Flavin–iodine coupled organocatalysis for the aerobic oxidative direct sulfenylation of indoles with thiols under mild conditions

Abstract

The environmentally friendly direct sulfenylation of indoles with thiols was performed by a unique coupled redox organocatalysis system using flavin and iodine.

Recent Advances in Iodine‐Promoted C−S/N−S Bonds Formation

“…In 2018, Lida andc o-workers described an iodine-flavin combined catalytic system for the synthesis of 3-thioindoles 111 at ambient temperature using oxygen as the sacrificial reagent, generating environmentally benign H 2 Oa st he sole byproduct (Scheme 36). [91] In this reaction, the sulfenylationh ardly occurredw ithout A•TfO,I 2 ,o rO 2 under standardc onditions. Dif- ferent from the general reports, the reactionr ate with thiols was enhanced compared with that of disulfides, which may be because the flavin (A•TfO)-promoted system would not only oxidize the thiol to disulfide, but also storageH 2 O 2 to oxidize I À to I 2 .…”

The Hydrazine–O2 Redox Couple as a Platform for Organocatalytic Oxidation: Benzo[c]cinnoline‐Catalyzed Oxidation of Alkyl Halides to Aldehydes

“…[1] Oxidation platforms based on organic catalysts [2] are also of high interest, both for reasons of mechanistic diversity and because of the practical advantages that non-metal technologies can offer. [3] Notable examples of organocatalytic O 2 -coupled oxidants include quinones, [4] flavins, [5] nitroxyl radicals, [6] hypervalent iodine, [7] and perguanidinylated arenes. [8] However,b ecause of the difficulties inherent in the direct oxidation of organic molecules with molecular oxygen (autoxidation), [9] many of these platforms rely on am etal co-catalyst to facilitate the redox processes.Organocatalysts that achieve both substrate oxidation and O 2 reduction are relatively rare,a nd the development of such platforms,especially those that operate through unique mechanistic paradigms,i sacompelling goal.…”

Sulfenylation of Indoles Mediated by Iodine and Its Compounds

“…An organocatalytic approach to 3‐sulfenylated indoles was realized with the use of I 2 /flavin system. The aerobic reaction of thiols with indoles in MeCN at room temperature [24] and indolines in DMSO at 60 °C [25] delivered 3‐sulfenyl indoles in 65–94 % and 60–92 % yields respectively. Flavin‐iodine‐coupled organocatalysis also enabled the one‐pot three‐component atom‐efficient synthesis of 2‐azolyl‐3‐thioindoles from indoles, azoles, and thiols applying molecular oxygen as the terminal oxidant [26] .…”