Direct synthesis of oxaspirolactones in batch, photoflow, and silica gel-supported solvent-free conditions via visible-light photo- and heterogeneous Brønsted acid relay catalysis

Abstract

By fusing energy-transfer visible-light photocatalysis and heterogeneous Brønsted acid catalysis, an operationally straightforward synthesis of oxaspirolactones, natural scaffolds present in many molecules with therapeutic properties, is described. Sequential photooxygenation with singlet oxygen (¹O₂) and acid-facilitated ketalization of silylated hydroxyalkyl furans affords the target compounds in quantitative yields and broad scope while only using green solvents and an energy-saving light source. In addition, translation of the developed method into photoflow and chromatography-grade silica gel-supported solvent-free conditions demonstrates good scalability and simplification of the reaction process. The latter procedure was further shown to be amenable to sunlight and air as natural sources of light and molecular oxygen, which are necessary for the reaction. Preliminary control studies are also presented to further shed light into the mechanism of the transformation under study. Additionally, the EcoScale and green metrics of the established protocols were evaluated for benchmarking against some reported methodologies in the literature.