A Quantum-Guided Molecular Mechanics Force Field for the Ferrocene Scaffold

Area of Science:

• Organometallic Chemistry
• Computational Chemistry
• Catalysis

Background:

• Ferrocene derivatives are crucial ligands in asymmetric catalysis due to their stability and stereochemical properties.
• Existing molecular mechanics force fields lack accurate parameters for ferrocene compounds, limiting computational studies.

Purpose of the Study:

• To develop and validate a new MM3* force field for ferrocenyl ligands.
• To assess the accuracy of the developed force field in predicting stereochemical outcomes of catalytic reactions.

Main Methods:

• Generation of MM3* force field parameters for ferrocenyl ligands using the quantum-guided molecular mechanics (Q2MM) method.
• Validation against Density Functional Theory (DFT) calculations and crystal structure data.
• Integration with existing force fields for palladium-allyl complexes and transition states.

Main Results:

• The developed MM3* force field demonstrates high accuracy for ferrocenyl ligands, validated by DFT and crystallographic data.
• The force field is compatible with existing MM3* parameters for related systems.
• Successful prediction of stereochemical outcomes in palladium-catalyzed aminations with an R² of ~0.91.

Conclusions:

• The new MM3* force field provides an accurate computational tool for studying ferrocene-based ligands in catalysis.
• This development facilitates the design and optimization of chiral ferrocenyl ligands for asymmetric synthesis.
• The validated force field enables reliable prediction of reaction stereochemistry, aiding catalyst development.