Hypervalent Iodine Mediated One-Pot C-H Functionalization at 2α- or 3α-Position of Indole Derivatives

Abstract

The one-pot 2-and 3-functionalization of 2,3-disubstituted indoles using a hypervalent iodine reagent has been developed. The substitution at the 2-position of indoles took place using phenyliodinebis(trifluoroacetate) with oxygen and carbon nucleophiles in moderate yields. The combination of iodosobenzene and trimethylsilyl azide afforded 3-azide derivatives preferentially.The latter reaction was applied to other 2,3-disubstituted indoles.Recently, Ishibashi's group revealed the combination of phenyliodine diacetate (PIDA) and tetrabutylammonium iodide (TBAI) reacted with tetrahydrocarbazoles to give 2-acetoxy derivatives. 6 Alternatively, Du Bois and co-workers developed that the reaction of tetrahydrocarbazoles using imino  3 -iodanes with a rhodium catalyst affords 2-and 3-amino derivatives. 7Recently, we developed the concise 2-functionalization of indole derivatives using a thionium species generated from DMSO-TFAA (Scheme 1). 8

Metal-Free C–H Functionalization and Aromatization Sequence for the Synthesis of 1-(Indol-3-yl)carbazoles and Total Synthesis of 7-Bromo-1-(6-bromo-1H-indol-3-yl)-9H-carbazole

“…Moreover, this approach will provide 1-substituted tetrahydrocarbazoles and 1-substituted carbazoles where both of the scaffolds are biologically potent . Tetrahydrocarbazoles can be activated via thionium or peroxo- or chloroindolenine intermediates . The available methods for the activation of tetrahydrocarbazole at its 1-position require (1) combination of reagents/oxidizing agents, (2) low temperature, (3) higher equivalents of nucleophiles, (4) longer reaction time, (5) protection of N–H.…”