Singlet Oxygen Generation from a Water-Soluble Hypervalent Iodine(V) Reagent AIBX and H₂O₂: An Access to Artemisinin

Herein, we report an efficient method for the chemical generation of ¹O₂ by treatment of H₂O₂ with AIBX, a highly water-soluble, bench-stable, recyclable hypervalent iodine(V) reagent developed by our group. The generation of ¹O₂ was confirmed by the following results: (1) capture of ¹O₂ with the sodium salt of anthracene-9,10-bis(ethanesulfonate) produced the corresponding endoperoxide and (2) TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) produced by the oxidation of 2,2,6,6-tetramethylpiperidine with ¹O₂ generated using the AIBX/H₂O₂ system was detected by electron spin resonance spectroscopy. To illustrate the potential utility of this method for organic synthesis, we used the AIBX/H₂O₂ system to perform typical reactions of ¹O₂: [2 + 2]/[4 + 2] cycloadditions, Schenck ene reactions, and heteroatom oxidation reactions, which afforded the corresponding products in high yields. Moreover, we used the method to synthesize the antimalarial drug artemisinin. Finally, we demonstrated that AIBX could be regenerated after the reaction by means of a workup involving extraction and removal of water to obtain a precursor of AIBX, which could then be re-oxidized.