Synthesis of hydroxy lactones by selenium-mediated oxidation/cyclization of alkenoic acids under eco-flow conditions

During the last decade, there have been extraordinary advances in the development of novel methods for synthetic and medicinal chemistry programs. A significant contribution in the field has come from the use and application of flow technologyrev whose advantages have been demonstrated in the definition of safer and greener conditions for existing or novel reactions, in the preparation of compounds' libraries for biological screenings, as well as in the optimization of robust and reliable scale-up processes at lower costs and increased efficiency. In this communication, we describe a novel, efficient and green synthesis of hydroxy lactones under continuous flow conditions. The hydroxy lactone nucleus is the common structural framework and a valuable building block of numerous natural products and bioactive compounds, and its preparation is therefore considered an important target for synthesis. Although several approaches have been reported for the preparation of this scaffold, most of them suffer from certain limitations including the use of toxic and/or expensive catalysts and reagents, long reaction times, low regio- and stereoselectivity, as well as the restricted versatility in terms of substrate scope. Our method is based on a selenium-mediated cyclo-oxidation of alkenoic acids conducted in an integrated flow system and involves the use of benzenperseleninic acid and hydrogen peroxide as reagents, green solvents and mild reaction conditions. The results obtained will be discussed in terms of regio- and stereo-selectivity, substrate scope, scaling-out and eco-sustainability.