Driving Forces in the Sharpless Epoxidation Reaction: A Coupled AIMD/QTAIM Study

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Catalysis

Background:

• The Sharpless epoxidation is a crucial reaction in organic synthesis for creating chiral epoxides.
• Understanding the detailed mechanism, particularly the oxygen-transfer step, is key to optimizing this process.

Purpose of the Study:

• To elucidate the epoxide-formation step in the Sharpless epoxidation.
• To investigate the influence of various ligands and substrates on reaction energetics and kinetics.
• To analyze the role of the active catalyst in reaction outcomes.

Main Methods:

• Density Functional Theory (DFT) calculations for 263 oxygen-transfer reactions.
• Bader's Quantum Theory of Atoms in Molecules (QTAIM) analysis for electronic structure.
• Ab initio molecular dynamics (AIMD) simulations for a subset of reactions.

Main Results:

• Vanadium(V) tert-butylhydroperoxide adducts were identified as the most exoenergetic catalysts.
• Ligands showed a limited effect on reaction thermodynamics and kinetics.
• No preference was observed for epoxidizing allylic alcohols over unfunctionalized alkenes.
• Substrate orientation significantly impacts the reaction pathway, confirming regioselectivity.

Conclusions:

• The active catalyst's identity is crucial for the thermodynamic outcome of Sharpless epoxidation.
• Ligand and substrate variations have minor effects on reaction modulation.
• Reaction path selectivity is primarily governed by substrate approach orientation.