Switchable and Chemoselective Arene Hydrogenation for Efficient Late Stage Applications

Abstract

The incorporation of three-dimensional structures into drug molecules has demonstrated significant improvements in clinical success. Late-stage saturation of drug molecules provides a direct pathway for this transformation. However, achieving selective and controllable reduction of aromatic rings remains challenging, particularly when multiple aromatic rings coexist. Herein, we present the switchable and chemoselective hydrogenation of benzene and pyridine rings. The utility of the protocol has been comprehensively investigated in diversified substrates with the assistance of a fragment-screening technique. This approach provides convenient access to a diverse array of cyclohexane and piperidine compounds, prevalent in various bioactive molecules and drugs. Furthermore, it discloses promising avenues for applications in the late-stage switchable saturation of drugs, facilitating an increase in the fraction of sp³-carbons which holds the potential to enhance the medicinal properties of drugs.