Tandem Iridium-Catalyzed Decarbonylative C–H Activation of Indole: Sacrificial Electron-Rich Ketone-Assisted Bis-arylsulfenylation

Abstract

Described herein is a decarbonylative tandem C–H bis-arylsulfenylation of indole at the C2 and C4 C–H bonds through the use of pentamethylcyclopentadienyl iridium dichloride dimer ([Cp*IrCl 2 ] 2 ) catalyst and disulfides. A new sacrificial electron-rich adamantoyl-directing group facilitates indole C–H bis-functionalization with a traceless in situ removal. Various differently substituted disulfides can be easily accommodated in this reaction by a coordination to Ir(III) through the formation of six- and five-membered iridacycles at the C2 and C4 positions, respectively. Mechanistic studies show that a C–H activation-induced C–C activation is involved in the catalytic cycle.

Iridium catalysed C2 site-selective methylation of indoles using a pivaloyl directing group through weak chelation-assistance

“…We then focussed on the mechanism of the iridium catalysed methylation reaction using a series of isotope experiments (Scheme SI-1 † ). Based upon our supporting experimental findings together with previous studies, 18 a plausible catalytic cycle for the iridium( iii ) catalysed methylation reaction can be presented ( Fig. 2 ).…”

“…Moreover, in the absence of AgOAc no product was obtained (Table 1, entry 17), and the use of silver carbonate in place of silver acetate resulted in lower yield. Even the use of silver oxide was not efficient (Table 1, entries [18][19]. Control experiments veried that the iridium catalyst and an excess of potassium triuoromethyl borate are both essential to obtain the very good, isolated yields (Table 1, entries 20-21).…”

“…Recently, we reported a tandem iridium-catalysed decabonylative C–H activation of indoles using a sacrificial electron rich ketone for bis-arylsulfenylation reactions. 18 Using this efficient iridium( iii ) catalytic system as a starting point, we pondered whether the catalytic conditions could be applicable to the C2-selective methylation of indoles by switching the inherently preferred regioselectivity. We initiated our studies with a screening of potential directing groups (ESI, Table S1, † ) using potassium trifluoromethyl borate (2) to investigate potential for the iridium catalysed C2-selective methylation reactions.…”

Recent advances in selective mono-/dichalcogenation and exclusive dichalcogenation of C(sp2)–H and C(sp3)–H bonds

“…In 2021, Nicholls and coworkers reported an iridium-catalyzed tandem decarbonylative C2- and C4-diarylthiolation of indoles 34 with disulfides 33 using electron-rich adamantoyl as a traceless directing group, [IrCp*Cl 2 ] 2 as the catalyst, AgNTf 2 as the additive and Ag 2 CO 3 as both a promoter and a terminal oxidant (Scheme 4). 135 No monothiolated products were observed during the reactions. The protocol was tolerant of a diversity of aryl disulfides but proved unfruitful for dialkyl disulfides and 1,2-di(pyridin-2-yl)disulfane.…”

Transition metal catalysed direct sulfanylation of unreactive C–H bonds: an overview of the last two decades

“…109 In this regard, in 2021, Nicholls and co-workers reported a new complementary strategy for the direct sulfanylation of indoles under Ir( iii ) catalysis (Scheme 142). 110 The authors point out that the direct and regioselective direct sulfanylation of indoles at the C2 and C4 positions still constitutes a significant challenge in organochalcogen chemistry, where traditional methods involve the use of non-removable directing groups or stoichiometric quantities of reagents to remove the directing groups in additional steps. To overcome these drawbacks, they designed an Ir( iii )-catalysed domino decarbonylative C–H bis-sulfanylation using indoles containing the sacrificial adamantoyl directing group at the C3 position ( 166 ) and diaryl disulfides ( 3 ).…”