Iodine/Manganese Catalyzed Sulfenylation of Indole via Dehydrogenative Oxidative Coupling in Anisole

Abstract

This protocol describes an iodine/manganese catalytic system for dehydrogenative oxidative coupling reaction of indoles with thiols in anisole. Particularly, the dual roles of anisole have been first demonstrated as a solvent and as a promoter via the formation of an oxonium ion intermediate to accelerate the generation of products. A series of sulfenylindoles are readily constructed under aerobic mild reaction conditions. In addition, the achievement for preparing anticancer and anti‐AIDS drugs testifies the practicability of this approach. The mechanism studies disclose probable alternative pathways and a single‐electron transfer process are involved in this transformation.magnified image

Sulfenylation of Indoles Mediated by Iodine and Its Compounds

“…A wide range or indoles with electron‐donating and electron‐withdrawing groups, as well as aromatic and aliphatic thiols were compatible with this process. Yields of the desired products were 44–99 % [28] …”

TFA/DMSO‐Promoted Cross‐Dehydrogenative Coupling of Hetaryl Thiols with Indoles: Access to 3‐(Hetarylsulfenyl)indole under Mild Conditions

“…Accordingly, the sulfenylation reaction of indoles using directly thiophenols has become an excellent solution to the above-mentioned drawbacks. Various oxidative coupling conditions have been developed: Selectfluor, [27] NO 2 BF 4 , [28] molecular iodine, [29] NaOH/DMSO, [30] Cs 2 CO 3 /DMSO, [31] KIO 3 /DMSO, [32] HBr/DMSO, [33] air/photocatalyst, [34] graphene oxide/O 2 , [35] flavin/ I 2 /O 2 , [36] MnO 2 /I 2 /O 2 [37] or electrolytic conditions. [38] However, the direct sulfenylation reaction of indoles with heterocyclic thiols [39] was considered as a difficult task with only few examples reported [40] using strong oxidants such as I 2 , [40a-c] oxone, [40d] KIO 3 , [40e] or Mn(III).…”

“…Accordingly, the sulfenylation reaction of indoles using directly thiophenols has become an excellent solution to the above‐mentioned drawbacks. Various oxidative coupling conditions have been developed: Selectfluor, [27] NO 2 BF 4 , [28] molecular iodine, [29] NaOH/DMSO, [30] Cs 2 CO 3 /DMSO, [31] KIO 3 /DMSO, [32] HBr/DMSO, [33] air/photocatalyst, [34] graphene oxide/O 2 , [35] flavin/I 2 /O 2 , [36] MnO 2 /I 2 /O 2 [37] or electrolytic conditions [38] …”

“…However, the direct sulfenylation reaction of indoles with heterocyclic thiols [39] was considered as a difficult task with only few examples reported [40] using strong oxidants such as I 2 , [40a–c] oxone, [40d] KIO 3 , [40e] or Mn(III) [37] …”

“…[38] However, the direct sulfenylation reaction of indoles with heterocyclic thiols [39] was considered as a difficult task with only few examples reported [40] using strong oxidants such as I 2 , [40a-c] oxone, [40d] KIO 3 , [40e] or Mn(III). [37] Herein, we report the TFA/DMSO combination as a simple, practical and efficient system for direct sulfenylation of indoles with heterocyclic thiols under mild reaction conditions, leading to 3-sulfenylindoles containing heterocyclic sulfide scaffold.…”