Study On Flavin-Catalyzed Aerobic Oxidative Sulfenylation Of Aryl-Fused Cyclic Amines

Sulfur-containing heterocyclics are widely applied in the materials science and pharmaceuticals.In this thesis,the aryl sulfides are constructed by flavin/I₂-catalyzed aerobic oxidative C–H sulfenylation of aryl-fused cyclic amines.The paper includes the following two parts:Part ?:Flavin/I₂-catalyzed aerobic oxidation-sulfenylation of indolines.A flavin/I₂-catalyzed aerobic oxidative C–H sulfenylation of indolines was developed to synthesize 3-sulfenyl indoles in high yields.First,reaction conditions,such as,solvent,flavin catalyst,iodides,and temperature etc.were optimized.Next,a wide range of indolines and thiophenols were explored.It was found that the effect of the substituent on the reaction activity was not obvious:different electron-donating and electron-withdrawing groups at different positions of thiophenol were all well tolerated.Furthermore,heteroaryl thiols and aliphatic thiols underwent oxidative coupling to give corresponding products in moderate yields.Finally,based on our control experiments,a mechanism for this flavin/I₂-catalyzed oxidative sulfenylation is proposed in two consecutive steps:1)flavin-catalyzed disulfide formation and dehydrogenation of indoline to form indole;2)reaction of in situ generated disulfide with I₂ to form sulfenyl iodide,which is then nucleophilically attacked by the newly formed indole to obtain final products.Part ?:Flavin/I₂-catalyzed aerobic sulfenylation-oxidation of tetrahydroquinolines.To further demonstrate the synthetic diversity,coupling reactions of tetrahydroquinolines with thiols were then tested.When flavin 2 and iodine were applied as co-catalysts,6-thiophenyl substituted quinolines could be obtained under oxygen atmosphere in good yields.Control experiments revealed that the regioselectivity of this reaction caused by two consecutive steps:sulfenylation and oxidative aromatization.In summary,an oxidative C-H sulfenylation of aryl-fused cyclic amines with various thiols catalyzed by flavin/I₂ system with high atom-efficiency and excellent functional compatibility is reported for the first time.By using molecular oxygen as the only terminal oxidant,different flavin derivatives could catalyze the C-H sulfenylation of aryl-fused cyclic amines to form corresponding 3-sulfenylindoles and6-sulfenylquinolines in good yields in the absence of metal-catalysts or peroxides.