Reaction Environment Design for Multigram Synthesis via Sonogashira Coupling over Heterogeneous Palladium Single-Atom...

Area of Science:

• Heterogeneous catalysis
• Green chemistry
• Organic synthesis

Background:

• Single-atom catalysts (SACs) offer atomic precision and high metal utilization.
• Current understanding of SACs is limited to model substrates, hindering broader application.
• Optimizing SACs requires understanding their interaction with the reaction environment.

Purpose of the Study:

• Investigate the influence of reaction environment (solvent, base, cocatalyst, ligand) on palladium SAC performance.
• Evaluate SACs in Sonogashira-Hagihara cross-couplings.
• Assess the potential for upscaling and sustainability.

Main Methods:

• Systematic variation of reaction parameters (solvent, base, cocatalyst, ligand).
• Testing palladium SACs in Sonogashira-Hagihara cross-couplings with various substrates.
• Multigram scale synthesis and catalyst reusability tests.
• Life-cycle assessment for upscaling and environmental impact.

Main Results:

• SAC performance deviates from homogeneous catalyst trends, indicating unique environmental interplay.
• Effective cross-couplings achieved with aryl iodides and acetylenes.
• Challenges remain for bromides and chlorides.
• Demonstrated multigram synthesis of an Erlotinib intermediate with catalyst stability and reusability.
• Life-cycle assessment highlights environmental and financial benefits.

Conclusions:

• Reaction environment significantly impacts SAC performance in cross-couplings.
• Palladium SACs demonstrate potential for sustainable organic synthesis.
• Further research is needed to fully elucidate SAC-environment interactions for broader application.