Photochemical Hydrothiolation of Amorphadiene and Formal Synthesis of Artemisinin via a Pummerer Rearrangement

A new access to artemisinin is reported based on a selective photochemical hydrothiolation of amorphadiene, a waste product of the industrial semisynthetic route. This study highlights the discovery of two distinctive activation pathways under solvent-free conditions or using a photocatalyst promoting H-abstraction. Subsequently, a chemoselective oxidation of the resulting photochemically generated thioether, followed by a Pummerer rearrangement, affords dihydroartemisinic aldehyde, a key intermediate in the synthesis of artemisinin.

Automated summary

A new method for the preparation of artemisinin was reported based on selective photochemical hydrothiolation of amorphadiene. Two distinctive activation pathways were discovered under solvent-free conditions or using a photocatalyst promoting H-abstraction. The key intermediate dihydroartemisinic aldehyde in the synthesis of artemisinin was obtained through chemoselective oxidation of the photochemically generated thioether followed by Pummerer rearrangement.