A Question on the Role of Triplet Oxygen in the Formation of Artemisinin
I offer the following thoughts on the paper you cite regarding the formation of artemisinin 9 from carboxylic acid 1. You are correct that the allylic hydroperoxide 2 is formed by an ene reaction with singlet oxygen (1O2). The stereochemistry of the hydroperoxide group is the result of the ene reaction occurring on the convex face of the unsaturated cis-decalin 1. The crude hydroperoxide 2 was exposed to an atmosphere of triplet oxygen (3O2) in a vigorously stirred mixture of petroleum ether and catalytic trifluoroacetic acid. The initial steps are 2 --> 6 via radicals 3, 4 and 5. Triplet oxygen forms hydroperoxide radical 3 which undergoes cyclization to 1,2-dioxetanyl radical 4. It is likely that radical 4 reacts with triplet oxygen prior to dioxetane fragmentation owing to the stereochemistry of the hydroperoxy radical in 5. The chain reaction is completed by the reaction of radical 5 with hydroperoxide 2. In the transformation 2 --> 3 the radical HOO was formed and can also intercede as a source of a hydrogen atom regenerating oxygen. Finally, acid-catalyzed cyclization of 6 leads to artemisinin (qinghaosu) 9. There is no issue of "forbidden" reactions.