1,6-Hydrosulfonylation of p-quinone methides enabled via strain-release-/aromaticity-driven alkyl radical generation and SO2-capture: synthesis and antiproliferative studies of sulfonylated diarylmethanes

Abstract

The integration of γ-keto sulfones, despite being medicinally relevant building blocks, with the bioactive diarylmethane motif remains elusive. On the other hand, the fixation of SO₂ into organic molecules for accessing value-added products is gaining wide attention in organic synthesis. Herein, we disclose the 1,6-hydrosulfonylation of p-quinone methides via the strain-release driven ring-scission of strained 3°-cyclopropanols in the presence of a SO₂-surrogate like K₂S₂O₅ and a Brønsted 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-quinone methides has been developed via aromaticity-driven bond-scission in pro-aromatics like 4-alkyl-1,4-DHPs in the presence of K₂S₂O₅ and a Brønsted 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.