Abstract:

The nucleophilic addition of Grignard reagents with carbonyl compounds is a classical reaction to construct C-C bonds, which is frequently accompanied by side-reactions, mainly including the enolization and reduction of carbonyl compounds. To explore the molecular mechanism of these three reactions, quantum chemical calculations were performed on the reaction of ethylmagnesium bromide (EtMgBr) with diisopropyl ketone (CO(iPr)₂), a prototypical reaction of Grignard reagents with carbonyl compounds. It is found that diethyl magnesium (MgEt₂) obtained from the Schlenk equilibrium of EtMgBr, is more active toward CO(iPr)₂ than EtMgBr, which is generally described as the virtual active species in the textbook. The diethylether is shown to play a substantial role in the reactivity, especially in favor of nucleophilic addition reaction. The calculated energy barriers of the three reactions can rationalized the experimentally observed main product to by-products yield ratio.

Key words: Grignard reagents, Carbonyl compounds, Nucleophilic addition, Reduction, Enolization