Electrochemical Generation of Peroxy Radicals and Subsequent Peroxidation of 1,3-Dicarbonyls in an Undivided Cell

Abstract

The generation of peroxy radicals from hydroperoxides with subsequent selective peroxidation of 1,3-dicarbonyls in an undivided electrochemical cell under constant current conditions is reported. The method provides a variety of peroxy-containing barbituric acids and 4-hydroxy-2(5H)furanones with yields of up to 74%. Only the combination of anodic and cathodic processes provides efficient peroxidation by generating a set of alkoxy and peroxy radicals. NaNO 3 acts as both an electrolyte and a redox mediator of radical reactions.O rganic peroxides have been widely used as radical initiators in polymer industry and material science over the last century. 1 Recently, organic peroxides were recognized as attractive synthetic targets on their own due to their high antimalarial, 2,3 antihelmintic, 4 cytotoxic, 5 fungicidal, 6,7 and antiviral 8,9 activities. Stable peroxides open up a new dimension in medicinal chemistry, providing a basis for new drugs 10 such as the Nobel Prize-winning antimalarial artemisinin. 11 Therefore, developing selective approaches to introduce a peroxide fragment into organic compounds represents a timely task. Despite the growing body of high-quality research, the scope of peroxide construction approaches still lags behind those of the more common oxygen-containing organic functionalities. State of the art peroxidation methods are generally based on the application of several key intermediates: H 2 O 2 or hydroperoxides as nucleophiles, 12 O 3 , 13,14 O 2 , and peroxy radicals. 15,16 Peroxy radicals can be formed from available hydroperoxides by heating, 17,18 irradiation, 19 and redox reactions with transition metals 20−22 or iodine species (Scheme 1). 23 The main idea of our study is to generate peroxy radicals from hydroperoxides with electric current and to use these reactive species for further peroxidation (Scheme 1). Previously, the use of electrochemistry to generate peroxy radicals from TBHP resulted exclusively in active oxygen transfer oxidation with the formation of ketones (Scheme 2c). 24 Electroorganic synthesis is now regarded as one of the most rapidly advancing areas of organic chemistry. 25−30 Much attention is paid to electrochemical approaches to C−H functionalization, 31 metal complex catalysis, 32,33 and radical processes. 34−36 Nowadays, peroxide chemistry meets electrochemistry usually in H 2 O 2 electrogeneration via oxygen reduction reaction (ORR) or water oxidation (WOR) reactions, which have various potential applications in energy storage, and wastewater treatment (Scheme 2a). 37−39 The electrogenerated