Cu(ii)-catalyzed aerobic oxidative coupling of furans with indoles enables expeditious synthesis of indolyl-furans with blue fluorescence.

With the purpose of incorporating sustainability in chemical processes, there has been a renewed focus on utilizing earth-abundant metal catalysts to expand the repertoire of organic reactions and processes. In this work, we have explored the atom-economic oxidative coupling between two important electron-rich heterocycles - indoles and furans - using commonly available, inexpensive metal catalyst CuCl2·2H2O (<0.25$ per g) to develop an expeditious synthesis of indolyl-furans. Moreover, the reaction proceeded well in the presence of the so-called 'ultimate oxidant' - air, without the need for any external ligand or additive. The reaction was found to be scalable and to work even under partially aqueous conditions. This makes the methodology highly economical, practical, operationally simple and sustainable. In addition, the methodology provides direct access to novel indole-furan-thiophene (IFT)-based electron-rich π-conjugated systems, which show green-yellow fluorescence with large Stokes shift and high quantum yields. Mechanistic investigations reveal that the reaction proceeds through chemoselective oxidation of indole by the metal catalyst followed by the nucleophilic attack by furan.

Aerobic Catalytic Cross-Dehydrogenative Coupling of Furans with Indoles Provides Access to Fluorophores with Large Stokes Shift.

Sustainability in chemical processes is a crucial aspect in contemporary chemistry with sustainable catalysis as a vital parameter of the same. There has been a renewed focus on utilizing earth-abundant metal catalysts to expand the repertoire of organic reactions. Furan is a versatile heterocycle of natural origin used for multiple applications. However, it has scarcely been used in cross-dehydrogenative coupling. In this work, we have explored the cross-dehydrogentive coupling of furans with indoles using commonly available, inexpensive FeCl3 ⋅ 6H2 O (<0.25 $/g) as catalyst in the presence of so called 'ultimate oxidant' - oxygen, without the need for any external ligand or additive. The reactions were found to be scalable and to work even under partially aqueous conditions. This makes the reaction highly economical, practical, operationally simple and sustainable. The methodology provides direct access to π-conjugated short oligomers consisting of furan, thiophene and indole. These compounds were found to show interesting fluorescence properties with remarkably large Stokes shift (up to 205 nm). Mechanistic investigations reveal that the reaction proceeds through chemoselective oxidation of indole by the metal catalyst followed by nucleophilic trapping by furan.

Copper-Catalyzed Aerobic Cross-Dehydrogenative Coupling of ß-Oxime Ether Furan with Indole.

Heterobiaryls serve as relevant structural motifs in many fields of high applicative importance such as drugs, agrochemicals, organic functional materials etc. Cross-dehydrogenative coupling involving direct oxidation of two C-H bonds to construct a C-C bond is actively being pursued as a more benign and 'greener' alternative for synthesizing heterobiaryls. Herein, we report a Cu(I)-catalyzed cross-dehydrogenative coupling of indoles and furans, two of the most important aromatic heterocycles using air as the terminal oxidant. The reaction proceeds with regio- and chemoselectivity to give the cross-coupled products in good to excellent yields generally. A broad substrate scope with respect to both the coupling partners has been demonstrated to prove the generality of this reaction. This represents the hitherto unexplored cross-dehydrogenative coupling methodology to obtain an indole-furan biaryl motif.