Copper‐Catalyzed Coupling of Indoles with Dimethylformamide as a Methylenating Reagent

Abstract

By using N,N-dimethylformamide (DMF) as am ethylenating reagent, the copper-catalyzed C À Ha ctivation of indole was demonstrated as an efficient and facile protocolf or synthesizing 3,3'-diindolylmethane (DIM)a nd its derivatives.T he results indicatet hat copper chloride was the best catalyst among the investigatedt ransitionm etal salts, which affords an excellent regioselectivity and good yield when tert-butyl hydroperoxide (TBHP) was used as an oxidant.

Iodine/tert‐Butyl Hydroperoxide‐Mediated Reaction of Indoles with Dimethylformamide/Dimethylacetamide to Synthesize Bis‐ and Tris(indolyl)methanes

“…As the formation of both 8 a and TIM is arrested in absence of H 2 O, we believe that the oxygen atom of ‐CHO of 8 a comes from the H 2 O molecule. We, therefore, propose a tentative mechanism for the formation of 2 and 3 on the basis of our control experiments and relevant reports (Scheme ) –. First, electrophilic iodine species (I + ) and tert ‐butoxy radical (tBuO . )…”

“…Although DMF/DMA/DMSO have been successfully used as one carbon synthon, however, their use as a sources of ‐CH 2 and ‐CH unit is less explored. Very recently, few reports published related to the synthesis of 3,3‐bis(indolyl)methane (BIM) by using DMF and DMA as methylene sources in the presence of copper and vanadium salt catalysts . Although the methods give moderate yield, but they either require long time heating or 2‐arylindoles as the starting materials.…”

Visible‐Light‐Promoted Alkylation of Indoles with Tertiary Amines by the Oxidation of a sp3 C‐H Bond

“…We believe that both energy transfer and photoredox catalysis are possibly involved in the reaction. [30] Intermediate VIII accepts N,Ndimethylaniline to generate the final product 3 a. Tertiary amines can be oxidized by singlet oxygen.…”

Methylene Surrogates for the Synthesis of 3,3’‐Diindolylmethanes

“…al. [27] reported a Cu(I) catalysed strategy for the synthesis of DIMs in the presence of TBHP as oxidizing agent and DMF as the methenyl source. The key aspect in the process is the in situ generation of 1-methyl-3-methylene-3H-indol-1ium ion.…”