Access To Polycyclic Thienoindolines Via Formal [2+2+1] Cyclization Reactions Of Alkynyl Indoles With Potassium Sulfide

The syntheses of polycyclic thienoindolines bearing a dihydrothiophene or tetrahydrothiophene subunit have not been reported,despite the fact that such compounds may have interesting medicinal properties and there have been in-depth studies on the medicinal and physicochemical properties of similar natural products.In this thesis,the synthesis of polycyclic thioindole of dihydrothiophene and tetrahydrothiophene was realized by using cheap K₂S and S₈and the synthesis method of polycyclic thioindole was extended.This thesis is divided into two parts:（1）We report a protocol for access to polycyclic dihydrothiophenes by means of formal S₃^·--initiated[2+2+1]intramolecular dearomatizing cyclization reactions of alkynyl indoles with K₂S and S₈ as green sources of sulfide.A new method for obtaining polycyclic dihydrothiophene was provided,and the substrate scope study was carried out to explore the effect of different groups on the reaction yield.Taken together,the above-described findings indicate that the optimal reaction conditions for the preparation of 2a involved using substrate 1（0.3 mmol,1.0 equiv,94.8 mg）,1.5 equiv of elemental sulfur（0.45 mmol,14.4 mg）and 0.6 equiv of K₂S（0.18 mmol,19.8 mg）as the[S]sources and 2/0.6（v/v,m L）DMF/i-Pr OH as the solvent at 120°C under N₂.The target product yield is 64%.（2）In addition,tetrahydrothienoindolines were stereoselectively synthesized via a one-pot,two-step protocol involving Ag NO₃-catalyzed alkenyl dearomatization followed by two nucleophilic addition reactions involving K₂S.At the same time,the study of substrate scope study was carried out.The above-described findings indicate that the optimal reaction conditions for the preparation of 2a:1.0 equiv of substrate 1（0.3 mmol,94.8 mg）,10 mol%of Ag NO₃（0.03 mol,5 mg）,Me CN（3）（2.0 m L）were added.The mixture was stirred at 80^oC for 4 h.After cooling the reaction mixture to room temperature,under N₂ atmosphere equipped,1.2 equiv of K₂S（0.36 mmol,39.7 mg）and Et OH（1.0 m L）were added.The mixture was stirred at 120 ^oC for 12 h.The target product yield is 80%.This article developed a protocol for access to polycyclic dihydro-and tetrahydrothienoindolines by means of formal intramolecular[2+2+1]dearomatizing cyclization reactions of alkynyl indoles with K₂S.Mechanistic experiments indicated that formation of the dihydrothienoindolines may proceed via a free-radical cyclization initiated by S₃^·-generated in situ from both K₂S and S₈.These findings can be expected to facilitate the development of new reactions for the synthesis of structurally complex thioethers.