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 di-aryl 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 a TfOH catalyst. The devised protocol offers scalability and remarkable tolerance towards various functional groups. Control experiments provide insights into the reaction mechanism, 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 efficiently synthesising the anticoagulant drug Phenprocoumon and the rodent control agent Coumatetralyl.