1,6-Hydrosulfonylation of para-Quinone Methides Enabled via Strain Release-/Aromaticity-Driven Alkyl Radical Generation and SO2-Capture: Synthesis, Computational and Antiproliferative Activity of Sulfonylated Diarylmethanes

Integrating γ-keto sulfones with the bioactive diarylmethane motif remains elusive despite being a medicinally relevant building block. On the other hand, the fixation of SO2 in organic molecules for accessing value-added products is gaining wide attention in organic synthesis. Herein, we disclose the 1,6-hydrosulfonylation of p-quinomethides via the strain-release driven ring-scission of strained 3°-cyclopropanols in the presence of a SO2-surrogate like K2S2O5 and a Bronsted acid under visible-light photoredox catalysis to access a library of γ-keto alkylsulfonylated diarylmethanes in moderate to good yields. Also, the 1,6-hydrosulfonylation of p-quinomethides is developed via the aromaticity-driven bond-scission in pro-aromatics like 4-alkyl-1,4-DHPs in the presence of K2S2O5 and a Bronsted acid under visible-light photoredox catalysis to access a library of alkylsulfonylated diarylmethanes. The efficiency of the developed reactions has been established through broad substrate-scope studies, and the mechanistic probing studies have been complemented with DFT calculations to support the proposed mechanisms. In addition, antiproliferative studies revealed oral cancer activity for some of the synthesized sulfonylated diarylmethane derivatives.