Switchable and Chemoselective Arene Hydrogenation for Efficient Late Stage Applications

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Drug Discovery

Background:

• Incorporating 3D structures into drug molecules improves clinical success.
• Late-stage saturation of drug molecules is a key strategy for 3D structure formation.
• Selective reduction of aromatic rings, especially in complex molecules, remains a significant challenge.

Purpose of the Study:

• To develop a switchable and chemoselective hydrogenation method for benzene and pyridine rings.
• To provide a versatile protocol for accessing saturated cyclohexane and piperidine scaffolds.
• To explore the application of this method in late-stage drug functionalization.

Main Methods:

• Developed a novel catalytic system for selective hydrogenation of aromatic rings.
• Employed a fragment-screening technique to investigate substrate scope and utility.
• Applied the protocol to diverse molecular structures, including those with multiple aromatic systems.

Main Results:

• Achieved switchable and chemoselective hydrogenation of benzene and pyridine rings.
• Demonstrated broad substrate scope, yielding diverse cyclohexane and piperidine derivatives.
• Successfully applied the method to late-stage saturation of complex molecules.

Conclusions:

• The developed protocol offers a convenient route to saturated heterocyclic compounds prevalent in pharmaceuticals.
• This approach facilitates the late-stage modification of drug molecules, increasing sp3-carbon content.
• Enhancing sp3-carbon fractions holds potential for improving drug efficacy and medicinal properties.