Photochemical Ring Editing: Access to Privileged 1,2,5-Thiadiazole Scaffolds via Efficient Carbon Excision from Thiadiazines Under Ambient, Aerobic Conditions

Thiadiazoles are a privileged motif in medicinal chemistry, however selective mono-oxidation of the endocyclic sulfur, without over oxidation, is challenging. Herein, we report the quantitative conversion of 1,2,6-thiadiazines to 1,2,5-thiadiazole 1-oxides in the presence of visible light and molecular oxygen under ambient conditions. Experimental and computational studies reveal a probable mechanistic pathway for the cycloaddition-ring contraction cascade: under visible light irradiation in the presence of molecular oxygen, 1,2,6-thiadiazines act as triplet photosensitisers that produce singlet oxygen and subsequently undergo an unprecedented, chemoselective [3 + 2] cycloaddition reaction. The resulting endoperoxide undergoes a ring contraction, with selective carbon atom excision and complete atom economy. The reaction was optimised under both batch and continuous-flow conditions and proven to be efficient in wide range of solvents, including green solvents. Flow conditions enabled precise control over irradiance exposure, enabling exclusive access to photosensitive thiadiazole products. A comprehensive scope of 1,2,6-thiadiazines provided 35 examples of novel, difficult-to-access 1,2,5-thiadiazole 1-oxide structures.