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 O-1(2) by treatment of H2O2 with AIBX, a highly water-soluble, bench-stable, recyclable hypervalent iodine(V) reagent developed by our group. The generation of O-1(2) was confirmed by the following results: (1) capture of (1)O(2 )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 O-1(2) 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 O-1(2) : [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.

Automated summary

In this study, a efficient method for the generation of O-1(2) by treating H2O2 with AIBX was reported. The generation of O-1(2) was confirmed by experimental results, and the potential utility of this method for organic synthesis was demonstrated.