The Birch reduction is a cornerstone transformation in synthetic chemistry, yet its widespread application is limited by harsh conditions, poor functional group tolerance, and safety concerns. Recent photochemical strategies have offered milder alternatives but have largely been restricted to polycyclic arenes (Ered ∼ -2.6 V vs SCE) and poorly suited for complex molecules of pharmaceutical relevance. Here, we report a practical organocatalytic system that enables Birch-type reductions of electron-rich benzenes (Ered = 3-rich spirocyclic scaffolds, a valuable motif in medicinal chemistry. Demonstrated scalability in both batch and continuous-flow operation further underscores the translational potential of this system. This collaborative work with colleagues at Johnson & Johnson highlights the power of light-driven organocatalysis to deliver industrially relevant methods for the synthesis of complex drug-like molecules.
Schiel et al. (Tue,) studied this question.