterocycles,such as thiazoles,thiazolines and thiazolinones.Compared with other thiocarbonyl compounds,thioamides are odorless and more stable.The chemical reactivity and excellent physical properties of thioamides make them very valuable intermediates.Hypervalent iodine?III?reagents as an important class of oxidants have similar reaction properties to transition-metal catalysts.Generally,they can be used as a less toxic and safer alternative to metal oxidants.In addition,iodobenzene diacetate?PIDA?,phenyliodine bis?trifluoroacetate??PIFA?and Koser's reagent?HTIB?are often used in intramolecular oxidative coupling reactions to form carbon-heteroatom bonds of heterocyclic compounds.In this thesis,hypervalent iodine?III?-promoted intramolecular dehydrogenative C-S bond coupling of thioamides has been developed starting from N-benzylthioamides and HTIB.Based on a series of experiments,the optimal conditions were determined as the ratio of N-benzylthioamides and HTIBwas 1:1,hexafluoroisopropanol was used as the solvent,and the reaction proceeds smoothly at room temperature within 1 min under metal-free conditions.In addition,the substituent effect has been systematically studied which shows that the reaction tolerates various functional groups.Various substituted 1,3-benzothiazine derivatives?31 examples?were synthesized via this protocol.The structures of all new compounds have been characterized by ¹H NMR,¹³C NMR and HRMS.Furthermore,1,3-benzothiazines could be obtained by one-pot reactions using isothiocyanates and diarylphosphine oxides.Preliminary mechanistic studies indicate that two different pathways might involved.