An organophotocatalytic redox-neutral strategy for late-stage drug functionalization with SO2 gas

Abstract

Sulfur dioxide (SO₂), a widely considered air pollutant, imposes major effects on ecosystems, human health, and the climate. A promising solution combines synthetic chemistry through SO₂ gas capture, transforming it into valuable pharmaceutical and agrochemical products such as sulfonamides, thiosulfonates, sulfonate esters, etc. Direct SO₂ gas capture and its catalytic functionalization are currently limited and require redox-non-neutral transition metal-based catalysts, harsh conditions, and expensive SO₂ substitutes/surrogates in stoichiometric amounts. This work presents a metal-free and redox-neutral organophotocatalytic strategy for direct SO₂ gas capture and its catalytic functionalization with various fine chemicals such as amines, alcohols, and thiols. It utilizes phenalenyl-based molecule as a photocatalyst. In-depth studies (EPR, UV-Vis, and fluorescence quenching) shed light on the reaction mechanism and elucidate the complete SO₂ activation cycle. A diverse array of bioactive motifs and clinically active molecules in the categories of antihistamine, antiplatelet, antipsychotic, antidementia, antidepressant, antioxidant, and antimalarial drugs, as well as terpenoids, natural products, amino acids, and peptides, were catalytically functionalized with gaseous SO₂ under metal-free conditions highlighting the synthetic potential of this protocol.