Water‐Assisted and Catalyst‐Free Hetero‐Michael Additions: Mechanistic Insights from DFT Investigations

Abstract The reaction mechanism of six catalyst‐free hetero‐Michael addition reactions in water has been investigated using DFT calculations. Our theoretical results revealed the direct involvement of multiple water molecules in the transition states. The water molecules play a catalytic role in lowering the activation barrier for the three thia‐Michael reactions. Concerted transition state with two bridging water molecules yields the lowest energy barrier. The formation of a hydrogen bonding network via one or more water molecules in the transition state facilitates proton shuttling from the nucleophile to the electrophile. For the aza‐Michael reactions considered, they follow a stepwise mechanism involving the formation of a stable zwitterionic intermediate. In these cases, water influences the reactions via strong (nonspecific) solvent effect and the catalytic role of water is less important for enones that adopt a stable s ‐cis conformation. The calculated low reaction barriers (44–83 kJ/mol) of the six studied reactions are in excellent accord with the observed facile hetero‐Michael reactions in water.