Silane‐Mediated Alkylation of Arenes via Reductive Friedel‐Crafts Reaction Using Carbonyl Compounds

Abstract

A metal‐free one‐pot synthesis route has been documented for the production of 1,1‐unsymmetrical diaryl alkanes via reductive Friedel−Crafts alkylation of arenes with carbonyl compounds in 1,1,1,3,3,3,‐hexafluoroisopropanol (HFIP) solvent. This approach exhibits a wide substrate scope accommodating diverse functionalities. The transformation of carbonyl compounds into alkylated products is facilitated by dimethylchlorosilane (Me2SiClH) reduction, succeeded via nucleophilic attack of arenes. The established protocol demonstrates a promising strategy for converting indoline‐2,3‐dione into α‐aryl oxindoles with high yields. The reaction involves reduction with Me2SiClH, followed by the attack of arenes in the presence of TfOH catalyst. The devised protocol offers scalability and remarkable tolerance towards various functional groups. Control experiments provide insights into the reaction mechanism, indicating an ionic pathway and highlighting the crucial roles of HFIP and Me2SiClH. Furthermore, the method is adaptable for late‐stage functionalization of numerous natural products and pharmaceuticals such as Sesamol, Thymol, Paracetamol, Menthol, and Nerol. Significantly, the technique has proven effective in the efficient synthesis of the anticoagulant drug Phenprocoumon and the rodent control agent Coumatetralyl.