Iron photocatalysis unlocks ozone's power for ultrafast sulfide-to-sulfone oxidation in continuous flow

Abstract

Sulfones are privileged structures, yet their synthesis heavily relies on toxic, waste-intensive oxidants. Adopting potent, greener oxidants like ozone (O₃) offers sustainability, but inherent mass and heat transfer bottlenecks in batch reactors provoke hazardous accumulation and severe explosion risks. While continuous-flow technology safely harnesses these energetic oxidants, it exposes a kinetic paradox: within ultrashort, second-scale residence times, even ozone's intrinsic reactivity is insufficient, causing the oxidation to arrest prematurely at the sulfoxide intermediate. Herein, we report a robust and sustainable continuous-flow strategy enabled by Earth-abundant iron photocatalysis that unlocks the oxidative potential of ozone. This unique activation paradigm achieves the direct, highly selective oxidation of diverse sulfides to sulfones using exclusively an elemental oxygen-based oxidant within a mere 7–9 seconds. Using an inexpensive iron(III) nitrate catalyst under visible light, the protocol's green credentials and robustness are demonstrated by its broad scope, gram-scale scalability, seamless catalyst recyclability, and successful application to pharmaceuticals, key drug intermediates, and novel herbicides. Mechanistic studies reveal that iron photocatalysis generates reactive oxygen species (˙O₂⁻ and ¹O₂) in situ, effectively surmounting the kinetic barrier. This work offers an environmentally benign, efficient route to sulfones while conceptualizing a new paradigm for overcoming kinetic limitations in ultrafast flow chemistry.