Aza-Michael Addition in Explicit Solvent: A Relative Energy Gradient-Interacting Quantum Atoms Study

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Physical Chemistry

Background:

• Aza-Michael additions are fundamental transformations in organic synthesis.
• Understanding solvent effects is crucial for controlling reaction outcomes and rates.
• Predicting electrophilicity is essential for designing efficient synthetic strategies.

Purpose of the Study:

• To investigate aza-Michael additions using theoretical and computational methods.
• To elucidate the role of dimethylsulfoxide as an explicit solvent in these reactions.
• To establish a connection between computational analysis and experimental measurements of electrophilicity.

Main Methods:

• Utilized the Relative Energy Gradient-Interacting Quantum Atoms (REG-IQA) method.
• Performed quantum topological energy decomposition analysis.
• Focused on the rate-limiting addition step of aza-Michael reactions.

Main Results:

• Detailed analysis of the rate-limiting step in aza-Michael additions with varying electrophiles.
• Quantified the influence of dimethylsulfoxide (DMSO) as an explicit solvent on reaction mechanisms.
• Established the first correlation between REG-IQA analysis and experimental data for predicting Mayr electrophilicity.

Conclusions:

• The REG-IQA method provides valuable insights into the mechanistic details of aza-Michael additions.
• Explicit solvent effects play a significant role in modulating reaction pathways and rates.
• This study bridges theoretical calculations with experimental observations, enhancing predictive capabilities in organic synthesis.